Role of protease inhibition in myocardial preservation in prolonged hypothermic cardioplegia followed by reperfusion. Effect of aprotinin in an experimental model.
The effects of aprotinin on canine myocardium subjected to cardioplegia and global ischemia for 4 hours and then reperfused for 1 hour were investigated. Lysosomal and mitochondrial enzymes and cyclic nucleotides (adenosine cyclic monophosphate and guanosine cyclic monophosphate) were measured in coronary sinus blood. Aprotinin was given intravenously before cardiopulmonary bypass at total doses of 10 X 10(3) kallikrein units per kilogram (group A, six dogs) and 20 X 10(3) KU/kg (group B, six dogs). In group A, three dogs survived but with poor cardiac function; all dogs in group B survived and had better cardiac function. Lysosomal (N-acetyl-beta-D-glucosaminidase) and mitochondrial (aspartate aminotransferase) enzymes in coronary sinus blood at 60 minutes of reperfusion were significantly (p less than 0.05) lower in group B than in group A. In both groups, guanosine cyclic monophosphate was significantly (p less than 0.01) lower during reperfusion than before cardiopulmonary bypass; however, the values were significantly (p less than 0.05) higher in group B than in group A. Serum adenosine cyclic monophosphate was lower during reperfusion than before bypass in both groups, but it recovered during reperfusion in group B. Myocardial adenosine triphosphate was well preserved in both groups but creatine phosphate was decreased (p less than 0.01) in group A. These results suggest that aprotinin at a dose of 20 X 10(3) KU/kg may be effective in preserving myocardial viability and function after prolonged cardioplegia.
Sunamori
M
M
Department of Thoracic-Cardiovascular Surgery, Tokyo Medical and Dental University School of Medicine, Japan.
Innami
R
R
Amano
J
J
Suzuki
A
A
Harrison
C E
CE
D000118:Acetylglucosaminidase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D005966:Glucuronidase / Q000378:metabolism; D006324:Heart Arrest, Induced; D006439:Hemodynamics / Q000187:drug effects; D007527:Isoenzymes; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D010725:Phosphocreatine / Q000378:metabolism
D007527:Isoenzymes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D007611:Aprotinin; D000242:Cyclic AMP; D003402:Creatine Kinase; D005966:Glucuronidase; D000118:Acetylglucosaminidase; D006152:Cyclic GMP