Enhanced recovery of brain electrical activity by adenosine 3′,5′-cyclic monophosphate following complete global cerebral ischemia in dogs

Thomas J K Toung, Jeffrey Kirsch, Richard J. Traystman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: To test the hypothesis that adenosine 3′,5′-cyclic monophosphate (cAMP) or dibutyl-cAMP (a more lipid-soluble, less rapidly metabolized analog of cAMP) would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow during the reperfusion period. Design: Randomized, controlled, prospective study. Setting: University research laboratory. Subjects: Twenty-five male beagle dogs. Interventions: Nine control dogs received saline (20-mL/kg bolus and 0.01 mL/kg/min) intravenously, beginning 25 mins before 12 mins of cerebral global ischemia (by aortic occlusion). The dogs in the experimental groups received either cAMP (40 mg/kg 25 mins before ischemia and 0.2 mg/kg/min throughout reperfusion, n = 7), or dibutyl-cAMP (6 mg/kg 25 mins before ischemia and 3 mg/kg at 60,90, and 120 mins of reperfusion, n = 9). Measurements and Main Results: Total and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion. Pretreatment with dibutyl-cAMP resulted in increased postischemic hyperemia at 30 mins of reperfusion (e.g., whole brain: control 40 ± 6; cAMP 56 ± 9; dibutyl-cAMP 67 ± 10 ml/min/100 g [mean ± SEM, p <.05 control vs. dibutyl-cAMP group]) but no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. All groups demonstrated rapid ablation of the amplitude of somatosensory evoked potentials during ischemia, with no difference between the groups. At 180 mins of reperfusion, somatosensory evoked potentials recovered to 28 ± 4% of the preischemic baseline value in dogs treated with saline, whereas the somatosensory evoked potentials recovered to 58 ± 4% of preischemic baseline value in the cAMP-pretreated group (p <.05), and to 70 ± 6% of preischemic baseline value in dogs treated with dibutyl-cAMP (p <.05). Conclusions: cAMP and dibutyl-cAMP improve recovery of cerebral electrical function after complete transient global cerebral ischemia. Although hyperemia was more prolonged in cAMP-and dibutyl-cAMP-treated dogs, there was no difference between groups in degree of postischemic delayed hypoperfusion. Therefore, we believe that the mechanism for cerebral protection afforded by cAMP and dibutyl-cAMP is not related to cerebral circu latory effects.

Original languageEnglish (US)
Pages (from-to)103-108
Number of pages6
JournalCritical Care Medicine
Volume24
Issue number1 SUPPL.
StatePublished - 1996
Externally publishedYes

Fingerprint

Brain Ischemia
Adenosine
Reperfusion
Cerebrovascular Circulation
Dogs
Somatosensory Evoked Potentials
Brain
Ischemia
Transient Ischemic Attack
Hyperemia
Oxygen Consumption
Regional Blood Flow
Prospective Studies
Lipids
Research

Keywords

  • Aortic cross-clamp
  • Brain
  • Cerebral circulation
  • Cerebral ischemia
  • Cerebral metabolism
  • Cyclic AMP
  • Hypoperfusion
  • Neurologic emergencies
  • Oxygen consumption
  • Somatosensory evoked potentials

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Enhanced recovery of brain electrical activity by adenosine 3′,5′-cyclic monophosphate following complete global cerebral ischemia in dogs. / Toung, Thomas J K; Kirsch, Jeffrey; Traystman, Richard J.

In: Critical Care Medicine, Vol. 24, No. 1 SUPPL., 1996, p. 103-108.

Research output: Contribution to journalArticle

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abstract = "Objective: To test the hypothesis that adenosine 3′,5′-cyclic monophosphate (cAMP) or dibutyl-cAMP (a more lipid-soluble, less rapidly metabolized analog of cAMP) would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow during the reperfusion period. Design: Randomized, controlled, prospective study. Setting: University research laboratory. Subjects: Twenty-five male beagle dogs. Interventions: Nine control dogs received saline (20-mL/kg bolus and 0.01 mL/kg/min) intravenously, beginning 25 mins before 12 mins of cerebral global ischemia (by aortic occlusion). The dogs in the experimental groups received either cAMP (40 mg/kg 25 mins before ischemia and 0.2 mg/kg/min throughout reperfusion, n = 7), or dibutyl-cAMP (6 mg/kg 25 mins before ischemia and 3 mg/kg at 60,90, and 120 mins of reperfusion, n = 9). Measurements and Main Results: Total and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion. Pretreatment with dibutyl-cAMP resulted in increased postischemic hyperemia at 30 mins of reperfusion (e.g., whole brain: control 40 ± 6; cAMP 56 ± 9; dibutyl-cAMP 67 ± 10 ml/min/100 g [mean ± SEM, p <.05 control vs. dibutyl-cAMP group]) but no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. All groups demonstrated rapid ablation of the amplitude of somatosensory evoked potentials during ischemia, with no difference between the groups. At 180 mins of reperfusion, somatosensory evoked potentials recovered to 28 ± 4{\%} of the preischemic baseline value in dogs treated with saline, whereas the somatosensory evoked potentials recovered to 58 ± 4{\%} of preischemic baseline value in the cAMP-pretreated group (p <.05), and to 70 ± 6{\%} of preischemic baseline value in dogs treated with dibutyl-cAMP (p <.05). Conclusions: cAMP and dibutyl-cAMP improve recovery of cerebral electrical function after complete transient global cerebral ischemia. Although hyperemia was more prolonged in cAMP-and dibutyl-cAMP-treated dogs, there was no difference between groups in degree of postischemic delayed hypoperfusion. Therefore, we believe that the mechanism for cerebral protection afforded by cAMP and dibutyl-cAMP is not related to cerebral circu latory effects.",
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T1 - Enhanced recovery of brain electrical activity by adenosine 3′,5′-cyclic monophosphate following complete global cerebral ischemia in dogs

AU - Toung, Thomas J K

AU - Kirsch, Jeffrey

AU - Traystman, Richard J.

