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Isolated Perfused Hearts (isolated + perfused_heart)
Selected AbstractsMouse isolated perfused heart: Characteristics and cautionsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2003Fiona J Sutherland Summary 1.,Owing to the considerable potential for manipulating the murine genome and, as a consequence, the increasing availability of genetically modified models of cardiovascular diseases, the mouse is fast becoming a cornerstone of animal research. However, progress in the use of various murine preparations is hampered by the lack of facilities and skills for the adequate physiological assessment of genetically modified mice. 2.,We have attempted to address this problem by refining and characterizing a mouse isolated heart preparation that was originally developed for use with larger hearts. 3.,We used the isolated buffer-perfused Langendorff preparation (perfused at constant flow or constant pressure) to characterize: (i) the frequency,response characteristics; (ii) heart isolation conditions; (iii) perfusion chamber conditions; (iv) temperature,function relationships; (v) stability over extended periods of perfusion; (vi) perfusate calcium,function relationships; (vii) pressure,volume relationships; (viii) pressure,rate relationships; and (ix) flow,function relationships. [source] Losartan but not enalaprilat acutely reduces reperfusion ventricular tachyarrhythmias in hypertrophied rat hearts after low-flow ischaemiaJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2004Silvia Butz ABSTRACT Based on clinical and experimental studies, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors have been proposed to exert acute anti-arrhythmic effects in heart failure patients. Therefore, the goal of this study was to assess acute anti-arrhythmic effects of losartan and enalaprilat in hypertrophied rat hearts during low-flow ischaemia and reperfusion. In dose-finding experiments in non-hypertrophied isolated perfused hearts, we performed dose-response curves of losartan and enalaprilat studying monophasic action potential duration at 90% repolarisation (MAPD90%) and ventricular fibrillation (VF) threshold. Subsequently, we determined the effects of losartan and enalaprilat (in therapeutically relevant concentrations) on ventricular tachyarrhythmias induced by low-flow ischaemia/reperfusion in hearts demonstrating left ventricular (LV) hypertrophy 70 days after aortic banding. We found that neither drug significantly affected MAPD90% (1 nm -1 mm) or VF threshold (1 ,m losartan and 10 ,m enalaprilat) in non-hypertrophied hearts. Similarly in hypertrophied hearts, neither drug significantly affected the incidence or the duration of ventricular tachyarrhythmias (ventricular tachycardia and VF) during low-flow ischaemia. However, 1 ,m losartan significantly reduced the duration of ventricular tachyarrhythmias during reperfusion. In conclusion, neither losartan nor enalaprilat is acutely anti-arrhythmic in hypertrophied rat hearts during low-flow ischaemia. During reperfusion, however, losartan but not enalaprilat exerts acute anti-arrhythmic effects. [source] Two-component diffusion tensor MRI of isolated perfused heartsMAGNETIC RESONANCE IN MEDICINE, Issue 6 2001Edward W. Hsu Abstract Nonmonoexponential MR diffusion decay behavior has been observed at high diffusion-weighting strengths for cell aggregates and tissues, including the myocardium; however, implications for myocardial MR diffusion tensor imaging are largely unknown. In this study, a slow-exchange-limit, two-component diffusion tensor model was fitted to diffusion-weighted images obtained in isolated, perfused rat hearts. Results indicate that there are at least two distinct components of anisotropic diffusion, characterized by a "fast" component whose principal diffusivity is comparable to that of the perfusate, and a highly anisotropic "slow" component. It is speculated that the two components correspond to tissue compartments and have a general agreement with the orientations of anisotropy, or fiber orientations, in the myocardium. Moreover, consideration of previous studies of myocardial diffusion suggests that the presently observed fast component may likely be dominated by