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Haemodynamics
Kinds of Haemodynamics Terms modified by Haemodynamics Selected AbstractsSildenafil Improves the Beneficial Haemodynamic Effects of Intravenous Nitrite Infusion during Acute Pulmonary EmbolismBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2008Carlos A. Dias-Junior While previous studies have shown that sildenafil (an inhibitor of cGMP-specific phosphodiesterase type 5) or nitrite (a storage molecule for nitric oxide) produces beneficial effects during acute pulmonary embolism, no previous study has examined whether the combination of these drugs can produce additive effects. Here, we expand previous findings and examine whether sildenafil enhances the beneficial haemodynamic effects produced by a low-dose infusion of nitrite in a dog model of acute pulmonary embolism. Haemodynamic and arterial blood gas evaluations were performed in non-embolized dogs treated with saline (n = 4), and in embolized dogs (intravenous injections of microspheres) that received nitrite (6.75 µmol/kg intravenously over 15 min. followed by 0.28 µmol/kg/min.) and sildenafil (0.25 mg/kg over 30 min.; n = 8), or nitrite followed by saline (n = 8), or saline followed by sildenafil (n = 7), or only saline (n = 8). Plasma thiobarbituric acid-reactive substances (TBARS) concentrations were determined using a fluorometric method. Acute pulmonary embolism increased pulmonary artery pressure by ,24 mmHg. While the infusion of nitrite or sildenafil infusions reversed this increase by ,42% (both P < 0.05), the combined infusion of both drugs reversed this increase by ,58% (P < 0.05). Similar effects were seen on the pulmonary vascular resistance index. Nitrite or sildenafil alone produced no significant hypotension. However, the combined infusion of both drugs caused transient hypotension (P < 0.05). Both dugs, either alone or combined, blunted the increase in TBARS concentrations caused by acute pulmonary embolism (all P < 0.05). These results suggest that sildenafil improves the beneficial haemodynamic effects of nitrite during acute pulmonary embolism. [source] PRETREATMENT WITH INTRAVENOUS ASCORBIC ACID PRESERVES ENDOTHELIAL FUNCTION DURING ACUTE HYPERGLYCAEMIA (R1)CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2005Brian A Mullan SUMMARY 1.,Acute hyperglycaemia may impair endothelial function. Ascorbic acid (AA), administered intra-arterially, has been reported to improve endothelium-dependent vasodilatation during a forearm hyperglycaemic clamp. Using a randomized, double-blind, placebo-controlled, cross-over study, we investigated the potential for intravenous ascorbic acid to modify the endothelial response to acute systemic hyperglycaemia in humans. 2.,Nine healthy male volunteers were recruited from the hospital staff. Endothelial function was determined by measuring the forearm blood flow responses to intrabrachial infusions of endothelium-dependent (ED) and endothelium-independent (EID) vasodilators. The endothelial function index (EFI) was derived from the ratio of ED and EID vasodilatation. Haemodynamic and endothelial function measurements were performed at baseline and then repeated 2 h after a systemic hyperglycaemic clamp (14 mmol/L). The subjects, studied on two separate occasions, were randomized to placebo or 2 g intravenous ascorbic acid prior to the initiation of hyperglycaemia. 3.,After systemic hyperglycaemia with placebo pretreatment, the EFI fell from 1.08 ± 0.21 to 0.74 ± 0.13 (difference (95% confidence interval): 0.34 (0.20, 0.47); P < 0.001). When subjects were pretreated with ascorbic acid, the EFI was not affected by hyperglycaemia (1.11 ± 0.21 to 1.12 ± 0.17; P = 0.938). This difference between placebo and ascorbic acid was significant (P < 0.001). Plasma ascorbate concentrations decreased during hyperglycaemia and correlated directly with the reduction in the EFI (r = 0.798; P < 0.001). 4.,Pretreatment with an intravenous bolus of ascorbic acid can prevent endothelial dysfunction during acute systemic hyperglycaemia. Therefore, ascorbic acid may have potential therapeutic use in clinical situations where acute hyperglycaemia may be a complication. [source] Role of neuronal nitric oxide synthase in response to hypertonic saline loading in ratsACTA PHYSIOLOGICA, Issue 4 2004R. Wangensteen Abstract Aims:, This study analyses the influence of neuronal nitric oxide synthase (nNOS) blockade with 7-nitroindazole (7NI) on the haemodynamic and renal response to a hypertonic saline load (HSL). We also evaluated the effects of non-specific NOS inhibitor N, -nitro- l -arginine methyl ester (l -NAME). Methods:, The following groups were used: controls, rats treated with 7NI at 0.5 or 5 mg kg,1, and rats treated with l -NAME at 0.5 or 5 mg kg,1. A further five groups received an isotonic saline load (ISL). Results:, Mean arterial pressure (MAP) was significantly increased in control rats after HSL. MAP was further increased in both 7NI-treated groups, and the l -NAME groups showed marked dose-related pressor responses. During ISL, MAP was only significantly increased in the group treated with 5 mg kg,1 of l -NAME. The pressure,natriuresis relationship during the experimental period after the HSL was reduced in the 7NI group treated with 5 mg kg,1 and severely attenuated in both l -NAME groups. The increase in plasma sodium was significantly greater after the HSL in both 7NI groups and both l -NAME groups compared with controls. Conclusions:, The present results suggest that nNOS and other NOS isozymes play a counter-regulatory role in the pressor response to HSL. Moreover, the blockade of nNOS with the higher dose of 7NI produces a blunted pressure,natriuresis relationship in response to the HSL. Finally, it is concluded that nNOS participates in the homeostatic cardiovascular and renal response to hypertonic saline loading by attenuating the blood pressure increase and hypernatremia, and facilitating natriuresis. [source] Effect of angiotensin II and endothelin-1 receptor blockade on the haemodynamic and hormonal changes after acute blood loss and after retransfusion in conscious dogsACTA PHYSIOLOGICA, Issue 4 2004R. C. E. Francis Abstract Aim:, This study investigates angiotensin II and endothelin-1 mediated mechanisms involved in the haemodynamic, hormonal, and renal response towards acute hypotensive haemorrhage. Methods:, Conscious dogs were pre-treated with angiotensin II type 1 (AT1) and/or endothelin-A (ETA) receptor blockers or not. Protocol 1: After a 60-min baseline period, 25% of the dog's blood was rapidly withdrawn. The blood was retransfused 60 min later and data recorded for another hour. Protocol 2: Likewise, but preceded by AT1 blockade with i.v. Losartan. Protocol 3: Likewise, but preceded by ETA blockade with i.v. ABT-627. Protocol 4: Likewise, but with combined AT1plus ETAblockade. Results:, In controls, haemorrhage decreased mean arterial pressure (MAP) by approximately 25%, cardiac output by approximately 40%, and urine volume by approximately 60%, increased angiotensin II (3.1-fold), endothelin-1 (1.13-fold), vasopressin (116-fold), and adrenaline concentrations (3.2-fold). Glomerular filtration rate and noradrenaline concentrations