The influence of 2,3-Butanedione monoxime (BDM) on the human myocardium's tolerance to cold ischemia was analyzed in two experimental series.
Methods: I) Left ventricular human muscle fibers (0.6 x 4.0 mm) were obtained from recipient hearts (n = 10) and loaded with the fluorescent dye Fura-2. Simultaneous measurements of intracellular calcium transients ("ratio-method"; excitation wave lengths: 340 nm and 380 nm) and isometric force development of electrically driven (1 Hz) muscle fibers were carried out at BDM concentrations ranging from 0 to 30 mM at a bath temperature of 37 degrees C; II) Left ventricular human muscle strips were obtained from beating recipient hearts (n = 10), and right atrial fibers from patients operated upon for aortic valve stenosis or combined mitral valve disease (n = 14). Muscle strips of these hearts were incubated for parallel measurements in the following solutions: a) a 37 degrees C oxygenated Krebs-Henseleit solution (KHS), b) a 4 degrees C Bretschneider's cardioplegic solution (HTK) without oxygenation and c) a 4 degrees C KHS containing 30 mM BDM without oxygenation (BDM solution). After standardized time intervals the muscle fibers were removed from the storage solutions, reperfused in KHS solution at 37 degrees C and stretched to optimal length (supramaximal electrical stimulation). After obtaining a steady state of force development, the contractile behavior under isometric and isotonic measurement conditions was measured. The influence of the incubation periods and the incubation solution was analyzed.
Results: I) BDM reduced the isometric force development of the electrically driven isolated human myocardial muscle strip in a dose-dependent way.(ABSTRACT TRUNCATED AT 250 WORDS)