Schleien C L, Kuluz J W, Gelman B
Department of Pediatrics, University of Miami School of Medicine, Florida 33101, USA.
Am J Physiol. 1998 Apr;274(4):H1378-85. doi: 10.1152/ajpheart.1998.274.4.H1378.
Using infant piglets, we studied the effects of nonspecific inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg) on vascular pressures, regional blood flow, and cerebral metabolism before 8 min of cardiac arrest, during 6 min of cardiopulmonary resuscitation (CPR), and at 10 and 60 min of reperfusion. We tested the hypotheses that nonspecific NO synthase inhibition 1) will attenuate early postreperfusion hyperemia while still allowing for successful resuscitation after cardiac arrest, 2) will allow for normalization of blood flow to the kidneys and intestines after cardiac arrest, and 3) will maintain cerebral metabolism in the face of altered cerebral blood flow after reperfusion. Before cardiac arrest, L-NAME increased vascular pressures and cardiac output and decreased blood flow to brain (by 18%), heart (by 36%), kidney (by 46%), and intestine (by 52%) compared with placebo. During CPR, myocardial flow was maintained in all groups to successfully resuscitate 24 of 28 animals [P value not significant (NS)]. Significantly, L-NAME attenuated postresuscitation hyperemia in cerebellum, diencephalon, anterior cerebral, and anterior-middle watershed cortical brain regions and to the heart. Likewise, cerebral metabolic rates of glucose (CMRGluc) and of lactate production (CMRLac) were not elevated at 10 min of reperfusion. These cerebral blood flow and metabolic effects were reversed by L-arginine. Flows returned to baseline levels by 60 min of reperfusion. Kidney and intestinal flow, however, remained depressed throughout reperfusion in all three groups. Thus nonspecific inhibition of NO synthase did not adversely affect the rate of resuscitation from cardiac arrest while attenuating cerebral and myocardial hyperemia. Even though CMRGluc and CMRLac early after resuscitation were decreased, they were maintained at baseline levels. This may be clinically advantageous in protecting the brain and heart from the damaging effects of hyperemia, such as blood-brain barrier disruption.
我们使用幼猪研究了在心脏骤停8分钟前、心肺复苏（CPR）6分钟期间以及再灌注10分钟和60分钟时，NG-硝基-L-精氨酸甲酯（L-NAME；3mg/kg）对一氧化氮（NO）合酶的非特异性抑制作用对血管压力、局部血流量和脑代谢的影响。我们检验了以下假设：非特异性NO合酶抑制1）将减轻再灌注后早期充血，同时仍能使心脏骤停后成功复苏，2）将使心脏骤停后肾脏和肠道的血流恢复正常，3）在再灌注后脑血流改变的情况下将维持脑代谢。在心脏骤停前，与安慰剂相比，L-NAME增加了血管压力和心输出量，并减少了流向脑（减少18%）、心脏（减少36%）、肾脏（减少46%）和肠道（减少52%）的血流量。在CPR期间，所有组的心肌血流均得以维持，使28只动物中的24只成功复苏[P值无显著性差异（NS）]。值得注意的是，L-NAME减轻了小脑、间脑、大脑前部和前中分水岭皮质脑区以及心脏的复苏后充血。同样，在再灌注10分钟时，脑葡萄糖代谢率（CMRGluc）和乳酸生成代谢率（CMRLac）没有升高。这些脑血流和代谢效应被L-精氨酸逆转。到再灌注60分钟时，血流恢复到基线水平。然而，在所有三组的整个再灌注过程中，肾脏和肠道的血流仍然降低。因此，非特异性抑制NO合酶在减轻脑和心肌充血的同时，并未对心脏骤停的复苏率产生不利影响。尽管复苏后早期CMRGluc和CMRLac降低，但它们维持在基线水平。这在临床上可能有利于保护脑和心脏免受充血的损害作用，如血脑屏障破坏。
