Changes in bradykinin level in coronary sinus blood after experimental coronary occlusion, and their relationships to hemodynamic changes.

The cause of chest pain in angina pectoris and myocardial infarction is not yet clear at present. As one of its mechanisms Lewis, Katz, Raab and other authors ascribed it to the pain producing substances originated from the ischemic region of the myocardium. More recently bradykinin, which is known to have strong pain producing and hypotensive actions, was suggested by Burch and DePasqualel as a substance responsible for the pain in angina pectoris. Sicuteri and co-workers2 also stated the concept that bradykinin would be the cause of pain and cardiogenic shock in myocardial infarction. However, in these studies bradykinin itself was not determined. The present work has been undertaken to study whether bradykinin is a possible cause of anginal pain and also whether it affects the cardiac function in ischemic heart disease. For this purpose the changes of bradykinin levels in the coronary sinus blood and of hemodynamics were examined after the experimental occlusion of a coronary artery in dogs. Method: Dogs were anesthetized by the intravenous administration of thiopenthal sodium at a dose of 30 mg/Kg under respiratory control by the Bird's respirator. The chest was opened and the pericardium was incised along the right vagus nerve. A canula was inserted into the coronary sinus from the right auricle, and the origin of the left anterior descending artery was ligated. Through this canula, the blood was drawn before and 1, 2, 5, 10, 15, 30 and 60 minutes after ligation, respectively. For comparison, femoral venous blood was also drawn before the thoracotomy. ECG was monitored continuously from the beginning of the experiment to the end. Blood samples thus obtained were then analyzed not only for bradykinin, but also for bradykininogen, an inactive precursor of bradykinin, and bradykininase, a bradykinin destroying enzyme. Bradykinin and bradykininase were measured by the method of Abe and co-workers3.4 with some modifications and bradykininogen by the method of Brocklehurst and Zeitlin5. In order to study the changes of hemodynamics after coronary ligation, a 8F Cournand catheter was inserted into the cavity of left ventricle through the femoral artery. Heart rate, left ventricular systolic pressure, left ventricular end -diastolic pressure, and the maximum dp/dt were measured and the Veragut's index for myocardial contractility (max. dp/dt/IP)6 was calculated before and 1, 2, 5, 10 minutes after coronary ligation together with measurement bradykinin. In addition, changes of these parameters were also examined in dogs after intravenous administration of 20.000 units/Kg of aprotinine (Trasylol), an inhibitor of bradykinin forming enzyme. The changes of these parameters after ligation were compared between the groups with and without pretreatment of aprotinine.