Adachi T, Hori S, Miyazaki K, Nakagawa M, Inoue S, Ohnishi Y, Nakazawa H, Aikawa N, Ogawa S
Department of Internal Medicine, Keio University, Tokyo, Japan.
Shock. 1998 Mar;9(3):204-9. doi: 10.1097/00024382-199803000-00008.
In hemorrhagic shock (HS), nitric oxide synthase (NOS) inhibitor is known to increase blood pressure and prolong survival time. On the other hand, NOS inhibitor decreases coronary flow and worsens myocardial ischemia. Therefore, we hypothesized that the beneficial effect of NOS inhibitor is attributable to the increased coronary perfusion pressure and that it outcompetes the coronary vasodilating effects of nitric oxide. To investigate the direct effect of NOS inhibitor on the regulation of coronary circulation and the induction of myocardial ischemia in HS, we used a canine model at a constant aortic pressure of 40 mmHg with an aortic reservoir. In seven dogs, intravenous administration of Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) at 10 min after induction of HS increased both systemic and coronary vascular resistances and further increased the serum catecholamine concentration at 10 min after L-NAME. In another 14 dogs, the beating hearts were rapidly cross-sectioned (120 ms) and freeze clamped (-190 degrees C) by a specially developed sampling device after 10 min of HS. Transmurally distributed myocardial ischemia was visualized by the enhanced reduced nicotinamide adenine dinucleotide fluorescence, which was significantly increased with L-NAME (n=7). Chemical analysis revealed a decrease in the myocardial ATP concentration with L-NAME in the subendocardial ischemic region in HS. In conclusion, with the use of an aortic reservoir to keep the aortic pressure constant in HS, NOS blockade significantly worsened myocardial ischemia by decreasing coronary flow and augmenting the serum catecholamine concentration.
在失血性休克（HS）中，已知一氧化氮合酶（NOS）抑制剂可升高血压并延长存活时间。另一方面，NOS抑制剂会减少冠状动脉血流量并加重心肌缺血。因此，我们推测NOS抑制剂的有益作用归因于冠状动脉灌注压的升高，并且它胜过一氧化氮的冠状动脉舒张作用。为了研究NOS抑制剂对HS中冠状动脉循环调节和心肌缺血诱导的直接影响，我们使用了一种犬模型，通过主动脉储液器将主动脉压力维持在40 mmHg恒定水平。在7只犬中，HS诱导后10分钟静脉注射Nω-硝基-L-精氨酸甲酯（L-NAME，30 mg/kg），可增加全身和冠状动脉血管阻力，并在注射L-NAME后10分钟进一步提高血清儿茶酚胺浓度。在另外14只犬中，HS诱导10分钟后，通过专门开发的采样装置将跳动的心脏快速横切（120毫秒）并冷冻钳夹（-190℃）。通过增强的还原型烟酰胺腺嘌呤二核苷酸荧光观察到透壁分布的心肌缺血，L-NAME可使其显著增加（n = 7）。化学分析显示，HS下心内膜下缺血区域中L-NAME可使心肌ATP浓度降低。总之，在HS中使用主动脉储液器维持主动脉压力恒定的情况下，NOS阻断通过减少冠状动脉血流量和增加血清儿茶酚胺浓度，显著加重了心肌缺血。
