Search

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.

Objective: In pigs, the infarct size (IS) reduction achieved by a strong preconditioning stimulus (IPs) of 10 min ischemia and 15 min reperfusion is greater than that by a weaker preconditioning stimulus (IPw) of 3 min ischemia and 15 min reperfusion. The cardioprotection achieved by IPw is completely abolished by blockade of bradykinin-B(2)-receptors. Since activation of bradykinin-B(2)-receptors subsequently activates cyclooxygenase, we now tested whether or not inhibition of cyclooxygenase with indomethacin interferes with IS reduction by IP., Methods and Results: In 42 enflurane-anesthetized pigs, the LAD coronary artery was cannulated, and subendocardial blood flow (ENDO, microspheres, ml/min/g) and IS (%, TTC-staining) were determined. Following 90 min ischemia and 120 min reperfusion, IS averaged 25.5+/-3.8 (S.E.M.) (ENDO: 0.05+/-0.01). IS was reduced by IPw to 6.3+/-2.1 (ENDO: 0.07+/-0.01) and further reduced by IPs to 2.4+/-1.0 (ENDO: 0.06+/-0.01). Indomethacin (10 mg/kg i.v.) did not alter IS per se (20.9+/-5.4, ENDO: 0.06+/-0.02), but completely abolished the IS reduction by IPw (23.2+/-5.9, ENDO: 0.06+/-0.01). In contrast, indomethacin abolished the IS reduction by IPs in only two of seven pigs (16.1+/-7.4, ENDO: 0.05+/-0.01)., Conclusion: Prostaglandins are involved in IP. However, with stronger IP stimuli other triggers/mediators can compensate for the lack of prostaglandins.

Endogenous nitric oxide (NO) is involved in the protection by classical ischemic preconditioning (IP) against ischemia-induced arrhythmias in anesthetized dogs. Furthermore, NO triggers and mediates protection against infarction and stunning in delayed IP in conscious rabbits. Up to now it is unclear whether or not endogenous NO is also involved in the protection against infarction by classical IP in vivo. In 45 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 min followed by 2 h of reperfusion resulted in an infarct size (IS, triphenyl tetrazolium chloride-staining) of 20.5+/-5.4% (S.E.M.) of the area at risk. Inhibition of NO synthase by l -nitro arginine (l -NA, 30 mg/kg i.v.) increased left ventricular (LV) peak pressure from 93+/-3 to 120+/-1 mmHg (P<0.05), but did not alter IS (22.4+/-5. 6%). With aortic constriction to match the increase in LV peak pressure with l -NA, IS was unchanged (18.1+/-5.1%). IP by 10 min ischemia and 15 min reperfusion preceding the 90 min target ischemia reduced IS to 2.0+/-0.8% (P<0.05 v. non-preconditioned groups). This reduction of IS by IP was not affected by l -NA (1.3+/-0.9%, P<0.05 v. non-preconditioned groups). Area at risk and myocardial blood flow (microspheres) during ischemia were not different among groups. Relationships between IS and subendocardial blood flow with l -NA or aortic constriction, respectively, were not different from that with placebo, but were significantly shifted downwards by IP with and without l -NA. Thus, endogenous NO does not alter infarct size development per se and is not involved in the protection against infarction by classical IP in pigs in vivo., (Copyright 2000 Academic Press.)