Effects of clonidine pre-treatment on bupivacaine and ropivacaine cardiotoxicity in rats.
OBJECTIVE
Clonidine has cardiac and systemic effects that can modify the potentially lethal cardiovascular effects of local anaesthetics. We evaluated the effects of clonidine pre-treatment on cardiotoxicity induced by an infusion of bupivacaine or ropivacaine and the success rate of resuscitation in anaesthetized rats.


METHODS
Thirty-two Sprague-Dawley rats (250-300 g) were anaesthetized with thiopental and ketamine. Lung ventilation was maintained mechanically, and the electrocardiograph and invasive blood pressure were recorded continuously. Two separate groups of rats were treated with intravenous clonidine 5 microg kg(-1) (n = 16) or saline (n = 16) in a randomized fashion. Fifteen minutes later, each group was randomly subdivided into two equal groups and an infusion of bupivacaine or ropivacaine, 3 mg kg(-1) min(-1), was given until cardiac arrest (asystole) occurred. The times when the cardiotoxic events (25%, 50% and 75% reduction of arterial pressure and heart rate, first dysrhythmia and asystole, respectively), induced by the local anaesthetic, occurred and the resuscitation outcome scores were recorded.


RESULTS
Clonidine reduced heart rate and arterial pressure (P < 0.01). Clonidine did not alter cardiotoxicity or the success rate of resuscitation in bupivacaine-treated rats. In the ropivacaine group, clonidine increased the 25%, 50% and 75% reduction times of arterial pressure and the 50% and 75% reduction times of heart rate, times to first dysrhythmia and asystole (P < 0.05). Clonidine also increased the success rate of resuscitation in ropivacaine-treated rats (P < 0.05).


CONCLUSIONS
Although pre-treatment with clonidine protects the effects of ropivacaine cardiotoxicity and increases the success rate of resuscitation, it does not affect bupivacaine toxicity.
Gulec
S
S
Osmangazi University Medical School, Department of Anaesthesiology, Eskisehir, Turkey. sgulec@ogu.edu.tr
Aydin
Y
Y
Uzuner
K
K
Yelken
B
B
Senturk
Y
Y
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000577:Amides / Q000633:toxicity*; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000633:toxicity*; D003000:Clonidine / Q000494:pharmacology*; D004347:Drug Interactions; D062787:Drug Overdose; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006323:Heart Arrest / Q000139:chemically induced / Q000517:prevention & control; D006336:Heart Massage; D011292:Premedication; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D000077212:Ropivacaine
D000316:Adrenergic alpha-Agonists; D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D003000:Clonidine; D002045:Bupivacaine