Pressure volume loops

Animals were anesthetized using 0.4 mg kg⁻¹ medetomidine, 5 mg kg⁻¹ midazolam and 500 μg kg⁻¹ fentanyl injected intraperitoneally. Body temperature was maintained at 37 °C using a homeothermic blanket (Harvard Apparatus, Edenbridge Kent, UK). Mice were catheterized through the left carotid artery with a 1.2 Fr catheter and PVL were measured in the left ventricle. Left ventricular volumes were extrapolated from admittance magnitude and admittance phase in real time using the ADVantage PV system (Scisense, Transonic, Maastricht, The Netherlands). Pressure and volume data were recorded using a Scisense 404-16 Bit Four Channel Recorder (Scisense) with LabScribe2 Software (Scisense). Indices of systolic function included end-systolic pressure, stroke volume and stroke work. Load-dependent myocardial contractility was assessed by maximal rate of pressure development (dP/dt_max). Transient inferior vena caval compressions were applied to reduce preload and determine end-systolic elastance as a parameter of load-independent myocardial contractility as previously described by Bauer et al.³² Diastolic function was assessed by end-diastolic pressure, tau (Glantz method, regression of log of pressure vs time) and the maximal rate of pressure decay (dP/dt_min).