Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System (original) (raw)
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In Vitro Studies of Human Hearts
The Annals of Thoracic Surgery, 2005
Background. Isolated mammalian hearts have been used in numerous studies that have led to many important discoveries in cardiac physiology, pharmacology, and surgery. Multiple methods of perfusion have been described including retrograde and/or antegrade flows and crystalloid or blood perfusates. Furthermore, multiple species have been utilized for such studies including the following: rat, rabbit, guinea pig, canine, and swine. The objective of this study was to describe a unique isolated heart preparation, utilizing human hearts not viable for transplant, which allows for physiologic perfusion and endocardial imaging.
Experimental models of heart failure
Cardiovascular Research, 1985
Background Most successful and reproducible animal models of chronic heart failure (HF) include: increased peripheral resistance, rapid ventricular pacing, arteriovenous shunt, supravalvular stenosis, chronic heart block, repetitive transmyocardial direct current (DC) shock. The main limitation of all these approaches was the lack of stability of the left ventricular (LV) dysfunction. Methods We have described a stable and reproducible animal model of LV dysfunction mediated by ischemic loss of contractive myocardium, which is suitable for chronically studying the complex pathophysiology of HF. This model incorporates conscious dogs with a chronic anterior myocardial infarction (MI). Once the MI is stabilized the progression of the ischemic disease is produced by injecting into the circumflex coronary artery 1-2 cc of latex microspheres to cause embolization of microcirculation. This procedure is repeated 3-5 times over several weeks and, at the end, it results in a spread ischemic damage and a significant loss of ventricular systolic function. Results The healed MI results in a depression of heart rate variability and baroreflex sensitivity in a subgroup of dogs. In these dogs the depressed vagal control of the heart is associated with elevated arrhythmic risk. On the contrary in dogs with preserved cardiac reflexes the arrhythmic risk is low. In the high risk group a profound electrophysiological remodelling occurs with the MI and progresses once LV dysfunction is created while the low risk dogs tolerate the embolization procedure with a loss in LV function but without the changes in the cardiac electrical stability. Conclusion Experimental preparations based on a chronic MI and progression of the ischemic damage toward a chronic LV dysfunction has provided important information concerning autonomic and electrophysiologic alterations associated with sudden cardiac death.
Circulation Research, 1989
Determination of the effect of inotropic stimulation on regionally ischemic and hypokinetic myocardium is complicated when intravenous administration of the inotropic agent also causes stimulation of nonischemic adjacent and distant regions, thereby altering global ventricular hemodynamics. To obviate such events, 16 anesthetized swine were studied during regional inotropic stimulation by infusion of dobutamine hydrochloride (2.5±1 /ig/min) into the cannulated left anterior descending coronary artery. Coronary inflow was controlled by a pump in an extracorporeal circuit. Two groups of swine with different degrees of ischemia were studied. In the first group of animals (n=8), reduction in coronary inflow to produce a fall in coronary artery pressure (CAP) from 114±7 mm Hg to 62±2 mm Hg caused a decrease in percent systolic wall thickening (%WTh) from 34.6±8.1% to 25.4±5.8% (p<0.005). In the second group of animals (n=8), CAP was decreased to 46±5 mm Hg (control: 115±8 mm Hg) and %WTh decreased from 34.1±16.4% to 10.4±6.9% (p<0.001). Subendocardlal blood flow was reduced from 1.41 ±0.38 ml/min/g to 0.65±0.13 ml/min/g (group 1, p<0.001) and from 1.08±0.22 ml/min/g to 0.24±0.08 ml/min/g (group 2, p<0.001). Regional infusion of dobutamine caused asynchronous ventricular contraction with early systolic augmentation in wall thickening followed by late systolic thinning. Therefore, during hypoperfusion regional myocardial function assessed by %WTh remained unchanged (26.2±5.8%, p=NS) in group 1 and decreased significantly to 1.6±5.1% (p<0.041) in group 2. Subendocardial blood flow decreased to 0.44±0.15 ml/min/g in group 1 (p<0.005) and to 0.15±0.07 ml/min/g in group 2 (p<0.012). To account for the augmented early systolic thickening that occurred during asynchronous contraction, a myocardial work Index was developed in which the sum of the instantaneous left ventricular pressure-wall thickness product was calculated for estimation of regional myocardial work. Increases in this work index were apparent with the addition of dobutamine at both levels of hypoperfusion. This significant enhancement in regional myocardial function in group 2 caused a significant increase of 16% (p<0.009) in overall left ventricular power during ejection. Thus, regional inotropic stimulation with dobutamine caused enhancement of maximum work of the ischemic myocardium in the steady state despite a further decrease in subendocardial blood flow.
