The Impact of Hemodynamic Reflex Compensation Following Myocardial Infarction on Subsequent Ventricular Remodeling.

Patients who survive a myocardial infarction (MI) are at risk for ventricular dilation and heart failure. While infarct size is an important determinant of post-MI remodeling, different patients with the same size infarct often display different levels of left ventricular (LV) dilation. The acute physiologic response to MI involves reflex compensation, whereby increases in heart rate, arterial resistance, venoconstriction, and contractility of the surviving myocardium act to maintain mean arterial pressure. We hypothesized that variability in compensation might underlie some of the reported variability in post-MI remodeling, a hypothesis that is difficult to test using experimental data alone because some responses are difficult or impossible to measure directly. We therefore employed a computational model to estimate the balance of compensatory mechanisms from experimentally reported hemodynamic data. We found a strikingly wide range of compensatory reflex profiles in response to MI in dogs and verified that pharmacologic blockade of sympathetic and parasympathetic reflexes nearly abolished this variability. Then, using a previously published model of post-infarction remodeling, we showed that observed variability in compensation translated to variability in predicted LV dilation consistent with published data. Treatment with a vasodilator shifted the compensatory response away from arterial and venous vasoconstriction and towards increased heart rate and myocardial contractility. Importantly, this shift reduced predicted dilation, a prediction that matched prior experimental studies. Thus, post-infarction reflex compensation could represent both a source of individual variability in the extent of LV remodeling and a target for therapies aimed at reducing that remodeling.