remained unchanged. During AT1 blockade, the MAP decrease was exaggerated (,40%) and glomerular filtration rate fell. During ETA blockade, noradrenaline increased after haemorrhage instead of adrenaline, and the MAP recovery after retransfusion was blunted. The decrease in cardiac output was similar in all protocols. Conclusions:, Angiotensin II is more important than endothelin-1 for the short-term regulation of MAP and glomerular filtration rate after haemorrhage, whereas endothelin-1 seems necessary for complete MAP recovery after retransfusion. After haemorrhage, endothelin-1 seems to facilitate adrenaline release and to blunt noradrenaline release. Haemorrhage-induced compensatory mechanisms maintain blood flow more effectively than blood pressure, as the decrease in cardiac output , but not MAP , was similar in all protocols. [source] Cardiac hypertrophy and failure: lessons learned from genetically engineered miceACTA PHYSIOLOGICA, Issue 1 2001Y. Takeishi Congestive heart failure is a major and growing public health problem. Because of improved survival of myocardial infarction patients produced by thrombolytic therapy or per-cutaneous revascularization it represents the only form of cardiovascular disease with significantly increased incidence and prevalence. Clinicians view this clinical syndrome as the final common pathway of diverse pathologies such as myocardial infarction and haemodynamic overload. Insights into mechanisms for heart failure historically derived from physiological and biochemical studies which identified compensatory adaptations for the haemodynamic burden associated with the pathological condition including utilization of the Frank Starling mechanism, augmentation of muscle mass, and neurohormonal activation to increase contractility. Therapy has largely been phenomenological and designed to prevent or limit the deleterious effects of these compensatory processes. More recently insights from molecular and cell biology have contributed to a more mechanistic understanding of potential causes of cardiac hypertrophy and failure. Many different analytical approaches have been employed for this purpose. These include the use of conventional animal models which permit serial observation of the onset and progression of heart failure and a sequential analysis of underlying biochemical and molecular events. Neonatal murine cardiomyocytes have been a powerful tool to examine in vitro subcellular mechanisms devoid of the confounding functional effects of multicellular preparations and heterogeneity of cell type. Finally, significant progress has been made by utilizing tissue from human cardiomyopathic hearts explanted at the time of orthotopic transplantation. Each of these methods has significant advantages and disadvantages. Arguably the greatest advance in our understanding of cardiac hypertrophy and failure over the past decade has been the exploitation of genetically engineered mice as biological reagents to study in vivo the effects of alterations in the murine genome. The power of this approach, in principle, derives from the ability to precisely overexpress or ablate a gene of interest and examine the phenotypic consequences in a cardiac specific post-natal manner. In contrast to conventional animal models of human disease which employ some form of environmental stress, genetic engineering involves a signal known molecular perturbation which produces the phenotype. [source] Bilateral optic atrophy following diabetic ketoacidosisDIABETIC MEDICINE, Issue 5 2000S. H. Song Summary Diabetic ketoacidosis (DKA) can result in neuropathic abnormalities of the somatic and the autonomous nervous systems. We report the case of a 50-year-old man with Type 1 diabetes of 20-year duration who after severe DKA lost vision in his right eye and only retain partial vision in his left. This case demonstrates that optic neural tissue is vunerable to haemodynamic and metabolic complications of DKA. [source] Cardiopulmonary, blood and peritoneal fluid alterations associated with abdominal insufflation of carbon dioxide in standing horsesEQUINE VETERINARY JOURNAL, Issue 3 2003F. G. LATIMER Summary Reasons for performing study: Abdominal insufflation is performed routinely during laparoscopy in horses to improve visualisation and facilitate instrument and visceral manipulations during surgery. It has been shown that high-pressure pneumoperitoneum with carbon dioxide (CO2) has deleterious cardiopulmonary effects in dorsally recumbent, mechanically ventilated, halothane-anaesthetised horses. There is no information on the effects of CO2 pneumoperitoneum on cardiopulmonary function and haematology, plasma chemistry and peritoneal fluid (PF) variables in standing sedated horses during laparoscopic surgery. Objectives: To determine the effects of high pressure CO2 pneumoperitoneum in standing sedated horses on cardiopulmonary function, blood gas, haematology, plasma chemistry and PF variables. Methods: Six healthy, mature horses were sedated with an i.v. bolus of detomidine (0.02 mg/kg bwt) and butorphanol (0.02 mg/kg bwt) and instrumented to determine the changes in cardiopulmonary function, haematology, serum chemistry and PF values during and after pneumoperitoneum with CO2 to 15 mmHg pressure for standing laparoscopy. Each horse was assigned at random to either a standing left flank exploratory laparoscopy (LFL) with CO2 pneumoperitoneum or sham procedure (SLFL) without insufflation, and instrumented for measurement of cardiopulmonary variables. Each horse underwent a second procedure in crossover fashion one month later so that all 6 horses had both an LFL and SLFL performed. Cardiopulmonary variables and blood gas analyses were obtained 5 mins after sedation and every 15 mins during 60 mins baseline (BL), insufflation (15 mmHg) and desufflation. Haematology, serum chemistry analysis and PF analysis were performed at BL, insufflation and desufflation, and 24 h after the conclusion of each procedure. Results: Significant decreases in heart rate, cardiac output and cardiac index and significant increases in mean right atrial pressure, systemic vascular resistance and pulmonary vascular resistance were recorded immediately after and during sedation in both groups of horses. Pneumoperitoneum with CO2 at 15 mmHg had no significant effect on cardiopulmonary function during surgery. There were no significant differences in blood gas, haematology or plasma chemistry values within or between groups at any time interval during the study. There was a significant increase in the PF total nucleated cell count 24 h following LFL compared to baseline values for LFL or SLFL at 24 h. There were no differences in PF protein concentrations within or between groups at any time interval. Conclusions: Pneumoperitoneum with CO2 during standing laparoscopy in healthy horses does not cause adverse alterations in cardiopulmonary, haematology or plasma chemistry variables, but does induce a mild inflammatory response within the peritoneal cavity. Potential relevance: High pressure (15 mmHg) pneumoperitoneum in standing sedated mature horses for laparoscopic surgery can be performed safely without any short-term or cumulative adverse