Left ventricular remodeling after myocardial infarction: characterization of a swine model on beta-blocker therapy

Abstract

Current guidelines recommend beta blockers for patients after myocardial infarction (MI). Novel therapies for heart failure should be tested in combination with this medication before entering clinical trials. In this methodologic study, we sought to describe the time course of systolic and diastolic parameters of cardiac performance over a 6-wk period in closed-chest model of swine MI treated with a beta blocker. Myocardial infarction in pigs (n = 10) was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Echocardiography and pressure-volume data were collected before and at 1 and 6 wk after MI; histopathology was assessed at 6 wk. Left-ventricular (LV) volume increased significantly over 6 wk, with significant decreases in ejection fraction, wall motion index, stroke work, rate of pressure development (dP/dt(max)), preload recruitable stroke work, and mechanical efficiency. Impairment of diastolic function was manifested by a significant increase in the exponential beta coefficient of the LV end-diastolic pressure-volume relation and reduction of LV pressure decay. At 6 wk, histopathologic analysis showed that the size of the infarct area was 16.3% +/- 4.4%, and the LV mass and myocyte cross-sectional area in both the infarct border and remote zones were increased compared with those of noninfarcted pigs (n = 5). These findings suggest a dynamic pattern of remodeling over time in a closed-chest ischemia-reperfusion swine model of acute MI on beta-blocker therapy and may guide future studies.

Figure 1.

Left ventricular remodeling before (baseline) and 1 and 6 wk after acute MI in swine. (A) End-systolic and (B) and end-diastolic volumes (mean ± SEM) are significantly increased when compared with values at baseline and from control (noninfarcted) animals. *, P < 0.05 between values for infarcted and noninfarcted animals at the same time point; #, P < 0.05 between values from infarcted animals at successive time points.

Figure 2.

Representative steady-state pressure–volume loops from 1 pig each at baseline (blue) and 1 wk (green) and 6 wk (red) after MI. Pressure–volume loops were constructed by plotting instantaneous pressure versus volume. The loop repeated with each cardiac cycle and showed how the heart transitioned from its end-diastolic state to the end-systolic state. After infarction, the pressure–volume loops narrowed, indicating reduction in stroke work, and shifted rightward due to increasing volume.

Figure 3.

Representative pathologic sections from (A) a pig 6 wk after MI and (B) a control noninfarcted animal. Infarcted tissue is thinner and more pale compared with the equivalent region in the noninfarcted heart (black arrows).

Figure 4.

Correlation between infarct size (%) and LV ejection fraction (%) in pigs (r = – 0.917; P = 0.002); y = −1.3846 x + 54.051).

Figure 5.

Representative immunohistochemistry of (A) infarcted border zone and (B) noninfarcted area reveals increased myocyte cross-sectional area, associated with compensatory hypertrophy, in the infarcted border zone. Red arrows indicate sites where the cross-sectional measurements were taken. Scale bar, 50 µm.