Dimethyl sulfoxide (DMSO) is the solvent of choice for SR141716A and SR144528 (CB₁ and CB₂ receptor antagonists, respectively). Therefore, the aim of this study was to investigate whether DMSO alters cannabinoid-induced infarct size reduction prior to pharmacological characterisation of the cannabinoid response.

Hearts taken from male Wistar rats (250-350g) were perfused (Krebs bicarbonate solution + insulin, 100 mU.ml^-1) at a constant pressure (80 mmHg) and maintained at 37˚C. Left ventricular developed pressure (LVDP) was measured by means of a pressurised balloon inserted into the left ventricle and connected to a pressure transducer and heart rate (HR) calculated from the pressure signal. Coronary flow (CF) was measured with a flow probe placed on the aortic inflow line. Baseline mechanical function was recorded during an initial 15 min aerobic perfusion. Regional ischaemia was induced by tying a snare around the left anterior descending coronary artery. After 40 min the snare was released and hearts reperfused for 60 min. Infarct size (estimated with triphenyltetrazolium chloride staining) expressed as a percentage of the area at risk (AAR, determined with Evans blue dye staining) was measured at the end of reperfusion. Methanandamide (mAEA, 1 µM) or its vehicle (Tocrisolve100^TM) was infused at 10% of CF 5 min before and continuing throughout reperfusion. DMSO, where used (at 0.01% or 0.1% vol.vol^-1), was present throughout the protocol. Values of cardiac function, AAR and infarct size (expressed as mean ± s.e.m) obtained after 60 min reperfusion were compared by means of an unpaired Student’s t-test, P<0.05 was taken as significant.

Baseline values for cardiac function (LVDP, CF and HR) did not significantly vary among experimental groups. There were no significant differences in AAR among the experimental groups. The recovery of LVDP, CF or HR was similar for mAEA- and vehicle-treated hearts in the absence of DMSO, however, infarct size was significantly reduced the values being 4±4% of AAR (n=6) and 35±7% of AAR (n=5), respectively. In the presence of 0.01% (vol.vol^-1) DMSO, recovery of LVDP was similar between mAEA- and vehicle-treated hearts. However, HR and CF were significantly lower in mAEA-treated hearts (113±15 bpm and 1.9±0.2 ml.min^-1, respectively, n = 7) compared to vehicle-treated hearts (172±11 bpm and 3.7±0.8 ml.min^-1, respectively, n = 5). Infarct size was significantly lower in mAEA- compared to vehicle-treated hearts (13±4% and 34±5% of AAR, respectively). In the presence of 0.1% (vol.vol^-1) DMSO, HR recovered to a similar degree in mAEA- and vehicle-treated hearts. However, recovery of LVDP and CF were significantly reduced in mAEA-treated hearts (39±8 mmHg and 1.9±0.6 ml.min^-1, respectively, n=3) compared to vehicle-treated hearts (68±4 mmHg and 6.6±1.2 ml.min^-1, respectively, n=4). Infarct size did not significantly vary between mAEA- and vehicle-treated hearts (34±6% and 30±8% of AAR, respectively).

Cannabinoid-mediated infarct size limitation after regional ischaemia-reperfusion is reduced by the presence of DMSO.