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Myocardial Ischaemia (myocardial + ischaemia)
Kinds of Myocardial Ischaemia Selected AbstractsCardiac evaluation of haemodialysis-related hypotension using dobutamine stress echocardiographyNEPHROLOGY, Issue 3 2001Don Poldermans SUMMARY: Haemodialysis-related hypotension occurs in approximately 30% of patients. Myocardial ischaemia and/or insufficient contractile reserve in response to sympathetic stress may be involved in the pathogenesis of hypotension during dialysis. Using dobutamine stress echocardiography, left ventricular function at rest, myocardial contractile reserve and the presence and extent of ischaemia can be assessed in a non-invasive way. This short review will focus on the potential value of dobutamine stress echocardiography for the evaluation of hypotension-prone haemodialysis patients. [source] Activated platelets contribute to stimulation of cardiac afferents during ischaemia in cats: role of 5-HT3 receptorsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2002Liang-Wu Fu Myocardial ischaemia activates blood platelets and cardiac sympathetic afferents, which mediate chest pain and cardiovascular reflex responses. We have demonstrated that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents. Platelets absorb and release 5-hydroxytryptamine (5-HT) when they are activated. In the present study we hypothesized that, by releasing 5-HT, activated platelets stimulate cardiac afferents during ischaemia through a 5-HT3 receptor mechanism. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from cats. Activation of platelets in PRP was induced by thrombin (5 units ml,1) or collagen (2 mg kg,1). Using high-performance liquid chromatography, we observed that the concentration of 5-HT was increased significantly in suspensions of platelets activated with thrombin (PRP+thrombin, 28 ± 1.7 ,m) or collagen (PRP+collagen, 27 ± 2.5 ,m) compared with suspensions of unactivated platelets (PRP+saline, 2.3 ± 0.8 ,m) and PPP. During myocardial ischaemia and reperfusion, tirofiban, a specific inhibitor of platelet glycoprotein (GP) IIb-IIIa receptors (100 ,g kg,1, I.V., followed by 5 ,g kg,1 min,1), significantly reduced the increase in the concentration of 5-HT in cardiac venous plasma from ischaemic region. Nerve activity of single-unit cardiac afferents was recorded from the left sympathetic chain (T2-T5) in anaesthetized cats. Eighty ischaemically sensitive and seven ischaemically insensitive cardiac afferents were identified. Tirofiban reduced the ischaemia-related increase in activity of seven cardiac sympathetic afferents by 50 %. Injection of 1.5 ml of PRP+collagen or PRP+thrombin into the left atrium (LA) increased activity of 16 cardiac afferents. Tropisetron (300 ,g kg,1, I.V.), a selective 5-HT3 receptor antagonist, eliminated the afferent's responses to platelets activated with collagen or thrombin. Moreover, LA injection of 5-HT (20-40 ,g kg,1) and PBG (100 ,g kg,1), a 5-HT3 receptor agonist, stimulated nine ischaemically sensitive cardiac sympathetic afferents, significantly increasing the activity of these afferents. However, injection of ,-M-5-HT (100 ,g kg,1, LA), a 5-HT2 receptor agonist, stimulated only two of the nine ischaemically sensitive cardiac afferents, and thus did not significantly alter impulse activity of this group of afferents. Both the 5-HT1 (5-CT, 100 ,g kg,1, LA) and 5-HT4 receptor agonists (SC53116, 100 ,g kg,1, LA) did not stimulate any of the nine afferents tested. Tropisetron (300 ,g kg,1, I.V.) also eliminated the response of seven ischaemically sensitive cardiac afferents to exogenous 5-HT and attenuated the ischaemia-related increase in activity of nine cardiac sympathetic afferents by 41 %. Conversely, LA injection of 5-HT (40 ,g kg,1) did not stimulate any of seven ischaemically insensitive cardiac afferents, although this group of afferents consistently responded to bradykinin (3 ,g, LA). These data indicate that during myocardial ischaemia the activated platelets stimulate cardiac sympathetic afferents, at least in part, through a 5-HT3 receptor mechanism. [source] AMP-activated protein kinase: a core signalling pathway in the heartACTA PHYSIOLOGICA, Issue 1 2009A. S. Kim Abstract Over the past decade, AMP-activated protein kinase (AMPK) has emerged as an important intracellular signalling pathway in the heart. Activated AMPK stimulates the production of ATP by regulating key steps in both glucose and fatty acid metabolism. It has an inhibitory effect on cardiac protein synthesis. AMPK also interacts with additional intracellular signalling pathways in a coordinated network that modulates essential cellular processes in the heart. Evidence is accumulating that AMPK may protect the heart from ischaemic injury and limit the development of cardiac myocyte hypertrophy to various stimuli. Heart AMPK is activated by hormones, cytokines and oral hypoglycaemic drugs that are used in the treatment of type 2 diabetes. The tumour suppressor LKB1 is the major regulator of AMPK activity, but additional upstream kinases and protein phosphatases also contribute. Mutations in the regulatory ,2 subunit of AMPK lead to an inherited syndrome of hypertrophic cardiomyopathy and ventricular pre-excitation, which appears to be due to intracellular glycogen accumulation. Future research promises to elucidate the molecular mechanisms responsible for AMPK activation, novel downstream AMPK targets, and the therapeutic