Effects of catecholamine stimulation on myocardial hibernation.
We have recently shown that low-flow (10%) ischemia in the isolated piglet heart causes an abrupt fall in mechanical function and metabolic activity (acute hibernation), with nearly complete preservation of high-energy phosphates and glycogen after 2 hours of ischemia. We attempted to determine if norepinephrine, as occurs in vivo, would modify the hibernation process. Piglet hearts were perfused at 37 degrees C with red blood cell-enhanced Krebs-Henseleit solution. Performance of the left ventricle was assessed isovolumetrically. With control coronary flow, norepinephrine (40 ng/ml) caused a approximately 50% increase in pressure-rate product and the rate of change of pressure. When coronary flow was reduced to 10%, these measures fell to levels identical to those of ischemic hearts not exposed to norepinephrine. Changes in myocardial O2 metabolism paralleled mechanical function. Lactate release was quantitatively similar in both groups. However, myocardial adenosine triphosphate was reduced from 29 +/- 1 to 13 +/- 2 mumol/gm and glycogen from 300 +/- 46 to 77 +/- 15 mumol/gm by the presence of norepinephrine. Left ventricular compliance was reduced to 51 +/- 5%, compared with 87 +/- 8% in the group without norepinephrine (p less than 0.001). In the norepinephrine group, correlation between left ventricular stiffness and adenosine triphosphate was poor (r = -0.32). Thus hibernating myocardium does not manifest progressive deterioration in the presence of high concentrations of norepinephrine. Diastolic function is less well preserved, however.
Downing
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Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.
Chen
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
D007773:Lactates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D009638:Norepinephrine