Anesthetic methods in rats determine outcome after experimental focal cerebral ischemia: mechanical ventilation is required to obtain controlled experimental conditions.
OBJECTIVE
Anesthetic agents, pH, blood gases and blood pressure have all been found to influence the pathophysiology of experimental stroke. In experimental research, rats are predominantly used to investigate the effects of focal cerebral ischemia. Chloral hydrate, applied intraperitoneally (i.p.), and halothane, applied via face-mask in spontaneously breathing animals or via endotracheal tube in mechanically ventilated animals are popular methods of anesthesia. We investigated the potential of these anesthetic methods to maintain physiologic conditions during focal cerebral ischemia and their influence on postischemic mortality and histological outcome.


METHODS
Thirty male Sprague-Dawley rats were subjected to 90 min of middle cerebral artery occlusion by insertion of an intraluminal thread and assigned to one of three groups (n=10 each): (A) chloral hydrate i.p./spontaneously breathing; (B) halothane in 70:30 (%) N2O/O2 via face-mask/spontaneously breathing; and (C) halothane in 70:30 (%) N2O/O2 via endotracheal tube/mechanically ventilated. Physiologic parameters were measured before, during, and after ischemia. Infarct volume was histologically assessed after 7 days.


RESULTS
All anesthetic techniques except mechanical ventilation via an endotracheal tube resulted in considerably fluctuating blood gases levels, hypercapnia, acidosis and low blood pressure. All spontaneously breathing animals (groups A and B) exhibited a higher postischemic mortality and significantly larger infarct volumes than group C with intubated and ventilated animals.


CONCLUSIONS
Intra- and postischemic physiologic parameters such as blood pressure, pH, and blood gases critically determine outcome after focal cerebral ischemia. Although anesthesia by halothane via face-mask allowed better control of depth of anesthesia than chloral hydrate, we have found this method to be unsatisfactory due to insufficient control of ventilation and waste of anesthetic gases. Experiments with rats requiring normal physiologic parameters should be performed under conditions of controlled mechanical ventilation and sufficient analgesia.
Zausinger
S
S
Department of Neurosurgery, Ludwig-Maximilians-Universität, Klinikum Grosshadern, Marchioninistr. 15, 81377, Munich, Germany. stefan.zausinger@nc.med.uni-muenchen.de
Baethmann
A
A
Schmid-Elsaesser
R
R
D000142:Acidosis, Respiratory / Q000209:etiology / Q000503:physiopathology; D000758:Anesthesia / Q000009:adverse effects* / Q000379:methods*; D000777:Anesthetics / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D002697:Chloral Hydrate / Q000009:adverse effects; D004195:Disease Models, Animal; D006221:Halothane / Q000009:adverse effects; D006935:Hypercapnia / Q000209:etiology / Q000503:physiopathology; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology; D007442:Intubation, Intratracheal / Q000592:standards; D008297:Male; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D012121:Respiration, Artificial / Q000379:methods / Q000592:standards*; D014656:Vascular Surgical Procedures / Q000379:methods
D000777:Anesthetics; D002697:Chloral Hydrate; D010100:Oxygen; D006221:Halothane