effects on haemodynamic or cardiopulmonary function. [source] Effects of phlebotomy on haemodynamic characteristics during exercise in Standardbred trotters with red cell hypervolaemiaEQUINE VETERINARY JOURNAL, Issue 4 2001P. FUNKQUIST Summary Five Standardbred trotters with red cell hypervolaemia (RCHV) were compared before and after removal of approximately 22% (36 ml/kg bwt) of the total blood volume in order to evaluate the haemodynamic responses, haemorheological alterations and oxygen transport during exercise to fatigue. Data were recorded during submaximal exercise at 4 different speeds on a treadmill and then during continued running at the highest speed step until fatigue. Oxygen uptake (V,O2), pulmonary artery pressure (PAP), systemic artery pressure (SAP), heart rate (HR), haematocrit and haemoglobin concentrations (Hb) were measured. Arteriovenous O2 content difference (C(a-v,)O2), pulmonary vascular resistance (PVR) and total systemic resistance (TSR) were calculated. Whole blood and plasma viscosity and erythrocyte aggregation tendency were determined with a rotational viscometer. Endoscopy was performed after exercise. ANOVA was used for statistical analysis. Phlebotomy resulted in a decrease in haematocrit and Hb during the course of exercise. Blood and plasma viscosity were lower and erythrocyte aggregation tendency was higher after phlebotomy. Throughout exercise, including submaximal work and continued running to fatigue, PAP, SAP, PVR, TSR and C(a-v,)O2 were lower after phlebotomy. HR was higher after phlebotomy during submaximal exercise. Oxygen delivery and VO2 were lower after phlebotomy in the period from submaximal exercise to fatigue. Run time to fatigue was shorter after phlebotomy. Four horses showed exercise-induced pulmonary haemorrhage (EIPH) before phlebotomy and the degree of bleeding was diminished but not abolished after phlebotomy. The reductions in PVR, TSR, PAP and SAP after phlebotomy were probably a result of reduced blood viscosity. In conclusion, although a 22% reduction in blood volume improved the haemodynamic and haemorheological parameters and the degree of EIPH, it was found that RCHV trotters have to rely on high oxygen delivery to the working muscles for maintenance of maximal performance. [source] The effects of maximal treadmill graded exercise testing on haemorheological, haemodynamic and flow cytometry platelet markers in patients with systolic or diastolic heart failureEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2008I. Chung ABSTRACT Background, Acute exercise has been associated with activation of thrombosis, and this risk may be accentuated in patients with heart failure. Given the relation of platelets to atherothrombosis, we tested the hypothesis that acute exercise would adversely affect platelet indices and platelet activation markers in patients with systolic and diastolic heart failure. Materials and methods, We studied 20 patients with systolic heart failure (17 men, 3 women; mean age 64 ± 10 years, all with ejection fraction (EF) , 40%) and 20 patients with diastolic heart failure (14 men, 6 women; mean age 64 ± 8 years, mean EF = 66%) who were exercised to maximal intensity, who were compared to 13 healthy controls (6 men, 7 women; mean age 60 ± 4 years, mean EF = 73%). We measured platelet indices (platelet volume, mass and component) and platelet activation markers (platelet-bound CD62P%G, CD63%G and CD40L%G using flow cytometry, as well as plasma sCD40L and soluble P-selectin (sP-sel) levels). Results, Baseline Mean Platelet Volume (MPV), sP-sel, CD40L%G and CD63%G levels were significantly higher in patients with systolic and diastolic heart failure, when compared with controls. The mean exercise duration and VO2 peak in patients with systolic and diastolic heart failure were not significantly different, but lower than that seen in healthy controls. Following exercise, mean haematocrit, CD62P%G, and CD63%G significantly increased in all three subject groups (all P < 0·05). The proportional change in CD62P%G and CD63%G were not significantly different between healthy controls and heart failure patients (P > 0·05). Conclusion, Acute maximal graded exercise increases platelet activation markers, with no disproportionate differences between heart failure patients and healthy controls, despite the former group having a lower exercise tolerance and VO2 peak. [source] Circulating levels of copeptin, a novel biomarker, in lower respiratory tract infectionsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2007B. Müller Abstract Background, Vasopressin has haemodynamic as well as osmoregulatory effects, and reflects the individual stress response. Copeptin is cosynthesized with vasopressin, directly mirroring vasopressin levels, but is more stable in plasma and serum. Both levels are increased in patients with septic shock. Lower respiratory tract infections (LRTI) are a precursor of sepsis. Thus, we investigated circulating levels and the prognostic use of copeptin for the severity and outcome in patients with LRTI. Materials and methods, Five hundred and forty-five consecutive patients with LRTI and 50 healthy controls were evaluated. Serum copeptin levels were measured with a new chemiluminescens sandwich immunoassay. Results, Of the 545 patients, 373 had community-acquired pneumonia (CAP), 60 acute exacerbations of chronic obstructive pulmonary disease (COPD), 59 acute bronchitis, 13 exacerbations of asthma and 40 other final diagnoses. Copeptin levels were significantly higher in patients with LRTI as compared to controls (P < 0·001) with highest levels in patients with CAP. Copeptin levels increased with increasing severity of CAP, as classified by the pneumonia severity index (PSI) (P < 0·001). In patients who died, copeptin levels on admission were significantly higher as compared to levels in survivors [70·0 (28·8,149·0) vs. 24·3 (10·8,43·8) pmol L,1, P < 0·001]. The area under the receiver operating curve (AUC) for survival was 0·75 for copeptin, which was significantly higher as compared to C-reactive protein (AUC 0·61, P = 0·01), leukocyte count (AUC 0·59, P = 0·01) and similar to procalcitonin (AUC 0·68, P = 0·21). Conclusions, Copeptin levels are increased with increasing severity of LRTI namely in patients with CAP and unfavourable outcome. Copeptin levels, as a novel biomarker, might be a useful tool in the risk stratification of patients with LRTI. [source] New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathologyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2004G. Wolf Abstract Although debated for many years whether haemodynamic or structural changes are more important in the development of diabetic nephropathy, it is now clear that these processes are interwoven and present two sides of one coin. On a molecular level, hyperglycaemia and proteins altered by high blood glucose such as Amadori products and advanced glycation end-products (AGEs) are key players in the development of diabetic nephropathy. Recent evidence suggests that an increase in reactive oxygen species (ROS) formation induced by high glucose-mediated activation of the mitochondrial electron-transport chain is an early event in the development