potential of targeting AMPK for the prevention and treatment of myocardial ischaemia or cardiac hypertrophy. [source] How hypoglycaemia can affect the life of a person with diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2008Brian M. Frier Abstract Hypoglycaemia is the commonest side-effect of insulin treatment for diabetes, and is the single greatest barrier to achieving and maintaining good glycaemic control. Severe hypoglycaemia (requiring assistance for recovery) is associated with significant morbidity and is feared by most people with type 1 diabetes and their families. It causes stress and anxiety and may influence self-management and glycaemic control. The annual prevalence of severe hypoglycaemia is around 30% in people with type 1 diabetes, and is higher in those with risk factors such as strict glycaemic control, impaired awareness of hypoglycaemia and increasing duration of diabetes. It is also common during sleep (nocturnal hypoglycaemia). Neurological manifestations include coma, convulsions, transient hemiparesis and stroke, while reduced consciousness and cognitive dysfunction may cause accidents and injuries. Cardiac events may be precipitated such as arrhythmias, myocardial ischaemia and cardiac failure. Hypoglycaemia can affect all aspects of life, including employment, driving, recreational activities involving exercise, and travel, and measures should be taken in all of these situations to avoid this potentially dangerous side-effect of insulin therapy. Copyright © 2007 John Wiley & Sons, Ltd. [source] Prognostic significance of asymptomatic coronary artery disease in patients with diabetes and need for early revascularization therapyDIABETIC MEDICINE, Issue 9 2007E.-K. Choi Abstract Aims, Information on the clinical outcome of patients with diabetes with silent myocardial ischaemia is limited. We compared the clinical and angiographic characteristics, and the clinical outcomes of diabetic patients with asymptomatic or symptomatic coronary artery disease (CAD). Methods, Three hundred and ten consecutive diabetic patients with CAD were divided into two groups according to the presence of angina and followed for a mean of 5 years. Fifty-six asymptomatic patients with a positive stress test and CAD on coronary angiography were compared with 254 symptomatic patients, 167 with unstable angina and 87 with chronic stable angina. Results, Although the severity of coronary atherosclerosis was similar in asymptomatic and symptomatic patients, revascularization therapy was performed less frequently in the asymptomatic than the symptomatic patients (26.8 vs. 62.0%; P < 0.001). Asymptomatic patients experienced a similar number of major adverse cardiac events (MACEs; death, non-fatal myocardial infarction, and revascularization; 32 vs. 28%; P = 0.57), but had higher cardiac mortality than symptomatic patients (26 vs. 9%; P < 0.001). However, patients who underwent revascularization therapy at the time of CAD diagnosis in these two groups showed similar MACE and cardiac mortality (20.0 vs. 22.5%, 6.7 vs. 5.3%, respectively; all P > 0.05). Conclusions, This study suggests that diabetic patients with asymptomatic CAD have a higher cardiac mortality risk than those with symptomatic CAD, and that lack of revascularization therapy may be responsible for the poorer survival. [source] Prevalence of silent myocardial ischaemia in new-onset middle-aged Type 2 diabetic patients without other cardiovascular risk factorsDIABETIC MEDICINE, Issue 7 2006P. Fornengo Abstract Aims Coronary artery disease (CAD) is the leading cause of death in patients with Type 2 diabetes and is often asymptomatic. Silent myocardial ischaemia (SMI) is frequent in diabetic subjects and is responsible for a late diagnosis of CAD; its early detection is important. There are some data about the prevalence of SMI in Type 2 diabetic patients at high risk for cardiovascular disease, while no data are available in subjects at the onset of diabetes without other cardiovascular risk factors. Methods We screened 274 consecutive patients (mean age 64.3 ± 8.4 years, 66% male) at the time of diagnosis of Type 2 diabetes; we enrolled 111 subjects without other cardiovascular disease risk factors (dyslipidaemia, hypertension, peripheral vascular disease, retinopathy, microalbuminuria, history of heart disease) and with normal resting electrocardiogram (ECG). Participants performed a maximal ECG exercise protocol and, if positive, underwent coronary angiography. Results The ECG exercise test was positive in 19 patients (17.1%); of those 14 (13%) had angiographic coronary disease (one with three-vessel disease, three with two vessels and 10 with one vessel involved). The positive predictive value of the exercise ECG for predicting angiographic coronary disease was 73%. Conclusions The prevalence of SMI was 17% and angiographic coronary disease was found in 13% of middle-aged subjects with new-onset Type 2 diabetes without other cardiovascular risk factors. This prevalence is similar to that observed in studies of subjects with long duration diabetes who have additional cardiovascular risk factors. [source] Use of midregional proadrenomedullin in the detection of myocardial ischaemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2007D. Staub No abstract is available for this article. [source] Towards predictive modelling of the electrophysiology of the heartEXPERIMENTAL PHYSIOLOGY, Issue 5 2009Edward Vigmond The simulation