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Vasoactive Drugs (vasoactive + drug)
Selected AbstractsEarly Vasoactive Drugs Improve Heart Failure OutcomesCONGESTIVE HEART FAILURE, Issue 6 2009William Frank Peacock MD Vasoactive therapy is often used to treat acute decompensated heart failure (ADHF). The authors sought to determine whether clinical outcomes are temporally associated with time to vasoactive therapy (vasoactive time) in ADHF. Using the Acute Decompensated Heart Failure (ADHERE) Registry, the authors examined the relationship between vasoactive time and inpatient mortality within 48 hours of hospitalization. Vasoactive agents were used early (defined as <6 hours) in 22,788 (63.8%) patients and late in 12,912 (36.2%). Median vasoactive time was 1.7 and 14.7 hours in the early and late groups, respectively. In-hospital mortality was significantly lower in the early group (odds ratio, 0.87; 95% confidence interval, 0.79,0.96; P=.006), and the adjusted odds of death increased 6.8% for every 6 hours of treatment delay (95% confidence interval, 4.2,9.6; P<.0001). Early vasoactive initiation is associated with improved outcomes in patients hospitalized for ADHF. [source] Inflammation and the etiology of type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2006Åke Sjöholm Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-,. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis. Copyright © 2005 John Wiley & Sons, Ltd. [source] Pharmacological treatment of sepsisFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2008Armand R.J. Girbes Abstract The incidence of sepsis, the combination of a systemic inflammatory response syndrome and documented infection, is as high as up to 95 cases per 100,000 people per year. The understanding of the pathophysiology of sepsis has much increased over the last 20 years. However, sepsis combined with shock is still associated with a high mortality rate varying from 35 to 55%. Causative treatment, source control and antibiotics started as soon as possible, are the cornerstone of therapy in combination with symptomatic treatment in the ICU. The pharmacological interventions, including fluid resuscitation, vasoactive drugs and adjunctive drugs such as steroids, activated protein C are discussed. The possible beneficial role of strict glucose control is also addressed. Since many drug intervention studies were negative, lessons should be learned from earlier experiences for future trials. Source control and level of intensive care should be eliminated as confounders. [source] Upper digestive bleeding in cirrhosis.HEPATOLOGY, Issue 3 2003Post-therapeutic outcome, prognostic indicators Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis. The aim of this multicenter, prospective, cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis. A training set of 291 and a test set of 174 bleeding cirrhotic patients were included. Treatment was according to the preferences of each center and the follow-up period was 6 weeks. Predictive rules for 5-day failure (uncontrolled bleeding, rebleeding, or death) and 6-week mortality were developed by the logistic model in the training set and validated in the test set. Initial treatment controlled bleeding in 90% of patients, including vasoactive drugs in 27%, endoscopic therapy in 10%, combined (endoscopic and vasoactive) in 45%, balloon tamponade alone in 1%, and none in 17%. The 5-day failure rate was 13%, 6-week rebleeding was 17%, and mortality was 20%. Corresponding findings for variceal versus nonvariceal bleeding were 15% versus 7% (P = .034), 19% versus 10% (P = .019), and 20% versus 15% (P = .22). Active bleeding on endoscopy, hematocrit levels, aminotransferase levels, Child-Pugh class, and portal vein thrombosis were significant predictors of 5-day failure; alcohol-induced etiology, bilirubin, albumin, encephalopathy, and hepatocarcinoma were predictors of 6-week mortality. Prognostic reassessment including blood transfusions improved the predictive accuracy. All the developed prognostic models were superior to the Child-Pugh score. In conclusion, prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades. Initial treatment stops bleeding in 90% of patients. Accurate predictive rules are provided for early recognition of high-risk patients. [source] Extubation score in the operating room after liver transplantationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2010S. SKURZAK Background: Early extubation after liver transplantation (LT) is an increasingly applied safe practice. The aim of the present study was to provide a simple extubation rule for accelerated weaning in the operating room (OR). Methods: Data of 597 patients transplanted at the LT center of Turin (Italy) were retrospectively analyzed. Fifty-two nonextubated patients (excluding those with a scheduled early reoperation) were compared with 545 successfully extubated patients (not in need of reintubation within the first 48 h). Significant variables at univariate analysis were entered