1. Parathyroid hormone-related peptide improves contractile function of stunned myocardium in rats and pigs.
- Author
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Jansen J, Gres P, Umschlag C, Heinzel FR, Degenhardt H, Schluter KD, Heusch G, and Schulz R
- Subjects
- Animals, Coronary Circulation drug effects, Heart physiopathology, Hemodynamics drug effects, In Vitro Techniques, Myocardial Stunning, Myocardium metabolism, Myocytes, Cardiac drug effects, Myocytes, Cardiac physiology, Oxygen Consumption drug effects, Parathyroid Hormone-Related Protein, Peptide Hormones physiology, Rats, Rats, Wistar, Swine, Swine, Miniature, Vascular Resistance drug effects, Ventricular Function drug effects, Heart drug effects, Myocardial Contraction drug effects, Parathyroid Hormone pharmacology, Peptide Fragments pharmacology
- 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 microg) 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 microg (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 by d-Trp(12)-Tyr(34)-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.
- Published
- 2003
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