of cardiac electrical function is an example of a successful integrative multiscale modelling approach that is directly relevant to human disease. Today we stand at the threshold of a new era, in which anatomically detailed, tomographically reconstructed models are being developed that integrate from the ion channel to the electromechanical interactions in the intact heart. Such models hold high promise for interpretation of clinical and physiological measurements, for improving the basic understanding of the mechanisms of dysfunction in disease, such as arrhythmias, myocardial ischaemia and heart failure, and for the development and performance optimization of medical devices. The goal of this article is to present an overview of current state-of-art advances towards predictive computational modelling of the heart as developed recently by the authors of this article. We first outline the methodology for constructing electrophysiological models of the heart. We then provide three examples that demonstrate the use of these models, focusing specifically on the mechanisms for arrhythmogenesis and defibrillation in the heart. These include: (1) uncovering the role of ventricular structure in defibrillation; (2) examining the contribution of Purkinje fibres to the failure of the shock; and (3) using magnetic resonance imaging reconstructed heart models to investigate the re-entrant circuits formed in the presence of an infarct scar. [source] Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate-mediated attenuationEXPERIMENTAL PHYSIOLOGY, Issue 8 2008Carlos L. Del Rio Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia-induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro-arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min,1), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 ± 9 ,, from 611 ± 24 ,, n= 16) when compared with intact control dogs (+43 ± 5 ,, from 620 ± 20 ,, n= 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 ± 11 to 193 ± 15 beats min,1) and MEI (+12 ± 1.1 ,, from 663 ± 18 ,). In contrast, VNS during ischaemia (n= 11) abruptly reduced HR (from 206 ± 6 to 73 ± 9 beats min,1) and MEI (,16 ± 2 ,, from 700 ± 44 ,). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG-derived indices of ischaemia (e.g. ST segment, 0.22 ± 0.03 versus 0.15 ± 0.03 mV) and of rate-corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 ± 4.2 versus 65.8 ± 5.9 ms; QTc, 340 ± 8 versus 254 ± 16 ms]. Vagal nerve stimulation during myocardial ischaemia exerts negative chronotropic effects, limiting early ischaemic electrotonic uncoupling and dispersion of repolarization, possibly via a decreased myocardial metabolic demand. [source] Remote myocardium gene expression after 30 and 120 min of ischaemia in the ratEXPERIMENTAL PHYSIOLOGY, Issue 2 2006Miguel S. Guerra The aim of the present study was to investigate how early the onset of ischaemia-induced changes in gene expression is in remote myocardium, and whether these changes would be different for left and right ventricles. Wistar rats (n= 27) were randomly assigned to left coronary artery (LCA) ligation for 30 or 120 min and sham groups. Evans Blue infusion revealed antero-apical left ventricle (LV) and left intraventricular (IV) septal ischaemia (35.5 ± 0.6% of LV mass). LCA ligation induced transient LV systolic dysfunction and sustained biventricular slowing of relaxation. Regarding mRNA levels, type B natriuretic peptide (BNP) was upregulated in the LV at 30 (+370 ± 191%) and 120 min (+221 ± 112%), whilst in the right ventricle (RV) this was only significant at 120 min (+128 ± 39%). Hipoxia-inducible factor 1, and interleukin 6 overexpression positively correlated with BNP. Inducible NO synthase upregulation was present in both ventricles at 120 min (LV, +327 ± 195%; RV, +311 ± 122%), but only in the RV at 30 min (+256 ± 88%). Insulin-like growth factor 1 increased in both ventricles at 30 (RV, +59 ± 18%; LV, +567 ± 192%) and 120 min (RV, +69 ± 33%; LV, +120 ± 24%). Prepro-endothelin-1 was upregulated in the RV at 120 min (+77 ± 25%). Ca2+ -handling proteins were selectively changed in the LV at 120 min (sarcoplasmic reticulum Ca2+ ATPase, 53 ± 7%; phospholamban, +31 ± 4%; Na+,Ca2+ exchanger, 31 ± 6%), while Na+,H+ exchanger was altered only in the RV (,79 ± 5%, 30 min; +155 ± 70%, 120 min). Tumour necrosis factor-, and angiotensin converting enzyme were not significantly altered. A very rapid modulation of remote myocardium gene expression takes place during myocardial ischaemia, involving not only the LV but also the RV. These changes are different in the two ventricles and in the same direction as those observed in heart failure. [source] Therapeutic angiogenesis and vasculogenesis for tissue regenerationEXPERIMENTAL PHYSIOLOGY, Issue 3 2005Paolo Madeddu Therapeutic angiogenesis/vasculogenesis holds promise for the cure of ischaemic disease. The approach postulates the manipulation of spontaneous healing response by supplementation of growth factors or transplantation of vascular progenitor cells. These supplements are intended to foster the formation of arterial collaterals and promote the regeneration of damaged tissues. Angiogenic factors are generally delivered in the form of recombinant proteins or by gene transfer using viral vectors. In addition, new non-viral methods are gaining importance for their safer profile. The association of growth factors with different biological activity might offer distinct advantages in