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

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Patients who survive a myocardial infarction (MI) are at high 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 (HR), arterial resistance, venoconstriction, and contractility of the surviving myocardium act to maintain mean arterial pressure (MAP). We
hypothesized that variability in reflex 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 reflex 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 postinfarction 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 toward
increased HR and myocardial contractility. Importantly, this shift reduced predicted dilation, a prediction that matched prior experimental studies. Thus, postinfarction 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.