title: A rest and exercise haemodynamic evaluation of a new cardio-selective beta-adrenoceptor blocker celiprolol alone and in combination with nitroglycerine in ischaemic heart disease.
abstract: The symptomatic benefits of combining beta-adrenoceptor blockers and nitrates in angina pectoris are well recognised. Their actions on cardiac haemodynamics and volumes when combined have been poorly characterized. Accordingly this study investigated a new cardioselective beta-adrenoceptor blocking agent celiprolol and buccal nitroglycerine in 24 patients with angiographically documented coronary artery disease. Following a control period, with confirmed stable haemodynamics, three groups (n = 8/group) of prospectively matched patients, were studied following intravenous celiprolol (8 mg), buccal nitrate (10 mg) or their combination. Haemodynamics and left ventricular ejection fraction (nuclear probe) were determined following each intervention. The actions of each regimen on the haemodynamics of exercise-induced angina were compared by exercise testing in the control state and following each regimen. At rest, celiprolol did not alter haemodynamic parameters. Nitrate therapy reduced left ventricular filling pressure (pulmonary artery occluded pressure--PAOP) and volumes; the ejection fraction and heart rate increased. Combination therapy resulted in a highly significant reduction in left ventricular preload and afterload (PAOP and mean arterial blood pressure) at an increased left ventricular ejection fraction and reduced cardiac volumes; there was a trend to reduce cardiac double product (HR X SBP). During exercise celiprolol reduced systolic blood pressure, heart rate and cardiac index; systemic vascular resistance index increased. Nitrate therapy reduced blood pressure and PAOP, and increased ejection fraction. Combination therapy reduced all components of the triple product (heart rate, systolic blood pressure and PAOP) without affecting the other haemodynamic or radionuclide parameters. These data suggest improvements in cardiac function from the combination of celiprolol and nitrate therapy which were not achieved by either agent when used as monotherapy; they afford an interesting insight into the manner in which such widely utilised therapeutic modalities interact in coronary artery disease.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D017272:Celiprolol; D003327:Coronary Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005080:Exercise Test; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage*; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D012146:Rest; D013667:Technetium
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D013667:Technetium; D017272:Celiprolol; D005996:Nitroglycerin