Functional traits of the heart in post-infarction myocardial remodeling

Abstract

Aim. The in vitro assessment of the functional peculiarities of heart failure (HF) linked to post-infarction remodeling of the myocardium in order to identify compensatory and decompensatory pathogenetic mechanisms. Material and methods. Myocardial infarction was reproduced in white laboratory rats by twice administration of isoproterenol (IMI). The functional state of the left ventricle (LV) of isolated heart was estimated at the end of the IMI model (initial) and after 4 weeks (the period of myocardial remodeling installing) in regard to following targets: study of myocardial inotropism to ET-1 action, including its effect on volume and resistance efforts, of myocardial tolerance to ischemia and reperfusion, as well as of coronary reactivity to various stimulations (eg, acetylcholine, bradykinin, adenosine, epoxyeicosatrienes). Results. Post-infarction remodeling of the myocardium was imposed by the reversal of ET-1 induced negative inotropic effect of the isolated heart to a positive response, manifested by increase in LV systolic pressure and cardiac output up to 10%. This improvement was associated with an increase of -dP/dTmax and +dP/dTmax values, indices of the isovolumic relaxation and contraction of the heart, by up to 9.3%, which led to a better hetero- and homeometric regulation of the heart, in particularly notable being the optimization of cardiac adaptation to resistance effort, including the condition of ET-1 premedication. The endothelium dependent coronary phenomenon Gregg was markedly improved such as the coronary functional reserve increased by up to 43% under the action of acetylcholine, adenosine and bradykinin. Remarkably, the post-infarction remodeling of the myocardium ensured a diminution of the B1-receptor mediated bradykinin induced coronary dilatation while the B2-receptors mediated bradykinin effect increased. Likewise, the increase of myocardium tolerance to ischemia (30 min) and reperfusion (45 min) was another disentangled benefit inherent to post-infarction remodeling, which was exhibited by significant lowered value of LV end-diastolic pressure. Conclusions. 1. The functional link of HF to post-infarction remodeling of the myocardium is outlined by the improvement of myocardial inotropism which led to appearance of the positive response to ET-1 manifested by the increase of LV systolic pressure and cardiac output. 2. Inotropic improvement was associated with an increase of isovolumic relaxation and contraction velocity, which contributed to the increased capacity of the homeometric regulation of the LV and of the heart adaptation to resistance effort as well. 3. An important pathophysiological hallmark of post-infarction HF is the increase of bradykinin induced coronary dilation mediated by B1 receptors, but its reduction in association with the increase of the coronary dilation mediated by B2 receptors is a prediction of a positive post-infarction remodeling of the myocardium and of HF evolution as well.