Use of embryonic heart grafted in oculo to assess neurohumoral controls of cardiac development.

Culture of embryonic heart in the anterior eye chamber allows neurohumoral and genetic controls of cardiac development to be separated from the influence of hemodynamic load. Hearts from 12-day gestation rat embryos grafted into the anterior eye chamber of an adult host rat attach to the iris and become vascularized and innervated by collaterals from the host iris. The spontaneous beating of grafts is pacemaker-driven and under functional neural control. Grafts do not beat against a pressure load, allowing the influence of neurohumoral factors to be separated from altered hemodynamic load. In oculo, embryonic heart differentiates into mature myocardium by most morphologic and biochemical criteria. Mature intercalated disks and myofibrils with well-defined Z-lines and M-lines are observed. Mature grafts express the high levels of alpha-myosin heavy chain characteristic of young adult myocardium. Surgical sympathetic denervation of the anterior eye chamber prior to grafting of embryonic hearts compromises growth and increases the intrinsic pacemaker rate. Since the grafts are perfused by the host circulation, the hormonal milieu of the graft can be altered by treatment of the host. Thus, the interaction between hormones and innervation of grafts can be studied using the in oculo model system.