terms of efficacy, yet combined approaches require further optimization. Alternatively, substances with pleiotropic activity might be considered, by virtue of their ability to target multiple mechanisms. For instance, some angiogenic factors not only stimulate the growth of arterioles and capillaries, but also inhibit vascular destabilization triggered by metabolic and oxidative stress. Transplantation of endothelial progenitor cells was recently proposed for the treatment of peripheral and myocardial ischaemia. Progenitor cells can be transplanted either without any preliminary conditioning or after ex vivo genetic manipulation. Delivery of genetically modified progenitor cells eliminates the drawback of immune response against viral vectors and makes feasible repeating the therapeutic procedure in case of injury recurrence. It is envisioned that these new approaches of regenerative medicine will open unprecedented opportunities for the care of life-threatening diseases. [source] Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidineFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2003William C. Stanley Abstract The primary result of myocardial ischaemia is reduced oxygen consumption and adenosine triphosphate (ATP) formation in the mitochondria, and accelerated anaerobic glycolysis, lactate accumulation and cell acidosis. Classic pharmacotherapy for demand-induced ischaemia is aimed at restoring the balance between ATP synthesis and breakdown by increasing the oxygen delivery (i.e. with long acting nitrates or Ca2+ channel antagonist) or by decreasing cardiac power by reducing blood pressure and heart rate (i.e. with , -blocker or Ca2+ channel antagonist). Animal studies show that fatty acids are the primary mitochondrial substrate during moderate severity myocardial ischaemia, and that they inhibit the oxidation of carbohydrate and drive the conversion of pyruvate to lactate. Drugs that partially inhibit myocardial fatty acid oxidation increase carbohydrate oxidation, which results in reduced lactate production and a higher cell pH during ischaemia. Trimetazidine (1-[2,3,4-trimethoxibenzyl]-piperazine) is the first and only registered drug in this class, and is available in over 90 countries world-wide. Trimetazidine selectively inhibits the fatty acid , -oxidation enzyme 3-keto-acyl-CoA dehydrogenase (3-KAT), and is devoid of any direct haemodynamic effects. In double-blind placebo-controlled trials trimetazidine significantly improved symptom-limited exercise performance in stable angina patients when used either as monotherapy or in combination with , -blockers or Ca2+ channel antagonists. Given available evidence, trimetazidine is an excellent alternative to classic haemodynamic agents, and is unique in its ability to reduce symptoms of angina when used in patients resistant to a haemodynamic treatment as vasodilators, , -blockers or Ca2+ channel antagonists. [source] Silent myocardial ischaemia following methysergide overdoseINTERNAL MEDICINE JOURNAL, Issue 6 2000A. A. FISHER Senior Registrar No abstract is available for this article. [source] Withdrawal syndrome following cessation of antihypertensive drug therapyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2005G. N. Karachalios Summary In this study, a review of the available information concerning abrupt withdrawal of antihypertensive drug therapy is presented. Abrupt withdrawal of these drugs can produce a syndrome of sympathetic overactivity that includes nervousness, tachycardia, headache, agitation and nausea 36,72 h after cessation of the drug. A withdrawal syndrome may occur after discontinuation of almost all types of antihypertensive drugs, but mostly occurs with clonidine, ,-blockers, methyldopa and guanabenz. Less commonly can produce a rapid increase of the blood pressure to pre-treatment levels or above, or both and/or myocardial ischaemia. Although the exact incidence of the syndrome is not known, it appears to be rare, at least in patients receiving standard doses of the above antihypertensive drugs. The best treatment is prevention. In this study regarding the withdrawal syndrome that follows cessation of antihypertensive drugs therapy, a reference to the abrupt discontinuation of the main categories of antihypertensive drugs is also attempted. [source] Intracoronary enalaprilat during angioplasty for acute myocardial infarction: alleviation of postischaemic neurohumoral and inflammatory stress?JOURNAL OF INTERNAL MEDICINE, Issue 2 2007U. Schaefer Abstract. Aims., Reperfusion after myocardial ischaemia is associated with a distinct ischaemia/reperfusion injury. Since ACE-inhibition, beyond its influence on cardiac angiotensin II formation and kinin metabolism, has been shown to be cardioprotective by decreasing leucocyte adhesion and endothelin-1 (ET-1) release, we investigated the effects of intracoronary (i.c.) enalaprilat during primary angioplasty in acute myocardial infarction. Methods and Results., Twenty-two patients were randomized to receive i.c. enalaprilat (50 ,g) or placebo immediately after reopening of the infarct-related artery (IRA). Plasma concentrations of soluble L-selectin, P-selectin, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), ET-1 and nitric oxide metabolite concentrations (NO(x)) were measured in pulmonary arterial blood. Coronary blood flow was assessed using corrected thrombolysis in myocardial infarction (TIMI) frame counts (CTFC). During reperfusion, there was