NATIVE BETA-ADRENERGIC SUPPORT FOR LEFT-VENTRICULAR DYSFUNCTION IN EXPERIMENTAL MITRAL REGURGITATION NORMALIZES INDEXES OF PUMP AND CONTRACTILE FUNCTION

Background It is generally accepted that the adrenergic nervous system provides inotropic support for the failing heart. However, the magnit ude of this support has never been studied extensively. The present st udy was performed to test the hypothesis that the adrenergic nervous s ystem is capable of maintaining indexes of pump and contractile functi on in the normal range despite significant innate myocardial depressio n. Methods and Results We used our model of experimental canine mitral regurgitation, which produces left ventricular dysfunction after 3 mo nths of volume overload. We studied indexes of contractile function on and off beta-blockade at baseline and again on and off beta-blockade 3 months after chronic mitral regurgitation had induced significant co ntractile dysfunction. At baseline, acute beta-blockade caused insigni ficant reductions in the mass-corrected slope of the end-ejection stre ss-volume relation (EESVR), the end-systolic stiffness constant, and t he ejection fraction-end-systolic stress and the mean velocity of circ umferential fiber shortening (VCF)-end-systolic stress relations. Afte r 3 months of chronic mitral regurgitation, all indexes of contractile function were normal in the unblocked state except for the VCF-stress relation, which was mildly reduced. However, after acute beta-blockad e after 3 months of chronic mitral regurgitation, the EESVR fell to 30 3+/-27 versus 443+/-24 during acute beta-blockade before mitral regurg itation was created (P<.05), and the end-systolic stiffness constant w as reduced to 2.54+/-0.15 versus 3.27+/-0.11 (P<.05). Only after beta- blockade was the ejection fraction-stress relation significantly reduc ed for dogs with chronic mitral regurgitation. The VCF-stress relation became markedly more abnormal. The viscosity-velocity relation of myo cytes isolated from the ventricles of the dogs with mitral regurgitati on confirmed that substantial innate contractile depression was presen t. Conclusions After 3 months of chronic mitral regurgitation, the adr energic nervous system was able to maintain most indexes of contractil e function in the normal range despite significant depression in innat e contractile function. Thus, in the absence of beta-blockade, signifi cant innate contractile depression may be obscured by adrenergic suppo rt.