Effects of exogenous cyclic adenosine monophosphate in hemorrhagic shock

Hemorrhageic shock produces potentially damaging alterations in the metabolism of cyclic adenosine 3',5'-monophosphate (cAMP), which is an intracellular second messenger for many hormones. The hypothesis that the administration of exogenous cAMP might have salutary effects on cardiovascular hemodynamics in shock was tested in canine experimetns. Intravenous bolus injection of dibutyryl cAMP (2 mg. per kilogram) produced hyperglycemia, but no changes occurred in heart rate, arerial pressure cardiac output, or in the first derivative of left ventricualr pressure (dp/dt). The findings were similar in conscious and anesthetized (Nembutal) normotensive dogs, in dogs after 3 hours of shock (at blood pressure of 40 mm. Hg) and after the reinfusion of shed blood. The only hemodynamic change noted was a transient hypotensionupon injection of massive doses of dibutyryl-(db-) cAMP or cAMP (greater than 10 mg. per kilogram). The implication of these findings in light of earlier reported hemodynamic effects of cAMP is discussed.