Ischemic preconditioning triggers phospholipase D signaling in rat heart.
Recent studies have indicated that repeated brief episodes of ischemia and reperfusion render the myocardium more tolerant to subsequent lethal ischemic injury. In view of the previous observations that ischemia-reperfusion potentiates phospholipase D signaling and that such signaling is beneficial for the heart, we investigated whether a similar phospholipase D signaling is responsible for the beneficial effects associated with repeated ischemia and reperfusion. Using an isolated perfused working rat heart model, we demonstrated that four brief episodes of 5 min of ischemia and 10 min of reperfusion reduced the incidence of ventricular arrhythmias, enhanced the postischemic ventricular performance, and decreased the release of creatine kinase from the reperfused heart, with simultaneous activation of phospholipase D generating the second messengers diacylglycerol and phosphatidic acid and leading to the translocation and activation of protein kinase C. The specific antiphospholipase D antibody blocked the activation of phospholipase D and attenuated the generation of diacylglycerol and phosphatidic acid and activation of protein kinase C. In concert, phospholipase D inhibition increased the incidence of ventricular arrhythmias, blocked the beneficial effects of preconditioning on the ventricular performance, and increased the amount of creatine kinase release from the coronary effluent. The results of this study indicate that repeated brief episodes of ischemia and reperfusion exert beneficial effects on the intact rat heart by triggering the activation of a phospholipase D signaling mechanism.
Tosaki
A
A
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110, USA.
Maulik
N
N
Cordis
G
G
Trifan
O C
OC
Popescu
L M
LM
Das
D K
DK
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning; D009206:Myocardium / Q000201:enzymology*; D019301:Oleic Acid / Q000494:pharmacology; D010739:Phospholipase D / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D016276:Ventricular Function / Q000187:drug effects
D000906:Antibodies; D019301:Oleic Acid; D003402:Creatine Kinase; D010739:Phospholipase D