Prasad K, Kalra J, Bharadwaj L
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Angiology. 1993 Apr;44(4):257-70. doi: 10.1177/000331979304400401.
In many clinical situations, including cardiac ischemia/reperfusion, elective cardiac arrest, and renal dialysis, the chances of increased production of oxygen free radicals (OFR) exist. OFR have been implicated as a causative factor of cell damage in several pathologic conditions. The effects of exogenous OFR, generated by xanthine plus xanthine oxidase, in the absence and in the presence of OFR scavenger (superoxide dismutase [SOD]) on the contractility of isolated perfused heart of rabbit were studied. OFR produced concentration-dependent decreases in the contractility of perfused heart. SOD prevented the OFR-induced decreases in the left ventricular contractility. Xanthine produced an increase in the contractility of isolated perfused rabbit's heart. Xanthine oxidase produced a marked decrease in the left ventricular contractility. Repeated administration of xanthine oxidase produced accelerated and greater decreases in the contractility of perfused heart when compared with that of the initial administration of the drug. Effects of xanthine or xanthine oxidase on the cardiac function and contractility were also studied in anesthetized dogs. Xanthine alone had no significant effect on the cardiac function and indices of myocardial contractility. However, xanthine oxidase produced a marked decrease in the mean aortic pressure, left ventricular work index, heart rate, cardiac index, left ventricular systolic pressure, left ventricular end-diastolic pressure, (+) and (-) dp/dt of left ventricular pressure, and other indices of myocardial contractility [(dp/dt)/PAW (pulmonary arterial wedge pressure)]; and an increase in the total systemic and pulmonary vascular resistance. Repeated administration of xanthine oxidase in anesthetized dogs had lesser effects on the cardiovascular system when compared with those from the initial dose of the drug. These results suggest that OFR are cardiac depressant. Clinical situations wherein there is an increased production of OFR or increased formation of xanthine and xanthine oxidase may be associated with decreased cardiac function and contractility. Scavengers of OFR may protect the heart from the deleterious effects of OFR in such clinical conditions.
在许多临床情况下，包括心脏缺血/再灌注、选择性心脏骤停和肾透析，都存在氧自由基（OFR）生成增加的可能性。在几种病理状况下，OFR被认为是细胞损伤的一个致病因素。研究了在不存在和存在OFR清除剂（超氧化物歧化酶[SOD]）的情况下，由黄嘌呤加黄嘌呤氧化酶产生的外源性OFR对兔离体灌注心脏收缩性的影响。OFR使灌注心脏的收缩性呈浓度依赖性降低。SOD可防止OFR引起的左心室收缩性降低。黄嘌呤使兔离体灌注心脏的收缩性增加。黄嘌呤氧化酶使左心室收缩性显著降低。与首次给药相比，重复给予黄嘌呤氧化酶会使灌注心脏的收缩性加速且更大程度地降低。还在麻醉犬中研究了黄嘌呤或黄嘌呤氧化酶对心脏功能和收缩性的影响。单独使用黄嘌呤对心脏功能和心肌收缩性指标无显著影响。然而，黄嘌呤氧化酶使平均主动脉压、左心室作功指数、心率、心脏指数、左心室收缩压、左心室舒张末期压力、左心室压力的（+）和（-）dp/dt以及其他心肌收缩性指标[（dp/dt）/PAW（肺动脉楔压）]显著降低；并使全身和肺血管总阻力增加。与首次给药相比，在麻醉犬中重复给予黄嘌呤氧化酶对心血管系统的影响较小。这些结果表明OFR具有心脏抑制作用。OFR生成增加或黄嘌呤和黄嘌呤氧化酶形成增加的临床情况可能与心脏功能和收缩性降低有关。在这种临床情况下，OFR清除剂可能保护心脏免受OFR的有害影响。
