Effects of cyclic AMP and dibutyryl cyclic AMP on cerebral hemodynamics and metabolism in the baboon.

Adenosine 3',5'-cycle monophosphate (cyclic AMP) (0.5 mg/kg) was infused into the carotid artery of baboons anesthesized with sodium pentobarbital, causing a biphasic increase in cerebral blood flow (CBF) and reduction in cerebrovascular resistance (CVR) associated in each phase with stimulation of cerebral metabolism evidenced by increased cerebral oxygen consumption (COMRO2) and cerebral glucose consumption (CMRG1). Intracarotid dibutyryl cyclic AMP (0.5 mg/kg) caused a monophasic increase in CBF and reduction of CVR but failed to alter cerebral metabolism. This may be due to its rapid removal from the circulation with ineffective passage across the blood-brain barrier since intracisternal infusion of dibutyryl cyclic AMP caused sustained increase in CBF, CMRO2 and CMRG1 and reduction in CVR. Intracarotid AMP (0.4 mg/kg) and adenosine (0.3 mg/kg) caused an immediate and more marked increase in CBF and decrease in CVR unassociated with cerebral metabolic change making it unlikely that the observed effects of cyclic AMP can be attributed to its breakdown products. Cyclic AMP or its dibutyryl derivative may alter cerebral metabolism secondary to neuronal activation but increase in glucose/oxygen utilization ratio after intracarotid cyclic AMP and intracisternal dibutytyl cyclic AMP also suggests an influence on enzymatic regulation of glucose metabolism.     

The control of hypertension with dibutyryl cyclic AMP

The effects of the rapid infusion of large doses of dibutyryl cyclic AMP (DBcAMP) were studied to clarify the clinical usefulness of its vasodilating action in 32 middle-aged patients, who underwent various types of surgery and developed systolic hypertension of over 160 mmHg during general anaesthesia. DBcAMP was given i.v. with an infusion pump at a rate of 0.6 mg kg-1 min-1 for 20 min. In all patients just after the infusion, systolic arterial pressure decreased from 174.0 +/- 20.7 to 129.0 +/- 23.9 mmHg, diastolic pressure decreased from 93.1 +/- 13.4 to 64.8 +/- 13.3 mmHg, heart rate increased from 81.2 +/- 15.7 to 91.5 +/- 19.5 beats min-1, and urine volume increased from 69.4 +/- 54.8 to 182.7 +/- 143.5 ml h-1. In three patients, cardiac index increased from 3.44 to 4.24 l min-1 m-2. In seven patients, tachycardia exceeding 120 beats min-1 developed. DBcAMP was also effective in patients with a history of hypertension. The strongest antihypertensive effect was observed in patients anaesthetized with nitrous oxide-oxygen and enflurane. We speculate that DBcAMP is useful to control hypertension and may be particularly indicated in patients with cardiac failure, renal disorders and essential hypertension.     

The effect of prostagiandin F2alpha on canine hepatic bile flow and biliary cyclic AMP secretion.

This study evaluates the effects of prostaglandin F_2α (PGF_2α) on canine hepatic bile flow and gastric hydrogen ion output and on biliary cyclic AMP excretion. During the experiments the enterohepatic circulation was maintained by intravenous bile salt infusion. PGF_2α was administered through either a separate intravenous or intra-arterial line in doses of 1, 2, 4, and 8 μ/kg/min. PGF_2α produced progressive increases in bile output and gastric hydrogen ion output. The choleresis was characterized by increased bile salt and chloride secretion suggesting that PGF_2α altered bile flow at the canalicular level. There was no greater response produced when the prostaglandins were administered intra-arterially compared to the response produced by intravenous PGF_2α. Bile cyclic AMP and cyclic GMP concentrations were measured by radioimmunoassay. Cyclic AMP concentrations were decreased by all doses of PGF_2α administered while cyclic AMP output was significantly decreased only by 8 μ/kg/min of PGF_2α. Cyclic GMP levels were consistently less than 0.8 pmol/ml and were not changed by PGF_2α. The results indicate that PFG_2α stimulates hepatic bile flow and gastric hydrogen ion output in a dose-related manner, the choleresis may be canalicular in nature, and metabolic degradation of PGF_2α by the lungs in these studies did not greatly influence the results obtained. Biliary cyclic AMP levels were decreased, suggesting that PGF_2α does not produce its response by stimulating the adenyl cyclase-cyclic AMP system.     

Effects of prostaglandin E1 and dibutyryl cyclic AMP on hemodynamics after cardiopulmonary bypass in valve replacement surgery]

In view of vasodilating action of prostaglandin E1 (PGE1) and dibutyryl cyclic AMP (DBcAMP) we investigated the effect of each agent on hemodynamics after weaning from cardiopulmonary bypass (CPB) comparing with the effect in control group. PGE1 and DBcAMP were administered to patients who underwent valve replacement surgery with continuous low dose infusion at an average rate of 0.026 micrograms.kg-1.min-1 and 7.25 micrograms.kg-1.min-1 respectively. Following result was obtained. In PGE1 administered group, a significant reduction in pulmonary vascular resistance (PVR) and a significant decrease in mean arterial pressure (MAP) were observed during CBP, while there were no significant differences in other parameters, such as platelet counts, differences between core and peripheral temperature (delta T), urine output, systemic vascular resistance (SVR), cardiac index (CI), right-to-left shunt (Qs/Qt), oxygen delivery (DO2) and oxygen consumption (VO2). However, CI and platelet counts tended to increase but delta T and SVR tended to decrease. In DBcAMP administered group, there were no significant differences in all parameters compared with those of control group, showing a tendency of less improvement in hemodynamics than in PGE1 group. We have shown that the use of PGE1 rather than DBcAMP as vasodilator agent seems advantageous during open-heart surgery in patients especially with severe pulmonary hypertension, but it tends to cause severe hypotension during CPB.     

Effect of hormones on cyclic AMP in dog pancreatic tissue and secretion

Secretin and cholecystokinin (CCK-PZ) were administered intravenously in graded doses to live anesthetized dogs. Pancreatic secretion and tissue biopsies were analyzed for cyclic AMP content. Both secretin and CCK-PZ caused an output of cyclic AMP into pancreatic secretion, secretin being a more potent stimulant than CCK-PZ. The concentration of cyclic AMP in the pancreatic juice increased with increasing doses of secretin but not with CCK-PZ. Tissue cyclic AMP content remained unchanged during infusion of either secretin or CCK-PZ. Infusion of aminophylline with secretin did not potentiate the action of secretin. It is concluded that synthesis of cyclic AMP in the dog pancreas is stimulated by both secretin and CCK-PZ and that the newly synthesized cyclic AMP is rapidly secreted into pancreatic juice, resulting in a steady content of tissue cyclic AMP.