Adaptive responses of coronary circulation and myocardium to chronic reduction in perfusion pressure and flow.
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.
Mills
I
I
Department of Medicine, Rhode Island Hospital.
Fallon
J T
JT
Wrenn
D
D
Sasken
H
H
Gray
W
W
Bier
J
J
Levine
D
D
Berman
S
S
Gilson
M
M
Gewirtz
H
H
D000064:Acclimatization; D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000378:metabolism / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D008715:Methionine / Q000378:metabolism; D008833:Microcirculation / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010313:Partial Pressure; D010477:Perfusion / Q000379:methods*; D011312:Pressure; D014176:Protein Biosynthesis; D012039:Regional Blood Flow; D013552:Swine; D014664:Vasodilation
D008715:Methionine; D010100:Oxygen