APOPTOSIS AND PLEOMORPHIC MICROMITOCHONDRIOSIS IN THE SINUS NODES SURGICALLY EXCISED FROM 5 PATIENTS WITH THE LONG QT SYNDROME

Sinus nodes of five symptomatic patients with the long QT syndrome wer e surgically excised and followed by permanent electronic pacing as pa rt of a new surgical treatment. We examined those sinus nodes by light and electron microscopy with tissue that was promptly fixed at the ti me of surgery. All five sinus nodes were similarly abnormal. By light microscopy we found distinctive focal fibrosis, some degenerating myoc ytes and neural elements, and numerous narrowed small vessels. Except in the nerves there was no evidence of inflammation. In electron micro graphs the mitochondria within nodal myocytes were abnormally abundant , remarkably pleomorphic, and smaller than those in normal human sinus nodal cells. The ultrastructural features of the degenerated nodal ce lls were typical of apoptosis, characterized by the absence of inflamm ation, well-preserved mitochondria, the presence of apoptotic bodies, phagocytosis of these cells by neighboring myocytes, and especially in smooth muscle cells of arterioles, nuclear chromatin margination and nucleolar disintegration. Apoptotic degeneration of nodal myocytes was stochastic, with adjacent cells appearing unaffected. Focal ischemia caused by narrowed vessels may be a contributory factor, and the nerve s may harbor some viral infection, but for the nodal myocytes the abno rmality appears to be primarily apoptosis, sometimes called programmed cell death. Both the typically episodic clinical features and the ter minal event in fatal cases of the long QT syndrome may be due to apopt osis.