Cardiovascular effects of tropacocaine in conscious and anesthetized rabbits: lack of evidence for neuro-cardiac interactions and acute neurotoxicity.
The cardiovascular effects of tropacocaine, a structural analog of cocaine, were investigated in both conscious and anesthetized New Zealand white rabbits to determine if such effects were mediated through the CNS as had been demonstrated with cocaine, i.e., did a neuro-cardiac pathway exist? To facilitate the requisite cardiovascular measurements in both urethane- and pentobarbital-anesthetized animals, the right femoral artery and vein were cannulated for the measurement of arterial blood pressure and subsequent delivery of drugs, respectively. In addition, urethane-anesthetized animals had a branch of the left renal nerve isolated and multiunit renal nerve activity was monitored to obtain measures of sympathetic nerve activity originating from the CNS. Animals utilized in conscious experiments were surgically prepared 3 days prior to drug administration by placing canulae in the femoral artery and vein that were tunneled subcutaneously to the back between the scapulae. ECG and respiratory activity were also monitored in each animal. Doses of 0.3, 1, 3, and 10 mg/kg of tropacocaine were administered in both an ascending and descending fashion at 15 min intervals to 5 animals in each group, i.e., conscious, urethane-, and pentobarbital-anesthetized. In urethane-anesthetized animals a comparison was made between sympathetic renal nerve activity, systolic and diastolic blood pressure, respiratory rate, and heart rate. No pressor effects were observed and the changes in renal nerve activity could not be assigned as the cause of the observed depressor effects at the higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Rhee
H M
HM
Food and Drug Administration, Division of Metabolism and Endocrine Drug Products, Rockville, Maryland 20857, USA.
Lee
S Y
SY
Lee
S M
SM
Valentine
J L
JL
D000779:Anesthetics, Local / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D009474:Neurons / Q000187:drug effects; D011817:Rabbits; D012119:Respiration / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000779:Anesthetics, Local; C005862:tropacocaine; D003042:Cocaine