CONSTRUCTIVE PRIMING OF MYOCARDIUM AGAINST ISCHEMIA-REPERFUSION INJURY

Ischemia and ischemic stress hormones induce endogenous cardiac protec tion against ischemia-reperfusion (I/R) injury. Although ischemia and ischemic stress hormones are accompanied by increased [Ca2+](i) it is unknown whether either opening of the sarcoplasmic reticular ryanodine Ca2+ channel (SR RyR) or inhibition of Ca2+ uptake by the sarcoendopl asmic reticular Ca2+-ATPase (SERCA) prior to I/R can similarly induce post-I/R functional protection. To study this, isolated, crystalloid p erfused Sprague-Dawley rat hearts were used to assess the effects of i nducing a pre-ischemic [Ca2+](i) load by either priming the SR RyR wit h ryanodine (Ry, 5 nM/2 min) or by transient blockade of the SERCA 10 min prior to global I/R (20 min). A pre-ischemic Ca2+ load by either S R RyR activation or SERCA blockade improved post-ischemic myocardial f unctional recovery (developed pressure, end diastolic pressure, corona ry flow, heart rate, and left ventricular creatine kinase activity). W e conclude that 1) Ca2+-induced myocardial functional protection invol ves the SR Ca2+ source, 2) a pre-ischemic Ca2+ load induced with eithe r Ry or thapsigargin constructively primes against myocardial I/R inju ry, and 3) Ca2+-induced cardioadaptation to I/R injury may have import ant therapeutic implications prior to planned ischemic events such as cardiac allograft preservation and cardiac bypass surgery.