Parathyroid hormone-related peptide improves contractile function of stunned myocardium in rats and pigs

Abstract

The effect of synthetic parathyroid hormone (PTH)-related peptide [PTHrP(1–34)] on regional myocardial function was studied in 11 anesthetized pigs. Intracoronary infusion of PTHrP (cumulative dose: 14 ± 1 μg) decreased coronary resistance to 33 ± 2% of baseline ( P < 0.05) and regional myocardial function to 90 ± 3% of baseline (not significant). Ischemia-reperfusion alters the activity of several kinases and therefore possibly the myocardial effects of PTHrP. In stunned myocardium, induced by 20-min ischemia and 30-min reperfusion, the dose of PTHrP reducing coronary resistance to a minimum of 29 ± 2% was decreased to 8 ± 2 μg ( P < 0.05). Regional myocardial function was no longer decreased but increased to 132 ± 9% ( P < 0.05). The increase in regional myocardial function during PTHrP was inversely related to baseline function at 30-min reperfusion in vivo ( r = 0.9) as well as in myocytes isolated from stunned pig hearts ( r = 0.7). In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, blockade of endogenous PTHrP byd-Trp12-Tyr34-PTH(7–34) attenuated the recovery of left ventricular developed pressure by 30 ± 14% ( P < 0.05). Thus endogenous and exogenous PTHrP impact on the function of stunned myocardium.