Consequences of regional inotropic stimulation of ischemic myocardium on regional myocardial blood flow and function in anesthetized swine

Abstract

Determination of the effect of inotropic stimulation on regionally ischemic and hypokinetic myocardium is complicated when intravenous administration of the inotropic agent also causes stimulation of nonischemic adjacent and distant regions, thereby altering global ventricular hemodynamics. To obviate such events, 16 anesthetized swine were studied during regional inotropic stimulation by infusion of dobutamine hydrochloride (2.5 ± 1 μg/min) into the cannulated left anterior descending coronary artery. Coronary inflow was controlled by a pump in an extracorporeal circuit. Two groups of swine with different degrees of ischemia were studied. In the first group of animals (n = 8), reduction in coronary inflow to produce a fall in coronary artery pressure (CAP) from 114 ± 7 mm Hg to 62 ± 2 mm Hg caused a decrease in percent systolic wall thickening (% WTh) from 34.6 ± 8.1% to 25.4 ± 5.8% (p < 0.005). In the second group of animals (n = 8), CAP was decreased to 46 ± 5 mm Hg (control: 115 ± 8 mm Hg) and % WTh decreased from 34.1 ± 16.4% to 10.4 ± 6.9% (p < 0.001). Subendocardial blood flow was reduced from 1.41 ± 0.38 ml/min/g to 0.65 ± 0.13 ml/min/g (group 1, p < 0.001) and from 1.08 ± 0.22 ml/min/g to 0.24 ± 0.08 ml/min/g (group 2, p < 0.001). Regional infusion of dobutamine caused asynchronous ventricular contraction with early systolic augmentation in wall thickening followed by late systolic thinning. Therefore, during hypoperfusion regional myocardial function assessed by % WTh remained unchanged (26.2 ± 5.8%, p = NS) in group 1 and decreased significantly to 1.6 ± 5.1% (p < 0.041) in group 2. Subendocardial blood flow decreased to 0.44 ± 0.15 ml/min/g in group 1 (p < 0.005) and to 0.15 ± 0.07 ml/min/g in group 2 (p < 0.012). To account for the augmented early systolic thickening that occurred during a synchronous contraction, a myocardial work index was developed in which the sum of the instanteous left ventricular pressure-wall thickness product was calculated for estimation of regional myocardial work. Increases in this work index were apparent with the addition of dobutamine at both levels of hypoperfusion. This significant enhancement in regional myocardial function in group 2 caused a significant increase of 16% (p < 0.009) in overall left ventricular power during ejection. Thus, regional inotropic stimulation with dobutamine caused enhancement of maximum work of the ischemic myocardium in the steady state despite a further decreasse in subendocardial blood flow.