a significant increase in sL-selectin, sP-selectin and ET-1 in the placebo group, which was greatly diminished by enalaprilat. Levels of sVCAM-1 and sICAM-1 were not affected in either group. CTFC in the placebo group remained higher than normal in both the IRA and nonculprit vessels, whereas myocardial blood flow improved with enalaprilat. Conclusion., Enalaprilat as adjunct to primary angioplasty might be a protective approach to prevent leucocyte adhesion and the release of ET-1, thereby improving coronary blood flow. [source] Hydrogen sulfide protects from intestinal ischaemia,reperfusion injury in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2009Hao Liu Abstract Objectives Hydrogen sulfide (H2S) is an endogenously gaseous mediator, regulating many pathophysiological functions in mammalian cells. H2S has been shown to inhibit myocardial ischaemia,reperfusion (I/R) injury. However, little is known about whether H2S could modulate intestinal I/R injury. This study aimed to investigate the effect of H2S on intestinal I/R injury and potential mechanism(s) underlying the action of H2S in regulating the development of intestinal I/R injury in rats. Methods Following surgical induction of intestinal I/R injury for 1 h, groups of Sprague-Dawley rats were treated with, or without, tetramethylpyrazine (8 mg/kg), or sodium hydrosulfide (NaHS, an H2S donor at 7 or 14 ,mol/kg) 30 min after occlusion. All rats were sacrificed immediately after the reperfusion. Their intestinal injury, together with that of sham-control rats, was histologically examined and their sera and intestinal malondialdehyde (MDA), superoxide dismutase (SOD), peroxidase (GSH-Px) activities were characterized by biochemical analysis. Key findings The results showed that NaHS significantly reduced intestinal I/R injury and the levels of sera and intestinal MDA activity, and dramatically increased the levels of serum and intestinal SOD and GSH-Px activity. Conclusions The results suggest that H2S protects from intestinal I/R injury in rats, which is associated with increase in the activity of antioxidant enzymes. [source] Interactions between histamine and bradykinin in stimulation of ischaemically sensitive cardiac afferents in felinesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Liang-Wu Fu Cardiac spinal afferents are activated during myocardial ischaemia. Our previous studies have shown that during ischaemia, histamine and bradykinin (BK) stimulate cardiac spinal afferents. Because the two mediators are released together during ischaemia, the present study examined the interactions between these two mediators with respect to their influence on ischaemically sensitive cardiac afferents. Single-unit cardiac afferent activity was recorded from the left sympathetic chain or rami communicantes (T2,T5) in anaesthetized cats. Fifty-five ischaemically sensitive cardiac afferents (conduction velocity (CV) = 0.2,5.6 m s,1, 8 A,- and 47 C-fibres) were identified. Administration of histamine (10 ,g kg,1) and BK (1 ,g) in combination into the left atrium (LA) caused an additive response in 16 afferents compared with administration of either BK or histamine alone (2.62 ± 0.39 versus 1.67 ± 0.20 versus 1.24 ± 0.23 impulses s,1 (imp s,1), BK + histamine versus BK versus histamine). To further evaluate interactions between these mediators, we observed that injection of histamine (10 ,g kg,1, LA) 4 min after the administration of BK (1 ,g, LA) induced a significantly larger cardiac afferent response than the response to histamine before BK (1.24 ± 0.23 versus 1.96 ± 0.39 imp s,1, before versus after, n= 10). In contrast, six other afferents responded reproducibly to repeated injections of histamine (10 ,g kg,1, LA) in the absence of BK. BK sensitization of the afferent response to histamine lasted for less than 10 min. Cyclooxygenase blockade with indomethacin (5 mg kg,1, i.v.) abolished BK sensitization of the response to histamine (1.09 ± 0.11 versus 1.11 ± 0.10 imp s,1, n= 10). Conversely, the response of most (7/9) cardiac afferents to repeat application of BK (1 ,g, LA) 4 min after histamine (10 ,g kg,1, LA) was attenuated compared with the BK response before histamine (1.84 ± 0.25 versus 1.31 ± 0.18 imp s,1, before versus after, P < 0.05). Repeat BK (1 ,g, LA) induced a consistent response in five other afferents in the absence of histamine. Thus, BK interacts with histamine, and together they cause a larger response than either one alone. BK sensitizes cardiac afferents responding to histamine in a time-dependent fashion, and the BK sensitization effect is dependent on an intact cyclooxygenase pathway. Conversely, histamine reduces the response of most afferents to BK. [source] Activated platelets contribute to stimulation of cardiac afferents during ischaemia in cats: role of 5-HT3 receptorsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2002Liang-Wu Fu Myocardial ischaemia activates blood platelets and cardiac sympathetic afferents, which mediate chest pain and cardiovascular reflex responses. We have demonstrated that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents. Platelets absorb and release 5-hydroxytryptamine (5-HT) when they are activated. In the present study we hypothesized that, by releasing 5-HT, activated platelets stimulate cardiac afferents during ischaemia through a 5-HT3 receptor mechanism. