Stephen E. Epstein

Dose-dependent smooth muscle cell proliferation induced by thermal injury with pulsed infrared lasers.

Pulsed infrared laser irradiation induced localized thermal lesions in arteries by transiently heating to ∼30°C above ambient and subsequent SMC proliferation in rabbits by 3–4 weeks. Neointimal proliferation exhibited a clear dose dependence both as laser fluence was increased (R=0.83) and for a fixed surface irradiation as the depth of the nearest arterial media was decreased (R=0.9S). Thermal injury to the arterial wall is shown to be potent stimulus for SMC proliferation, favoring reduction in energies used in laser or thermal angioplasty.

Plasma Verapamil Levels in Patients with Hypertrophic Cardiomyopathy: Interpatient Variability and Clinical Usefulness

Plasma verapamil levels were measured under various clinical conditions using a high-pressure liquid chromatography assay to determine their importance in guiding therapy in patients with hypertrophic cardiomyopathy. In 80 patients on chronic oral verapamil therapy, there was marked variability between patients in plasma verapamil levels for each dosage. In contrast, variability in peak and trough plasma verapamil levels for a given patientnwas relatively small (verapamil peak/trough ratio for 23 patients = 1.66 ±0.07). Plasma verapamil levels in 27 clinical responders, with improvement in NYHA functional class and >15% increase in exercise capacity, were not different from 15 nonresponders (responders = 153 ± 11, vs nonresponders = 175 ± 18 ng/ml (NS)). In 24 patients with serious electrophysiologic or hemodynamic side effects from verapamil, plasma verapamil levels ranged from 30 to 540 ng/ml (mean plasma verapamil level = 201 ± 23 ng/ml) and there was significant overlap in plasma verapamil levels compared with responders and nonresponders. Thus, in patients with hypertrophic cardiomyopathy on verapamil therapy (1) there is marked interpatient variability in plasma verapamil levels, which may be due to differences in first-pass hepatic metabolism and (2) there is considerable overlap of plasma verapamil levels in responders, nonresponders, and patients with serious side effects. Plasma verapamil levels therefore may be of limited usefulness in predicting therapeutic or toxic effects from oral verapamil therapy in patients with hypertrophic cardiomyopathy.

Dose-dependent smooth muscle cell proliferation induced by thermal injury with pulsed infrared lasers

Pulsed infrared laser irradiation induced localized thermal lesions in arteries by transiently heating to ∼30°C above ambient and subsequent SMC proliferation in rabbits by 3–4 weeks. Neointimal proliferation exhibited a clear dose dependence both as laser fluence was increased (R=0.83) and for a fixed surface irradiation as the depth of the nearest arterial media was decreased (R=0.9S). Thermal injury to the arterial wall is shown to be potent stimulus for SMC proliferation, favoring reduction in energies used in laser or thermal angioplasty.