of diabetic complications. A variety of growth factors and cytokines are then induced through complex signal transduction pathways involving protein kinase C, mitogen-activated protein kinases, and the transcription factor NF-,B. High glucose, AGEs, and ROS act in concert to induce growth factors and cytokines. Particularly, TGF-, is important in the development of renal hypertrophy and accumulation of extracellular matrix components. Activation of the renin-angiotensin system by high glucose, mechanical stress, and proteinuria with an increase in local formation of angiotensin II (ANG II) causes many of the pathophysiological changes associated with diabetic nephropathy. In fact, it has been shown that angiotensin II is involved in almost every pathophysiological process implicated in the development of diabetic nephropathy (haemodynamic changes, hypertrophy, extracellular matrix accumulation, growth factor/cytokine induction, ROS formation, podocyte damage, proteinuria, interstitial inflammation). Consequently, blocking these deleterious effects of ANG II is an essential part of every therapeutic regiment to prevent and treat diabetic nephropathy. Recent evidence suggests that regression of diabetic nephropathy could be achieved under certain circumstances. [source] Effect of epidural dexmedetomidine on intraoperative awareness and post-operative pain after one-lung ventilationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2010M. ELHAKIM Background: During combined general and regional anaesthesia, it is difficult to use autonomic signs to assess whether wakefulness is suppressed adequately. We compared the effects of a dexmedetomidine,bupivacaine mixture with plain bupivacaine for thoracic epidural anaesthesia on intraoperative awareness and analgesic benefits, when combined with superficial isoflurane anaesthesia (<0.05 maximum alveolar concentration) in patients undergoing thoracic surgery with one-lung ventilation (OLV). Methods: Fifty adult male patients were randomly assigned to receive either epidural dexmedetomidine 1 ,g/kg with bupivacaine 0.5% (group D) or bupivacaine 0.5% alone (group B) after induction of general anaesthesia. Gasometric, haemodynamic and bispectral index values were recorded. Post-operative verbal rating score for pain and observer's assessment of alertness/sedation scale were determined by a blinded observer. Results: Dexmedetomidine reduced the use of supplementary fentanyl during surgery. Patients in group B consumed more analgesics and had higher pain scores after operation than patients of group D. The level of sedation was similar between the two groups in the ICU. Two patients (8%) in group B reported possible intraoperative awareness. There was a limited decrease in PaO2 at OLV in group D compared with group B (P<0.05). Conclusion: In thoracic surgery with OLV, the use of epidural dexmedetomidine decreases the anaesthetic requirements significantly, prevents awareness during anaesthesia and improves intraoperative oxygenation and post-operative analgesia. [source] Opioids and opiates: analgesia with cardiovascular, haemodynamic and immune implications in critical illnessJOURNAL OF INTERNAL MEDICINE, Issue 2 2006P. E. MOLINA Abstract. Traumatic injury, surgical interventions and sepsis are amongst some of the clinical conditions that result in marked activation of neuroendocrine and opiate responses aimed at restoring haemodynamic and metabolic homeostasis. The central activation of the neuroendocrine and opiate systems, known collectively as the stress response, is elicited by diverse physical stressor conditions, including ischaemia, glucopenia and inflammation. The role of the hypothalamic,pituitary,adrenal axis and sympathetic nervous system in counterregulation of haemodynamic and metabolic alterations has been studied extensively. However, that of the endogenous opiates/opioid system is still unclear. In addition to activation of the opiate receptor through the endogenous release of opioids, pharmacotherapy with opiate receptor agonists is frequently used for sedation and analgesia of injured, septic and critically ill patients. How this affects the haemodynamic, cardiovascular, metabolic and immune responses is poorly understood. The variety of opiate receptor types, their specificity and ubiquitous location both in the central nervous system and in the periphery adds additional complicating factors to the clear understanding of their contribution to the stress response to the various physical perturbations. This review aims at discussing scientific evidence gathered from preclinical studies on the role of endogenous opioids as well as those administered as pharmacological agents on the host cardiovascular, neuroendocrine, metabolic and immune response mechanisms critical for survival from injury in perspective with clinical observations that provide parallel assessment of relevant outcome measures. When possible, the clinical relevance and corresponding scenarios where this evidence can be integrated into our understanding of the clinical implications of opiate effects will be examined. Overall, the scientific basis to enhance clinical judgment and expectations when using opioid sedation and analgesia in the management of the injured, septic or postsurgical patient will be discussed. [source] Clinical trial: a randomized controlled study on prevention of variceal rebleeding comparing nadolol + ligation vs. hepatic venous pressure gradient-guided pharmacological therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009C. VILLANUEVA Summary Background, Hepatic venous pressure gradient (HVPG) monitoring of therapy to prevent variceal rebleeding provides strong prognostic information. Treatment of nonresponders to ,-blockers ± nitrates has not been clarified. Aim, To assess the value of HVPG-guided therapy using nadolol + prazosin in nonresponders to nadolol + isosorbide-5-mononitrate (ISMN) compared with a control group treated with nadolol + ligation. Methods, Cirrhotic patients with variceal bleeding were randomized to HVPG-guided therapy (n = 30) or nadolol + ligation (n = 29). A Baseline haemodynamic study was performed and repeated within 1 month. In the guided-therapy group, nonresponders to nadolol + ISMN received nadolol and carefully titrated prazosin and had a third haemodynamic study. Results, Nadolol + prazosin decreased HVPG in nonresponders to nadolol + ISMN (P < 0.001). Finally, 74% of patients were responders in the guided-therapy group vs. 32% in the nadolol + ligation group (P < 0.01). The probability of rebleeding was lower in responders than in nonresponders in the guided therapy group (P < 0.01), but not in the nadolol + ligation group (P = 0.41). In all, 57% of nonresponders rebled in the guided-therapy group and 20% in the nadolol + ligation group (P = 0.05). The incidence of complications was similar. Conclusions, In patients treated to prevent variceal rebleeding, the association of nadolol and prazosin effectively rescued nonresponders to nadolol and ISMN, improving the haemodynamic response observed in controls receiving nadolol and endoscopic variceal ligation. Our results also suggest that ligation may rescue