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

Prolonged cold perfusion of the nonarrested newborn heart has been sho wn to induce stunning and subsequent contracture when followed by isch emia. The underlying mechanism remains unknown. To test whether this p henomenon is due to cytosolic calcium (Ca2+) overload, a Ca2+-channel blocker (verapamil hydrochloride) was used to pretreat the newborn hea rt immediately before prolonged cold perfusion. Twenty-eight newborn p iglets were studied in an isolated, Krebs-Henseleit-perfused Langendor ff 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 g lobal 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 protoc ol without ischemia. Baseline functional measurements were obtained wi th left ventricular balloon inflated at baseline pressure of 10 to 15 mm Hg prior to cold perfusion and after 30 minutes of normothermic rep erfusion. Perfusate creatine kinase level was analyzed, and electron m icroscopic examination was performed at the conclusion of each experim ent. Fifty percent of group I control hearts had no postischemic recov ery, and ultrastructural study revealed marked contraction bands. Func tional 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 o f developed pressure, 81.9% +/- 7.7% (II) versus 19.2% +/- 7.5 (I); ne gative first derivative of developed pressure, 78.9% +/- 6.0% (II) ver sus 14.6% +/- 5.9% (I); and left ventricular end-diastolic pressure, 1 5.7% +/- 1.7% (II) versus 56.8% +/- 10.4% (I). Verapamil prevented the stunning effect of prolonged prearrest cold perfusion alone in the ab sence of ischemic insult (group IV): left ventricular developed pressu re, 89.7% +/- 3.8% (IV) versus 67.6% +/- 2.7% (III); positive first de rivative 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 p retreatment significantly diminishes the adverse effects of prolonged hypothermic perfusion in the isolated newborn heart.