Cardiocytic apoptosis and capillary endothelial swelling as morphological evidence of myocardial ischemia in ventricular biopsies from patients with angina and normal coronary arteriograms.

Background: The cause of chest pain in patients with normal coronary arteriograms (CAG) remains poorly understood.
Methods and Results: Left ventricular endomyocardial biopsies from 11 anginal patients with normal CAG and normal left ventriculograms and from seven anginal patients with coronary stenosis were studied by light and electron microscopy. Biopsies from seven non-anginal patients (non-ischemic electrocardiogram abnormalities but no evident heart or systemic diseases) served as controls. In anginal patients with normal CAG, both cardiocytic diameter (17.2 +/- 5.5 microm) and interstitial space percentage area (37.6 +/- 14.9%) were significantly larger than those (13.7 +/- 0.9 microm, 14.9 +/- 2.9%) in control participants. Some cardiocytic nuclei (1.9% of 2000 randomly selected nuclei) exhibited DNA degradation by in-situ nick-end labeling. Electron microscopy revealed cardiocytic nuclei with distinct apoptotic ultrastructures (2.8% of 200 nuclei), phagocytic degradation of cardiocytic cytoplasm, and capillary endothelial swelling (7.1% of 200 capillary transverse sections). No significant infiltration of inflammatory cells was seen. In anginal patients with coronary narrowing (cardiocytic diameter, 16.8 +/- 1.1 microm; interstitial space, 20.1 +/- 5.8%; DNA degraded nuclei, 1.3%), there were however no apoptotic cardiocytic nuclei or cytoplasm and less capillary endothelial swelling (1.6%) in ultrastructure.
Conclusions: In biopsies from anginal patients with normal CAG, the presence of cardiocytic hypertrophy and replacement fibrosis are both abnormal. Cardiocytic apoptosis and capillary endothelial swelling, found by others as characteristic of experimental myocardial reperfusion injury, are evident. This supports the possibility of myocardial transient ischemia and reperfusion injury in patients with angina and normal CAG.