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Biomedical subjects

W S Colucci

Publications and source records attributed to W S Colucci.

At least 163 records · Page 9Linked to original sources
PubMed1983

New developments in alpha-adrenergic receptor pharmacology: implications for the initial treatment of hypertension.

The vascular postsynaptic alpha 1 receptor is the major locus through which adrenergically determined vascular tone is mediated. Therefore, blockade of this receptor is a particularly specific approach to the major pathophysiologic defect in hypertension--an elevation of peripheral vascular resistance. Although the mechanism responsible for this increase in peripheral vascular resistance in hypertension is not known, it is apparent that the sympathetic nervous system plays a key role. In addition, considerable evidence suggests that a common abnormality in hypertension is an increase in the sensitivity of vessels to alpha-adrenergic stimulation, a defect potentially located at the alpha-receptor level. Basic radioligand binding studies of vascular alpha 1 receptors, in fact, demonstrate that the affinity, or avidity, of binding of these sites is under the regulation of both neural and humoral factors. Although diuretics, and more recently, beta-adrenergic blocking agents, have been utilized for the initial treatment of hypertension, recent information about the adverse effects of these agents has led to a reappraisal of the role of alpha-receptor blockade as a rational approach to the initial treatment of hypertension.

Adrenergic alpha-Antagonists↗
PubMed1983

Right ventricular ejection fraction: an indicator of increased mortality in patients with congestive heart failure associated with coronary artery disease.

The predictive value of radionuclide ventriculography was studied in 34 patients with depressed left ventricular ejection fraction (less than 40%) and clinically evident congestive heart failure secondary to atherosclerotic coronary artery disease. In addition to left ventricular ejection fraction, right ventricular ejection fraction and extent of left ventricular paradox were obtained in an attempt to identify a subgroup at increased risk of mortality during the ensuing months. The 16 patients who were alive after a 2 year follow-up period had a higher right ventricular ejection fraction and less extensive left ventricular dyskinesia. When a right ventricular ejection fraction of less than 35% was used as a discriminant, mortality was significantly greater among the 21 patients with a depressed right ventricular ejection fraction (71 versus 23%), a finding confirmed by a life table analysis. Depressed right ventricular function was further linked to more severely compromised left ventricular function, as confirmed by a greater reduction in left ventricular ejection fraction and by an increased extent of left ventricular dyskinesia. These patients had a greater prevalence of chronic obstructive pulmonary disease and previous inferior myocardial infarction but the differences between groups were not statistically significant. It appears that the multiple factors contributing to the reduction in right ventricular ejection fraction make it a useful index not only for assessing biventricular function, but also for predicting patient outcome.

Actuarial Analysis↗
PubMed1982

Alpha-adrenergic receptor blockade with prazosin. Consideration of hypertension, heart failure, and potential new applications.

Prazosin, an orally active alpha-1 selective adrenergic antagonist, has been of value in treating patients with hypertension and congestive heart failure. In contrast to non-subtype-selective alpha-adrenergic antagonists and direct-acting vasodilators, prazosin's hypotensive action is accompanied by little or no increase in heart, rate, plasma renin, or plasma norepinephrine. Prazosin is a versatile drug that may be used alone or in combination to treat mild, moderate, or severe hypertension. The antihypertensive effect is sustained, and may increase during long-term therapy. The major side effect, postural hypotension after the first drug administration, is related to drug dose and intravascular volume depletion. Other side effects are mild and seldom limit therapy. In patients with congestive heart failure, prazosin results in balanced venous and arterial dilation, similar to that produced by nitroprusside. Attenuation of some or all of prazosin's initial hemodynamic effects has been seen during multiple short-term administrations. However, chronic studies have shown sustained symptomatic and hemodynamic improvement during long-term administration; initial hemodynamic attenuation may be transient or partial, and does not preclude long-term effectiveness, particularly during exercise. Preliminary studies indicate that prazosin may also be effective in treating patients with peripheral vasospasm due to Raynaud's phenomenon or ergotamine overdose.

Adrenergic alpha-Antagonists↗
PubMed1981

Decreased lymphocyte beta-adrenergic-receptor density in patients with heart failure and tolerance to the beta-adrenergic agonist pirbuterol.

We compared the initial and long-term effects of the beta-adrenergic agonist pirbuterol in 12 patients with chronic congestive heart failure. The drug's initial effect was a 35 per cent increase in cardiac index, but there was no significant change in heart rate or mean arterial pressure. After one month of therapy, the mean cardiac index and ejection fraction had returned to base-line values, and no clinical effect was evident in most patients. This apparent tolerance was not accompanied by changes in heart rate, blood pressure, or body weight, and it occurred in the presence of therapeutic drug levels during long-term therapy. The density of beta-adrenergic receptors on lymphocytes from patients treated with pirbuterol was significantly depressed as compared with that of patients with heart failure of comparable severity but not treated with pirbuterol. We conclude that tolerance to the hemodynamic and clinical effects of pirbuterol develops during long-term administration; this tolerance may be related to a decrease in myocardial or vascular beta-adrenergic receptors or both.

