The Significance of Coronary Collateral Flow in Occurrence of Ventricular Arrhythmias and Cardiac Metabolism during Acute Phase of Experimental Myocardial Infarction

Despite considerable progress in the management of ischemic heart disease, a high incidence of sudden prehospital death, probably caused by early ventricular arrhythmia （EVA） associated with acute myocardial infarction, still persists. On the other hand, the role of collateral circulation in EVA during the early phase of acute myocardial ischemia is not well known, although regional blood flow in the ischemic area seems to depend on coronary collateral flow. This study was designed to evaluate the functional significance of coronary collaterals in the occurrence of EVA during acute myocardial ischemia and its metabolic basis. The left anterior descending coronary artery （LAD） was cannulated and perfused from the left carotid artery in 20 anesthetized open chest dogs. In order to create two kinds of ischemic situations with or without collateral flow in the same area at risk in the same dog, the following procedures were performed: （a） LAD occlusion of 6 minutes （LADOCL）, （b） LADOCL with retrograde drainage of collateral flow from the distal segment of LAD. In 13 out of 20 dogs, myocardial tissue biopsies were performed at the end of each ischemic period on the ischemic and non-ischemic zones for measurement of the concentrations of adenosine triphosphate （ATP）, creatine phosphate （CP） and lactate in the inner and outer layers of myocardium. The severity of EVA during ischemia was estimated as EVA score; grade 0=no premature ventricular contractions （PVC）, grade 1=less than 10 uniform PVCs/min, grade 2=10 or more PVCs/min, grade 3=multiform PVCs, grade 4=ventricular tachycardia, and grade 5=ventricular fibrillation. The results were as follows: 1） No significant difference was found in heart rate, mean blood pressure and rate pressure product （RPP） between the dogs with and without retrograde drainage of collateral flow in the control ?and ischemic periods, respectively. However, LADOCL without collateral flow showed a significant increase of heart rate and decreases of mean blood pressure and RPP when compared with the pre-ischemic state. 2） The diversion of collateral flow during ischemia apparently increased the number of premature ventricular contraction and the incidence of EVA including the fatal arrhythmias, ventricular tachycardia and/or fibrillation （VTVF）. 3） LADOCL induced the reduction of the contents of ATP and CP and the accumulation of lactate at both inner and outer myocardia in the ischemic zones. Moreover, deprivation of collateral flow during LADOCL further augmented the CP depletion and lactate accumulation. However, no significant difference was obtained in the myocardial concentrations of ATP and CP between the inner and the outer layers. 4） The severity of EVA significantly correlated with the extents of CP depletion and lactate accumulation in both layers in the ischemic myocardium. 5） In the group with VTVF, a significant increase of heart rate and decreases of mean blood pressure and RPP were observed during LADOCL without collateral flow in spite of no differece in coronary blood flow, coronary collateral flow and metabolic changes when compared to the group without VTVF. These findings suggest that （1）coronary collateral flow is one of the most important factors to regulate the incidence and severity of EVA independent of the size of area at risk; （2）myocardial ischemic changes representing marked CP depletion and lactate accumulation caused by deprivation of coronary collateral flow were important as a metabolic basis of exacerbation of EVA; and （3）the hemodynamic alteration might be an additional influential factor to provoke the fatal arrhythmias （VTVF）.departmental bulletin pape