Tumor Necrosis Factor-a and Cardiomyopathy

he myocardium has limited options for responding toan injury sufficient to cause decreased global contrac-tile function. Myocardial pump performance can bequickly stabilized by increased adrenergic drive, whichthrough b-adrenergic mechanisms increases cardiac outputvia positive chronotropic and inotropic effects. In a kineticsense, the next available option for stabilizing pump functionis the Frank-Starling mechanism, whereby volume expansionplaces the ventricles at a higher position in the preload-per-formance relationship. The renin-angiotensin andb-adrener-gic systems appear to exert most of the signaling in thisregard. The third and slowest-to-develop option is to createmore contractile elements through a hypertrophic responseinvolving new synthesis of sarcomeres in individual cardiacmyocytes. The first two compensatory adjustments are verypowerful in humans and have probably evolved as protectiveresponses to trauma and blood loss. The hypertrophic re-sponse may also be considered in this context but in more ofa wound-healing paradigm that incorporates features of ageneralized inflammatory response. As such, a host of proin-flammatory cytokines have been shown to be increasedsystemically or in the myocardium of subjects with heartfailure. The first of these was tumor necrosis factor-a(TNF-a),