nonresponders. [source] Safety, efficacy, and long-term results of a modified version of rapid opiate detoxification under general anaesthesia: A prospective study in methadone, heroin, codeine and morphine addictsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2000M. Hensel Background: In the present study a method of rapid opiate detoxification under general anaesthesia has been evaluated regarding the safety, the efficacy in preventing withdrawal symptoms, and the long-term results. In addition, it was investigated whether the profile and severity of withdrawal symptoms depend on the type of opiate abused (methadone, heroin, codeine, morphine). Methods: Seventy-two opiate addicts were detoxified in an intensive care unit (ICU). Anaesthesia was induced and maintained using propofol infusion. Patients were endotracheally intubated. The opiate receptor antagonist naltrexon was administered into the stomach via a nasogastric tube. Withdrawal symptoms before and after the detoxification treatment were assessed using an objective and a subjective opiate withdrawal scale (OOWS, SOWS). After detoxification patients entered a long-term naltrexone maintenance programme as well as a supportive psychotherapy programme. Vital organ function was monitored using haemodynamic and respiratory parameters as well as body temperature. Results: Organ function parameters were stable during the whole treatment in all patients and no anaesthetic complications were registered. Minor side effects such as bradycardia or hypotension were observed in 20 patients. Compared to patients with pre-existing heroin, codeine, or morphine abuse respectively, patients from the methadone maintenance programme had significantly higher (P<0.01) OOWS as well as SOWS values after the treatment. Twelve months after the detoxification 49 patients (68%) were abstinent from opiates whereas 17 patients had relapsed during the period of follow-up. Six patients were lost during follow-up. Conclusions: Rapid opiate detoxification under general anaesthesia is a safe and efficient method to suppress withdrawal symptoms. This treatment may be of benefit in patients who particularly suffer from severe withdrawal symptoms during detoxification and who have failed repeatedly to complete conventional withdrawal. Methadone patients have more withdrawal symptoms than other opiate addicts. [source] Analgesia for paediatric tonsillectomy and adenoidectomy with intramuscular clonidinePEDIATRIC ANESTHESIA, Issue 7 2002Katherine O. Freeman MD SummaryBackground: After undergoing tonsillectomy and adenoidectomy (T&A), children may experience significant pain. Clonidine, an ,2 agonist, exhibits significant analgesic properties. The current investigation sought to determine whether intramuscular (I.M.) clonidine would decrease pain in paediatric patients undergoing T&A. Methods: Thirty-nine children undergoing elective T&A were studied. Following inhalational anaesthetic induction, fentanyl (2 ,g·kg,1) was given intravenously, acetaminophen (paracetamol) (30 mg·kg,1) was given rectally and the children then randomly received an i.m. injection of either normal saline or clonidine (2,g·kg,1). Perioperative analgesic requirements in the postanaesthesia care unit and at home following hospital discharge were evaluated. Results: There were no significant demographic, analgesic consumption, haemodynamic or pain score differences between the groups. Conclusions: We do not recommend adding i.m. clonidine (2 ,g·kg,1) to the analgesic regimen of children undergoing tonsillectomy and adenoidectomy. [source] A comparison of single dose caudal tramadol, tramadol plus bupivacaine and bupivacaine administration for postoperative analgesia in childrenPEDIATRIC ANESTHESIA, Issue 3 2001M Gunduz Background:,Our aim was to compare the effect of single dose caudal tramadol, tramadol plus bupivacaine and bupivacaine on the management of postoperative pain in children. Methods:,Sixty-three children in ASA groups I,II, between the ages of 1 and 5 were evaluated for postoperative pain randomly divided into three groups as follows: In group T, only tramadol was given caudally; in group TB, tramadol,bupivacaine was given caudally; in group B, bupivacaine was given alone. Pain was evaluated by using the paediatric objective pain scale (POPS). Sedation was evaluated with a 5-point test. There were no differences with age, weight, haemodynamic and respiratory parameters between groups. Results:,For 24 h postoperatively, the POPS value showed no statistically significant difference among groups (P > 0.05). Postoperative analgesia was maintained for 24 h. Nausea and vomiting was found to be higher in the tramadol group than in the bupivacaine group and tramadol,bupivacaine group (P < 0.001 and P < 0.01, respectively). Conclusion:,Tramadol used caudally is as effective as bupivacaine in the management of postoperative pain in children and the addition of tramadol to bupivacaine, when both drugs were administered caudally, did not prolong the duration of action of bupivacaine and is a safe agent in children. [source] Intermittent hypoxia reverses the diurnal glucose rhythm and causes pancreatic ,-cell replication in miceTHE JOURNAL OF PHYSIOLOGY, Issue 3 2008Takuya Yokoe Obstructive sleep apnoea (OSA) and type 2 diabetes frequently co-exist and potentially interact haemodynamically and metabolically. However, the confounding effects of obesity have obscured the examination of any independent or interactive effects of the hypoxic stress of OSA and the hyperglycaemia of type 2 diabetes on haemodynamic and metabolic outcomes. We have developed a chronically catheterized, unhandled, lean murine model to examine the effects of intermittent hypoxic (IH) exposure and exogenous glucose infusion on the diurnal pattern of arterial blood pressure and blood glucose, as well as pancreatic ,-cell growth and function. Four experimental groups of adult male C57BL/J mice were exposed to 80 h of (1) either IH (nadir of inspired oxygen 5,6% at 60 cycles h,1 for 12 h during light period) or intermittent air (IA; control) and (2) continuous infusion of either 50% dextrose or saline (control). IH exposure during saline infusion caused a sustained increase in arterial blood pressure of 10 mmHg (P < 0.0001), reversed the normal diurnal rhythm of blood glucose (P < 0.03), doubled corticosterone levels (P < 0.0001), and increased replication of pancreatic ,-cells from 1.5 ± 0.3 to 4.0 ± 0.8% bromodeoxyuridine (BrdU)-positive) ,-cells. The combined stimulus of IH exposure and glucose infusion attenuated the hypertension, exacerbated the reversed diurnal glucose rhythm, and produced the highest rates of apoptosis in ,-cells, without any additive effects on ,-cell replication. We conclude that, in contrast to the development of sustained hypertension, IH impaired glucose homeostasis only during periods of hypoxic exposure. IH acted as a stimulus to pancreatic ,-cell replication, but the presence of hyperglycaemia may increase the hypoxic susceptibility of ,-cells. This model will provide a basis for future mechanistic studies as well as assessing the metabolic impact of common comorbities in OSA, including obesity, insulin resistance and type 2 diabetes. [source] The optimum concentration of levobupivacaine for intra-operative caudal analgesia in children undergoing inguinal hernia repair at equal volumes of injectateANAESTHESIA, Issue 1 2009Y.