Temperature-response studies of the detrimental effects of multidose versus single-dose cardioplegic solution in the rabbit heart

Abstract

Both single-dose and multidose cardioplegia are protective in the ischemic adult heart under normothermic and hypothermic conditions, but in the hypothermic neonatal rabbit heart single-dose cardioplegia only is protective, whereas multidose cardioplegia is damaging. The present studies in the isolated perfused working heart from neonatal rabbits (aged 7 to 10 days) were designed to characterize the interrelationships between temperature, frequency of cardioplegic infusion, and tissue protection. Hearts (n = 8/group) were subjected to 1, 1.5, 1.5, 3, 10, 12, or 18 hours of ischemia at 37.0 degrees, 34.5 degrees, 32.0 degrees, 28.0 degrees, 20.0 degrees, 15.0 degrees, or 10.0 degrees C, respectively. These times were selected to achieve approximately 55% to 75% recovery of cardiac output in hearts during normothermic reperfusion when single-dose (2 minutes) St. Thomas' Hospital cardioplegic solution was given at the onset of each ischemic period. Under these conditions actual recoveries of cardiac output were 55.7% +/- 5.6%, 68.5% +/- 6.8%, 73.8% +/- 4.1%, 54.6% +/- 5.3%, 56.3% +/- 7.5%, 59.5% +/- 7.7%, and 81.3% +/- 2.3% of the preischemic control values, respectively. By contrast, with multidose cardioplegia (given every 60 minutes in the 3- to 18-hour experiments and every 30 minutes in the 1- and 1.5-hour experiments) there was a temperature-dependent loss of protection when compared with single-dose cardioplegia; the recoveries of cardiac output were 75.7% +/- 1.5%, 78.4% +/- 4.8%, 65.0% +/- 5.8%, 36.7% +/- 5.8%, 34.6% +/- 7.5%, 25.9% +/- 6.0%, and 9.6% +/- 6.4%, respectively. These results were reflected in other indices of cardiac function and in changes in vascular resistance during cardioplegic infusion and reperfusion. To ascertain whether the progressive loss of protection was related to the degree of hypothermia or the duration of ischemia (which had to be increased as the temperature was lowered to permit a 55% to 75% recovery in the single-dose cardioplegia group), we conducted studies at a fixed temperature (20 degrees C) with variable durations of ischemia (6, 8, 10, and 12 hours). Finally, multidose and single-dose cardioplegia at 10.0 degrees, 20.0 degrees, and 37.0 degrees C were compared with hypothermia alone. We concluded that in the neonatal (in contrast to the adult) rabbit heart the protective properties of multidose cardioplegia relative to single-dose cardioplegia are progressively lost.(ABSTRACT TRUNCATED AT 400 WORDS)