Hemodynamic effects of nitric oxide synthase inhibition before and after cardiac arrest in infant piglets

Charles L. Schleien, John W. Kuluz, Barry Gelman

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 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 (CMR(Gluc)) and of lactate production (CMR(Lac)) 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 CMR(Gluc) and CMR(Lac) 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume274
Issue number4 43-4
StatePublished - Apr 1 1998

Fingerprint

Heart Arrest
Nitric Oxide Synthase
Reperfusion
NG-Nitroarginine Methyl Ester
Hyperemia
Hemodynamics
Cerebrovascular Circulation
Resuscitation
Cardiopulmonary Resuscitation
Kidney
Intestines
Blood Vessels
Brain
Pressure
Glucose
Diencephalon
Regional Blood Flow
Blood-Brain Barrier
Cardiac Output
Cerebellum

Keywords

  • Cardiopulmonary resuscitation
  • Cerebral blood flow
  • Cerebral metabolism
  • Intestine
  • Kidney
  • Myocardial blood flow

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Hemodynamic effects of nitric oxide synthase inhibition before and after cardiac arrest in infant piglets. / Schleien, Charles L.; Kuluz, John W.; Gelman, Barry.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 274, No. 4 43-4, 01.04.1998.

Research output: Contribution to journalArticle

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abstract = "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 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 (CMR(Gluc)) and of lactate production (CMR(Lac)) 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 CMR(Gluc) and CMR(Lac) 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.",
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