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Biomedical subjects

R J Cody

Publications and source records attributed to R J Cody.

At least 127 records · Page 7Linked to original sources
PubMed1983

Combined vasodilator therapy for chronic congestive heart failure.

There are few data to support the potential efficacy of combined vasodilator therapy for severe congestive heart failure. For documentation of the feasibility of such an approach, a short-term hemodynamic study utilizing captopril, an oral converting enzyme inhibitor, followed by the addition of nitroprusside infusion, was made of 11 patients with severe chronic congestive heart failure. Captopril alone resulted in reduction of mean arterial pressure (84 +/- 7 to 70 +/- 3 mm Hg), associated with increase of cardiac index and stroke index. There was also a significant reduction of systemic resistance and pulmonary wedge pressure. The initial hemodynamic response to captopril was correlated with initial plasma renin activity (all values at least p less than 0.05). The addition of nitroprusside to captopril resulted in further hemodynamic improvement. Reduction of mean arterial pressure, systemic vascular resistance, and pulmonary wedge pressure were all significant, as were increases of cardiac index and stroke index. The degree of hemodynamic improvement with this sequence of vasodilator therapy was linearly related to the reduction of mean arterial pressure. Therefore vasodilators with dissimilar mechanisms of action may have an additive effect. These data support the potential feasibility of combined, long-term oral vasodilator therapy in selected subgroups of patients with congestive heart failure.

Adult↗
PubMed1983

Association of hyponatremia with increased renin activity in chronic congestive heart failure: impact of diuretic therapy.

A correlation between hyponatremia and increased plasma renin activity (PRA) has been reported in patients with severe congestive heart failure (CHF), implying both clinical and pathophysiologic significance. To determine the impact of diuretic therapy on this relation, we evaluated the correlation of serum sodium, prerenal azotemia (blood urea nitrogen/creatinine ratio [BUN/Cr] ), and PRA in 44 patients with severe CHF who were maintained on diuretic therapy. Serum sodium level was inversely related to PRA (r = -0.389, p less than 0.02). However, a significant correlation also existed between the BUN/Cr ratio and PRA (r = 0.365, p less than 0.025) and an inverse correlation between serum sodium level and the BUN/Cr ratio (r = 0.332, p less than 0.025). Multiple regression analysis of the 3 variables yielded significant interdependence (p less than 0.01). To evaluate the effect of diuretic therapy, 12 patients with severe CHF discontinued diuretic therapy and received, for 1 week each, 10 and 100 mEq sodium diets in balance studies. PRA ranged from 0.14 to 16 ng/ml/h. Despite this range, there was no significant correlation between either serum sodium or BUN/Cr ratio and PRA. It is concluded that the presence of marked hyponatremia and prerenal azotemia in patients with diuretic-treated CHF may suggest increased PRA. However, substantial patient-to-patient variability limits the predictive value of these correlations. Although some clinical value may be derived from such correlations, they should not be used to draw major inferences regarding the severity of CHF or the pathophysiology of water balance in CHF.

Adult↗
PubMed1983

Suppression of the renin-angiotensin system by intravenous digoxin in chronic congestive heart failure.

Recent studies have demonstrated that therapy with digitalis preparations may be of inconsistent benefit in the treatment of chronic congestive heart failure. One explanation may be a varying effect on vasoconstrictor hormones, as digoxin has been shown to suppress plasma renin activity in normal and hypertensive persons. Therefore, the effect of short-term digoxin administration on plasma renin activity and plasma aldosterone in six patients with compensated, severe, chronic congestive heart failure was evaluated. Intravenous administration of digoxin (0.50 mg) resulted in a reduction of plasma renin activity from 4.3 +/- 0.9 to 2.0 +/- 0.9 ng/ml per hour and plasma aldosterone from 34 +/- 16 to 14 +/- 6 ng/dl (both p less than 0.05). Maximal response occurred at three hours after administration, with return to baseline by seven hours. Therefore, evaluation of the role of digitalis in chronic heart failure requires consideration of its direct or indirect effect on angiotensin-mediated vasoconstriction and aldosterone-mediated sodium retention, as well as other neurohormonal mechanisms of vasoconstriction.

Adult↗
PubMed1983

Evaluation of calcium-mediated vasoconstriction in chronic congestive heart failure.

