Cardioprotective effects of isoflurane in a rat model of stress-induced cardiomyopathy (takotsubo)

- No treatment exist for stress-induced cardiomyopathy (SIC) today.
- SIC is a common syndrome with substantial morbidity and mortality.
- We have reproducibly induced a SIC-like condition in rats by administering catecholamine.
- We show that isoflurane attenuates SIC-like cardiac dysfunction in rats.
- Isofluranes' effect was dose-dependent and was observed in independent sets of experiments.

BackgroundStress-induced cardiomyopathy (SIC) is a common syndrome with substantial morbidity and mortality. SIC is common in intensive care units' patients. No therapeutic intervention for SIC has been evaluated in randomized clinical trial so far. Our aim was to investigate whether isoflurane is cardioprotective in an experimental SIC model.MethodsWe induced SIC-like cardiac dysfunction in rats with intraperitoneal injection of isoprenaline (50 mg/kg) and performed this study in two parts. First, we pre-treated rats with isoflurane (1.5%, n = 12), pentobarbital (50 mg/kg, n = 12) and ketamine (80 mg/kg, n = 12) and compared to controls (n = 12). We used glyburide, an ATP-dependent potassium channel blocker (n = 6), to test whether isoflurane-protection is mediated through KATPm. In a second set of experiments, we treated rats with two different doses of isoflurane i.e. 0.75% (n = 12) and 1.5% (n = 12) before induction of SIC and compared to controls. We assessed left ventricular function and morphology in all rats by transthoracic echocardiography. We also measured peak body temperature, blood gases, acid-base homeostasis, blood pressure and heart rate.ResultsThe extent of apical akinesia was lowest and cardiac function was best in the isoflurane treated rats. The protective effects were not attenuated by glibenclamide. Higher dose of isoflurane was more cardioprotective than the lower dose. This was persistent after the adjustment for changes in hemodynamics and blood biochemistry induced by anesthesia.ConclusionsIsoflurane prevented SIC-like cardiac dysfunction in rats. This protection was not mediated via KATPm. Our study provides an experimental foundation for future clinical trials in SIC.