THE EFFECTS OF CHRONIC ORAL MILRINONE THERAPY ON EARLY POSTINFARCTIONLEFT-VENTRICULAR REMODELING

Left ventricular remodeling following acute transmural myocardial infa rction may result in early left ventricular enlargement. To characteri ze the effects of milrinone on components of early left ventricular di lation, rats (n = 120) underwent left coronary artery ligation or sham surgery. In the immediate postoperative period, rats received either no treatment or milrinone (3.17 +/- 0.08 mg/kg/day) dissolved in drink ing water for 20 days. Twenty-one days after the initial surgery, hemo dynamic measurements were made. The rats were then put to death and th e hearts arrested in diastole were excised and fixed at a constant pre ssure for morphometric analysis. To examine the effects of milrinone o n the relative contribution of infarcted and noninfarcted segments to early left ventricular dilation after acute myocardial infarction, a s ubgroup of infarcted rats chosen randomly was put to death 3 days afte r the initial surgery for morphometric analysis. Compared with infarct ed untreated rats, infarcted milrinone-treated rats had a lower left v entricular volume (1.41 +/- 0.07 ml/kg vs 2.16 +/- 0.19 ml/kg, p < 0.0 01), lower left ventricular wall stress (0.64 +/- 0.03 vs 0.91 +/- 0.0 6, p < 0.001), and a lower expansion index (1.61 +/- 0.12 vs 2.61 +/- 0.22, p < 0.001). Morphometric analysis revealed that the noninfarcted segment length did not differ between the two infarcted groups either 3 days or 21 days after left coronary artery ligation. Infarct segmen t length also did not differ between the two infarcted groups at 3 day s, but at 21 days infarct segment was shorter in the milrinone-treated group compared with the untreated group (p < 0.03). An increase in in farct segment length/total endocardial circumference ratio between day 3 and day 21 was observed only in the untreated group of rats. Thus m ilrinone begun in the immediate postinfarction period in a rat myocard ial infarction model attenuates left ventricular dilation when hearts are examined 3 weeks later. This attenuation of early postinfarction l eft ventricular dilation with milrinone appears to be related to its e ffects on infarct zone remodeling.