Intercellular vascular smooth muscle calcium results in vasoconstriction and is therefore a potentially adverse mechanism of increased afterload in chronic congestive heart failure. Therefore, an evaluation was made of supine and tilt hemodynamic data, sympathetic reflexes, and the hormonal response to calcium channel antagonism after administration of nifedipine in nine patients with severe chronic congestive heart failure. After a 10 mg oral dose, the peak hemodynamic response occurred at 30 minutes and was characterized primarily by afterload reduction, improvement of systemic flow, and reduction of pulmonary hypertension. Despite reduction of supine blood pressure, there was no orthostatic hypotension during head-up tilt at the same time of peak response. Reflex responses to sympathetic stimulation (cold pressor test) were improved but still attenuated when compared with normal responses. Plasma renin activity increased significantly, but a dissociation of the aldosterone response was observed. Plasma catecholamine levels were not significantly altered. In summary, calcium antagonism resulted in significant afterload reduction and hemodynamic improvement in chronic congestive heart failure. This was associated with improved reflex responsiveness and, potentially, altered other vasoconstrictor hormones independently of the hemodynamic response. Calcium antagonism may provide a means to further understand vasoconstrictor mechanisms in heart failure and enhance therapy in appropriate patient subsets.

Adult↗
PubMed1983

Evaluation of a long-acting converting enzyme inhibitor (enalapril) for the treatment of chronic congestive heart failure.

Converting enzyme inhibition of the renin-angiotensin system has proved a valuable therapeutic approach in patients with severe chronic congestive heart failure. In the present study, a new long-acting converting enzyme inhibitor (enalapril) was evaluated with acute single dose testing (10, 20 or 40 mg) in nine patients with severe chronic congestive heart failure. Four hours after administration, there was a significant reduction of systemic vascular resistance (-19%) and pulmonary wedge pressure (-19%); in addition, there were related increases of cardiac index (+16%) and stroke index (+19%) (probability [p] less than or equal to 0.05 for all changes). This was associated with an increase of plasma renin activity (9 +/- 3 to 35 +/- 11 ng/ml per hour) and a decrease of plasma aldosterone (19 +/- 4 to 9 +/- 2 ng/100 ml) (p less than 0.02 for both). With long-term therapy (1 month), there was improvement of exercise tolerance time and lessening of symptoms based on the New York Heart Association classification. Hemodynamic improvement was maintained in most, but not all, patients. There was no orthostatic hypotension during head-up tilt and hemodynamic values in the upright position were associated with normalization of intracardiac pressures. Long-term converting enzyme inhibition was indicated by a persistent increase of plasma renin activity (16 +/- 2 ng/ml per hour) and a decrease of plasma aldosterone (8 +/- 3 ng/100 ml). In addition, relative angiotensin II receptor occupancy was decreased as judged by the pharmacodynamic response to infusion of the angiotensin II analog saralasin. In conclusion, the long-acting converting enzyme inhibitor, enalapril, was effective in patients with chronic congestive heart failure; however, additional studies will be necessary to further delineate the optimal dose range and identify those patients who are most likely to respond to the drug.

Administration, Oral↗
PubMed1983

Profound bradycardia following release of cardiac tamponade. Hypothesis for reflex control.

A 58-year-old patient with chronic renal failure presented for routine hemodialysis, and was noted to have severe hypotension and findings on examination compatible with cardiac tamponade. The patient had emergency construction of a pericardial window. At the time of surgery, rapid evacuation of the pericardial space resulted in rebound hypertension associated with marked bradycardia. The features of the patient's case were analogous to the cardiovascular and reflex adjustments that normally occur during the Valsalva maneuver. These findings suggest that the cardiovascular changes occurring during the rapid decompression of cardiac tamponade may be reflexly-mediated, and gradually decompression of the pericardial space is therefore recommended to avoid reflex hypertension and bradycardia.

Bradycardia↗
PubMed1983

Converting enzyme inhibition to identify and treat renin-mediated or sodium-volume related forms of increased peripheral resistance in hypertension and in congestive heart failure.

Ten years of experience with three different converting enzyme inhibitors (CEI; teprotide, captopril and enalapril) in over 300 hypertensive patients reveals that CEI act largely to block renin-angiotensin mediated vasoconstriction. Thus, their effectiveness or lack of it is predicted by the baseline plasma renin measurement. Accordingly, responses to these pharmacological agents can be used to identify and quantify renin-mediated vasoconstriction in the spectrum of hypertensive diseases. The converse is also generally true. Patients failing to respond to CEI exhibit low renin values and their increased peripheral resistance appears related to other mechanisms, possibly involving a subtle increase in total body sodium. Thus, low renin states such as low-renin essential hypertension, primary aldosteronism, and anephric man exhibit little or no response to CEI. The relationship between the renin system activity and effectiveness of CEI reflects a specific interference with a particular pathogenic mechanism which is further supported by the fact that two other types of renin system inhibitors (beta-blockers and saralasin) are similarly effective or ineffective according to the operant renin profile also by studies in patients with congestive heart failure without hypertension in whom the same relationships can be demonstrated. Like hypertensives, heart failure patients exhibit a broad spectrum of renin activity values, and their pretreatment renin levels predict the responses to CEI. We have also found that plasma renin values in heart failure are dependent on sodium intake. When salt is administered, renin falls and patients then become unresponsive to CEI.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Captopril pharmacokinetics and the acute hemodynamic and hormonal response in patients with severe chronic congestive heart failure.