into a logistic regression model and the regression coefficients of independent predictors were used to yield a prognostic score called the safe operating room extubation after liver transplantation (SORELT) score. Results: Two major and three minor criteria were found. The major ones were blood transfusions (higher than/or equal to 7 U of packed red blood cells) and end of surgery lactate (higher than/or equal to 3.4 mmol/l). The minor ones were status before LT (home vs. hospitalized patient), duration of surgery (longer than/or equal to 5 h), vasoactive drugs at the end of surgery (dopamine higher than 5 ,g/kg/min or norepinephrine higher than 0.05 ,g/kg/min). Patients who fulfill the SORELT score-derived criteria (fewer than two major/one major plus two minor/three minor criteria) can be considered for OR extubation. Conclusion: Early extubation after LT requires a very careful assessment of the pre-operative, intraoperative, graft and post-operative care data available. The SORELT score helps as a simple and objective aid in considering such a decision. [source] Repeatability of measurements of the initial distribution volume of glucose in haemodynamically stable patientsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2004B. O. Rose MD Summary Aims:, The initial distribution volume of glucose (IDVG) has been proposed to provide a useful tool to estimate the central extracellular fluid volume. The purpose of this study was to determine the repetition interval of two consecutive measurements in haemodynamically stable patients without presence of recent changes in fluid status. Methods:, Twenty-nine patients admitted to the general intensive care unit of the University of Hirosaki Hospital were entered into this study. After achieving a haemodynamically stable state in each patient regardless of an infusion of vasoactive drugs, two glucose challenges at an interval of either 30 or 60 min, were carried out to calculate the IDVG. The IDVG was calculated using a one-compartment model after intravenous administration of glucose (5 g) followed by serial arterial blood sampling. Results:, Although plasma glucose levels immediately before the second glucose challenge in either group were increased compared with those of the first challenge (P < 0·001, respectively), the bias of the IDVG measurements was 0·08 ± 0·32 L (SD) for the 30-min group and ,0·19 ± 0·28 L for the 60-min group. Conclusions:, Our results indicate that IDVG determinations can be reliably repeated within a minimum interval of 30 min. [source] Effects of levosimendan on indocyanine green plasma disappearance rate and the gastric mucosal,arterial pCO2 gradient in abdominal aortic aneurysm surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2008H. LEPPIKANGAS Background: Levosimendan has a dual mechanism of action: it improves myocardial contractility and causes vasodilatation without increasing myocardial oxygen demand. In a laboratory setting, it selectively increases gastric mucosal oxygenation in particular and splanchnic perfusion in general. The aim of our study was to describe the effects of levosimendan on systemic and splanchnic circulation during and after abdominal aortic surgery. Methods: Twenty abdominal aortic aneurysm surgery patients were randomized to receive either levosimendan (n=10) or placebo (n=10) in a double-blinded manner. Both the mode of anaesthesia and the surgical procedures were performed according to the local guidelines. Automatic gas tonometry was used to measure the gastric mucosal partial pressure of carbon dioxide. Systemic indocyanine green clearance plasma disappearance rate (ICG-PDR) was used to estimate the total splanchnic blood flow. Results: The immediate post-operative recovery was uneventful in the two groups with a comparable, overnight length of stay in the intensive care unit. Cumulative doses of additional vasoactive drugs were comparable between the groups, with a tendency towards a higher cumulative dose of noradrenaline in the levosimendan group. After aortic clamping, the cardiac index was higher [4(3.8,4.7) l/min/m2 vs. 2.6(2.3,3.6) l/min/m2; P<0.05] and the gastric mucosal,arterial pCO2 gradient was lower in levosimendan-treated patients [0.9(0.6,1.2) kPa vs. 1.7(1.2,2.1) kPa; (P<0.05)]. However, the total splanchnic blood flow, estimated by ICG-PDR, was comparable [29(21,29)% vs. 20(19,25)%; NS]. Organ dysfunction scores (sequential organ dysfunction assessment) were similar between the groups on the fifth post-operative day. Conclusion: Levosimendan favours gastric perfusion but appears not to have a major effect on total splanchnic perfusion in patients undergoing an elective aortic aneurysm operation. [source] New Expression Profiles of Voltage-gated Ion Channels in Arteries Exposed to High Blood PressureMICROCIRCULATION, Issue 4 2002Robert H. Cox The diameters of small arteries and arterioles are tightly regulated by the dynamic interaction between Ca2+ and K+ channels in the vascular smooth muscle cells. Calcium influx