Adrenergic beta-Agonists↗
PubMed1981

Problems in assessment of new pharmacologic agents for the heart failure patient.

Modern management of congestive heart failure (CHF) employs inotropic drugs, vasodilators, and diuretics. Although pharmacologic classification of drugs is possible in animals, identification of predominant hemodynamic mechanisms in humans is more complex, because many effects of vasodilators and inotropic drugs are similar. We compared the effects of a vasodilator, prazosin, and two agents with both inotropic and vasodilatory properties, amrinone and pirbuterol, on cardiac index (CI), mean aortic pressure, left ventricular stroke work index (LVSWI), LV filling pressure (LVFP), systemic vascular resistance, LV ejection fraction (LVEF), and myocardial O2 consumption (MVO2) in 34 patients with advanced CHF. We concluded that (1) a rise in CI and LVEF, together with a fall in LVFP, does not necessarily indicate an inotropic effect; (2)both CI and LVEF may be increased by an inotropic mechanism in advanced CHF without a rise in MVO2; and (3) a drug-induced rise in LVSWI with stable or lower LVFP suggests an inotropic mechanism of action.

Aminopyridines↗
PubMed1981

Clinical, hemodynamic, and neuroendocrine effects of chronic prazosin therapy for congestive heart failure.

We report our hemodynamic, clinical, and neuroendocrine observations during long-term (8 weeks) prazosin (PZN) administration to assess the efficacy of this agent in the long-term therapy of congestive heart failure (CHF) and to emphasize the potential role of neuroendocrine mechanisms in the determination of overall drug effect. During long-term PZN therapy there is improvement in functional status, exercise tolerance, and left and right ventricular ejection fractions. However, we also observed an increase in fluid retention and attenuation of the initial hemodynamic and clinical responses to the drug. Plasma renin activity and plasma norepinephrine concentration are increased during long-term PZN therapy despite clinical and hemodynamic improvement and potentially may be involved in the pathogenesis of the increased fluid retention and hemodynamic attenuation. Three pharmacologic considerations appear relevant to the use of an alpha-adrenergic antagonist such as PZN in CHF therapy: (1) the drug response may be related to the baseline level of sympathetic tone. (2) The dose-response pattern exhibits a plateau phase, beyond which higher doses cause little further effect. (3) The overall drug effect is the sum of its direct actions and the secondary actions of the neuroendocrine response it elicits.

Drug Tolerance↗
PubMed1981

Improved right ventricular function and reduced pulmonary vascular resistance during prazosin therapy of congestive heart failure.

Although the effect of systemic vasodilator therapy on left ventricular function in congestive heart failure has been extensively evaluated, little is known about its effect on pulmonary vascular resistance and right ventricular function. Since pulmonary vascular resistance is mediated in part by alpha-adrenergic receptors, we studied the effects of the alpha-adrenergic antagonist prazosin on right ventricular function as determined by a radionuclide ventriculographic technique which assessed right and left ventricular ejection fractions simultaneously. In 11 patients treated for two months with prazosin, right ventricular ejection fraction increased from 0.28 +/- 0.04 to 0.44 +/- 0.07 (p less than 0.01). In 10 patients who received a single dose of prazosin 48 hours after withdrawal of prior prazosin therapy, right ventricular ejection fraction increased from 0.29 to 0.05 to 0.38 +/- 0.06 (p less than 0.02). In nine patients who received a single dose of prazosin during right sided heart catheterization, pulmonary vascular resistance decreased from 358 +/- 70 to 236 +/- 60 dyne-sec-cm -5 (p less than 0.01). These studies suggest that prazosin has beneficial effects on right ventricular function both immediately and long-term in patients with severe congestive heart failure. Although the mechanism of this effect is not known, possibilities include a direct effect of prazosin on the pulmonary vasculature, a secondary reduction in right ventricular afterload due to improved left ventricular performance and a withdrawal of reflex-mediated pulmonary vasoconstriction due to improved left ventricular performance.

Adrenergic alpha-Antagonists↗
PubMed1981

Mechanisms and implications of vasodilator tolerance in the treatment of congestive heart failure.