-S. Yao Summary Probit analysis was used to predict the median effective concentration (EC50) and the 95% effective concentration (EC95) values of levobupivacaine for caudal analgesia in children at equal volumes of injectate. Sixty children scheduled for inguinal herniorrhaphy were recruited. Anaesthesia was induced with sevofurane and nitrous oxide. Then caudal block (total volume of local anaesthetic 1 ml.kg,1) was performed. Patients randomly received one of six concentrations (0.08%, 0.10%, 0.12%, 0.14%, 0.16% or 0.18%) of levobupivacaine. Thereafter, inhalational anaesthetics were discontinued and intravenous midazolam 0.1 mg.kg,1 was administered to maintain sedation. The effective caudal analgesia was defined as an absence of gross movements and a haemodynamic (heart rate or blood pressure) reaction < 20% compared with baseline in response to surgical incision. Our data indicated that the EC50 and EC95 values of levobupivacaine for caudal analgesia were 0.109% (95% confidence intervals 0.098,0.120%) and 0.151% (95% confidence intervals 0.135,0.193%) when using the same volume (1 ml.kg,1), respectively. [source] Evaluation of the Pneupac Ventipac portable ventilator in critically ill patientsANAESTHESIA, Issue 11 2001apparatus We assessed adequacy of ventilation in 20 critically ill patients with multiple organ failure using a Pneupac Ventipac portable ventilator and the effects on patients' haemodynamic stability. Baseline data were recorded over 15 min for a range of respiratory, haemodynamic and oxygen transport variables during ventilation with a standard intensive care ventilator (Engström Erica). Patients were then ventilated for 40 min using the portable ventilator. Finally, they were ventilated for a further 40 min using the standard intensive care ventilator. Heart rate, arterial and pulmonary artery pressures were recorded at 5-min intervals throughout the study period. Cardiac index and other haemodynamic data derived from a pulmonary artery catheter were recorded at 20-min intervals. Blood gas analysis was performed and oxygen transport data (oxygen delivery, oxygen consumption and physiological shunt) were calculated at the end of each of the three periods of ventilation. In general, no significant adverse effects of ventilation using the portable ventilator were observed for any of the variables studied. Arterial Po2 increased significantly during ventilation with the portable ventilator, reflecting the use of a higher inspired oxygen fraction during this part of the study. Oxygen consumption decreased significantly in one patient during ventilation by the portable ventilator although none of the other variables measured in this patient was altered. We conclude that ventilation of critically ill patients using the Pneupac Ventipac portable ventilator was safe, satisfactory and associated with minimal adverse effects on respiratory, haemodynamic and oxygen transport variables. [source] Physiological Effects of a Novel Immune Stimulator Drug, (1,4)-,- d -Glucan, in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009Ravishankar Koppada We investigated physiological and immunological effects of a low and a high dose of ,- d -glucan (0.5 and 10 mg/kg), in vivo, testing the hypothesis that intravenous administration of ,- d -glucan does not affect haemodynamic, respiratory, haematological, and immune responses in normal rats. Male rats (300,400 g) were anaesthetized, tracheostomized, and catheterized in one femoral artery and vein. The mean arterial blood pressure and heart rate were continuously recorded. The baselines for gas exchange, differential blood cell count, and plasma concentration of TNF-,, IL-1,, IL-4, IL-6, and IFN-, were determined. Rats were then randomly assigned to controls (n = 7), a low dose (0.5 mg/kg; n = 10), and a high dose (10 mg/kg; n = 7) of ,- d -glucan for a six 6 hr study period. Gas exchange, differential cell count, plasma concentration of TNF-,, IL-1,, IL-4, IL-6, and IFN-,, and mean arterial blood pressure values remained within physiological range. Intravenous administration of 10 mg/kg ,- d -glucan created tachycardia, associated with hyperventilation, and significant reductions in the blood haemoglobin and haematocrit concentrations. We suggest that these in vivo effects of ,- d -glucan should be considered for future clinical and/or experimental trials. [source] Low plasma volume following pregnancy complicated by pre-eclampsia predisposes for hypertensive disease in a next pregnancyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2003Robert Aardenburg Objective A large number of women with a history of pre-eclampsia/HELLP have a low plasma volume at least six months postpartum. The objective of this study was to determine whether a low plasma volume in formerly pre-eclamptic women and HELLP patients is associated with an increased risk for recurrent hypertensive complications in a next pregnancy. Design Prospective observational study. Setting Tertiary obstetric centre. Sample Formerly pre-eclamptic women and controls. Methods In 316 women with a history of pre-eclampsia and/or HELLP, we measured, plasma volume along with haemodynamic, metabolic and haemostatic variables at least six months postpartum. A group of 22 healthy parous controls was used as a reference. After standardising plasma volume for body mass index, women were subdivided into normotensive and normal plasma volume (n = 199), normotensive and low plasma volume (n = 76) and hypertensive (n = 41) subgroups, which were compared for demography, clinical parameters and course of a next pregnancy. Main outcome measures Recurrent hypertensive disease of pregnancy. Results Relative to the normal plasma volume subgroup, normotensive women in the low plasma volume subgroup have a higher body mass index, a lower total vascular compliance and a shorter estimated systemic circulation time. They have a higher HOMA index and higher fasting triglyceride levels. In normotensive and hypertensive former patients alike, low plasma volume is associated with a higher recurrence of hypertensive complications in a next pregnancy compared with normotensive women with normal plasma volume. Conclusion Low plasma volume in normotensive women with a history of pre-eclampsia and/or HELLP is associated with overweight, reduced vascular compliance and insulin resistance and a predisposition for recurrent pre-eclampsia and HELLP syndrome in a next pregnancy. [source] The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effectsBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2007D G Johns Background and purpose: Atypical cannabinoids are thought to cause vasodilatation through an as-yet unidentified ,CBx' receptor. Recent reports suggest GPR55 is an atypical cannabinoid receptor, making it a candidate for the vasodilator ,CBx' receptor. The purpose of the present study was to test the hypothesis that human recombinant GPR55 is activated by atypical cannabinoids and mediates vasodilator responses to these agents. Experimental