Little attention has been directed toward the action of atrial peptides on integrated cardiovascular function. In conscious dogs intravenous injection of atriopeptin 24 (10 micrograms/kg) reduced mean arterial pressure (11 +/- 3.2%), mean left atrial pressure (32 +/- 8.6%), left ventricular (LV) end-diastolic pressure (24 +/- 4.3%), and increased heart rate (25 +/- 6.2%). LV dP/dt and stroke volume increased 17 +/- 4.0 and 12 +/- 3.3%, respectively. Cardiac output increased 39 +/- 6.3%. These effects were only acute, lasting less than 10 min. The tachycardia and increase in LV dP/dt were abolished by combined beta-adrenergic and muscarinic cholinergic blocking agents. During an infusion of atriopeptin 24 (10 micrograms X kg-1 X min-1) blood flow, as measured with radioactive microspheres, increased to both the left (101 +/- 35%) and right kidney (122 +/- 37%) and to the spleen (140 +/- 50%). However, blood flow to the stomach, large and small intestine, pancreas, liver, and skeletal muscle did not change, indicating the selectivity of the atriopeptin. Blood flow in the right ventricle, septum, and in all layers of the left ventricle increased slightly, resulting in no change in the endocardial-to-epicardial blood flow ratio most likely due to the changes in myocardial function, i.e., heart rate and stroke volume. Thus, in conscious dogs, atriopeptins increase myocardial performance most likely indirectly secondary to baroreflex unloading after the direct hypotensive effects of atriopeptin 24. This serves to increase cardiac output at a time when renal and splenic blood flows are increased.

Summary:A regularly scheduled physical training program seems to have antithrombotic effects. Moreover, the hemostatic changes occurring in patients with coronary artery disease during acute exercise have not been clearly elucidated. Since stress testing is routinely performed in clinical cardiology, it would be helpful to assess whether patients with coronary artery disease are exposed to acute coronary thrombosis during or soon after sustained physical exercise. This study was designed to evaluate the effect of acute physical exercise (stress test by bicycle ergometer) on blood coagulation in a group of patients with previous myocardial infarction, and to determine whether the antithrombotic therapy commonly administered favorably influences hemostatic equilibrium. Our results suggest that exercise testing is not harmful to patients with previous myocardial infarction in regard to hemostasis and fibrinolysis and that antithrombotic therapy reduces postexercise increase in platelets. platelet aggregability. In spite of these data, studies on the effect of stress test on blood coagulation and fibrinolysis yielded conflicting Particularly, the hemostatic changes in patients with coronary artery disease during acute exercise are not clearly elucidated. Some investigators suggested that the majority of patients with myocardial ischemia show increased platelet activity and decreased fibrinolysis at rest, l 3 whereas others were unable to demonstrate such changes.*.l4Since sustained physical exercise is routinely performed for clinical evaluation in cardiology, it would be helpful to assess whether or not patients with coronary artery disease are exposed to acute coronary thrombosis during or soon after stress testing.This study was designed to evaluate the effect of acute physical exercise on blood coagulation and fibrinolysis in a group of patients with previous myocardial infarction and to determine whether the antithrombotic therapy commonly administered to postinfarction patients favorably influences the hemostatic equilibrium.

3 Intravenous injection of celiprolol (3 mgkg-') in nine dogs, increased LV dP/dt by 13 + 2.6%, velocity of shortening (LV dD/dt) by 9.2 + 3.4%, and heart rate by 19 + 4.6% and decreased LV end-diastolic diameter by 1.8 + 0.8%, all significantly (P < 0.05). Celiprolol blocked the inotropic actions of isoprenaline (0.5 ygkg-') but only partially reduced its hypotensive effects. Propranolol, in contrast, reduced LV dP/dt by 17 + 3.3% and heart rate by 8.1 + 2.7% (P < 0.05) while totally abolishing the hypotension, tachycardia and increase in LV dP/dt caused by isoprenaline. Following fi-adrenoceptor blockade with propranolol and with heart rate held constant by electrical pacing, celiprolol increased LV dP/dt by 16 + 4.0%, LV dD/dt by 12 + 3.0% and reduced LV end-diastolic diameter by 3.5 + 0.5% (P < 0.05). 4 Thus, in conscious dogs, celiprolol increases inotropic state and reduces preload independently of fl-adrenoceptor mechanisms and the Bowditch phenomenon, while effectively blocking fil-receptors in the heart. These properties would make celiprolol useful in patients where a conventional f-adrenoceptor blocking agent might lead to pump failure.

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