The effects of chronic oral milrinone therapy on early postinfarction left ventricular remodeling

Abstract

Left ventricular remodeling following acute transmural myocardial infarction may result in early left ventricular enlargement. To characterize the effects of milrinone on components of early left ventricular dilation, 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 drinking water for 20 days. Twenty-one days after the initial surgery, hemodynamic measurements were made. The rats were then put to death and the hearts arrested in diastole were excised and fixed at a constant pressure for morphometric analysis. To examine the effects of milrinone on the relative contribution of infarcted and noninfarcted segments to early left ventricular dilation after acute myocardial infarction, a subgroup of infarcted rats chosen randomly was put to death 3 days after the initial surgery for morphometric analysis. Compared with infarcted untreated rats, infarcted milrinone-treated rats had a lower left ventricular volume (1.41 ± 0.07 ml/kg vs 2.16 ± 0.19 ml/kg, p < 0.001), lower left ventricular wall stress (0.64 ± 0.03 vs 0.91 ± 0.06, 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 segment length also did not differ between the two infarcted groups at 3 days, but at 21 days infarct segment was shorter in the milrinone-treated group compared with the untreated group ( p < 0.03). An increase in infarct segment length/total endocardial circumference ratio between day 3 and day 21 was observed only in the untreated group of rats. Thus milrinone begun in the immediate postinfarction period in a rat myocardial infarction model attenuates left ventricular dilation when hearts are examined 3 weeks later. This attenuation of early postinfarction left ventricular dilation with milrinone appears to be related to its effects on infarct zone remodeling.