Krieger W J, Fiolet J W, Willebrands A F, ter Welle H F, van Dam R T
Basic Res Cardiol. 1980 Nov-Dec;75(6):728-38. doi: 10.1007/BF01910450.
Isolated rat hearts perfused with various substrates were subjected to oxygen restriction followed by sudden reoxygenation. The incidence of ventricular arrhythmias occurring after reoxygenation appeared to be dependent on the substrate present during oxygen restriction; it was low with glucose (11 mM) and significantly higher with oleic acid (FFA to albumin molar ratio 4), with beta-hydroxy butyrate (11 mM), with acetate (11 mM) or without added substrate. When verapamil (1 muM) was also present in the medium, these arrhythmias were largely prevented. When glucose or verapamil were present during the reoxygenation period only, the incidence of reoxygenation arrhythmias was high. Tissue levels of long-chain acyl-CoA increased during oxygen restriction under all substrate conditions tested. At the moment when reoxygenation was started they were most elevated in hearts perfused with oleic acid. Verapamil did not influence levels of long-chain acyl-CoA. The amount of creatine-kinase (CK) released from the heart after reoxygenation did not correlate with the observed arrhythmias and was greatest in hearts perfused with oleic acid. Verapamil protected against CK release in the absence of added substrate, but not when oleic acid was present. It is concluded that ventricular arrhythmias after reoxygenation are not necessarily caused by FFA or long-chain acyl-CoA.
用各种底物灌注的离体大鼠心脏先经历氧限制，然后突然再给氧。再给氧后发生室性心律失常的发生率似乎取决于氧限制期间存在的底物；用葡萄糖（11 mM）时发生率较低，而用油酸（游离脂肪酸与白蛋白摩尔比为4）、β-羟基丁酸（11 mM）、乙酸盐（11 mM）或不添加底物时发生率显著更高。当培养基中也存在维拉帕米（1 μM）时，这些心律失常在很大程度上得到预防。当仅在再给氧期间存在葡萄糖或维拉帕米时，再给氧心律失常的发生率很高。在所有测试的底物条件下，氧限制期间长链酰基辅酶A的组织水平都会升高。在开始再给氧的时刻，用油酸灌注的心脏中其水平升高最为明显。维拉帕米不影响长链酰基辅酶A的水平。再给氧后心脏释放的肌酸激酶（CK）量与观察到的心律失常无关，在用油酸灌注的心脏中释放量最大。在不添加底物的情况下，维拉帕米可防止CK释放，但在存在油酸时则不能。结论是，再给氧后的室性心律失常不一定由游离脂肪酸或长链酰基辅酶A引起。