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from cats. Activation of platelets in PRP was induced by thrombin (5 units ml,1) or collagen (2 mg kg,1). Using high-performance liquid chromatography, we observed that the concentration of 5-HT was increased significantly in suspensions of platelets activated with thrombin (PRP+thrombin, 28 ± 1.7 ,m) or collagen (PRP+collagen, 27 ± 2.5 ,m) compared with suspensions of unactivated platelets (PRP+saline, 2.3 ± 0.8 ,m) and PPP. During myocardial ischaemia and reperfusion, tirofiban, a specific inhibitor of platelet glycoprotein (GP) IIb-IIIa receptors (100 ,g kg,1, I.V., followed by 5 ,g kg,1 min,1), significantly reduced the increase in the concentration of 5-HT in cardiac venous plasma from ischaemic region. Nerve activity of single-unit cardiac afferents was recorded from the left sympathetic chain (T2-T5) in anaesthetized cats. Eighty ischaemically sensitive and seven ischaemically insensitive cardiac afferents were identified. Tirofiban reduced the ischaemia-related increase in activity of seven cardiac sympathetic afferents by 50 %. Injection of 1.5 ml of PRP+collagen or PRP+thrombin into the left atrium (LA) increased activity of 16 cardiac afferents. Tropisetron (300 ,g kg,1, I.V.), a selective 5-HT3 receptor antagonist, eliminated the afferent's responses to platelets activated with collagen or thrombin. Moreover, LA injection of 5-HT (20-40 ,g kg,1) and PBG (100 ,g kg,1), a 5-HT3 receptor agonist, stimulated nine ischaemically sensitive cardiac sympathetic afferents, significantly increasing the activity of these afferents. However, injection of ,-M-5-HT (100 ,g kg,1, LA), a 5-HT2 receptor agonist, stimulated only two of the nine ischaemically sensitive cardiac afferents, and thus did not significantly alter impulse activity of this group of afferents. Both the 5-HT1 (5-CT, 100 ,g kg,1, LA) and 5-HT4 receptor agonists (SC53116, 100 ,g kg,1, LA) did not stimulate any of the nine afferents tested. Tropisetron (300 ,g kg,1, I.V.) also eliminated the response of seven ischaemically sensitive cardiac afferents to exogenous 5-HT and attenuated the ischaemia-related increase in activity of nine cardiac sympathetic afferents by 41 %. Conversely, LA injection of 5-HT (40 ,g kg,1) did not stimulate any of seven ischaemically insensitive cardiac afferents, although this group of afferents consistently responded to bradykinin (3 ,g, LA). These data indicate that during myocardial ischaemia the activated platelets stimulate cardiac sympathetic afferents, at least in part, through a 5-HT3 receptor mechanism. [source] The pathophysiology of peri-operative myocardial infarctionANAESTHESIA, Issue 7 2010B. M. Biccard Summary It is generally believed that plaque rupture and myocardial oxygen supply-demand imbalance contribute approximately equally to the burden of peri-operative myocardial infarction. This review critically analyses data of post-mortem, pre-operative coronary angiography, troponin surveillance, other pre-operative non-invasive investigations, and peri-operative haemodynamic predictors of myocardial ischaemia and/or myocardial infarction. The current evidence suggests that myocardial oxygen supply-demand imbalance predominates in the early postoperative period. It is likely that flow stagnation and thrombus formation is an important pathway in the development of a peri-operative myocardial infarction, in addition to the more commonly recognised role of peri-operative tachycardia. Research and therapeutic interventions should be focused on the prediction and therapy of flow stagnation and thrombus formation. Plaque rupture appears to be a more random event, distributed over the entire peri-operative admission. [source] Rudimentary Coronary Artery in Syrian Hamsters (Mesocricetus auratus)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 4 2009A. C. Durán Summary Congenital underdevelopment of one or more main branches of the coronary arteries has been reported in man, but not in non-human mammals. In man, this defective coronary artery arrangement may cause myocardial ischaemia and even sudden death. The main goal of this study was to describe the coronary artery distribution patterns associated with the presence of a markedly underdeveloped (rudimentary) coronary artery in Syrian hamsters. Moreover, an attempt was made to explain the morphogenesis of these patterns, according to current knowledge on coronary artery development. Eleven affected hamsters belonging to a laboratory inbred family were examined by means of internal casts of the heart, great arterial trunks and coronary arteries. The aortic valve was tricuspid (normal) in seven hamsters and bicuspid in the other four. A rudimentary coronary artery arose from the right side of the aortic valve in four specimens, from the left side of the aortic valve in a further three, and from the dorsal aortic sinus in the remaining four. In all cases, a second, well-developed coronary artery provided for all the coronary blood flow. Except for the existence of a rudimentary coronary artery, the present anomalous coronary artery distribution patterns are similar to coronary artery patterns reported in Syrian hamsters, dogs and humans in association with a solitary coronary ostium in aorta. We suggest that an unusual prolonged time interval in the development of the embryonic coronary stems might be a key factor in the formation of coronary arteries displaying significantly dissimilar developmental degrees. [source] Mast cells, peptides and cardioprotection , an unlikely marriage?AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2009S. K. Walsh Summary 1,Mast cells have classically been regarded as the ,bad guys' in the setting of acute myocardial ischaemia, where their released contents are believed to contribute both to tissue injury and electrical disturbances resulting from ischaemia. Recent evidence suggests, however, that if mast cell degranulation occurs in advance of ischaemia onset, this may be cardioprotective by virtue of the depletion of mast cell contents that can no longer act as instruments of injury when the tissue becomes ischaemic. 