Reperfusion of hibernating myocardium: contractile function, high-energy phosphate content, and myocyte injury after 3 hours of sublethal ischemia and 3 hours of reperfusion in the canine model.
Hibernating myocardium has been defined as a persistent impairment of contractile function resulting from reduced coronary blood flow that can be partially or completely resolved once coronary perfusion is restored. In fact, recent clinical reports have documented a dramatic improvement in contractile function after relief of chronic sublethal ischemia. To investigate the phenomenon of sublethal ischemia followed by reperfusion, we assessed myocyte morphology, high-energy phosphate content, and regional contractile function in dogs undergoing (1) 3 hours of subtotal coronary artery occlusion (CO) and 3 hours of reflow or (2) 3 hours of total CO followed by reflow, in which myocyte viability was maintained by extensive collateral perfusion during ischemia (total CO/negligible necrosis). Data were compared with findings in a third group of dogs with total CO and low collateral blood flow during ischemia, in which large confluent infarcts developed. Endocardial blood flow averaged 30 +/- 6% (p less than 0.01) and 27 +/- 4% (p less than 0.01) of baseline preocclusion values during ischemia in the groups with subtotal CO and total CO/negligible necrosis, versus 3 +/- 1% of baseline values in dogs with total CO/confluent necrosis. Both the subtotal CO and total CO/negligible necrosis groups exhibited only mild-to-moderate reversible myocyte injury (assessed by electron microscopy) and had essentially no necrosis: infarct size was 1 +/- 1% (p less than 0.01) and 4 +/- 2% (p less than 0.01) of the risk region in the subtotal CO and total CO/negligible necrosis groups, versus 55 +/- 9% of the risk region in the total CO/confluent necrosis group. Furthermore, myocardial high-energy phosphate stores were in part preserved in all dogs that underwent sublethal ischemia: endocardial adenosine triphosphate (ATP) content was 55 +/- 11% (p less than 0.01) and 56 +/- 8% (p less than 0.01) versus 11 +/- 2% of baseline values in the subtotal CO, total CO/negligible necrosis, and total CO/confluent necrosis groups, respectively. At 3 hours post occlusion, segment shortening averaged +21 +/- 10% of baseline values in dogs with subtotal CO, (p less than 0.01 versus both total CO groups), -29 +/- 9% in dogs with total CO/negligible necrosis, and -36 +/- 13% in dogs with total CO/confluent necrosis. Reperfusion after sublethal ischemia produced an acute improvement in contractile function in both the subtotal CO and total CO/negligible necrosis groups.(ABSTRACT TRUNCATED AT 400 WORDS)
Przyklenk
K
K
Heart Institute, Hospital of the Good Samaritan, Los Angeles, CA 90017.
Bauer
B
B
Kloner
R A
RA
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D003097:Collateral Circulation / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology*; D010725:Phosphocreatine / Q000032:analysis; D013997:Time Factors
D010725:Phosphocreatine; D000255:Adenosine Triphosphate