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Biomedical subjects

R J Cody

Publications and source records attributed to R J Cody.

At least 91 records · Page 5Linked to original sources
PubMed1988

Renal responses to atrial natriuretic factor in patients with congestive heart failure.

It is now recognised after many years of speculation regarding the role of mammalian atria in the direct regulation of intravascular volume, that atrial myocites produce a peptide hormone that results in natriuresis and diuresis, under the condition of atrial distention. This atrial natriuretic factor (ANF) is secreted in normal subjects and is increased in patients with congestive heart failure. Atrial natriuretic factor may be administered exogenously and the results of studies performed by our group indicate that natriuresis and diuresis are induced in normal subjects but not in patients with congestive heart failure. These findings, when taken together, suggest that ANF is increased in heart failure patients in response to the atrial distention associated with ventricular dysfunction and intrinsic renal insufficiency. The mechanism for the blunted renal response to atrial natriuretic factor in heart failure patients requires further clarification.

Atrial Natriuretic Factor↗
PubMed1988

Wideband external pulse recording during cuff deflation: a new technique for evaluation of the arterial pressure pulse and measurement of blood pressure.

Analysis of the external brachial pulse recorded during standard blood pressure cuff deflation with use of a transducer with a wide frequency response has revealed a reproducible pattern with three distinct components that we have labeled K1, K2, and K3. K1 is a low-amplitude, low-frequency signal that is present with cuff pressures above systolic pressure. K2 is a triphasic signal appearing at systolic pressure and disappearing at diastolic pressure, which approximately corresponds to the audible Korotkoff sound. K3 appears with cuff pressure between systolic and diastolic pressure and continues to be present below diastolic pressure. Intra-arterial pressure recordings made with a high-fidelity Millar catheter-tip manometer revealed K2 and K3 analogs. K3 resembles the intra-arterial pressure waveform and when calibrated according to the pulse pressure, noninvasive dK3/dt determinations correlated well with intra-arterial dP/dt measurements. The appearance/disappearance property of K2 was designated as the "K2 algorithm" and represents a new, objective noninvasive method for measurement of blood pressure. The K2 algorithm compares favorably with intra-arterial measurements, is more accurate than the auscultatory technique, and may be especially useful in clinical situations in which the auscultatory technique does not work well.

Adolescent↗
PubMed1987

Identification of normal neurohormonal activity in mild congestive heart failure and stimulating effect of upright posture and diuretics.

To characterize further the pathophysiology of the neurohormonal vasoconstrictor pathways in congestive heart failure (CHF), plasma renin activity, plasma norepinephrine, blood pressure, blood volume and renal hemodynamics were measured in 12 patients with mild to moderate CHF. In addition, the response to the gravitational stress of head-up tilt and the influence of 3 weeks of furosemide treatment as stimuli of neurohormonal activity were assessed. Supine plasma renin activity before diuretics was relatively normal at 1.94 +/- 1.6 ng/ml/hr and was significantly increased to 3.9 +/- 2.7 ng/ml/hr after diuretics. During tilt, there was a significant reflex increase in plasma renin activity both before and after diuretics. Plasma norepinephrine was also relatively normal before diuretics (325 +/- 211 pg/ml), did not increase after diuretics, but showed significant increases during tilt both before and after diuretics. Diuretic administration led to decreases in both systolic and diastolic blood pressures, but there was no change in body weight or total blood volume. In addition, diuretic administration did not result in any significant changes of renal blood flow (546 +/- 119 to 634 +/- 204 ml/min/1.73m2), glomerular filtration rate (81 +/- 22 to 90 +/- 27 ml/min/1.73m2) or filtration fraction (0.26 to 0.25). The present study demonstrates that the renin-angiotensin system and the sympathetic nervous system were not activated in the early symptomatic stages of CHF and that baroreceptor stimulation of these pathways during head-up tilt was relatively preserved. Renin secretion increased during diuretic administration, suggesting that the macula densa signal for renin release was also preserved in patients with relatively mild CHF.

Aged↗
PubMed1987

Use of invasive ergometric exercise to assess the hemodynamic response to nicardipine.

The calcium antagonists are potent vasodilators. This physiologic property suggests that these agents have a potential role in the treatment of patients with hypertension and congestive heart failure. Although the clinical response to calcium antagonism in hypertension is promising, the response in patients with congestive heart failure is less than hoped for; this is due to the fact that this class of agents may induce a hemodynamically important degree of negative inotropic effect. To test the hemodynamic response to nicardipine, a second-generation dihydropyridine, the hemodynamic response to maximal ergometric exercise was evaluated in a group of patients with moderate to severe chronic congestive heart failure. One week of nicardipine therapy was associated with a significant reversal of vasoconstriction at rest and during peak exercise with a secondary increase of cardiac index, and a decrease in pulmonary wedge pressure. The reversal of vasoconstriction was associated with a decrease in mean arterial pressure, with no change in the heart rate. There was no change in oxygen consumption or carbon dioxide production; however, there was a decrease in arteriovenous oxygen difference, consistent with a reduction of oxygen extraction. This short-term study identified the potent vasodilator properties of nicardipine in patients with chronic congestive heart failure; a hemodynamically significant negative inotropic effect could not be identified. Although the use of calcium antagonists for the treatment of congestive heart failure may have a limited role, this study nonetheless suggests that nicardipine may have a favorable vasodilator effect without an overt negative inotropic effect. This would be of considerable advantage in the treatment of hypertension, when compared with beta-adrenergic blocking agents.

