Pathology of intrinsic cardiac neurons from ischemic human hearts

Various populations of intrinsic cardiac neurons influence regional cardiac function tonically. It is not known whether such neurons are affected by disease states and, if so, in what manner. Therefore, the morphology of intrinsic cardiac ganglia obtained from patients with angiographic evidence of compromised regional coronary blood supply was studied. Posterior atrial ganglia and surrounding fat, removed at the time of cardiac surgery, were placed immediately in saline and within 15-120 min (average of about 40 min) in 0.5% paraformaldehyde/2.5% glutaraldehyde. In 32 studied ganglia, 35% of 473 intrinsic cardiac neurons displayed striking pathological changes at the light and ultrastructural level. The other cells displayed normal morphology. The cytoplasm of 74% of the abnormal cells had one or more of three types of inclusions: (1) darkly stained lamellated inclusions (Type I), (2) membrane-bound whorls and parallel arrays of lightly stained membranes, as well as fine granular material (Type II), or (3) concentric layers of lightly stained membranes with a darker, granular core (Type III). Neurons with inclusions were markedly enlarged (66 x 54 microm vs. 40 x 34 microm for normal neurons) and displayed fewer dendrites. Some neurons contained electron lucent vacuoles indicative of degeneration while others showed frank degeneration, being fragmented, shrunken, and misshapen. Phagocytic cells containing lamellated inclusions and cellular debris were found in ganglia with abnormal neurons. Some axon terminals also displayed degenerative changes. The identification of pathological changes in the human intrinsic cardiac nervous system has implications with respect to the functional integrity of this final common regulator of cardiac function in disease states.