Protective effect of nisoldipine on dipyridamole-induced myocardial ischemia: correlation with exercise...

Nisoldipine, a dihydropyridine calcium channel blocker with strong coronary dilatative action, is commonly used in the treatment of myocardial ischaemia; its beneficial effect on effort angina has been demonstrated by several previous reports. Infusion of dipyridamole in doses sufficient to provoke myocardial ischaemia in patients with significant coronary artery disease is used safely in imaging studies for diagnostic purposes.

To evaluate the potential effect of nisoldipine on dipyridamole-induced ischaemia and to compare the results with the effect of nisoldipine on exercise-induced ischaemia.

Twelve patients (10 men and two women, mean age 62 +/- 8 years) with significant coronary artery disease (at least 70% lumen reduction in at least one major coronary vessel) were selected for inclusion in the study. In accordance with the inclusion criteria, the patients exhibited an ischaemic diagnostic response to a multistage exercise electrocardiography stress test (> 0.15 mV ST segment depression compared with the resting electrocardiographic tracing) and to a dipyridamole-echocardiography test (transient left ventricular dyssynergy of contraction during infusion of dipyridamole up to 0.84 mg/kg over 10 min), after 3 days' cessation of antianginal treatment. After treatment with oral nisoldipine (10 mg twice daily) was introduced, the patients repeated the two tests, within 18 days of the first evaluation.

The dipyridamole-echocardiography test was positive for ischaemia in 12 patients who were not receiving nisoldipine and in eight patients who were receiving the drug (100% and 67% respectively, P < 0.05). In the eight patients who gave positive dipyridamole-echocardiography tests both with and without treatment, dipyridamole time (time to onset of dyssynergy during the test) increased from 7.9 +/- 2.9 min to 10.2 +/- 3.1 min (P < 0.01). In these patients, no significant changes were observed, at ischaemia, in the severity and extent of induced dyssynergy, evaluated as wall motion score index (each of 16 left ventricular segments scored from 1 = normal to 4 = dyskinetic) after treatment (score variations from baseline to ischaemia: 0.20 +/- 0.11 without nisoldipine and 0.16 +/- 0.06 with nisoldipine; NS). Variations in dipyridamole time (arbitrarily considered to be 15 min in the negative dipyridamole-echocardiography test) were significantly correlated with variations in exercise time (duration of exercise to exhaustion or diagnostic positive response on the electrocardiogram): r = 0.75 (P < 0.01). No significant differences were recorded in rate-pressure product (beats/min x mmHg x 100) at peak ischaemia between patients who were or were not receiving nisoldipine, during either the exercise electrocardiography stress test (233 +/- 36 with nisoldipine and 244 +/- 39 without nisoldipine; NS) or the dipyridamole-echocardiography test (147 +/- 21 with nisoldipine and 133 +/- 30 without nisoldipine; NS).

Nisoldipine treatment can protect from dipyridamole-induced ischaemia, being associated with a longer stress time, and completely preventing the development of ischaemia in some patients. The therapy-induced changes in ischaemic threshold during the dipyridamole-echocardiography test correlate with variations in exercise tolerance.