Wide-spread myocardial remodeling after acute myocardial infarction in rat. Features for heart failure progression.

ABSTRACT

The aim of the present study was to assess the relationship between hemodynamic function and cardiac remodeling post-myocardial infarction (MI) in Sprague-Dawley rats - the most commonly used species in pre-clinical studies. The experimental MI was induced by left coronary artery occlusion and the hemodynamics (working heart set-up) were measured at 2, 4, 6, 11, 21, 28, 35 or 70 days as well as morphological features. The maximal increase of coronary and aortic flow (CF, AF), the aortic systolic pressure (AoS) and contraction (+dP/dt; -dP/dt) values were observed at day 4 in comparison to sham-operated rats. By contrast, the preload pressure and aortic diastolic pressure (PP, AoD) were significantly decreased. These drastic changes were followed by recent cardiomyocyte necrosis, hyperemic capillaries and proliferating young vessels. At day 6, a deep drop down of AoS, +dP/dt, -dP/dt and CF was noted, while AF, AoD and PP approximated to the sham values. The recovery was reached in the case of AoS, -dP/dt and AF at day 28, +dP/dt did not recover till day 70, while CF was markedly increased. Accordingly, the inflammatory infiltration was diminished, connective tissue and collagenized scar with a number of capillaries was observed. The recent cardiomyopathy was observed at day 28 and fixed at day 35 with significant decline of AoS, AoD and CF. Clearly, the all natural post-MI compensatory mechanisms (remodeling) were exhausted between 28 and 35 days, while most of the parameters remained unchanged up to 70 days. These changes showed nonlinear, three-phase development of the post-MI heart function in non-treated rat (I, up to 4; II, 6-28; III, 70 days). The morphological processes correlated hemodynamically, however, they were slightly delayed. This model could be fast and relevant in pre-clinical study.