Positive inotropic effects of midazolam anaesthesia in rats during noninvasive heart studies

Introduction

Pinhole gated single photon emission computed tomography (SPECT) and transthoracic echocardiography (TTE) are easier, more time sparing and much more animal friendly in the assessment of the left ventricular (LV) function in rats compared with the techniques used in the past. Where the aim of previous studies was to determine the cardiac function under different anaesthetics in an extracorporeal model, the aim of our study is to find the ideal anaesthetic for the assessment of the cardiac function in the rat.

Methods

Two different studies were performed using pinhole gated SPECT and TTE in male Wistar rats. For the TTE study 32 rats were randomised to four groups and were anaesthetized with two different products with a washout period of 3 days. A linear probe was used for assessing M-mode images and LV volumes (ml) were calculated using an ellipsoid model 10 minutes after administration of anaesthesia. Pentobarbital (50 mg/kg) intraperitoneally, propofol (200 mg/kg) intraperitoneally, midazolam (70 mg/kg) intraperitoneally, isoflurane (2%), sevoflurane (2%) or desflurane (7%) were the anaesthetics studied. For the pinhole gated SPECT study, 48 rats were scanned two times with a 1-week interval: once under pentobarbital (60 mg/kg intraperitoneally) anesthesia for the control study, and a second time using the same anesthetics as the TTE study. Pinhole gated SPECT was performed 1 hour after intravenous injection of 330 MBq ^99mTc-MIBI. Parameters of cardiac function were derived using quantitative gated SPECT.

Results

Augmented ejection fractions were observed for midazolam compared with all other anaesthetics (85% in the SPECT study and 91% in the TTE study). Anterior wall thickening was remarkably augmented: 84 ± 9% compared with propofol 51 ± 12% (P < 0.001) and pentobarbital 64 ± 23 (P = 0.03) in the TTE study, but no difference was observed in the inferior thickening. In the SPECT study, augmented wall thickening was observed in the lateral, inferior, septal and anterior region (all P < 0.001) compared with pentobarbital.

Conclusion

Anaesthetic agents seem to play a role in regional contractile function, affecting global LV function. Previous studies demonstrate conflicting results concerning the effect of midazolam on cardiac function. Both of our studies suggest that, at the given dose, midazolam has a positive inotropic effect.