BRADYKININ ANTAGONISM INHIBITS THE ANTIGROWTH EFFECT OF CONVERTING-ENZYME INHIBITION IN THE DOG MYOCARDIUM AFTER DISCRETE TRANSMURAL MYOCARDIAL NECROSIS

Background Converting enzyme inhibitor (CEI) therapy, but not angioten sin II subtype I receptor blockade, has been shown to attenuate left v entricular remodeling in the dog after transmyocardial direct current (DC) shock. The purpose of this study was to address the importance of preservation of bradykinin to the antiremodeling effect of CEI treatm ent in this model. Methods and Results Twenty-four hours after DC shoc k, adult mongrel dogs were assigned to one of three groups: a control group; a group treated with ramipril 10 mg BID; and a group treated wi th ramipril 10 mg BID along with a continuous subcutaneous infusion of HOE 140, a bradykinin antagonist. To assess change in left and right ventricular structure, a magnetic resonance imaging (MRI) study was pe rformed 4 weeks after DC shock and compared with a baseline MRI study performed before DC shock. The increase in left ventricular mass (mean +/-SEM) in the control group was similar to that observed in the CEI-H OE 140 group (+0.73+/-0.19 versus +0.75+/-0.18 g/kg, P=NS), but both w ere greater than the change in mass in the ramipril group (-0.48+/-0.1 3 g/kg, P=.004 and P=.0005, respectively). No significant change occur red in left ventricular volume or right ventricular structure in any g roup. Mean arterial pressure was reduced by ramipril compared with the control group (-8+/-2 versus +7+/-2 mm Hg, P=.03), and this effect wa s not blunted by the addition of HOE 140 (-7+/-3 mmHg). Conclusions Pr evention by ramipril of the early increase in left ventricular mass in the DC shock model appears to be related to the preservation of brady kinin.