Eight hours of cold static storage with adenosine and lidocaine (Adenocaine) heart preservation solutions: toward therapeutic suspended animation.

Abstract

Most cardiac preservation solutions provide safe cold ischemic storage times for 4 to 5 hours. Our aim was to investigate the effects of 8 hours of cold static storage (4°C) using 2 normokalemic, polarizing adenosine-lidocaine (Adenocaine; Hibernation Therapeutics Global Ltd, Kilquade, Ireland) solutions and to compare their functional recovery with hearts preserved in gold standard histidine-tryptophan-ketoglutarate (Custodiol-HTK; Essential Pharma, Newtown, Pa) and Celsior (Genzyme, Cambridge, Mass) solutions. Male Sprague-Dawley rats (350-450 g) were randomly assigned to 1 of 4 groups (n = 8): (1) adenosine-lidocaine cardioplegia with low Ca(2+)/high Mg(2+); (2) 2× adenosine-lidocaine cardioplegia, low Ca(2+)/high Mg(2+), melatonin, and insulin (2× adenosine, lidocaine, melatonin, and insulin); (3) histidine-tryptophan-ketoglutarate solution; or (4) Celsior. Hearts were perfused in working mode, arrested (37°C), removed, stored for 8 hours at 4°C, reattached in Langendorff mode and rewarmed for 5 minutes (37°C), and switched to working mode for 60 minutes. Myocardial oxygen consumption, effluent lactates, and troponin T levels were measured. Hearts preserved for 8 hours in adenosine-lidocaine and 2× adenosine, lidocaine, melatonin, and insulin returned 50% and 76% of aortic flow and 70% and 86% of coronary flow, respectively, at 60 minutes of reperfusion. In contrast, Custodiol-HTK and Celsior hearts returned 2% and 17% of aortic flow and 11% and 48% of coronary flow, respectively, at 60 minutes of reperfusion. Hearts preserved in adenosine-lidocaine and 2× adenosine, lidocaine, melatonin, and insulin returned 90% and 100% of developed pressures and 101% and 104% of heart rate, respectively. Hearts preserved in histidine-tryptophan-ketoglutarate failed to increase systolic pressure greater than 14 mm Hg (11% baseline) and diastolic pressure greater than 10 mm Hg (17% baseline), and recovered only 16% of heart rate. Hearts preserved in Celsior developed 70% of baseline systolic pressures and 86% recovery of heart rate. At 5 minutes of rewarming after cold storage, the myocardial oxygen consumption for hearts preserved in adenosine-lidocaine, 2× adenosine, lidocaine, melatonin, and insulin, Custodiol-HTK, and Celsior was 23.0 ± 5, 20 ± 4, 15 ± 1, and 10 ± 2 μmol O(2)/min/g dry wt, respectively, with corresponding lactate outputs of 1.8 ± 0.8, 1.5 ± 0.7, 2.6 ± 0.7, and 3.2 ± 1.4 μmol lactate/min/g dry weight. Troponin T was not detected in the coronary effluent of adenosine-lidocaine or 2× adenosine, lidocaine, melatonin, and insulin hearts, whereas Custodiol-HTK and Celsior hearts had troponin T levels of 0.08 and 0.24 μg/mL, respectively. We report a 78% return of cardiac output, 90% to 100% return of developed pressures, and 101% to 104% return of heart rate after 8 hours of cold static storage using normokalemic, adenosine, lidocaine, melatonin, and insulin preservation solution in the isolated rat heart compared with 55% cardiac output with polarizing adenosine-lidocaine cardioplegia alone, 4% cardiac output with Custodiol-HTK, and 25% cardiac output in Celsior preservation solutions.