DIRECT AND INTERACTIVE EFFECTS OF CARDIOPLEGIC ARREST AND PROTAMINE ON MYOCYTE CONTRACTILITY

Background. Cardioplegic arrest with rewarming and protamine administr ation have been implicated in causing transient left ventricular dysfu nction perioperatively. However, whether interactive effects between c ardioplegic arrest and rewarming with protamine occur with respect to myocyte contractile processes remains unclear. Accordingly, using an i solated myocyte model, the present study tested the hypothesis that si mulated cardioplegic arrest with rewarming and protamine would have di rect and interactive effects on myocyte contractile function. Methods. Left ventricular isolated myocyte contractile function was examined u sing computer-aided videomicroscopy under normothermic conditions (37 degrees C, cell medium; n = 183) and after simulated hypothermic, hype rkalemic cardioplegic arrest with rewarming (4 degrees C, 24 mEq/L K+, 2 hours; then 37 degrees C, cell medium, 5 minutes; n = 268). Myocyte function was then examined in the presence of protamine (10 to 40 mu g/mL) under normothermic conditions (n = 102) and after cardioplegic a rrest with rewarming (n = 175). Results. Myocyte contractile function decreased by 43% from baseline after simulated cardioplegic arrest wit h rewarming. Under normothermic conditions, protamine (29 mu g/ml) red uced myocyte contractile function by 43.9% +/- 4.3%, whereas myocyte c ontractile function decreased by only 31.1% +/- 2.7% with protamine (2 0 mu g/mL) after cardioplegic arrest with rewarming. Thus, the negativ e effects of protamine on myocyte contractility were attenuated after cardioplegic arrest when compared with normothermic conditions. Conclu sions. The present study demonstrated that simulated cardioplegic arre st with rewarming and protamine have direct and interactive effects on myocyte contractile function, which are not additive or synergistic.