Twelve patients with severe chronic congestive heart failure (CHF) underwent simultaneous evaluation of the pharmacokinetic, pharmacodynamic, and neurohumoral actions of a single 25 mg oral dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (CPT). Following drug administration, which raised plasma renin activity (PRA) and thereby indicated significant ACE inhibition, both free (unchanged) and total CPT (including active metabolites) were detectable in the blood with 40 minutes and peak blood levels of the agent were recorded 1 hour after CPT. Total CPT concentration was higher and persisted longer than free CPT, which became virtually nondetectable 8 hours after ingestion. Concomitantly, left ventricular function was markedly augmented by the oral ACE inhibition in all patients, with the magnitude of this improvement being closely related to the baseline PRA. Thus, the overall hemodynamic response to CPT, which rapidly appears in the bloodstream following drug intake in patients with advanced CHF, is a function of the extent of baseline renin-angiotensin-aldosterone activity.

Adult↗
PubMed1982

Use of captopril to estimate renin-angiotensin-aldosterone activity in the pathophysiology of chronic heart failure.

Although the renin-angiotensin-aldosterone system has been implicated in the pathophysiology of chronic heart failure, the factors influencing the extent of renin activity have not been clarified. In the present study, we evaluated 34 patients with severe chronic congestive heart failure in terms of baseline plasma renin activity (PRA). No uniform relationships between PRA and urinary sodium excretion have been established. Although baseline PRA did not correlate with the baseline hemodynamic values, the extent of hemodynamic improvement following acute oral captopril (CPT) therapy (25 mg) was highly correlated with baseline PRA. The onset of action was rapid, so that the initial acute response could be readily assessed and at the same time could be used as a means to estimate baseline renin-angiotension-aldosterone activity. For long-term therapy, however, the response to CPT must be assessed in the context of several potentially simultaneous factors that might either enhance or compromise its effectiveness.

Adult↗
PubMed1982

The effect of captopril on postural hemodynamics and autonomic responses in chronic heart failure.

Both postural abnormalities and autonomic dysfunction have been identified in patients with chronic congestive heart failure (CHF). However, the effect of long-term vasodilator therapy on these phenomena has not been assessed. In this study the hemodynamic and plasma norepinephrine (PNE) responses to upright posture, as well as the cold pressor test and Valsalva's maneuver in 12 patients with severe chronic CHF during both acute and long-term captopril (CPT) therapy, were evaluated. This revealed an absence of the normal hemodynamic adjustments to upright posture and a blunted response of PNE. The heart rate and blood pressure responses to the cold pressor test and Valsalva's maneuver were similarly blunted. The reflex adjustments of systemic resistance during tilt improved with CPT therapy, but the absence of reflex tachycardia in the upright posture persisted. Additionally, there was improvement of the PNE response, and the responses of heart rate and blood pressure to the cold pressor test were virtually normalized during long-term CPT therapy. The abnormal response to the Valsalva maneuver persisted. In conclusion, hemodynamic and reflex-mediated responses to upright posture and the standard assessment of autonomic control mechanisms revealed abnormal patterns in heart failure. While the hemodynamic adjustment to postural changes and sympathetic responsiveness were improved with CPT, complete correction of these abnormalities did not occur. Whether the improvement was a nonspecific vasodilator effect or the result of specific CPT therapy remains to be determined.

Adult↗
PubMed1982

Postural hypotension during tilt with chronic captopril and diuretic therapy of severe congestive heart failure.

The hemodynamic mechanism by which patients with chronic congestive heart failure (CHF) maintain their blood pressure (BP) in the upright posture is distinct from that of normal and hypertensive individuals. There are little data regarding the effects of chronic vasodilator therapy on the mechanisms controlling this response, especially in the presence of diuretic therapy. Therefore, 10 consecutive patients with severe chronic CHF underwent hemodynamic tilt study following acute and chronic captopril therapy. One patient developed orthostatic hypotension following first-dose captopril, but 6 of 10 had a mean BP decrease of 70 +/- 6 to 56 +/- 3 mm Hg on tilt following chronic captopril. This associated with significant reduction of plasma aldosterone, and was abolished on re-tilt following acute saline infusion. Therefore, during chronic captopril therapy of CHF, a reduction of diuretic dosage may be necessary to prevent orthostatic hypotension.

