Vinten-Johansen J, Chiantella V, Faust K B, Johnston W E, McCain B L, Hartman M, Mills S A, Hester T O, Cordell A R
Department of Surgery (Section on Cardiothoracic Surgery), Bowman Gray School of Medicine, Wake Forest University Medical Center, Winston-Salem, NC 27103.
Ann Thorac Surg. 1988 Mar;45(3):319-26. doi: 10.1016/s0003-4975(10)62472-1.
Myocellular injury mediated by oxygen radicals potentially limits myocardial protection in ischemically damaged hearts. This damage may be greater with oxygen-carrying blood cardioplegic solutions. A major mechanism of oxygen radical production is the conversion of hypoxanthine to uric acid by xanthine oxidase. In 16 anesthetized dogs, we studied whether adding allopurinol, a xanthine oxidase inhibitor, to blood cardioplegia would improve recovery of left ventricular (LV) performance and oxygen consumption. Millar transducer-tipped catheters and minor axis ultrasonic crystals were placed to assess LV performance by the slope of the end-systolic pressure-minor axis diameter relationships (Emax). Following total vented bypass, the hearts underwent 30 minutes of normothermic ischemia and then hypothermic blood cardioplegia with 1 mM allopurinol (N = 8) or without allopurinol (N = 8). Postischemic LV performance was significantly better with allopurinol than without (49.5 +/- 8.0 versus 17.4 +/- 4.1% of preischemic Emax; p less than 0.004). Postischemic LV oxygen consumption in the beating working state, calculated from LV blood flow (15 microm microspheres) and oxygen extraction, was comparable to preischemic values with and without allopurinol (10.2 +/- 1.2 versus 8.6 +/- 1.2 ml O2/100 gm/min). We conclude that allopurinol enhancement of blood cardioplegia increases myocardial protection in severely ischemic ventricles.
氧自由基介导的心肌细胞损伤可能会限制对缺血性损伤心脏的心肌保护作用。携带氧的血液停搏液可能会使这种损伤更大。氧自由基产生的一个主要机制是黄嘌呤氧化酶将次黄嘌呤转化为尿酸。在16只麻醉犬中，我们研究了在血液停搏液中添加黄嘌呤氧化酶抑制剂别嘌呤醇是否会改善左心室（LV）功能恢复和氧消耗。放置Millar导管尖端换能器和短轴超声晶体，通过收缩末期压力-短轴直径关系斜率（Emax）来评估LV功能。在完全体外循环后，心脏经历30分钟的常温缺血，然后用含1 mM别嘌呤醇（N = 8）或不含别嘌呤醇（N = 8）的低温血液停搏液灌注。缺血后使用别嘌呤醇时LV功能明显优于未使用别嘌呤醇时（分别为缺血前Emax的49.5 +/- 8.0%和17.4 +/- 4.1%；p < 0.004）。根据LV血流量（15微米微球）和氧摄取计算的缺血后LV在搏动工作状态下的氧消耗，使用和未使用别嘌呤醇时均与缺血前值相当（分别为10.2 +/- 1.2和8.6 +/- 1.2 ml O2/100 gm/min）。我们得出结论，别嘌呤醇增强血液停搏液可增加对严重缺血心室的心肌保护作用。