through voltage-gated Ca2+ channels induces vasoconstriction, whereas the opening of K+ channels mediates hyperpolarization, inactivation of voltage-gated Ca2+ channels, and vasodilation. Three types of voltage-sensitive ion channels have been highly implicated in the regulation of resting vascular tone. These include the L-type Ca2+ (CaL) channels, voltage-gated K+ (KV) channels, and high-conductance voltage- and Ca2+ -sensitive K+ (BKCa) channels. Recently, abnormal expression profiles of these ion channels have been identified as part of the pathogenesis of arterial hypertension and other vasospastic diseases. An increasing number of studies suggest that high blood pressure may trigger cellular signaling cascades that dynamically alter the expression profile of arterial ion channels to further modify vascular tone. This article will briefly review the properties of CaL, KV, and BKCa channels, present evidence that their expression profile is altered during systemic hypertension, and suggest potential mechanisms by which the signal of elevated blood pressure may result in altered ion channel expression. A final section will discuss emerging concepts and opportunities for the development of new vasoactive drugs, which may rely on targeting disease-specific changes in ion channel expression as a mechanism to lower vascular tone during hypertensive diseases. [source] Gadolinium inhibits group III but not group IV muscle afferent responses to dynamic exerciseTHE JOURNAL OF PHYSIOLOGY, Issue 4 2009Shawn G. Hayes Dynamic exercise has been shown to stimulate rapidly both group III and IV muscle afferents. The often rapid (i.e. 2 s) onset latencies of the group IV afferents is particularly surprising because these unmyelinated afferents are thought to respond to the gradual accumulation of metabolites signalling a mismatch between blood/oxygen demand and supply in exercising muscles. One explanation for the rapid onset to exercise by group IV afferents is that they are mechanosensitive, a concept that has been supported by the finding that these afferents were stimulated by vasodilatation induced by injection of vasoactive drugs. We therefore examined in decerebrated cats the effect of gadolinium, a blocker of mechanogated channels, on the responses of group III and IV muscle afferents to dynamic exercise induced by electrical stimulation of the mesencephalic locomotor region. We found that gadolinium (10 mm; 1 ml) injected into the abdominal aorta had no significant effect (P > 0.05) on the responses of 11 group IV afferents to dynamic exercise. In contrast, gadolinium markedly attenuated the responses of 11 group III afferents to exercise (P < 0.05). Our findings suggest that group IV afferents are not responding to a mechanical stimulus during exercise. Instead their rapid response to dynamic exercise might be caused by a chemical substance whose concentration is directly proportional to blood flow, which increases in the skeletal muscles when they are dynamically exercising. [source] The effects of syringe plunger design on drug delivery during vertical displacement of syringe pumpsANAESTHESIA, Issue 11 2000M. Weiss Fluid delivery from four types of commercially available 50-ml syringes was measured using an electronic balance at an infusion rate of 1 ml.h,1. Retrograde aspiration volume and zero-drug delivery time were recorded after lowering the syringe pump by 50 cm. Syringe compliance was calculated from the volume of bolus released after occlusion at 100 mmHg. Zero-drug delivery times differed significantly between syringes, ranging from [mean (SD)] 3.26 (0.40) min to 6.38 (0.56) min (F = 55.5, d.f. = 3/20, p < 0.0001). Syringe compliance correlated well with aspiration volume (Pearson r2 = 0.92, p < 0.001) and zero-drug delivery time (r2 = 0.90, p < 0.001). Syringe design affected the internal syringe compliance. All syringes were associated with potentially relevant zero-drug delivery times after moderate vertical displacement. To minimise this risk, vertical displacement of syringe pumps delivering highly vasoactive drugs should be avoided. [source] Baroreflex Sensitivity: Measurement and Clinical ImplicationsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2008Maria Teresa La Rovere M.D. Alterations of the baroreceptor-heart rate reflex (baroreflex sensitivity, BRS) contribute to the reciprocal reduction of parasympathetic activity and increase of sympathetic activity that accompany the development and progression of cardiovascular diseases. Therefore, the measurement of the baroreflex is a source of valuable information in the clinical management of cardiac disease patients, particularly in risk stratification. This article briefly recalls the pathophysiological background of baroreflex control, and reviews the most relevant methods that have been developed so far for the measurement of BRS. They include three "classic" methods: (i) the use of vasoactive drugs, particularly the ,-adrenoreceptor agonist phenylephrine, (ii) the Valsalva