Adult↗
PubMed1982

The contributions of sympathetic tone and the renin-angiotensin system to severe chronic congestive heart failure: response to specific inhibitors (prazosin and captopril).

The contribution of sympathetic tone and the renin-angiotensin system to the pathogenesis of chronic heart failure was evaluated. In 20 paired studies of the same 10 patients, the baseline hemodynamic and humoral correlates of congestive heart failure, and the response to alpha adrenergic blockade (prazosin) and angiotensin converting enzyme inhibition (captopril) were assessed. Despite the extent of failure, baseline plasma renin activity ranged from normal to very high. In contrast, baseline plasma catecholamine levels were always elevated. Baseline plasma norepinephrine reflected the severity of heart failure, correlating inversely with baseline cardiac index before administration of both drugs. Comparable improvement in left ventricular function was noted after acute therapy. Baseline renin and norepinephrine did not predict the response to prazosin, but baseline renin did predict the response to captopril: pulmonary wedge pressure (r=-0.776, p less than 0.01), stroke index (r=0.752, p less than 0.02), systemic vascular resistance (r=-0.673, p less than 0.05). In summary, elevated levels of plasma norepinephrine were inversely correlated with baseline cardiac function but norepinephrine levels did not change despite improved hemodynamics with specific prazosin therapy. The renin-angiotensin system exhibited a wide spectrum of activity and hemodynamic improvement with captopril was related to this activity. Absence of a correlation between plasma norepinephrine and plasma renin activity suggested that their contributions to vasoconstriction were not interdependent. Increased sympathetic tone was consistent in severe heart failure, whereas renin-angiotensin activity differed widely. The response to captopril can be used to identify a subset of patients with severe heart failure and adverse angiotensin-mediated vasoconstriction.

Aged↗
PubMed1982

Sympathetic responsiveness and plasma norepinephrine during therapy of chronic congestive heart failure with captopril.

The interaction of cardiac function and sympathetic tone in severe chronic heart failure was evaluated in 24 patients by assessing the cardiac index/plasma norepinephrine relationship. Potential changes were assessed during first-dose and long-term captopril therapy including sympathetic responsiveness to the gravitational stress of head-up tilt. Because cardiac index and norepinephrine levels demonstrated a significant inverse correlation (r = -0.640, p less than 0.001). Norepinephrine decreased from 803 +/- 116 to 635 +/- 76 pg/ml following first-dose captopril therapy (p less than 0.02), with overall hemodynamic improvement. However significant first-dose correlations were not observed. During long-term therapy, norepinephrine decreased from 694 +/- 118 to 457 +/- 106 pg/ml, associated with improvement of symptoms and exercise tolerance. The extent of cardiac index increase was matched by norepinephrine reduction, so that their correlation was maintained (r = -0.540, p less than 0.02). First-dose and long-term therapy were associated with improved responsiveness of sympathetic tone to the reduction of cardiac index induced by the gravitational stress of tilt. In summary, sympathetic tone was increased in severe heart failure, correlating inversely with cardiac function. Although there was improvement of cardiac function with first-dose captopril therapy, significant correlations of supine improvement with reduction of sympathetic tone were noted primarily with long-term therapy. Responsiveness of sympathetic tone to the stress of tilt however, was evident during first-dose and long-term therapy.

Adult↗
PubMed1982

Captopril kinetics in chronic congestive heart failure.

We investigated the kinetics of 25 mg captopril by mouth in 12 patients with congestive heart failure and correlated them with the hormonal and hemodynamic changes associated with the drug. Observations were made after a single dose (25 mg orally), and after short-term therapy (25 mg t.i.d. for 3 days). Captopril kinetics were as previously reported in normal subjects, with the exception that time to maximum concentration (tmax) to free captopril was slightly higher and the half-life (t1/2) was slightly shorter than in normal subjects. Total captopril t1/2 was longer than normal, suggesting cumulation. Urinary excretion was slower than normal. Differences between captopril kinetics on days 1 and 5 were that the tmax developed somewhat sooner, with a shorter t1/2 on day 5 and total captopril blood levels were higher on day 5 than on day 1. Urinary excretion was greater on day 5 than on day 1. Hemodynamic improvement after a single oral dose of captopril was significant and correlated with baseline plasma renin activity (PRA). The onset of converting-enzyme inhibition, as determined by PRA and hemodynamic improvement correlated with captopril blood levels.

Adult↗