Adenosine triphosphate-induced arterial hypotension in the dog.
This study was designed to investigate the potential use of adenosine triphosphate (ATP), a naturally occurring vasodilator, for producing profound intraoperative hypotension. Six mongrel dogs were anesthetized with morphine, nitrous oxide, and oxygen, paralyzed with pancuronium, and ventilated to a PaCO2 of 40. The mean arterial pressure was lowered to 40 mm Hg with an intravenous infusion of ATP (10.6 +/- 3.5 (SE) mg/kg/minute). Blood flow was determined using the radioactive microsphere technique. Measurements were made before and 20, 40, and 60 minutes after the induction of hypotension and after a 40-minute recovery. Infusion of ATP to lower the mean arterial pressure to 40 mm Hg resulted in a reduction of mean arterial pressure of 64% and an increase in heart rate of 11% accompanied by frequent cardiac arrhythmias. However, cardiac output decreased only 8%. Myocardial flow increased 137%, kidney flow decreased 71%, and masseter muscle flow increased 333%. A severe metabolic acidosis developed with a reduction in pH from control values of 7.39 +/- 0.03 to 7.16 +/- 0.03 after 60 minutes of hypotension. The cerebral metabolic rate of oxygen, determined using the oxygen content of the sagittal sinus, was not affected. Cerebral hemisphere blood flow decreased 21%, caudate nucleus flow decreased 31%, and corpus callosum flow decreased 43%. Blood flow to the brain stem and cerebellum was unchanged. Hypotension was readily induced, maintained, and reversed using ATP, without apparent tachyphylaxis. However, the profound metabolic acidosis and cardiac arrhythmias that occurred may be serious contraindications to the use of this agent clinically.
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007023:Hypotension, Controlled / Q000379:methods*; D012039:Regional Blood Flow / Q000187:drug effects
D000255:Adenosine Triphosphate