HEMODYNAMIC-EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITION BEFORE AND AFTER CARDIAC-ARREST IN INFANT PIGLETS

Using infant piglets, we studied the effects of nonspecific inhibition of nitric oxide (NO) synthase by N-G-nitro-L-arginine methyl ester (L -NAME; 3 mg/kg) on vascular pressures, regional blood flow and cerebra l metabolism before 8 min of cardiac arrest, during 6 min of cardiopul monary resuscitation (CPR), and at 10 and 60 min of repel-fusion. We t ested the hypotheses that nonspecific NO synthase inhibition 1)will at tenuate early postreperfusion hyperemia while still allowing for succe ssful resuscitation after cardiac arrest, 2) will allow for normalizat ion of blood flow to the kidneys and intestines after cardiac arrest, and 3) will maintain cerebral metabolism in the face of altered cerebr al blood flow after reperfusion. Before cardiac arrest, L-NAME increas ed vascular pressures and cardiac output and decreased blood flow to b rain (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 s ignificant (NS)]. Significantly, L-NAME attenuated postresuscitation h yperemia in cerebellum, diencephalon, anterior cerebral, and anterior- middle watershed cortical brain regions and to the heart. Likewise, ce rebral metabolic rates of glucose (CMRGluc) and of lactate production (CMRLac) were not elevated at 10 min of reperfusion. These cerebral bl ood flow and metabolic effects were reversed by L-arginine. Flows retu rned to baseline levels by 60 min of reperfusion. Kidney and intestina l flow however remained depressed throughout reperfusion in all three groups. Thus nonspecific inhibition of NO synthase did not adversely a ffect the rate of resuscitation from cardiac arrest while attenuating cerebral and myocardial hyperemia. Even though CMRGluc and CMRLac earl y after resuscitation were decreased, they were maintained at baseline levels. This may be clinically advantageous in protecting the brain a nd heart from the damaging effects of hyperemia, such as blood-brain b arrier disruption.