diffusion in the vascular space, whereas the slow component may include the intracellular and interstitial compartments. The implications of the results for myocardial fiber orientation mapping and limitations of the current two-component model used are also discussed. Magn Reson Med 45:1039,1045, 2001. © 2001 Wiley-Liss, Inc. [source] Chronic Amiodarone Effects on Epicardial Conduction and Repolarization in the Isolated Porcine HeartPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 7 2000DOMINIQUE LACROIX Amiodarone is a potent antiarrhythmic agent with complex chronic effects, notably on repolarization and conduction, that are not fully understood. Its low arrhythmogenic potential has been related to a lack of increase in repolarizution dispersion. Since its effects are not documented in pigs we conducted a mapping study of activation and repolarization in isolated perfused porcine hearts. Amio20 female pigs (n = 7) received amiodarone 20 mg/kg per day over 4 weeks while Amio 5O female pigs (n = 7) received 50 mg/kg per day over 4 weeks. Concentrations of the drug encompassed values found in clinical studies. Then, activation patterns and activation-to-recovery intervals (ARI) were mapped epicardially from 128 unipolar electrograms in isolated perfused hearts in corroboration of epicardial action potential recordings. Mean ARI was longer in Amio20 experiments compared to the seven control hearts (325 ±11 ms vs 288 ± 5 m.s at 1,000 ms), whereas ARI dispersion was not different, being comprised between 7 and 11 ms and generating smooth gradients. In Amio5O experiments, mean ARI was further prolonged (390 ±10 ms at 1,500 ms) with an exaggerated reverse rate dependence concomitant with a depressant effect on the plateau of the action potential. Again, ARI dispersion did not differ from controls. Finally, the drug depressed the maximal rate of depolarization (Vmax) and slowed conduction in a rate dependent and concentration dependent fashion. In conclusion, chronic amiodarone induces Class I and Class HI antiarrhythmic effects in ventricular porcine epicardium that are concentration dependent but does not affect dispersion of repolarization. This may partly explain its low arrhythmogenic potential. [source] Contribution of cytochrome P450 metabolites of arachidonic acid to hypertension and end-organ damage in spontaneously hypertensive rats treated with l -NAMEAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2005I. F. Benter Summary 1 The purpose of this study was to examine the effect of inhibition of the formation of cytochrome P450 metabolites of arachidonic acid with 1-aminobenzotriazole (ABT) on the development of hypertension and end-organ damage in spontaneously hypertensive rats (SHR) chronically treated with nitric oxide synthesis inhibitor l -NAME (SHR- l -NAME). 2 Administration of l -NAME in drinking water (80 mg l,1) to SHR for 3 weeks significantly elevated mean arterial blood pressure (MABP) (223 ± 4 mmHg) as compared to SHR controls drinking regular water (165 ± 3 mmHg). The administration of ABT (50 mg kg,1 i.p. alt diem) for 6 days significantly attenuated elevation of blood pressure in SHR- l -NAME (204 ± 4 mmHg). 3 l -NAME-induced increase in urine volume and protein was significantly lower in ABT-treated animals. 4 The impaired vascular responsiveness to noradrenaline and isoprenaline in the perfused mesenteric vascular bed of SHR- l -NAME-treated animals was significantly improved by ABT treatment. 5 Morphological studies of the kidneys and hearts showed that treatment with ABT minimized the extensive arterial fibrinoid necrosis, arterial thrombosis, significant narrowing of arterial lumen with marked arterial hyperplastic arterial changes that were observed in vehicle treated SHR- l -NAME. 6 In isolated perfused hearts, recovery of left ventricular function from 40 min of global ischaemia was significantly better in ABT-treated SHR- l -NAME. 7 These results suggest that in hypertensive individuals with endothelial dysfunction and chronic NO deficiency, inhibitors of 20-HETE synthesis may be able to attenuate development of high blood pressure and end-organ damage. [source] Testosterone protects rat hearts against ischaemic insults by enhancing the effects of ,1 -adrenoceptor stimulationBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2008S Tsang Background and purpose: Testosterone alleviates symptoms in patients with ischaemic heart disease. Androgen receptors are present in the heart, and testosterone upregulates gene expression of cardiac ,1 -adrenoceptors. We hypothesize that testosterone may confer cardioprotection by interacting with adrenoceptors. Experimental approach: In isolated perfused hearts and ventricular myocytes from orchidectomized rats without or with testosterone (200 ,g/100 g) replacement, we first determined the effect of ischaemia/reperfusion in the presence of noradrenaline (10,7 M). Then we determined the contribution of interactions between testosterone and ,1 - or ,1 -adrenoceptors in cardiac injury/protection (infarct size, release of lactate dehydrogenase, viability of myocytes, recovery of contractile function and incidence of arrhythmias) upon ischaemia/reperfusion by pharmacological manipulation using selective adrenoceptor agonists (,1 -adrenoceptor agonist: phenylephrine 10,6 M; non-selective ,-adrenoceptor agonist: isoprenaline 10,7 M) and antagonists (,1: prazosin or benoxathian 10,6 M; ,1: CGP 20712A 5 × 10,7 M). We also determined the expression of ,1 and ,1 -adrenoceptor in the hearts from rats with and without testosterone. Key results: Testosterone reduced injury induced by ischaemia/reperfusion and noradrenaline. This was achieved by enhancing the beneficial effect of ,1 -adrenoceptor stimulation, which was greater than the deleterious effect of ,1 -adrenoceptor stimulation (also enhanced by testosterone). The effects of testosterone were abolished or attenuated by blockade of androgen receptors. Testosterone also enhanced the expression of ,1A and ,1 -adrenoceptor. Conclusions and implications: Testosterone conferred cardioprotection by upregulating the cardiac ,1 -adrenoceptor and enhancing the effects of stimulation of this adrenoceptor. The effect of testosterone was at least partly mediated by androgen receptors. British Journal of Pharmacology (2008) 153, 693,709; doi:10.1038/sj.bjp.0707624; published online 24 December 2007 [source] Activation Of ,1 -Adrenoceptors Is Not Essential For The Mediation Of Ischaemic Preconditioning In Rat HeartCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2002E Vasara SUMMARY 1. The aim of the present study was to clarify the role of ,1 -adrenoceptors in the mechanism of ischaemic preconditioning (IP). 2. Rat isolated perfused hearts were either non- preconditioned, preconditioned with 5 min ischaemia or treated for 5 min with ,1 -adrenoceptor agonists (50 ,mol/L phenylephrine; 0.1, 0.5 and 1 ,mol/L methoxamine) before being subjected to 45 min of sustained ischaemia followed by 60 min reperfusion. 3. Within each of the above protocols, hearts were divided into groups to which ,1 -adrenoceptor antagonists (prazosin, 5,-methyl urapidil and chloroethylclonidine (CEC)) were administered. Functional recovery and infarct size were used as indices of the effects of ischaemia. Ischaemic contracture characteristics and maximal diastolic pressure during reflow were also assessed. 4. Blockade of ,1 -adrenoceptors with prazosin or the subtype-selective antagonists 5,-methyl urapidil and CEC did not abolish the protective effect of IP with respect to both functional recovery and infarct size reduction. 5. Protection afforded by phenylephrine was attenuated in hearts treated with prazosin or the ,1B -adrenoceptor- selective antagonist CEC, but not in those treated with the ,1A -adrenoceptor-selective antagonist 5,-methyl urapidil. 6. Treatment with low concentrations of methoxamine, considered to be ,1A -adrenoceptor selective, did not confer any protection to the ischaemic myocardium. 7. A close relationship between accelerated ischaemic contracture and enhanced cardioprotection was observed. 8. The results suggest that ,1 -adrenoceptor stimulation mimics IP, but it is not an essential component in the mechanism behind the protective effect of IP in rat heart. In addition, the present study demonstrates that stimulation of the ,1B - but not the ,1A -adrenoceptor subtype is responsible for the catecholamine-induced protection of ischaemic myocardium in rat. [source] | ||||||||||