Anandamide preserves cardiac function and geometry in an acute doxorubicin cardiotoxicity rat model.
We investigated the use of the endocannabinoid anandamide as a means of cardioprotection against doxorubicin-induced cardiac dysfunction. Male rats received doxorubicin with or without anandamide pretreatment. Cardiac function was assessed in vivo using transthoracic echocardiography and ex vivo using the isolated working heart 5 days posttreatment. Doxorubicin administration without anandamide pretreatment resulted in a decline in fractional shortening (P < .05) and left ventricular wall thickness when compared to controls (P < .05). Ex vivo cardiac function analysis revealed a reduction in left ventricular developed pressure in hearts from animals receiving doxorubicin without anandamide pretreatment when compared to controls (P < .05). Left ventricles from animals receiving anandamide pretreatment before doxorubicin administration did not exhibit depressed fractional shortening, ventricular wall thickness, or developed pressure when compared to controls (P > .05). These results suggest that a potential therapy for doxorubicin-induced cardiotoxicity involves targeting the endogenous cannabinoid system.
Hydock
David S
DS
School of Sport and Exercise Science, University of Northern Colorado, Greeley, Colorado 80639, USA.
Lien
Chia-Ying
CY
Hayward
Reid
R
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004317:Doxorubicin; D015150:Echocardiography, Doppler; D063388:Endocannabinoids; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002316:Cardiotonic Agents; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D004317:Doxorubicin; C078814:anandamide