cannabidiol and Myocardial-Infarction

Topics: Activities of Daily Living; Aged; Cannabidiol; Clopidogrel; Humans; Hypertension; Male; Myocardial Infarction; Pain; Platelet Aggregation Inhibitors; Stroke

Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

Topics: Animals; Cannabidiol; Disease Models, Animal; Magnetic Resonance Imaging; Myocardial Infarction; Myocardial Reperfusion Injury; Rabbits; Troponin I

Cannabidiol (CBD) is a phytocannabinoid, with anti-apoptotic, anti-inflammatory and antioxidant effects and has recently been shown to exert a tissue sparing effect during chronic myocardial ischaemia and reperfusion (I/R). However, it is not known whether CBD is cardioprotective in the acute phase of I/R injury and the present studies tested this hypothesis.. Male Sprague-Dawley rats received either vehicle or CBD (10 or 50 microg kg(-1) i.v.) 10 min before 30 min coronary artery occlusion or CBD (50 microg kg(-1) i.v.) 10 min before reperfusion (2 h). The appearance of ventricular arrhythmias during the ischaemic and immediate post-reperfusion periods were recorded and the hearts excised for infarct size determination and assessment of mast cell degranulation. Arterial blood was withdrawn at the end of the reperfusion period to assess platelet aggregation in response to collagen.. CBD reduced both the total number of ischaemia-induced arrhythmias and infarct size when administered prior to ischaemia, an effect that was dose-dependent. Infarct size was also reduced when CBD was given prior to reperfusion. CBD (50 microg kg(-1) i.v.) given prior to ischaemia, but not at reperfusion, attenuated collagen-induced platelet aggregation compared with control, but had no effect on ischaemia-induced mast cell degranulation.. This study demonstrates that CBD is cardioprotective in the acute phase of I/R by both reducing ventricular arrhythmias and attenuating infarct size. The anti-arrhythmic effect, but not the tissue sparing effect, may be mediated through an inhibitory effect on platelet activation.

Topics: Animals; Arrhythmias, Cardiac; Cannabidiol; Cardiotonic Agents; Collagen; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Mast Cells; Myocardial Infarction; Myocardial Reperfusion Injury; Platelet Aggregation; Rats; Rats, Sprague-Dawley

Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling. Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts. For the in vivo studies, the left anterior descending coronary artery was transiently ligated for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg ip) or vehicle. Cardiac function was studied by echocardiography. Infarcts were examined morphometrically and histologically. For ex vivo evaluation, CBD was administered 24 and 1 h before the animals were killed, and hearts were harvested for physiological measurements. In vivo studies showed preservation of shortening fraction in CBD-treated animals: from 48 +/- 8 to 39 +/- 8% and from 44 +/- 5 to 32 +/- 9% in CBD-treated and control rats, respectively (n = 14, P < 0.05). Infarct size was reduced by 66% in CBD-treated animals, despite nearly identical areas at risk (9.6 +/- 3.9 and 28.2 +/- 7.0% in CBD and controls, respectively, P < 0.001) and granulation tissue proportion as assessed qualitatively. Infarcts in CBD-treated animals were associated with reduced myocardial inflammation and reduced IL-6 levels (254 +/- 22 and 2,812 +/- 500 pg/ml in CBD and control rats, respectively, P < 0.01). In isolated hearts, no significant difference in infarct size, left ventricular developed pressures during ischemia and reperfusion, or coronary flow could be detected between CBD-treated and control hearts. Our study shows that CBD induces a substantial in vivo cardioprotective effect from ischemia that is not observed ex vivo. Inasmuch as CBD has previously been administered to humans without causing side effects, it may represent a promising novel treatment for myocardial ischemia.

Topics: Animals; Anti-Inflammatory Agents; C-Reactive Protein; Cannabidiol; Cannabis; Cardiovascular Agents; Coronary Circulation; Coronary Vessels; Disease Models, Animal; Echocardiography; Granulation Tissue; Interleukin-6; Ligation; Male; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Rats; Rats, Sprague-Dawley; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Pressure