approach: Human recombinant GPR55 was expressed in HEK293T cells and specific GTP,S activity was monitored as an index of receptor activation. In GPR55-deficient and wild-type littermate control mice, in vivo blood pressure measurement and isolated resistance artery myography were used to determine GPR55 dependence of atypical cannabinoid-induced haemodynamic and vasodilator responses. Key results: Atypical cannabinoids O-1602 and abnormal cannabidiol both stimulated GPR55-dependent GTP,S activity (EC50 approximately 2 nM), whereas the CB1 and CB2 -selective agonist WIN 55,212-2 showed no effect in GPR55-expressing HEK293T cell membranes. Baseline mean arterial pressure and heart rate were not different between WT and GPR55 KO mice. The blood pressure-lowering response to abnormal cannabidiol was not different between WT and KO mice (WT 20±2%, KO 26±5% change from baseline), nor was the vasodilator response to abnormal cannabidiol in isolated mesenteric arteries (IC50 approximately 3 ,M for WT and KO). The abnormal cannabidiol vasodilator response was antagonized equivalently by O-1918 in both strains. Conclusions: These results demonstrate that while GPR55 is activated by atypical cannabinoids, it does not appear to mediate the vasodilator effects of these agents. British Journal of Pharmacology (2007) 152, 825,831; doi:10.1038/sj.bjp.0707419; published online 20 August 2007 [source] Nitric oxide (NO) modulation of PAF-induced cardiopulmonary action: interaction between NO synthase and cyclo-oxygenase-2 pathwaysBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Fulvia Fabi To further investigate into the mechanisms of PAF-induced cardiopulmonary actions, we examined the effects of the nitric oxide synthase (NOS) inhibitor L -N, -nitro- L -arginine (L -NNA), of the specific cyclooxygenase-2 (COX-2) inhibitor NS 398, and of the combined presence of both COX and NOS inhibitors on the PAF responses in the heart lung preparation of guinea-pig (HLP). In HLPs perfused with homologous blood, dose-response curves for the haemodynamic and bronchial effects of PAF (1 , 32 ng) were carried out in the absence or presence of L -NNA (200 ,M). L -NNA caused an increase in the resting pulmonary arterial pressure (PAP) without affecting the other basal values, and strongly potentiated the bronchoconstriction and pulmonary hypertension elicited by PAF. An enhancement of the PAF-induced actions on right atrial pressure (RAP) and cardiac output (CO) was also observed. All the effects of L -NNA were antagonized by L -arginine (2 mM). The presence of L -NNA in the perfusing blood of HLPs failed to affect the pulmonary hypertensive and bronchoconstrictor responses induced by the thromboxane A2 mimetic U46619 (0.05 , 1.6 ,g), 5-hydroxytryptamine (0.1 , 1.6 ,g), and histamine (0.1 , 1.6 ,g), thus suggesting that these PAF secondary mediators are not responsible for the hyper-responsiveness to PAF induced by L -NNA. Blocking COX-2 pathway with NS 398 (15 , 30 ,M) did not alter the cardiopulmonary resting variables. However, a reduction of the PAF-mediated pulmonary hypertension, but not of bronchoconstriction, was observed. When L -NNA was added to the perfusing medium of HLPs pre-treated with NS 398 or with indomethacin (15 ,M), the basal PAP values were enhanced. However, in the combined presence of COX and NOS inhibitors, only a slight increase in the hypertensive responses to the highest doses of PAF was observed, whereas the PAF mediated actions at bronchial and cardiac level were unaffected. This study indicates that (i) the cardiopulmonary actions induced by PAF are specifically modulated by endogenous NO through the NOS pathway, and (ii) COX-2 isoform is involved in the pulmonary hypertensive, but not bronchoconstrictor, effects of PAF. Furthermore, an interaction between PAF stimulated COX, particularly COX-2, and NOS pathways appears to take a functional role at both bronchial and cardiovascular level. British Journal of Pharmacology (2001) 134, 777,788; doi:10.1038/sj.bjp.0704311 [source] Combined blockade of endothelin-1 and thromboxane A2 receptors against postischaemic contractile dysfunction in rat heartsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2001Pius S Hornstein Endothelin-1 (ET-1) may play a role in myocardial ischaemia/reperfusion injury because both the release and vasoconstrictor effect of ET-1 are increased after ischaemia. Since the increased vasoconstrictor effect of ET-1 can be mediated by ET-1-induced release of thromboxane A2 (TXA2), the aim of this study was to test whether combined blockade of ET and TXA2 receptors protects the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion. Bosentan (antagonist for ETA and ETB receptors, 1 ,M based on concentration-response curves of ET-1), SQ 30,741 (antagonist of TXA2 receptors, 0.1 ,M), or the combination thereof was administered to isolated perfused rat hearts undergoing 15 min of global ischaemia and 60 min of reperfusion. Neither bosentan or SQ 30,741 alone, nor the combination thereof, improved the incomplete postischaemic recovery of coronary flow, left ventricular developed pressure, phosphocreatine, or ATP. However, they attenuated ischaemia-induced acidosis but this did not translate into a measurable effect on haemodynamic or metabolic variables. Thus, combined blockade of ET and TXA2 receptors does not protect the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion in isolated perfused rat hearts. This finding suggests that neither ET-1 nor ET-1-induced release of TXA2 play a major role in the postischaemic recovery of the cardiac contractile function and energy metabolism. British Journal of Pharmacology (2001) 132, 234,240; doi:10.1038/sj.bjp.0703773 [source] Aberrant processing of deviant stimuli in schizophrenia revealed by fusion of fMRI and EEG dataACTA NEUROPSYCHIATRICA, Issue 3 2010Vince D. Calhoun Calhoun VD, Wu L, Kiehl KA, Eichele T, Pearlson GD. Aberrant processing of deviant stimuli in schizophrenia revealed by fusion of fMRI and EEG data. Background: Aberrant electrophysiological and haemodynamic processing of auditory oddball stimuli is among the most robustly documented findings in patients with schizophrenia. However, no study to date has directly examined linked patterns of electrical and haemodynamic differences in patients and controls. Methods: In a recent paper we demonstrated a data-driven approach, joint independent component analysis (jICA) to fuse together functional magnetic resonance imaging (fMRI) and event-related potential (ERP) data and elucidated the chronometry of auditory oddball target detection in healthy control subjects. In this paper we extend our fusion method to identify specific differences in the neuronal chronometry of target detection for chronic schizophrenia patients compared to healthy controls. Results: We found one linked source, consistent with the N2 response, known to be related to cognitive processing of deviant stimuli, spatially localized to bilateral fronto-temporal regions. This source showed significant between-group differences both in amplitude response and in the fMRI/ERP distribution pattern. These findings are consistent with previous work showing N2 amplitude and