An animal model of chronic coronary stenosis resulting in hibernating myocardium

Abstract

An experimental animal model of hibernating myocardium is presented. Sixteen animals were initially prepared of which seven were selected for final review. Hearts were instrumented in two separate surgical procedures such that maximum phasic flow velocity in the left anterior descending (LAD) coronary artery was reduced by 50% and followed over 1 wk. Regional shortening declined at 1 wk to 62% of aerobic values (P less than 0.048) and did not improve over 2 h reperfusion. Metabolic determinations, obtained after 1 wk of coronary stenosis and immediately sampled before and after release of the LAD flow constrictor, showed no evidence of acidosis, hypercarbia, or an inability to extract oxygen at the tissue level. Thereafter, during the 2-h reperfusion period, hearts were able to respond to dobutamine (10 micrograms/kg infusion over 1 min) challenge with an appropriate shift in an end-systolic length estimate of contractility. Mitochondrial respiration at the conclusion of the studies in the reperfused bed demonstrated near normal recovery compared with aerobic values. None of the seven hearts showed gross evidence of infarction and only one heart was noted to have a few microfocal changes of healing infarction. Thus a new model of coronary stenosis is presented, which affected substantial reductions in mechanical function consistent with the concepts of hibernating myocardium. These mechanical events were not associated with marked metabolic abnormalities, reflecting advanced ischemia or mitochondrial dysfunction and could be transiently improved with inotropic stimuli. This model may prove beneficial as a tool in understanding mechanistic events underlying the hibernating heart.

Persistent Stunning Induces Myocardial Hibernation and Protection

“…1,16 Similarly, several studies also demonstrated a maintained flow/function relationship in the presence of reduced myocardial blood flow induced by coronary stenosis, so called short-term hibernation. 11,[17][18][19][20] However, no study has reported the flow/function relationship during persistent stunning. In the present study, persistent myocardial stunning was maintained in response to the 6 episodes of repetitive coronary stenosis and reperfusion.…”

Ineffective Perfusion-Contraction Matching in Conscious, Chronically Instrumented Pigs With an Extended Period of Coronary Stenosis

“…Numerous models have been established for what is currently referred to as acute or short-term hibernation, [5][6][7][8][9] but few long-term models exist that have documented both continuous monitoring of CBF reduction in the conscious state and an associated histopathological evaluation of the AAR. Some of the current models of chronic hibernation, although they document reduced mechanical function after chronic coronary artery stenosis, either have not measured CBF 10,11 or have measured CBF but found it not to be reduced. [12][13][14][15] Importantly, in many recent studies in patients with hibernating myocardium, CBF has been measured with positron emission tomography and also been found not to be reduced substantially.…”

Dissociation of Regional Adaptations to Ischemia and Global Myolysis in an Accelerated Swine Model of Chronic Hibernating Myocardium

“…For example, circumflex ameroid models (rapidly progressing stenoses) in dogs usually have normal resting function, with a well-developed collateral circulation, yet hibernating myocardium can develop when source collateral flow is limited. 2,22 Bolukoglu et al 23 produced a near-critical stenosis in swine, but flow reserve was not continuously monitored, and hyperemic flow at the end of the study was not lower than control. Although regional function was depressed in this model, resting perfusion was normal, consistent with chronic myocardial stunning.…”