Takeo S, Tanonaka K, Miyake K, Imago M
Department of Physiology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.
J Mol Cell Cardiol. 1988 Mar;20(3):187-99. doi: 10.1016/s0022-2828(88)80052-x.
In a previous study, we demonstrated a significant release of adenosine, inosine and hypoxanthine during hypoxia and subsequent reoxygenation. The present study was designed to determine whether or not exogenous adenosine, inosine and hypoxanthine are beneficial for the recovery of hypoxia-induced loss of cardiac contractile force. Hearts were perfused for 20 min under hypoxic conditions, followed by 45 min-perfusion under reoxygenated conditions, and changes in contractile force, resting tension and metabolic parameters of the perfused heart were examined. When either adenosine, inosine or hypoxanthine were exogenously infused during hypoxia at the rate of 3 mumol/min, remarkable recovery (61 to 68%) of cardiac contractile force was observed upon reoxygenation. The recovery was accompanied by a significant restoration of myocardial ATP (90 to 100%) and CP contents (80 to 86%), suggesting that exogenous metabolites are utilized for the restoration of myocardial ATP during reoxygenation, which may lead to a beneficial recovery of hypoxia-induced loss of cardiac contractile force upon reoxygenation. Infusion of exogenous metabolites also resulted in an almost complete inhibition of hypoxia- and reoxygenation-induced release of creatine phosphokinase from the perfused heart as well as a significant depression of hypoxia-induced calcium accumulation in the cardiac tissue. Since these phenomena are considered to represent increases in cell membrane permeability, protection of the myocardium against hypoxia- and reoxygenation-induced changes in cell membrane permeability may be an alternative mechanism for the beneficial effect of adenosine, inosine and hypoxanthine on the hypoxic myocardium.
在先前的一项研究中，我们证明了在缺氧及随后的复氧过程中，腺苷、肌苷和次黄嘌呤会大量释放。本研究旨在确定外源性腺苷、肌苷和次黄嘌呤是否有利于恢复缺氧诱导的心脏收缩力丧失。心脏在缺氧条件下灌注20分钟，随后在复氧条件下灌注45分钟，并检测灌注心脏的收缩力、静息张力和代谢参数的变化。当在缺氧期间以3 μmol/分钟的速率外源性注入腺苷、肌苷或次黄嘌呤时，复氧时观察到心脏收缩力有显著恢复（61%至68%）。这种恢复伴随着心肌ATP含量（90%至100%）和磷酸肌酸（CP）含量（80%至86%）的显著恢复，这表明外源性代谢产物在复氧过程中被用于恢复心肌ATP，这可能导致复氧时缺氧诱导的心脏收缩力丧失得到有益的恢复。注入外源性代谢产物还几乎完全抑制了缺氧和复氧诱导的灌注心脏中肌酸磷酸激酶的释放，以及显著降低了缺氧诱导的心脏组织中钙的积累。由于这些现象被认为代表细胞膜通透性增加，保护心肌免受缺氧和复氧诱导的细胞膜通透性变化可能是腺苷、肌苷和次黄嘌呤对缺氧心肌产生有益作用的另一种机制。
