Contraction uncoupling with butanedione monoxime versus low calcium or high potassium solutions on flow and contractile function of isolated hearts after prolonged hypothermic perfusion.

Abstract

BACKGROUND Normal ionic perfusate containing butanedione monoxime (BDM), a reversible myofilament inhibitor, could be better than either a high potassium (KCl) or a low calcium (CaCl2) perfusate for long-term cardiac preservation. This hypothesis was tested in 70 isolated guinea pig hearts. METHODS AND RESULTS Three groups--time control (8 hours, 37 degrees C), cold control (22 hours, 3.8 degrees C), and cold+BDM (22 hours)--were perfused with typical Krebs-Ringer solution (2.5 mmol/L CaCl2 and 4.5 mmol/L KCl). Two other groups were cold perfused for 22 hours either with 2.5 mmol/L CaCl2 + 20 mmol/L KCl (high) or with 0.5 mmol/L CaCl2 (low) + 4.5 mmol/L KCl. These changes were maintained from 20 minutes before cold perfusion until 30 minutes after rewarming to 37 degrees C. Coronary vasodilator reserve was tested before cold perfusion and 2 hours after warm reperfusion with adenosine (Ade), acetylcholine (Ach, endothelium dependent), and nitroprusside (NP, endothelium independent). Each treatment decreased left ventricular pressure (LVP) by more than 80% before cold perfusion. During warm reperfusion, LVP was lower in cold control (-72 +/- 5%), high KCl (-76 +/- 4%), and low CaCl2 (-80 +/- 4%) groups than in BDM (-38 +/- 3%) or time control (-18 +/- 4%) groups; coronary flow (CF) was lower in high KCl (-67 +/- 4%) and low CaCl2 (-54 +/- 7%) groups than in cold control (-37 +/- 6%), BDM (-30 +/- 5%), or time control (+2 +/- 3%) groups; and percent oxygen extraction (controls, 62 +/- 4%) was higher in the high KCl group (83 +/- 6%) than in cold control (72 +/- 3%), BDM (73 +/- 3%), low CaCl2 (72 +/- 5%), or time control (63 +/- 3%) groups. CF responses to Ade, Ach, and NP (+103 +/- 7%, +24 +/- 5%, and +34 +/- 5% before cold) were attenuated (+76 +/- 6%, +18 +/- 5%, and +23 +/- 4%) in the time control group (5 hours later), were reduced but present in the BDM group (+10 +/- 5%, -5 +/- 5%, and -5 +/- 5%), and were absent in both low CaCl2 and high KCl groups after 2 hours of reperfusion. CONCLUSIONS Normal ionic BDM solution better preserves cardiac function and basal CF after prolonged cold perfusion than do cold control, high KCl, and low CaCl2 solutions. Vasodilatory capacity is markedly diminished after perfusion with either the high KCl or the low CaCl2 solution.