CARDIAC STRESS PROTEIN ELEVATION 24 HOURS AFTER BRIEF ISCHEMIA OR HEAT-STRESS IS ASSOCIATED WITH RESISTANCE TO MYOCARDIAL-INFARCTION

Background. To test the hypothesis that the heat shock response is ass ociated with myocardial salvage, the heat stress protein (HSP) content of cardiac tissue was increased by either ischemic or thermal stress. Methods and Results. Rabbits were divided into four groups. Ischemic pretreatment (n=15) comprised four 5-minute episodes of coronary ligat ion separated by 10 minutes of reperfusion. The corresponding control group (n=21) underwent surgical preparation without coronary ligation. Thermal pretreatment (n=16) involved whole-body temperature elevation to 42-degrees-C for 15 minutes; corresponding controls (n= 15) were t reated with anesthetic alone. Twenty-four hours later, hearts were rem oved for HSP estimation or infarct size assessment after a 30-minute c oronary ligation. Myocardial HSP72 content assessed by Western blottin g was elevated by both ischemic and thermal pretreatments (2.5+/-0.2 u nits, n=4, and 2.8+/-0.3 units, n=4, mean+/-SEM; P=NS, respectively) c ompared with the corresponding control groups (1.0+/-0.3, n=4, P less- than-or-equal-to .01 and 0.3+/-0.1, n=4, P less-than-or-equal-to .01, respectively). HSP60 was preferentially elevated by ischemic pretreatm ent. After a 30-minute coronary occlusion and 120 minutes of reperfusi on, ischemic and thermal pretreatments limited infarct size as a perce ntage of the volume at risk by 28.8+/-5.2% vs 52.0+/-5.2%, P less-than -or-equal-to .01 and 32.8+/-3.8% vs 56.9+/-6.5%, P less-than-or-equal- to .01, respectively. Conclusions. Myocardial stress protein induced b y either sublethal thermal or ischemic injury is associated with myoca rdial salvage. Our findings suggest that stress protein elevation, rat her than the nonspecific effects of thermal or ischemic stress, may be responsible for the myocardial protection seen in this model. Our obs ervations may have important implications regarding myocardial adaptat ion to brief periods of ischemia.