Influence of collateral blood flow and of variations in MVO2 on tissue-ATP content in ischemic and infarcted myocardium.
The left anterior descending coronary artery was occluded for 22.5, 45, 90, 180, and 360 mins in anesthesized open-chest dogs and pigs and thereafter reperfused for 30 min. Myocardial oxygen consumption was varied in dogs by cholinergic stimulation (bradycardia) and by cutting of the right and left vagus nerve (tachycardia). Regional myocardial blood flow was measured with radioactive tracer microspheres at the end of the occlusion period and 5 and 30 min after reflow. Tissue content of adenine nucleotides and of phosphocreatine were determined in the subendo- and subepicardium of transmural biopsies at the end of reflow. Infarct size was determined with nitrobluetetrazolium and compared with risk region size. Porcine hearts developed infarcts sooner. Those canines with a high MVO2 due to tachycardia had larger infarcts than those with bradycardia and resembled infarct development in the pig. The evolution of infarcts with time depended strongly on collateral flow which was significantly higher in canine hearts. Higher collateral flow and lower MVO2 in one group of canine hearts also resulted in better preserved tissue ATP. The fall in tissue ATP with time after coronary occlusion was compared with the O2-supply via collateral flow during occlusion. Assuming that the oxygen entering ischemic myocardium was used for ADP phosphorylation, we could estimate the degree of ATP-"overspending". Overspending was highest in low-flow ischemia and it correlated well with the speed of infarction. The ATP-data are best explained by the phosphocreatine energy shuttle model and by assuming slow access of cytosolic ATP to the ATP-splitting sites at the myofibrils. In conclusion, we postulate that both collateral flow as well as myocardial oxygen consumption before and during occlusion determine infarct size.
D000227:Adenine Nucleotides / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D001794:Blood Pressure; D003097:Collateral Circulation; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D006339:Heart Rate; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000032:analysis*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000032:analysis; D013552:Swine
D000227:Adenine Nucleotides; D010725:Phosphocreatine; D000255:Adenosine Triphosphate