2,Many peptides, such as ET-1, adrenomedullin, relaxin and atrial natriuretic peptide, have been demonstrated to be cardioprotective when given prior to the onset of myocardial ischaemia, although their physiological functions are varied and the mechanisms of their cardioprotective actions appear to be diverse and often ill defined. However, one common denominator that is emerging is the ability of these peptides to modulate mast cell degranulation, raising the possibility that peptide-induced mast cell degranulation or stabilization may hold the key to a common mechanism of their cardioprotection. 3,The aim of this review was to consolidate the evidence implying that mast cell degranulation could play both a detrimental and protective role in myocardial ischaemia, depending upon when it occurs, and that this may underlie the cardioprotective effects of a range of diverse peptides that exerts physiological effects within the cardiovascular system. [source] Mechanisms of Preventive Effect of Nicorandil on Ischaemia-Induced Ventricular Tachyarrhythmia in Isolated Arterially Perfused Canine Left Ventricular WedgesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2008Masamichi Hirose We examined effects of nicorandil on the induction of VT during acute myocardial ischaemia. Optical action potentials were recorded from the entire transmural wall of arterially perfused canine left ventricular wedges. Ischaemia was produced by arterial occlusion for 20 min. During endocardial pacing, nicorandil shortened mean action potential duration (APD) in the transmural wall before ischaemia and further shortened it during ischaemia without increasing dispersion of APD. HMR1098, a selective blocker of sarcolemmal ATP-sensitive K+ channels, inhibited the shortening of APD by nicorandil before and during ischaemia. Ischaemia decreased transmural conduction velocity (CV). Nicorandil partially restored CV to a similar extent in the absence and presence of HMR1098. In contrast, HMR1098 did not suppress the ischaemic conduction slowing in the absence of nicorandil. Nicorandil suppressed the increased dispersion of local CV during ischaemia. Isochrone maps on the initiation of VT showed that reentry in the transmural surface resulted from the excitation of the epicardial region of transmural surface. Nicorandil significantly increased the size of non-excited area in the epicardial region of the transmural wall, thereby significantly reducing the incidence of VT induced during ischaemia. HMR1098 inhibited this effect of nicorandil. These results suggest that nicorandil prevents VT during acute global ischaemia primarily by augmenting the inactivation of epicardial muscle through the activation of sarcolemmal KATP channels. [source] Anti-inflammatory actions of aprotinin provide dose-dependent cardioprotection from reperfusion injuryBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2008J M Carter Background and purpose: Myocardial injury following ischaemia and reperfusion has been attributed to activation and transmigration of polymorphonuclear leukocytes (PMNs) with release of mediators including oxygen-derived radicals and proteases causing damage. Experimental approach: We studied the serine protease inhibitor aprotinin in an in vivo rabbit model of 1 h of myocardial ischaemia followed by 3 h of reperfusion (MI+R). Aprotinin (10 000 Ukg,1) or its vehicle were injected 5 min prior to the start of reperfusion. Key results: Myocardial injury was significantly reduced with aprotinin treatment as indicated by a reduced necrotic area (11±2.7% necrosis as percentage of area at risk after aprotinin; 24±3.1% after vehicle; P<0.05) and plasma creatine kinase activity (12.2±1.5 and 17.3±2.3 IU g,1 protein in aprotinin and vehicle groups, respectively, P<0.05). PMN infiltration (assessed by myeloperoxidase activity) was significantly decreased in aprotinin-treated animals compared to vehicle (P<0.01). Histological analysis also revealed a substantial increase in PMN infiltration following MI+R and this was significantly reduced by aprotinin therapy (44±15 vs 102±2 PMN mm2 in aprotinin vs vehicle-treated animals, P<0.05). In parallel in vitro experiments, aprotinin inhibited neutrophil-endothelium interaction by reducing PMN adhesion on isolated, activated aortic endothelium. Finally, immunohistochemical analysis illustrated aprotinin significantly reduced myocardial apoptosis following MI+R. Conclusions and implications: Inhibition of serine proteases by aprotinin inhibits an inflammatory cascade initiated by MI+R. The cardioprotective effect appears to be at least partly due to reduced PMN adhesion and infiltration with subsequently reduced myocardial necrosis and apoptosis. British Journal of Pharmacology (2008) 155, 93,102; doi:10.1038/bjp.2008.223; published online 9 June 2008 [source] Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury in vivoBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2002Emanuela Masini No abstract is available for this article. [source] Involvement of cannabinoids in the cardioprotection induced by lipopolysaccharideBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Caroline Lagneux We have examined the involvement of the endocannabinoid system in the cardioprotection triggered by lipopolysaccharide (LPS). Rats were treated with saline or LPS (10 ,g Kg,1). 