latency abnormalities in schizophrenia, and provide new information about the linkage between the two. Conclusions: In summary, we use a novel approach to isolate and identify a linked fMRI/ERP component which shows marked differences in chronic schizophrenia patients. We also show that jointly using both fMRI and ERP measures provides a fully picture of the underlying haemodynamic and electrical changes which are present in patients. Our approach also has broad applicability to other diseases such as autism, Alzheimer's disease, or bipolar disorder. [source] Physiological determinants of the variation in left ventricular mass from early adolescence to late adulthood in healthy subjectsCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 4 2007Peter A. Cain Summary Background:, The physiological determinants of left ventricular mass (LVM) measured by cardiac magnetic resonance (CMR) imaging are not well defined as prior investigators have studied either adults or adolescents in isolation or have not strictly excluded hypertension or accounted for the effects of exercise habits, haemodynamic, demographic, or body shape characteristics. Methods:, Ninety-seven healthy volunteers (11,81 years, 51 males) underwent CMR. All parameters [unstandardized and adjusted for body surface area (BSA)] were analysed according to gender and by adolescence versus adulthood (adolescents <20 years, adults ,20 years). The influence of haemodynamic factors, exercise and demographic factors on LVM were determined with multivariate linear regression. Results:, Left ventricular mass rose during adolescence and declined in adulthood. LVM and LVMBSA were higher in males both in adults (LVM: 188 ± 22 versus 140 ± 21 g, P<0·001; LVMBSA: 94 ± 11 versus 80 ± 11 g m,2, P<0·001) and in adolescents when adjusted for BSA (LVM: 128 ± 29 versus 107 ± 20 g, P = 0·063; LVMBSA: 82 ± 8 versus 71 ± 10 g m,2, P = 0·025). In adults, systolic blood pressure (SBP) and self-reported physical activity increased while meridional and circumferential wall stress were constant with age. Multivariate regression analysis revealed age, gender and BSA as the major determinants of LVM (global R2 = 0·68). Conclusions:, Normal LVM shows variation over a broad age range in both genders with a rise in adolescence and subsequent decline with increasing age in adulthood despite an increase in SBP and physical activity. BSA, age and gender were found to be major contributors to the variation in LVM in healthy adults, while haemodynamic factors, exercise and wall stress were not. [source] Cerebral oxygenation decreases but does not impair performance during self-paced, strenuous exerciseACTA PHYSIOLOGICA, Issue 4 2010F. Billaut Abstract Aim:, The reduction in cerebral oxygenation (Cox) is associated with the cessation of exercise during constant work rate and incremental tests to exhaustion. Yet in exercises of this nature, ecological validity is limited due to work rate being either fully or partly dictated by the protocol, and it is unknown whether cerebral deoxygenation also occurs during self-paced exercise. Here, we investigated the cerebral haemodynamics during a 5-km running time trial in trained runners. Methods:, Rating of perceived exertion (RPE) and surface electromyogram (EMG) of lower limb muscles were recorded every 0.5 km. Changes in Cox (prefrontal lobe) were monitored via near-infrared spectroscopy through concentration changes in oxy- and deoxyhaemoglobin (,[O2Hb], ,[HHb]). Changes in total Hb were calculated (,[THb] = ,[O2Hb] + ,[HHb]) and used as an index of change in regional blood volume. Results:, During the trial, RPE increased from 6.6 ± 0.6 to 19.1 ± 0.7 indicating maximal exertion. Cox rose from baseline to 2.5 km (,,[O2Hb], ,,[HHb], ,,[THb]), remained constant between 2.5 and 4.5 km, and fell from 4.5 to 5 km (,,[O2Hb], ,,[HHb], ,,[THb]). Interestingly, the drop in Cox at the end of the trial coincided with a final end spurt in treadmill speed and concomitant increase in skeletal muscle recruitment (as revealed by higher lower limb EMG). Conclusion:, Results confirm the large tolerance for change in Cox during exercise at sea level, yet further indicate that, in conditions of self-selected work rate, cerebral deoxygenation remains within a range that does not hinder strenuous exercise performance. [source] Systemic nitric oxide clamping in normal humans guided by total peripheral resistanceACTA PHYSIOLOGICA, Issue 2 2010J. A. Simonsen Abstract Aim:, We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. Methods:, Normal volunteers (23,28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor NG -nitro- l -arginine methyl ester (l -NAME) at 0.5 mg kg,1 h,1. One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l -NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. Results:,l -NAME increased MABP and total peripheral resistance (TPR, 1.02 ± 0.05 to 1.36 ± 0.07 mmHg s mL,1, mean ± SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 ± 0.05 mmHg s mL,1, P < 0.05). CO decreased with l -NAME (5.8 ± 0.3 to 4.7 ± 0.3 L min,1, P < 0.01) and returned to control when SNP was added (6.0 ± 0.3 L min,1). A decrease in plasma noradrenaline (42%, P < 0.01) during l -NAME administration was completely reversed by SNP. Plasma renin activity decreased during l -NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l -NAME and remained elevated. Conclusions:, Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation. [source] Stroke volume decreases during mild dynamic and static exercise in supine humansACTA PHYSIOLOGICA, Issue 2 2009M. Elstad Abstract Aim:, The contributions of cardiac output (CO) and total peripheral resistance to changes in arterial blood pressure are debated and differ between dynamic and static exercise. We studied the role stroke volume (SV) has in mild supine exercise. Methods:, We investigated 10 healthy, supine volunteers by continuous measurement of heart rate (HR), mean arterial blood pressure, SV (ultrasound Doppler) and femoral beat volume (ultrasound Doppler) during both dynamic mild leg exercise and static forearm exercise. This made it possible to study CO, femoral flow (FF) and both total and femoral peripheral resistance beat-by-beat. Results:, During a countdown period immediately prior to exercise, HR and mean arterial pressure increased, while SV decreased. During mild supine exercise, SV decreased by 5,8%, and most of this was explained by increased mean arterial pressure. Dynamic leg exercise doubled femoral beat volume, while static hand grip decreased femoral beat volume by 18%. FF is tightly regulated according to metabolic demand during both dynamic leg exercise and static forearm exercise. Conclusion:, Our three major findings are, firstly, that SV decreases during both dynamic and static mild supine exercise due to an increase in mean arterial pressure. Secondly, femoral beat volume decreases during static hand grip, but FF is unchanged due to the increase in HR. Finally, anticipatory responses to exercise are apparent prior to both dynamic and static exercise. SV changes contribute to CO changes and should be included in studies of central haemodynamics during exercise. [source] | ||||||||||||||||||||||||||||||||||