EARLY AND DELAYED PRECONDITIONING - DIFFERENTIAL MECHANISMS AND ADDITIVE PROTECTION

The purposes of this study were to determine whether 1) 24-h endotoxin (ETX) pretreatment induces delayed (''second window'') myocardial pro tection against ischemia-reperfusion (I/R), 2) acute adenosine (Ado) o r phenylephrine (PE) pretreatment confers similar protection, 3) the m echanisms of Ado- and PE-induced early protection remain intact after endotoxemia, 4) Ado- and RE-induced protection may combine with ETX-in duced delayed protection to optimize cardiac protection, and 5) these strategies of early and/or delayed myocardial protection require de no vo protein synthesis. Rats (n = 6-8/group) were treated with ETX (0.5 mg/kg IF) or vehicle, with or without prior inhibition of protein synt hesis. Twenty-four hours later, the hearts were isolated, perfused, an d acutely pretreated with Ado or PE before I/R (20-min ischemia and 40 -min reperfusion). Developed pressure, coronary flow, compliance (end- diastolic pressure), and reperfusion creatine kinase leak were measure d. Results indicated that 1) Ado, PE, and ETX independently induced my ocardial functional protection; 2) either Ado or PE acutely enhanced E TX induced protection; and 3) cycloheximide abolished delayed, but not acute, protection. We conclude that early and delayed forms of protec tion 1) may be combined to optimize protection and 2) differentially r ely on de novo protein synthesis.