Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
School of Engineering, University of Alabama, Birmingham, AL, USA.
J Mol Cell Cardiol. 2022 Feb;163:156-166. doi: 10.1016/j.yjmcc.2021.10.008. Epub 2021 Oct 29.
Ventricular enlargement and heart failure are common in patients who survive a myocardial infarction (MI). There is striking variability in the degree of post-infarction ventricular remodeling, however, and no one factor or set of factors have been identified that predicts heart failure risk well. Sympathetic activation directly and indirectly modulates hypertrophic stimuli by altering both neurohormonal milieu and ventricular loading. In a recent study, we developed a method to identify the balance of reflex compensatory mechanisms employed by individual animals following MI based on measured hemodynamics. Here, we conducted prospective studies of acute myocardial infarction in rats to test the degree of variability in reflex compensation as well as whether responses to pharmacologic agents targeted at those reflex mechanisms could be anticipated in individual animals. We found that individual animals use very different mixtures of reflex compensation in response to experimental coronary ligation. Some of these mechanisms were related - animals that compensated strongly with venoconstriction tended to exhibit a decrease in the contractility of the surviving myocardium and those that increased contractility tended to exhibit venodilation. Furthermore, some compensatory mechanisms - such as venoconstriction - increased the extent of predicted ventricular enlargement. Unfortunately, initial reflex responses to infarction were a poor predictor of subsequent responses to pharmacologic agents, suggesting that customizing pharmacologic therapy to individuals based on an initial response will be challenging.
心室扩大和心力衰竭在心肌梗死后存活的患者中很常见。然而，梗死后心室重构的程度存在显著差异，目前还没有发现一种或一组因素能够很好地预测心力衰竭风险。交感神经激活通过改变神经激素环境和心室负荷，直接和间接地调节肥厚刺激。在最近的一项研究中，我们开发了一种方法，根据测量的血流动力学来确定个体动物在心肌梗死后使用的反射补偿机制的平衡。在这里，我们对大鼠急性心肌梗死进行了前瞻性研究，以测试反射补偿的可变性程度，以及是否可以预测个体动物对针对这些反射机制的药物的反应。我们发现，个体动物在对实验性冠状动脉结扎的反应中使用非常不同的反射补偿混合物。其中一些机制是相关的——强烈通过静脉收缩补偿的动物往往表现出存活心肌收缩力下降，而增加收缩力的动物往往表现出静脉扩张。此外，一些补偿机制，如静脉收缩，增加了预测心室扩大的程度。不幸的是，梗死后的初始反射反应是对随后药物反应的预测不良指标，这表明根据初始反应为个体定制药物治疗将具有挑战性。