Vasodilators play an important role in the treatment of the patient with severe heart failure and increased systemic vascular resistance. However, there are both clinical data and theoretic reasons to anticipate that some degree of tolerance may develop during the long-term use of most agents. The cause of the increased vascular resistance of heart failure is not completely understood, but it appears to be related to a number of neuroendocrine, molecular and physical mechanisms including increased activity of the sympathetic nervous and renin-angiotensin systems, and increased vascular stiffness due to intra- and extracellular sodium and fluid accumulation. Not surprisingly, a lowering of systemic vascular resistance either by direct smooth muscle relaxers or by blockade of specific neuroendocrine systems may result in a number of compensatory responses at the neuroendocrine and/or molecular level. The over-all effectiveness of a particular vasodilator is the net sum of its direct pharmacologic action, and the neuroendocrine and molecular responses to the drug. The specific compensatory mechanisms activated depend on several factors including the type of vasodilator used, the dose employed, the baseline neuroendocrine status of the patient, the severity of heart failure and the functional integrity of various reflex systems. Although not directly applicable to patients with heart failure, much information derived from the use of these agents to treat patients with hypertension and angina pectoris suggests several potential mechanisms by which tolerance may develop to virtually all classes of vasodilators. The major types of vasodilators are discussed with regard to their potential mechanisms of tolerance. Finally, the evidence currently available from long-term studies is reviewed in order to assess the potential relevance of vasodilator tolerance to the clinical management of the patient with heart failure.

Adrenergic alpha-Antagonists↗
PubMed1981

Acute effects of oral pirbuterol on myocardial oxygen metabolism and systemic hemodynamics in chronic congestive heart failure.

Pirbuterol hydrochloride, an orally effective beta-adrenergic agonist, improves hemodynamic abnormalities in patients with congestive heart failure, but its effects on myocardial oxygen consumption (MVO2) and coronary blood flow have not been characterized. We studied the effects of 20-30 mg of oral pirbuterol on myocardial metabolic and hemodynamic parameters in 12 patients (six with coronary artery disease) with chronic CHF refractory to standard medical therapy. Pirbuterol induced an increase in cardiac index (1.7 +/- 0.1 to 2.3 +/- 0.2 l/min/m2, p less than 0.05) and a fall in systemic vascular resistance (1884 +/- 118 to 1391 +/- 69 dyn-sec-cm-5, p less than 0.01) 2 hours after administration. Pulmonary capillary wedge pressure fell from arterial and right atrial pressures did not change. Heart rate remained constant. Arterial-coronary sinus oxygen content difference narrowed (from 12.9 +/- 0.4 to 11.1 +/- 0.3 vol%, p less than 0.05), while no significant change occurred in MVO2. Myocardial oxygen extraction ratio and myocardial lactate extraction ratio did not change, and no patient developed angina or electrocardiographic evidence of myocardial ischemia. Patients with coronary artery disease had hemodynamic and myocardial metabolic responses similar to those without coronary artery disease. Pirbuterol effects substantial acute hemodynamic improvement in patients with chronic congestive heart failure without increasing requirements for coronary blood flow or myocardial oxygen delivery and without provoking myocardial ischemia.

Adult↗
PubMed1980

Sustained effectiveness of converting-enzyme inhibition in patients with severe congestive heart failure.

Eight patients with severe congestive heart failure refractory to conventional therapy, including vasodilators, were given captopril (seven patients) or teprotide (one patient). All had dyspnea, edema, elevated pulmonary wedge pressure (28.0 +/- 2.6 mm Hg), low cardiac index (1.6 +/- 0.1 liters per minute per square meter), and elevated levels of serum creatinine (2.3 +/- 0.2 mg per deciliter [203.3 +/- 17.7 mumol per liter]), blood urea nitrogen (48 +/- 5 mg per deciliter [17.1 +/- 1.8 mmol of urea per liter]), plasma renin activity (21 +/- 7 ng of angiotensin I per milliliter per hour), plasma angiotensin II (271 +/- 51 pg per milliliter), and plasma aldosterone (65 +/- 14 ng per deciliter). After one week of therapy, all indexes improved. Creatinine and p-aminohippurate clearances were also increased (P less than 0.01). Improvement was sustained (more than six months) and was associated with a statistically significant increase in the cardiac ejection fraction (12 +/- 3 to 26 +/- 7 per cent). With a mean follow-up of seven months, the New York Heart Association Functional Class has been reduced from IV to II, and the number of days of hospitalization to less than 10 per cent of that before captopril therapy. We conclude that captopril reduces afterload in advanced congestive heart failure and induces sustained improvements in clinical status and renal function.

Adult↗
PubMed1980

Increased plasma norepinephrine levels during prazosin therapy for severe congestive heart failure.

To ascertain whether increased sympathetic nervous system activity may contribute to the attenuation of prazosin's effect on congestive heart failure, we measured plasma norepinephrine levels in 10 patients with severe heart failure before and after chronic prazosin therapy. Norcpinephrine levels were increased in eight of 10 patients while supine (145 +/- 133 pg/mL; after, 481 +/- 376 pg/mL; P < 0.01); levels measured in five patients while upright were also increased (before, 351 +/- 238 pg/mL; after, 651 +/- 258 pg/mL; P < 0.05). Left ventricular ejection fraction measured by gated blood pool scan was increased from 16.9% +/- 8.1% to 25.4% +/- 11.3% (N = 10, P < 0.01). Mean systemic blood pressure and heart rate were unchanged. Increased plasma norepinephrine levels may attenuate prazosin's vasodilator action in heart failure. The cause of the increase in norepinephrine levels is unclear and warrants further study.

Heart Failure↗