Steare S E, Yellon D M
Hatter Institute for Cardiovascular Studies, University College Hospital, London, United Kingdom.
Cardiovasc Res. 1994 Jul;28(7):1096-101. doi: 10.1093/cvr/28.7.1096.
The aim was to investigate the potential for the enhancement of endogenous catalase activity after heat stress to protect the isolated rat myocardium from the injurious effects of exogenous hydrogen peroxide.
Male Sprague-Dawley rats were randomised to either heat stress or sham treatment. At 24 and 48 h after treatment hearts were retrogradely perfused at a constant flow rate of 10 ml.min-1. After a 15 min stabilisation period hearts were perfused with 75 microM hydrogen peroxide for 85 min. Mechanical function was measured by an intraventricular isovolumic latex balloon while coronary perfusate was collected for measurement of lactate dehydrogenase activity. At the end of the perfusion period the glutathione status of the hearts was determined. In separate experiments baseline cardiac catalase activity and glutathione state were measured 24 and 48 h after heat stress or sham treatment.
Cardiac catalase activity was increased by 49% at both 24 and 48 h after heat stress in comparison with sham controls. Glutathione concentrations were reduced by 12% 24 h after heat stress but had recovered by 48 h. Perfusion of sham hearts with 75 microM hydrogen peroxide resulted in a progressive decline in mechanical function as evident by a fall in developed pressure and rise in diastolic pressure. Coronary resistance also rose during the perfusion period as shown by a progressive increase of coronary perfusion pressure. Coronary effluent lactate dehydrogenase release was only increased above basal concentrations at the end of the perfusion period, whereas cardiac glutathione concentrations were severely depleted. Hearts taken 24 h after heat stress showed a reduced resistance to the effect of 75 microM hydrogen peroxide on mechanical activity, although there was no difference in the pattern of lactate dehydrogenase release or depletion of glutathione. Perfusion of hearts taken 48 h after heat stress with 75 microM hydrogen peroxide resulted in the same effect on mechanical dysfunction, coronary resistance, lactate dehydrogenase release, and cardiac glutathione depletion as sham controls.
The increase in endogenous cardiac catalase activity caused by prior heat stress is insufficient to protect the isolated rat heart from injury induced by exogenous hydrogen peroxide.
研究热应激后内源性过氧化氢酶活性增强的可能性，以保护离体大鼠心肌免受外源性过氧化氢的损伤作用。
将雄性斯普拉格 - 道利大鼠随机分为热应激组或假处理组。处理后24小时和48小时，以10 ml·min⁻¹的恒定流速对心脏进行逆行灌注。在15分钟的稳定期后，用75微摩尔/升的过氧化氢灌注心脏85分钟。通过心室内等容乳胶球囊测量机械功能，同时收集冠状动脉灌注液以测量乳酸脱氢酶活性。在灌注期结束时，测定心脏的谷胱甘肽状态。在单独的实验中，在热应激或假处理后24小时和48小时测量基线心脏过氧化氢酶活性和谷胱甘肽状态。
与假处理对照组相比，热应激后24小时和48小时心脏过氧化氢酶活性均增加了49%。热应激后24小时谷胱甘肽浓度降低了12%，但在48小时时已恢复。用75微摩尔/升的过氧化氢灌注假处理心脏导致机械功能逐渐下降，表现为舒张末压下降和舒张压升高。如冠状动脉灌注压逐渐升高所示，灌注期冠状动脉阻力也升高。冠状动脉流出液中乳酸脱氢酶释放仅在灌注期结束时高于基础浓度增加，而心脏谷胱甘肽浓度严重耗竭。热应激后24小时取出的心脏对75微摩尔/升过氧化氢对机械活动的影响的抵抗力降低，尽管乳酸脱氢酶释放模式或谷胱甘肽耗竭没有差异。用75微摩尔/升的过氧化氢灌注热应激后48小时取出的心脏对机械功能障碍、冠状动脉阻力、乳酸脱氢酶释放和心脏谷胱甘肽耗竭的影响与假处理对照组相同。
先前热应激引起的内源性心脏过氧化氢酶活性增加不足以保护离体大鼠心脏免受外源性过氧化氢诱导的损伤。