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Y1 - 1996

N2 - Objective: To test the hypothesis that adenosine 3′,5′-cyclic monophosphate (cAMP) or dibutyl-cAMP (a more lipid-soluble, less rapidly metabolized analog of cAMP) would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow during the reperfusion period. Design: Randomized, controlled, prospective study. Setting: University research laboratory. Subjects: Twenty-five male beagle dogs. Interventions: Nine control dogs received saline (20-mL/kg bolus and 0.01 mL/kg/min) intravenously, beginning 25 mins before 12 mins of cerebral global ischemia (by aortic occlusion). The dogs in the experimental groups received either cAMP (40 mg/kg 25 mins before ischemia and 0.2 mg/kg/min throughout reperfusion, n = 7), or dibutyl-cAMP (6 mg/kg 25 mins before ischemia and 3 mg/kg at 60,90, and 120 mins of reperfusion, n = 9). Measurements and Main Results: Total and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion. Pretreatment with dibutyl-cAMP resulted in increased postischemic hyperemia at 30 mins of reperfusion (e.g., whole brain: control 40 ± 6; cAMP 56 ± 9; dibutyl-cAMP 67 ± 10 ml/min/100 g [mean ± SEM, p <.05 control vs. dibutyl-cAMP group]) but no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. All groups demonstrated rapid ablation of the amplitude of somatosensory evoked potentials during ischemia, with no difference between the groups. At 180 mins of reperfusion, somatosensory evoked potentials recovered to 28 ± 4% of the preischemic baseline value in dogs treated with saline, whereas the somatosensory evoked potentials recovered to 58 ± 4% of preischemic baseline value in the cAMP-pretreated group (p <.05), and to 70 ± 6% of preischemic baseline value in dogs treated with dibutyl-cAMP (p <.05). Conclusions: cAMP and dibutyl-cAMP improve recovery of cerebral electrical function after complete transient global cerebral ischemia. Although hyperemia was more prolonged in cAMP-and dibutyl-cAMP-treated dogs, there was no difference between groups in degree of postischemic delayed hypoperfusion. Therefore, we believe that the mechanism for cerebral protection afforded by cAMP and dibutyl-cAMP is not related to cerebral circu latory effects.

AB - Objective: To test the hypothesis that adenosine 3′,5′-cyclic monophosphate (cAMP) or dibutyl-cAMP (a more lipid-soluble, less rapidly metabolized analog of cAMP) would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow during the reperfusion period. Design: Randomized, controlled, prospective study. Setting: University research laboratory. Subjects: Twenty-five male beagle dogs. Interventions: Nine control dogs received saline (20-mL/kg bolus and 0.01 mL/kg/min) intravenously, beginning 25 mins before 12 mins of cerebral global ischemia (by aortic occlusion). The dogs in the experimental groups received either cAMP (40 mg/kg 25 mins before ischemia and 0.2 mg/kg/min throughout reperfusion, n = 7), or dibutyl-cAMP (6 mg/kg 25 mins before ischemia and 3 mg/kg at 60,90, and 120 mins of reperfusion, n = 9). Measurements and Main Results: Total and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion. Pretreatment with dibutyl-cAMP resulted in increased postischemic hyperemia at 30 mins of reperfusion (e.g., whole brain: control 40 ± 6; cAMP 56 ± 9; dibutyl-cAMP 67 ± 10 ml/min/100 g [mean ± SEM, p <.05 control vs. dibutyl-cAMP group]) but no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. All groups demonstrated rapid ablation of the amplitude of somatosensory evoked potentials during ischemia, with no difference between the groups. At 180 mins of reperfusion, somatosensory evoked potentials recovered to 28 ± 4% of the preischemic baseline value in dogs treated with saline, whereas the somatosensory evoked potentials recovered to 58 ± 4% of preischemic baseline value in the cAMP-pretreated group (p <.05), and to 70 ± 6% of preischemic baseline value in dogs treated with dibutyl-cAMP (p <.05). Conclusions: cAMP and dibutyl-cAMP improve recovery of cerebral electrical function after complete transient global cerebral ischemia. Although hyperemia was more prolonged in cAMP-and dibutyl-cAMP-treated dogs, there was no difference between groups in degree of postischemic delayed hypoperfusion. Therefore, we believe that the mechanism for cerebral protection afforded by cAMP and dibutyl-cAMP is not related to cerebral circu latory effects.

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KW - Cerebral ischemia

KW - Cerebral metabolism

KW - Cyclic AMP

KW - Hypoperfusion

KW - Neurologic emergencies

KW - Oxygen consumption

KW - Somatosensory evoked potentials

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