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Title: Studies of the cardiovascular effects of inotropic agents and vasodilators on the pulmonary and systemic circulation in man
Author: Wathen, Christopher George
ISNI:       0000 0001 3563 9523
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1988
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Many drugs have recently been introduced for the treatment of hypertension and heart failure. These drugs may primarily affect the heart or components of the peripheral circulation and may have adverse as well as beneficial effects. Although animal studies can give some indication of the mode of action, such drugs should be evaluated both by measurement of their effects on the circulation and by appropriate clinical trials to determine if there is any useful benefit. In this dissertation this principle has been applied to inotropic and vasodilator drugs used for treating heart failure and hypertension. To study the circulatory effects of drugs, I have modified standard radionuclide methods and developed a technique to examine peripheral venous capacitance. The problems of assessing ventricular function when afterload changes have been studied. To assess benefit I have organised and conducted appropriate clinical trials. The first section comprises two studies of drugs which modify inotropic state. The haemodynamic effects of the beta-adrenergic antagonist atenolol vere examined in patients with previously untreated essential hypertension. Blood pressure was lowered but the underlying circulatory abnormalities including the elevated peripheral vascular resistance were not corrected. Patients with cor pulmonale were given the betaadrenergic agonist pirbuterol and the cardiovascular effects compared with those of the pure vasodilator sodium nitroprusside. Pirbuterol was shown to act as a vasodilator with some selectivity for the pulmonary circulation but a minor positive inotropic effect was detected. The second section reports studies where calcium channel antagonist vasodilators were evaluated in hypertension. The cardiovascular effects of nifedipine were studied at rest and during exercise in hypertensive patients with and without beta-adrenergic blockade. In contrast to atenolol, nifedipine reduced peripheral vascular resistance but a negative inotropic effect was observed. Therefore the newer calcium antagonist felodipine, which in animal experiments had been shewn to be selective to the arterial circulation, was examined in patients and the lack of cardiac depression was confirmed. Following these promising results a clinical trial comparing felodipine with the most potent vasodilator available, minoxidil, in severe hypertension was undertaken. The results indicated that felodipine has an important role in the treatment of severe hypertension. This work demonstrates how cardiovascular effects of inotropic agents and vasodilators can be assessed in intact man. Therapeutic benefit can only be assessed by adequate clinical trials.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Hypertension drug treatment