title: Ischemic preconditioning is not additive to preservation with hypothermia or crystalloid cardioplegia in the globally ischemic rat heart.
abstract: The aim of this study was to evaluate the additive protective efficiency of ischemic preconditioning when used in combination with conventional clinically relevant cardioprotective methods of hypothermia or hypothermic cardioplegia during sustained global ischemia. Isolated rat hearts were aorta-perfused with Krebs-Henseleit buffer and were divided into six groups (n = 10 each). Group I: Ischemia at 34 degrees C for 60 min; Group PC + I: preconditioned (PC) ischemia at 34 degrees C, 2 episodes of 5 min ischemia and 10 min reperfusion at 34 degrees C followed by I; Group HI: hypothermic ischemia at 10 degrees C for 60 min; Group PC + HI: preconditioned (PC) hypothermic ischemia, 2 episodes of 5 min ischemia and 10 min reperfusion at 34 degrees C followed by HI; Group CPL + HI: single dose of 'Plegisol' cardioplegia followed by HI; Group PC + CPL + HI: preconditioned hypothermic cardioplegia, followed by CPL + HI. At the end of 60 min ischemia, all the hearts were reperfused at 34 degrees C for 30 min when post-ischemic recovery in left ventricular contractile function and coronary vascular dynamics was computed and compared. There was a significant depression in the post-ischemic recovery of developed pressure (Pmax), positive derivative of pressure (+dp/dt), negative derivative of pressure (-dp/dt) and heterometric autoregulation (HA) of contractile force in all the groups, with no major differences between the groups. Left ventricular end-diastolic pressure (LVEDP) was significantly elevated after I at 34 degrees C. Preconditioning (PC + I) prevented the rise in the LVEDP and this was accompanied by a significant reduction in the release of purine metabolites in the coronary effluents, particularly adenosine, during the immediate reperfusion period. Hypothermia (HI) provided essentially the same level of metabolic and mechanical preservation as offered by PC + I. Combination of hypothermia with preconditioning (PC + HI) or cardioplegia (PC + CPL + HI), did not further enhance the preservation. Post-ischemic recovery in the regional contractile function (segment shortening, %SS) followed nearly identical pattern to global (Pmax) recovery. Post-ischemic recovery in coronary flow (CF) was significantly reduced and coronary vascular resistance (CVR) was significantly increased in all the groups. Myogenic autoregulation (transient and sustained) was generally enhanced indicating increased vascular reactivity. Preconditioning did not alter the time-course of these changes. Preconditioned ischemia (34 degrees C) preserved left ventricular diastolic functions and prevented the contracture development after sustained ischemia reperfusion at 34 degrees C. This protective effect of preconditioning was possibly mediated by the reduction in the breakdown of purine metabolites. Hypothermia alone or in combination with crystalloid cardioplegia prevented the irreversibility of the ischemic injury but produced contractile and vascular stunning which was not improved by ischemic preconditioning. The results of this study indicate that preconditioning when combined with hypothermia or hypothermic cardioplegia offered no significant additional protection.
authors.affiliation: Department of Physiology, Faculty of Medicine, Kuwait University, Safat, Kuwait.
authors.forename: J S
authors.initials: JS
authors.lastname: Juggi
authors.forename: F
authors.initials: F
authors.lastname: al-Awadi
authors.forename: S
authors.initials: S
authors.lastname: Joseph
authors.forename: G
authors.initials: G
authors.lastname: Telahoun
authors.forename: A
authors.initials: A
authors.lastname: Prahash
mesh_terms: D000818:Animals; D006324:Heart Arrest, Induced / Q000379:methods; D007036:Hypothermia, Induced; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D011687:Purines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D011687:Purines