NEWBORN MYOCARDIAL PROTECTION AFTER PROLONGED PREARREST COOLING - A CALCIUM OVERLOAD PHENOMENON

Prolonged cold perfusion of the nonarrested newborn heart has been shown to induce stunning and subsequent contracture when followed by ischemia. The underlying mechanism remains unknown. To test whether this phenomenon is due to cytosolic calcium (Ca2+) overload, a Ca2+-channel blocker (verapamil hydrochloride) was used to pretreat the newborn heart immediately before prolonged cold perfusion. Twenty-eight newborn piglets were studied in an isolated, Krebs-Henseleit-perfused Langendorff cardiac model. Group I control hearts (n = 8) were subjected to 90 minutes of cold perfusion at 15 degrees C, followed by 90 minutes of global ischemia and then 30 minutes of normothermic reperfusion. Group II hearts (n = 6) were pretreated with verapamil (0.2 x 10(-7) mol/L) for 3 minutes prior to similar experimentation. Groups III (control, n = 8) and IV (verapamil pretreatment, n = 6) underwent the same protocol without ischemia. Baseline functional measurements were obtained with left ventricular balloon inflated at baseline pressure of 10 to 15 mm Hg prior to cold perfusion and after 30 minutes of normothermic reperfusion. Perfusate creatine kinase level was analyzed, and electron microscopic examination was performed at the conclusion of each experiment. Fifty percent of group I control hearts had no postischemic recovery, and ultrastructural study revealed marked contraction bands. Functional recovery was significantly improved (p < 0.05) in the group II verapamil-pretreated hearts: left ventricular developed pressure, 78.6% +/- 3.0% (II) versus 17.3% +/- 6.7% (I); positive first derivative of developed pressure, 81.9% +/- 7.7% (II) versus 19.2% +/- 7.5 (I); negative first derivative of developed pressure, 78.9% +/- 6.0% (II) versus 14.6% +/- 5.9% (I); and left ventricular end-diastolic pressure, 15.7% +/- 1.7% (II) versus 56.8% +/- 10.4% (I). Verapamil prevented the stunning effect of prolonged prearrest cold perfusion alone in the absence of ischemic insult (group IV): left ventricular developed pressure, 89.7% +/- 3.8% (IV) versus 67.6% +/- 2.7% (III); positive first derivative of developed pressure, 93.9% +/- 3.2% (IV) versus 72.9% +/- 4.6% (III); and negative first derivative of developed pressure, 94.1% +/- 3.4% (IV) versus 72.6% +/- 6.4% (III) (all, p < 0.05). Verapamil pretreatment significantly diminishes the adverse effects of prolonged hypothermic perfusion in the isolated newborn heart.