maneuver, which produces a natural challenge for the baroreceptors by voluntarily increasing intrathoracic and abdominal pressure through straining, and (iii) the neck chamber technique, which allows a selective activation/deactivation of carotid baroreceptors by application of a negative/positive pressure to the neck region. Two more recent methods based on the analysis of spontaneous oscillations of systolic arterial pressure and RR interval are also reviewed: (i) the sequence method, which analyzes the relationship between increasing/decreasing ramps of blood pressure and related increasing/decreasing changes in RR interval through linear regression, and (ii) spectral methods, which assess the relationship (in terms of gain) between specific oscillatory components of the two signals. The limitations of the coherence criterion for the computation of spectral BRS are discussed, and recent proposals for overcoming them are presented. Most relevant clinical applications of BRS measurement are finally reviewed with particular reference to patients with myocardial infarction and heart failure. [source] Effect of a Miniaturized Cardiopulmonary Bypass System on the Inflammatory Response and Cardiac Function in Neonatal PigletsARTIFICIAL ORGANS, Issue 11 2009Ko Yoshizumi Abstract The cognitive impairment and hemodynamic instability after neonatal cardiac surgery with cardiopulmonary bypass (CPB) might be exacerbated by hemodilution. Therefore, this study investigated the impact of different bloodless prime volumes on the hemodynamics and the inflammatory response by a miniaturized CPB system in neonatal piglets. The bypass circuit consisted of a Capiox RX05 (Capiox Baby RX, Terumo Corp., Tokyo, Japan) oxygenator and 3/16 internal diameter arterial and venous polyvinyl chloride tubing lines, with a minimum 75 mL prime volume. Twelve 1-week-old piglets were placed on a mild hypothermic CPB (32°C) at 120 mL/kg/min for 2 h. The animals were divided into two groups, based on the volume of the prime solution. The priming volume was 75 mL in Group I and 175 mL in Group II. No blood transfusions were performed, and no inotropic or vasoactive drugs were used. The interleukin-6 (IL-6) and thrombin-antithrombin (TAT) complex levels, as well as right ventricular and pulmonary functions, were measured before and after CPB. Group I had low levels of IL-6 and TAT immediately after CPB (4370 ± 2346 vs. 9058 ± 2307 pg/mL, P < 0.01 and 9.9 ± 7.7 vs. 25.1 ± 8.8 ng/mL, P < 0.01, respectively). Group I had significantly improved cardiopulmonary function, cardiac index (0.22 ± 0.03 vs. 0.11 ± 0.05 L/kg/min, P < 0.001), and pulmonary vascular resistance index (7366 ± 2860 vs. 28 620 ± 15 552 dynes/cm5/kg, P < 0.01) compared with Group II. The miniaturized bloodless prime circuit for neonatal CPB demonstrated that the influence of hemodilution can reduce the subsequent inflammatory response. In addition, a low prime volume could therefore be particularly effective for attenuating pulmonary vascular resistance and right ventricular dysfunction in neonates. [source] In vitro viability of human cavernosal endothelial and fibroblastic cells after exposure to papaverine/phentolamine and prostaglandin E1BJU INTERNATIONAL, Issue 9 2005Adrian Pilatz OBJECTIVE To investigate the influence of commercially available vasoactive drugs on human cavernosal endothelial and fibroblastic cells in vitro, as although corporal fibrosis is a well known side-effect of intracavernosal injection therapy for erectile dysfunction, the possible detrimental effect of these agents on the endothelium lining the cavernosal vascular spaces is uncertain. MATERIALS AND METHODS Cultured primary endothelial (13) and fibroblastic cells (12), obtained from potent patients undergoing penile surgery, were exposed to different physiological dilutions of prostaglandin E1 (PGE1), papaverine/phentolamine or the respective triple-mix of these agents for 30 min. Viable cells were counted and cell metabolic activity measured in these cultures 48 h after drug exposure. RESULTS There was a significant dose-dependent decrease in the viable cell count after exposure to papaverine-containing formulations, probably because of the low pH of this substance. This cytotoxic effect was more pronounced in endothelial than in fibroblastic cells, and was not apparent in the PGE1 groups. The relative increase in cell metabolic activity in cultures affected by a moderate cytotoxic effect indicated a regenerative process. CONCLUSION These comparative results in endothelial and fibroblastic cell cultures suggest that the endothelium rather than the interstitium of the corpus cavernosum is more sensitive to side-effects produced by intracavernosal injection therapy with papaverine. Thus, unfavourable consequences on the function of the endothelial layer might be as important as the risk of interstitial fibrosis. As these effects were not detected for PGE1 this drug should be preferred to papaverine in clinical practice. [source] | ||||||||||||||||||||||