24 h later, hearts were excised, retrogradely perfused, submitted to a low-flow ischaemia (0.6 ml min,1) for 90 min and reperfused for 60 min. Some hearts were perfused with either SR 141716A (a cannabinoid CB1, receptor antagonist 1 ,M), SR 144528 (a CB2 receptor anagonist ,M), NNLA (3 ,M) or sodium nitroprusside (1 ,M) 5 min before ischaemia and during the ischaemic period. The cardioprotective effects of LPS treatment, in terms of infarction and functional recovery, were not altered by the perfusion of SR 141716A but abolished by both SR 144528 and NNLA. Finally, SR 144528 abolished the beneficial effects of SNP perfusion. Our results suggest an involvement of endocannabinoids, acting through the CB2 receptors, in the cardioprotection triggered by LPS against myocardial ischaemia. This could be attributed to a relationship between cannabinoids and NO. British Journal of Pharmacology (2001) 132, 793,796; doi:10.1038/sj.bjp.0703902 [source] Heat stress increases endothelium-dependent relaxations and prevents reperfusion-induced endothelial dysfunctionCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2002Vincent Richard Summary 1.,Heat stress has been widely used to stimulate the expression of stress proteins and is associated with various cardiovascular changes, including anti-ischaemic effects. However, the effect of heat stress on endothelial function is less clear. 2.,Heat stress was induced in anaesthetized rats by increasing body temperature to 42°C for 15 min. Twenty-four hours later, segments of rat aorta and mesenteric and coronary arteries were mounted in organ chambers. 3.,Heat stress markedly increased relaxation to acetylcholine (ACh) in all three blood vessels studied, without affecting the response to the nitric oxide (NO) donor sydnonimine-1. 4.,Heat stress also increased aortic relaxation to histamine and the calcium ionophore A23187. 5.,In the aorta, an inhibitor of NO synthesis abolished the response to ACh in both control and heat stressed-rings, whereas a cyclo-oxygenase inhibitor had no effect. 6.,Heat stress also prevented completely the impaired response to ACh in coronary arteries isolated from rats subjected to myocardial ischaemia and reperfusion. 7.,Thus, heat stress increases the stimulated release of NO the rat aorta and mesenteric and coronary arteries and prevents reperfusion-induced injury at the level of the coronary endothelium. [source] Impaired Heart Function And Noradrenaline Release After Ischaemia In Stroke-Prone Spontaneously Hypertensive RatsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2000Hong Chen SUMMARY 1. Stroke-prone spontaneously hypertensive rats (SHRSP) are a strain of rat that exhibit severely high blood pressure and stroke attacks at an early age, but their heart function in vitro has seldom been studied in detail. Although the activity of the sympathetic nervous system is known to increase after myocardial ischaemia, there is little information about the cardiac release of noradrenaline (NA) associated with heart function after ischaemia in SHRSP. The aim of the present study was to examine heart function and cardiac NA release after ischaemia in SHRSP. 2. Isolated hearts of 4- and 8-month-old SHRSP and age-matched Wistar-Kyoto (WKY) rats were perfused in a working heart preparation and were subjected to 30 min ischaemia followed by 30 min reperfusion. Heart function and coronary flow were monitored throughout the experiment. Coronary effluent was collected for determination of NA using high- performance liquid chromatography coupled with electrochemical detection. 3. Under baseline conditions, cardiac output of 4-month-old SHRSP was slightly but significantly decreased compared with that of WKY rats (P < 0.05), although coronary flow was maintained normally at this age. Eight-month-old SHRSP showed a further impairment of systolic heart function, with lower coronary flow and higher coronary vascular resistance under baseline conditions. Elevated left ventricular end-diastolic pressure was evident in SHRSP at both ages before ischaemia. Heart function was severely damaged after 30 min global ischaemia in SHRSP from both age groups. Stroke-prone spontaneously hypertensive rats also showed lower coronary flow and higher coronary vascular resistance during reperfusion. 4. Coronary NA was not detectable in WKY rats or SHRSP at 4 months of age under baseline conditions. In 8-month-old SHRSP, pre-ischaemic NA release was significantly higher than that in age-matched WKY rat controls. The concentration of NA in the coronary effluent of SHRSP during reperfusion was also significantly higher than that of WKY rats at both ages. 5. These data demonstrate that SHRSP have early impairment of both systolic and diastolic heart function compared with WKY rats. Severe damage of heart function and coronary flow after ischaemia in SHRSP was accompanied with an increased release of NA, which may play a harmful role in heart function impairment in SHRSP after ischaemia. [source] | ||||||||||||||||||||||||||||