Reversible desensitization of the myocardial contractile apparatus for calcium. A new concept for improving tolerance to cold ischemia in human myocardium?

Abstract

The influence of 2,3-Butanedione monoxime (BDM) on the human myocardium's tolerance to cold ischemia was analyzed in two experimental series. 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. 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)