Summary: The function of isolated guinea pig hearts treated with 2,3 butanedione monoxime (BDM) before, during, and initially after 22 h of hypothermic perfusion was examined during 4 h of normothermic reperfusion. BDM is a vasodilatory and negative inotropic agent that reversibly decreases sensitivity of contractile proteins to Ca2 +. Also examined were the effects of adenosine (ADE) and nitroprusside (NP) in improving coronary flow (CF) and contractile function when given with BDM during rewarming and during the initial period of normothermic reperfusion. Isovolumetric left ventricular pressure (LVP), CF, and percentage of O2 extraction (%O2E) were measured in Krebs-Ringer-perfused hearts divided into three groups of 11 hearts each: drug-free controls (0 BDM); 10 mM BDM alone; and 10 mM BDM + 10 [mu]M ADE + 100 [mu]M NP. BDM was given 20 min before hypothermia, during hypothermia (3.8[degrees] [mu] 0.1[degrees]C) for 22 h, and for 30 min after rewarming to 37[degrees] [mu] 0.1[degrees]C; ADE was given with NP for only 20 min before and during rewarming and for 30 min after rewarming. Hearts were perfused at low constant flow with oxygenated Krebs' solution during hypothermia. After 2.5-h normothermic reperfusion, LVP (initial controls 108 [mu] 6 mm Hg) increased more with BDM +ADE + NP (80 [mu] 4% of control) than with BDM alone (62 [mu] 3%) or without BDM (28 [mu] 5%). CF (controls 6.0 [mu] 0.5 ml/g/min) decreased less with BDM + ADE + NP (77 [mu] 4% of control) than with BDM alone (60 [mu] 5%) or without BDM (53 [mu] 6%). %O2E (controls 59 [mu] 4%) was similar in the 0 BDM (76 [mu] 3%), BDM (74 [mu] 2%), and BDM + ADE + NP (79 [mu] 2%) groups. These results indicate that BDM given before, during, and initially after normothermic reperfusion restores cardiac function better after prolonged hypothermic perfusion and that ADE plus NP, given during the initial rewarming period with BDM, restores function better than does BDM given alone. Temporary use of ADE and NP with BDM may prove helpful in restoring vascular compliance and cardiac contractility in the early posttrans-plant period after prolonged hypothermic perfusion.
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