© 1993 by European Society of Cardiology
Copyright © 1993, European Society of Cardiology
Effect of prostaglandins I2 (prostacyclin) and F2
on function, energy metabolism, and calcium uptake in ischaemic/reperfused hearts
Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, USA: M Karmazyn, M Tani, J R Neely.
Correspondence to Dr Karmazyn, at Department of Pharmacology and Toxicology, Medical Sciences Building, University of Western Ontario, London, Ontario N6A 5C1, Canada. We regret to report that James Neely has died.
Objective: The aim was to examine the effect on cardiac function, energy metabolism, and calcium uptake of either prostaglandin I2 (PGI2, prostacyclin) or prostaglandin F2
(both 28.6 nM) on the response of isolated rat hearts to 25 min of total global ischaemia with or without 30 min reperfusion. Methods: Rat hearts were perfused by the Langendorff method and function assessed by left ventricular pressure. Energy metabolites were measured using enzymatic techniques and 45Ca2+ uptake determined by radioisotopic analysis. Results: Although there was no effect of either prostaglandin on contractile depression during ischaemia, both compounds accelerated the onset of and increased the magnitude of ischaemic contracture. High energy phosphate content at the end of the ischaemic period was not affected by prostaglandin treatment; however, tissue lactate levels were increased by PGI2, as was tissue calcium content. Under control conditions mean recovery of left ventricular developed pressure ranged from 66% to 83%. In the presence of PGI2 and PGF2, recovery of developed pressure was reduced to 20% and 38% of preischaemic values, respectively. The reduced recovery in developed pressure was accompanied by an approximately threefold increase in diastolic pressure (p<0.05). The depression of functional recovery in reperfused hearts treated with prostaglandins was associated with various disturbances of cellular metabolism including depressed ATP and creatine phosphate content and increased tissue lactate and calcium following 30 min of reperfusion. A significant correlation was found between the changes in developed pressure and diastolic pressure during reperfusion and the reduction in ATP and creatine phosphate repletion. The deficit in recovery of ventricular function also correlated significantly with increased lactate and calcium accumulation in the reperfused heart. Conclusions: Low concentrations of PGI2 and PGF2 can depress contractile recovery of the globally ischaemic heart through a mechanism associated with altered cellular energy metabolism and increased calcium accumulation.
Cardiovascular Research 1993;27:396-402
KEYWORDS prostaglandins; heart; rat; ischaemia; reperfusion; contractility; energy metabolism; calcium
This study was supported by NIH grant No HL37936 to the late Dr J R Neely. M Karinazyn was on sabbatical leave during the course of this study and was a recipient of a Canadian Heart Foundation visiting scientist award.
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