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Ketamine, but not S(+)-ketamine, blocks ischemic preconditioning in rabbit hearts in vivo
J Müllenheim1, J Frässdorf, B Preckel
1Institut für Klinische Anaesthesiologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Background:
Ketamine blocks KATP channels in isolated cells and abolishes the cardioprotective effect of ischemic preconditioning in vitro. The authors investigated the effects of ketamine and S(+)-ketamine on ischemic preconditioning in the rabbit heart in vivo.
Methods:
In 46 alpha-chloralose-anesthetized rabbits, left ventricular pressure (tip manometer), cardiac output (ultrasonic flow probe), and myocardial infarct size (triphenyltetrazolium staining) at the end of the experiment were measured. All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. The control group underwent the ischemia-reperfusion program without preconditioning. Ischemic preconditioning was elicited by 5-min coronary artery occlusion followed by 10 min of reperfusion before the 30 min period of myocardial ischemia (preconditioning group). To test whether ketamine or S(+)-ketamine blocks the preconditioning-induced cardioprotection, each (10 mg kg(-1)) was administered 5 min before the preconditioning ischemia. To test any effect of ketamine itself, ketamine was also administered without preconditioning at the corresponding time point.
Results:
Hemodynamic baseline values were not significantly different between groups [left ventricular pressure, 107 +/- 13 mmHg (mean +/- SD); cardiac output, 183 +/- 28 ml/min]. During coronary artery occlusion, left ventricular pressure was reduced to 83 +/- 14% of baseline and cardiac output to 84 +/- 19%. After 2 h of reperfusion, functional recovery was not significantly different among groups (left ventricular pressure, 77 +/- 19%; cardiac output, 86 +/- 18%). Infarct size was reduced from 45 +/- 16% of the area at risk in controls to 24 +/- 17% in the preconditioning group (P = 0.03). The administration of ketamine had no effect on infarct size in animals without preconditioning (48 +/- 18%), but abolished the cardioprotective effects of ischemic preconditioning (45 +/- 19%, P = 0.03). S(+)-ketamine did not affect ischemic preconditioning (25 +/- 11%, P = 1.0).
Conclusions:
Ketamine, but not S(+)-ketamine blocks the cardioprotective effect of ischemic preconditioning in vivo.
Insights
Ketamine blocks the heart-protective effects of ischemic preconditioning in rabbits, while S(+)-ketamine does not. This finding is crucial for understanding anesthetic interactions with cardiac protection strategies.
Area of Science:
- Cardiology
- Anesthesiology
- Pharmacology
Background:
- Ketamine is known to block KATP channels in isolated cells.
- This action abolishes the cardioprotective effect of ischemic preconditioning in vitro.
- The study aimed to investigate these effects in vivo.
Purpose of the Study:
- To determine if ketamine and S(+)-ketamine affect ischemic preconditioning in a rabbit heart model.
- To assess the impact of ketamine on cardioprotection during myocardial ischemia-reperfusion.
Main Methods:
- 46 rabbits underwent a 30-minute coronary artery occlusion followed by 2 hours of reperfusion.
- Ischemic preconditioning was induced by a brief occlusion-reperfusion period before the main ischemia.
- Ketamine or S(+)-ketamine (10 mg/kg) was administered to assess its effect on preconditioning-induced cardioprotection.
Main Results:
- Ischemic preconditioning reduced infarct size by 45% in control rabbits.
- Ketamine administration abolished the protective effect of ischemic preconditioning.
- S(+)-ketamine did not significantly alter the cardioprotective effects of ischemic preconditioning.
Conclusions:
- Ketamine blocks the cardioprotective effect of ischemic preconditioning in vivo.
- S(+)-ketamine does not exhibit this blocking effect.
- These findings highlight a differential effect of ketamine enantiomers on cardiac protection.