Adaptive responses of coronary circulation and myocardium to chronic reduction in perfusion pressure and flow

Abstract

We tested the hypothesis that chronic reduction in perfusion pressure and flow in the coronary circulation induces a state of myocardial "hibernation" characterized not only by a steady-state reduction in myocardial O2 consumption (MVO2) but also by evidence of persistent dilator reserve of the distal vasculature. Biochemical and morphological changes in the coronary vasculature were also assessed. Experiments were conducted in swine with an extraluminal coronary stenosis placed 4-32 wk before study. Stenosis reduced lumen diameter by approximately 80% at the time of final experimentation. Baseline, regional myocardial blood flow distal to the stenosis in both endocardial and epicardial layers was reduced vs. that of the normal zone. Vasodilator reserve persisted in both endocardial and epicardial layers of the stenosis zone. Flow increased in each layer in response to adenosine plus phenylephrine and failed to decline despite a marked reduction in perfusion pressure in response to adenosine alone. Regional MVO2 at baseline was reduced vs. historical controls without coronary stenosis. Protein synthesis rate in coronary vessels of the stenosis zone was reduced vs. that of the normal zone. Morphological responses of stenosis zone vessel walls were heterogeneous. Smaller microvessels exhibited mild hypertrophy of their walls, whereas walls of larger microvessels tended to atrophy. Thus chronic reduction in perfusion pressure and flow induces a state of myocardial hibernation characterized by a steady-state reduction in MVO2 in association with persistent dilator capacity. Biochemical and morphological changes occur in microvessel walls and may contribute to observed physiological responses.

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

“…Results of the present study extend previous work from our laboratory as well as others, in which pigs instrumented with a stenosis on the proximal LAD developed viable, chronically dysfunctional myocardium (17,18,26,27). We have previously shown there was a progression from chronically stunned to hibernating myocardium as stenosis severity increases (9,16).…”

“…We have previously shown there was a progression from chronically stunned to hibernating myocardium as stenosis severity increases (9,16). Transition to hibernating myocardium occurred after 3-4 mo (average 107 days) and was accompanied by regional reductions in oxygen consumption (27) and flow (17,18). Although the LAD supplies ϳ40% of the pig left ventricle (35), LV ejection fraction in animals with hibernating myocardium and one-vessel occlusion was the same as sham-instrumented controls (17).…”

Differential 18 F-2-Deoxyglucose Uptake in Viable Dysfunctional Myocardium With Normal Resting Perfusion

“…The present results taken together with those of our previous study 4 and results of others 5,9 suggest that there is a transition from stunning to hibernation, as was previously reported in dogs with collateral-dependent myocardium and limited collateral vasodilator reserve. 6 Figure 4 shows the relation among flow at rest, FDG uptake, and flow during vasodilation from our previous study in relation to the present groups of animals.…”

Impaired resting perfusion in viable myocardium distal to chronic coronary stenosis in rats

“…In pig hearts, resting perfusion distal to a fixed coronary stenosis was significantly reduced compared with remote myocardium after 1-8 mo. Such myocardium, which is characterized by a small increase in fibrosis, displayed a reduced function (14) and reduced regional oxygen consumption (19). In the present study, fibrosis in the poststenotic myocardium was more pronounced (36%) compared with that in the above-mentioned pig model (6%), potentially explaining the more pronounced decrease in poststenotic myocardial blood flow.…”