ABILITY OF CALCIUM-ENTRY BLOCKADE BY FELODIPINE TO DISCLOSE DIFFERENT PATHOGENETIC MECHANISMS BEHIND HYPERVENTILATION-INDUCED MYOCARDIAL-ISCHEMIA IN MEN

To verify that myocardial ischemia occurring during ither the overbreathing or recovery phase of the hyperventilation test is based on different pathogenetic mechanisms, 2 consecutive series of patients, selected on the basis of their response to a run-in hyperventilation test, were studied. Group I comprised 15 patients who developed ST-segment depression early during overbreathing, whereas group II consisted of 12 patients showing ST-segment depression late during the recovery phase. A single oral dose of felodipine 10 mg or of placebo was administered on 2 consecutive days according to a randomized, double-blind, crossover design, and the hyperventilation test was repeated, on both days of the study, 3 to 5 hours after drug intake. In group I, ST-segment depression occurred after placebo in all patients during overbreathing, with an increase in rate pressure product (from 112 ± 31 at baseline to 168 ± 55 mm Hg × beats/min/100 at the onset of ST-segment depression; p < 0.01). After felodipine, 13 patients continued to show ST-segment depression during overbreathing, together with an increase in rate pressure product (from 107 ± 24 at baseline to 158 ± 46 mm Hg × beats/ min/100 at the onset of electrocardiographic changes; p < 0.01). In group II, all 12 patients showed ST-segment depression during recovery after placebo, with a rate pressure product comparable to baseline conditions (112 ± 35 at baseline vs 102 ± 27 mm Hg × beats/min/100 at the onset of ST-segment depression; difference not significant). After felodipine, no patient developed ST-segment depression or chest pain. These findings confirm that early hyperventilation-induced ST-segment depression is related to increased oxygen consumption, which cannot be prevented by felodipine. On the other hand, felodipine is highly effective in preventing delayed ischemia, which is due to a primary reduction in coronary blood flow. © 1990.