Acta Physiologica Scandinavica, 2003
Aim: To study, for the first time, the effects of stunning on homeometric and heterometric autoregulation. Methods and results: Ischaemia (15 min)/reperfusion (30 min) was induced in the isovolumic blood-perfused dog heart preparation. Heart rate elevations (n ¼ 9) from 60 to 200 beats min )1 , in steps of 20 beats min )1 , promoted the same inotropic stimulation in control (C) and stunning (S), indicating that ischaemia/reperfusion does not affect the changes in calcium kinetics elicited by the Bowditch effect. Sudden ventricular dilation (VD) (n ¼ 10) evoked an instantaneous increase in developed pressure (D 1 DP) followed by a continuous slow performance increase (D 2 DP) in C and S. D 1 DP (C: 35 AE 2.2 mmHg; S: 27 AE 2.1 mmHg; P ¼ 0.002) and D 2 DP (C: 20 AE 1.6 mmHg; S: 14 AE 1.3 mmHg; P ¼ 0.002) decreased proportionally, while D 2 /D 1 DP (C: 0.57 AE 0.13; S: 0.58 AE 0.14) and slow response time course (T/2) were unchanged (C: 55 AE 6.6 s; S: 57 AE 7.7 s) after ischaemia/ reperfusion. The reduction of D 1 DP can be understood as a decline of the myofilaments calcium responsiveness, the main pathophysiological effect of stunning. The reason for the weakening of D 2 DP, due to intracellular calcium gain, was not determined but it was supposed that its complete manifestation could be restricted by cyclic adenosine monophosphate (cAMP) myocardial content reduction. As reported by others, D 2 DP depends on myocardial cAMP, and it has been shown that myocardial cAMP is decreased after ischaemia/reperfusion. Conclusions: Contractile depression due to stunning has no effect on the inotropic stimulation generated by the Bowditch phenomenon. Immediate and time-dependent enhancements of contraction evoked by sudden VD are proportionally reduced and the slow response time course is unaffected in the stunned myocardium.
Guidelines for Experimental Models of Myocardial Ischemia and Infarction
American journal of physiology. Heart and circulatory physiology, 2018
Myocardial infarction is a prevalent major cardiovascular event that arises from myocardial ischemia with or without reperfusion, and basic and translational research is needed to better understand its underlying mechanisms and consequences for cardiac structure and function. Ischemia underlies a broad range of clinical scenarios ranging from angina to hibernation to permanent occlusion, and while reperfusion is mandatory for salvage from ischemic injury, reperfusion also inflicts injury on its own. In this consensus statement, we present recommendations for animal models of myocardial ischemia and infarction. With increasing awareness of the need for rigor and reproducibility in designing and performing scientific research to ensure validation of results, the goal of this review is to provide best practice information regarding myocardial ischemia/reperfusion and infarction models.
Development and Long-Term Follow-Up of an Experimental Model of Myocardial Infarction in Rabbits
Animals
A chronic model of acute myocardial infarction was developed to study the mechanisms involved in adverse postinfarction ventricular remodeling. In an acute myocardial infarction (AMI), the left circumflex coronary artery of New Zealand White rabbits (n = 9) was occluded by ligature for 1 h, followed by reperfusion. A specific care protocol was applied before, during, and after the intervention, and the results were compared with those of a sham operated group (n = 7). After 5 weeks, programmed stimulation and high-resolution mapping were performed on isolated and perfused hearts using the Langendorff technique. The infarct size determined by 2,3,5-triphenyltetrazolium chloride inside of the area at risk (thioflavin-S) was then determined. The area at risk was similar in both groups (54.33% (experimental infarct group) vs. 58.59% (sham group), ns). The infarct size was 73.16% as a percentage of the risk area. The experimental infarct group had a higher inducibility of ventricular arr...