Immunoregulatory Effects of Carvedilol on Rat Experimental Autoimmune Myocarditis

The cardioprotective effects of carvedilol were studied in a rat model of experimental autoimmune myocarditis (EAM). After immunization, rats were orally administered 10 mg/kg/day carvedilol (group C, n = 15) or a vehicle control (Group V, n = 12) for 3 weeks. On day 21, echocardiography and haemodynamic parameters, myocarditis areas, and cytokine concentrations were measured. Serum carvedilol concentrations ranged from 10.5 +/- 2.6 to 31.7 +/- 9.3 ng/ml over a 24 h period on day 20. Carvedilol decreased the myocarditis areas (23.07 +/- 1.6 versus 33.65 +/- 2.71%, P < 0.0001). The left ventricular fractional shortening and the absolute value of +dP/dt or -dP/dt were significantly higher in Group C. Heart rate, systolic blood pressure, left ventricular end-diastolic pressure and central venous pressure were significantly lower in Group C. The serum and mRNA levels of interleukin (IL)-1 beta (53.58 +/- 6.42 versus 98.75 +/- 6.53 pg/ml, P < 0.0001 and 0.298 +/- 0.04 versus 0.818 +/- 0.252, P < 0.0001, respectively) and TNF-alpha (14.82 +/- 1.95 versus 29.52 +/- 3.7 pg/ml, P = 0.0008 and 0.088 +/- 0.006 versus 0.168 +/- 0.072, P = 0.0051, respectively) were markedly decreased, whereas IL-10 (24.92 +/- 2.94 versus 15.25 +/- 3.13 pg/ml, P = 0.015 and 0.302 +/- 0.022 versus 0.107 +/- 0.02, P < 0.0001, respectively) and IL-1 receptor antagonist (1.95 +/- 0.28 versus 0.52 +/- 0.10 pg/ml, P < 0.0001 and 0.112 +/- 0.009 versus 0.051 +/- 0.002, P < 0.0001, respectively) were markedly increased in the Group C. These results indicate that in rats carvedilol protects against EAM.