Heat shock. A new approach for myocardial preservation in cardiac surgery

Recent studies have indicated that heat shock (HS) induces protective genes and HS protein (HSP) expression, which enhances cellular tolerance to ischemic injury. The present study sought to determine if 42 degrees C blood cardioplegia could be used to induce HSP expression and improved myocardial salvage after 2 hours of cardioplegic arrest.

To study this, pig hearts (n = 6) on cardiopulmonary bypass were subjected to HS by continuous infusion to the globally arrested heart of warm blood cardioplegia (K+ = 30 meq/l) at 42 degrees C for 15 minutes followed by 2 hours of intermittent hypothermic (4-6 degrees C) hyperkalemic (30 meq/l) crystalloid cardioplegic arrest and 1 hour of reperfusion (heat shock group). The control group (n = 6) was subjected to only 2 hours of hypothermic crystalloid cardioplegic arrest followed by 1 hour of reperfusion without HS. Left ventricular performance, coronary blood flow, and creatine kinase release were determined before arrest and during reperfusion. Prearrest control biopsies were taken in a separate group of pigs (n = 6) for both HSP and superoxide dismutase activity. Additional biopsies were taken for the same measurements in both control and HS groups at the completion of reperfusion. In a single additional pig in both the control and HS groups, biopsies were taken during the study to estimate changes in HSP expression. The cytosolic protein of ventricular tissue was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the HSP70 family protein was examined by Western blot analysis using monoclonal antibodies. HSP was found to be increasingly expressed from control levels after 15 minutes of HS pretreatment, increasing progressively to a level significantly above the non-HS group. Associated with this increased expression of HSP was a significant increase in superoxide dismutase activity in the HS animals and significant improvement in both global and regional functions and reduced creatine kinase release.

The results show that preconditioning the heart with HS improves postischemic ventricular performance and attenuates cellular injury. HS induces a change in cellular metabolism, prompting the expression of HSP and improving antioxidant activity, leading to improved function and reduced tissue injury during ischemia and reperfusion.