THE NOVEL EFFECTS OF 3,5,3'-TRIIODO-L-THYRONINE ON MYOCYTE CONTRACTILE FUNCTION AND BETA-ADRENERGIC RESPONSIVENESS IN DILATED CARDIOMYOPATHY

Medical management of patients with chronic left ventricular dysfuncti on continues to be a difficult problem. Recent clinical and experiment al studies have suggested that 3,5,3'-triiodo-L-thyronine improves lef t ventricular pump function. However, whether 3,5,3'-triiodo-L-thyroni ne directly improves myocyte contractile function in cardiomyopathic s tates is unknown. Accordingly, this study examined the direct effects of 3,5,3'-triiodo-L-thyronine on isolated myocyte contractile function in cardiocytes obtained from control (n = 6) pigs and pigs with tachy cardia-induced dilated cardiomyopathy (atrial pacing at 240 beats/min for 3 weeks; n = 6). Myocyte percent shortening and velocity of shorte ning were obtained at baseline and in the presence of 3,5,3'-triiodo-L -thyronine doses of 80 and 100 pmol/L. For both control and dilated ca rdiomyopathy groups, 3,5,3'-triiodo-L-thyronine caused a significant i ncrease in myocyte contractile function. For example, a 100 pmol/L dos e of 3,5,3'-triiodo-L-thyronine increased myocyte velocity of shorteni ng by 51 % in control myocytes and by 54 % in dilated cardiomyopathy m yocytes compared with baseline. A second series of experiments was per formed to determine whether 3,5,3'-triiodo-L-thyronine altered the res ponsiveness of the beta-adrenergic receptor system in control and dila ted cardiomyopathy myocytes. Myocyte contractile function was examined during beta-adrenergic stimulation with isoproterenol alone and in my ocytes preincubated with 3,5,3'-triiodo-L-thyronine doses of 80 and 10 0 pmol/L to which isoproterenol was added. Isoproterenol alone increas ed velocity of shortening by 139 % in control and by 233 % in dilated cardiomyopathy myocytes compared with baseline. This was significantly greater than the increase with 3,5,3'-triiodo-L-thyronine alone. 3,5, 3'-triiodo-L-thyronine followed by isoproterenol increased velocity of shortening by 245 % in control and 313 % in dilated cardiomyopathy my ocytes compared with baseline. This was significantly greater than the response with 3,5,3'-triiodo-L-thyronine or isoproterenol alone and a ppeared to be greater than an additive response. The results from this study clearly demonstrated that 3,5,3'-triiodo-L-thyronine directly a ugmented myocyte contractile function in both control and dilated card iomyopathy myocytes, In addition, 3,5,3'-triiodo-L-thyronine enhanced the contractile response to beta-adrenergic stimulation in dilated car diomyopathy. This study provides unique evidence to suggest that 3,5,3 '-triiodo-L-thyronine may be a useful adjunct to conventional inotropi c support in the setting of advanced left ventricular dysfunction.