title: Diltiazem-induced blockade of sympathetically mediated constriction of normal and diseased coronary arteries: lack of epicardial coronary dilatory effect in humans.
abstract: To determine mechanisms of benefit from diltiazem, 13 patients with coronary disease performed sustained isometric handgrip exercise and repeated the procedure during intravenous infusion of diltiazem (0.25 mg/kg bolus followed by 0.003 mg/kg/min). Cardiovascular responses to handgrip, diltiazem, their combination, and nitroglycerin were assessed by hemodynamic and electrocardiographic measurements and by computer-assisted measurements of normal and diseased segments of epicardial coronary arteries. Handgrip produced increases in heart rate (12%; p less than .001), pulmonary arterial pressure (19%; p less than .005), and pulmonary wedge pressure (33%; p less than .005). Diltiazem produced significant reductions in heart rate (7%; p less than .05) and aortic pressure (14%; p less than .001). Pulmonary arterial pressure and pulmonary wedge pressure were unchanged by diltiazem. Diltiazem did not prevent the increase in heart rate or in aortic or wedge pressure associated with handgrip. Diltiazem prolonged atrioventricular conduction from 0.18 +/- 0.03 to 0.20 +/- 0.03 sec (p less than .001). Compared with control values, nitroglycerin reduced aortic pressure (14%; p less than .005), pulmonary arterial pressure (38%; p less than .001), and pulmonary wedge pressure (42%; p less than .005). Heart rate was unchanged. The constriction (20%) in lumen area of normal coronary arterial segments during handgrip was effectively prevented by infusion of diltiazem (1%; p less than .001). Nitroglycerin produced a significantly greater increase (20%) in diameter of normal coronary arterial segments than diltiazem (3%; p less than .001) and tended to have a more favorable effect than diltiazem on stenosis minimum area and flow resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D004110:Diltiazem / Q000627:therapeutic use*; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use; D005082:Physical Exertion; D011669:Pulmonary Wedge Pressure / Q000187:drug effects
chemical_list: D001552:Benzazepines; D004110:Diltiazem; D005996:Nitroglycerin