Effect of prolonged inotropic stimulation on ventricular remodeling during healing after myocardial infarction in the dog: Mechanistic insights

Objectives. We hypothesized that positive inotropic stimulation during healing after myocardial infarction might increase contractile pull on the infarct segment, increase expansion and promote ventricular dilation. Background. The effect of prolonged inotropic stimulation on left ventricular remodeling during healing after myocardial infarction has not been studied. Methods. The effects of 6 weeks of inotropic stimulation on in vivo changes in left ventricular topography, function and mass (serial two-dimensional echocardiograms), hemodynamic variables, postmortem topography (planimetry) and collagen (hydroxyproline content) were studied in 36 chronically instrumented dogs randomized, 2 days after small anterior infarction, to digoxin (0.125 mg daily) and no digoxin (control group). Results. Heart rate and arterial and left atrial pressures were similar in the two groups, but the first derivative of left ventricular pressure (peak dP/dt), systolic thickening of the noninfarct wall and systolic thinning of the infarct wall were higher in the digoxin group during the 6 weeks. At 6 weeks, infarct scar size and collagen content were similar in both groups, but the digoxin group had more infarct expansion and thinning. Between 2 days and 6 weeks, the digoxin group showed more in vivo diastolic infarct expansion, thinning and bulging; more aneurysm but less global dilation and increase in mass; and no change in ejection fraction. The effects of inotropic stimulation on remodeling were more marked in infarcts with 100% than 85% transmurality. Conclusions. Prolonged inotropic stimulation with digoxin during healing after small anterior infarction increases infarct bulging without decreasing infarct collagen content and preserves global ventricular size, mass and systolic function.