Influence of Bretschneider's cardioplegia on norepinephrine release from isolated perfused guinea-pig hearts

It was the aim of the present study to investigate the influence of Bretsch neider's cardioplegia on norepinephrine (NE) release [determined by high pr essure liquid chromatography (HPLC) and electrochemical detection] in isola ted perfused guinea-pig hearts, The following resulted were noted, (1) Calc ium-dependent exocytotic NE release evoked by electrical field stimulation (12 Hz, 1 min) was completely suppressed after only 3 min of normothermic ( 37.5 degrees C) Bretschneider's cardioplegia. (2) Stop-flow ischemia is ass ociated with a substantial calcium-independent, non-exocytotic NE release, which is regarded as a sodium-dependent carrier-mediated process. According ly, it is inhibited by blockers of the sodium/proton-exchanger (e.g, amilor ide) and the neuronal uptake(1)-carrier (e.g. desipramine). Compared with s top-flow ischemia alone, cardioplegia with 3 min of Bretschneider's histidi ne-tryptophan-ketoglutarate (HTK)-solution preceding stop-flow enhanced NE release at all stop-flow durations (10-90 min) investigated (e.g. after 30 min of normothermic Bretschneider's cardioplegia: 1070 +/- 41 pmol/g, n = 4 5. v stop-flow alone: 764 +/- 43 pmol/g. n = 27, P<0.05). The NE concentrat ions determined in the cardiac effluent upon reperfusion followed a typical first order kinetic indicating that the transmitter release had already oc curred during stop-flow. Hypothermia reduced NE release in a temperature-de pendent manner down to intramyocardial temperatures of 27.5 degrees C. NE r elease evoked by Bretschneider's cardioplegia still exceeded that induced b y stop-flow ischemia alone by up to 60%. The NE release evoked by Bretschne ider's cardioplegia and stop-flow ischemia was calcium-independent, However , it was significantly reduced by desipramine and amiloride, but both agent s had a more pronounced inhibitory effect on NE release evoked by stop-flow ischemia alone. (3) This difference may be due to an intrinsic effect of B retschneider's HTK-solution, as continuous administration of normothermic B retschneider's HTK-solution induced a substantial NE release which was neit her calcium-dependent nor inhibited by blockade of either uptake, or sodium /proton-exchange. It is concluded that Bretschneider's cardioplegia is not neuroprotective, as it even augments the stop-flow ischemia-induced non-exo cytotic NE release. (C) 1999 Academic Press.