Adult↗
PubMed1987

Systemic and pulmonary hemodynamic responses to nicardipine during graded ergometric exercise in patients with moderate to severe essential hypertension.

In 10 patients with moderate to severe hypertension, the hemodynamic effects of ergometric exercise and nicardipine, a dihydropyridine calcium channel antagonist, were characterized under basal conditions and after 1 week of therapy. The responses of plasma renin activity and catecholamines were also assessed. Nicardipine induced significant reductions of systolic, diastolic and mean blood pressure under conditions of rest and peak exercise (p less than 0.001), mediated by reversal of vasoconstriction (p less than 0.001). Overall, cardiac index and stroke volume index responses were not significantly altered by nicardipine. Although rest pulmonary wedge pressure was unchanged (6 +/- 3 to 5 +/- 4 mm Hg), peak exercise pulmonary wedge pressure decreased from 24 +/- 22 to 7 +/- 5 mm Hg (p less than 0.001) with nicardipine therapy. This effect of nicardipine on pulmonary wedge pressure was present across all work loads studied, and was accompanied by reduction of peak exercise pulmonary artery pressure from 43 +/- 10 to 25 +/- 7 mm Hg (p less than 0.001). Oxygen consumption was unchanged, associated with reduction of arteriovenous oxygen difference (p less than 0.02). Both plasma renin activity (p less than 0.05) and norepinephrine (p less than 0.005) were significantly increased with nicardipine therapy. Thus, nicardipine produced significant blood pressure reduction by reversal of vasoconstriction in patients with essential hypertension. The preservation of cardiac output, with markedly reduced pulmonary wedge pressure, indicated that nicardipine improved ventricular performance in response to reversal of vasoconstriction.

Adult↗
PubMed1987

Influence of baseline hemodynamic status and sympathetic activity on the response to nicardipine, a new dihydropyridine, in patients with hypertension or chronic congestive heart failure.

We evaluated the immediate hemodynamic response to nicardipine, administered as an intravenous bolus and 30-minute sustaining infusion, in 10 patients with systemic hypertension (HTN) and 10 patients with chronic congestive heart failure (CHF). Baseline systemic vascular resistance and the response to nicardipine for HTN (1968 +/- 657 to 905 +/- 256 dynes X sec X cm-5) and CHF (2002 +/- 988 to 1089 +/- 216 +/- 99 dynes X sec X cm-5) were virtually identical (P less than 0.01). In both groups there was a significant increase of cardiac index in response to afterload reduction: HTN, 2.70 +/- 0.46 to 4.47 +/- 1.01; CHF, 1.90 +/- 0.33 to 2.88 +/- 0.80 L/min/m2 (P less than 0.01), so that a negative inotropic effect was not evident. In HTN the increase in cardiac index was primarily the result of reflex increase of heart rate (67 +/- 16 to 95 +/- 25 bpm [P less than 0.05]), associated with norepinephrine increase from 402 +/- 243 to 744 +/- 364 pg/ml (P less than 0.001). In CHF the cardiac index increase was caused by a stroke volume index increase (23 +/- 4 to 33 +/- 9 ml/min; P less than 0.01), with no significant change in heart rate or norepinephrine. Thus nicardipine, by means of calcium channel antagonism, induced reversal of vasoconstriction. Differences in the cardiac response identify the importance of characterizing the pathophysiologic status of cardiac impairment to more accurately interpret pharmacologic interventions.

Adult↗
PubMed1987

Relation of renin-angiotensin system activity to left ventricular hypertrophy and function in experimental and human hypertension.

This article examines available data concerning the hypothesis that the renin-angiotensin system directly stimulates cardiac hypertrophy and dysfunction in hypertension. Several experiments support a direct effect of angiotensin on myocardial protein synthesis and suggest that this may be independent of adrenergic influences. However, the role played by the renin system in the pathogenesis of hypertensive cardiac hypertrophy may be small, for left ventricular (LV) muscle mass is not systematically greater in high-renin as opposed to low-renin forms of experimental or human hypertension. In animal studies, regression of LV hypertrophy is more consistently observed in response to drugs that inhibit as opposed to those that stimulate renin-angiotensin system activity (i.e., converting enzyme inhibitors or beta-adrenoceptor blockers vs. diuretics or direct vasodilators), although the difference is more quantitative than absolute. Similarly, significant reductions in LV mass occurred in 13 of 16 human trials with converting enzyme inhibitors or beta blockers as opposed to 2 of 10 trials with diuretics or vasodilators (mean = 7.11; p less than 0.01). However, uncertainties regarding the degree of reduction in angiotensin II and adrenergic effects, possible interactions between these systems, and incomplete characterization of induced changes in hemodynamic load on the heart all limit the interpretation of available studies. Preliminary data suggest that an inverse relation exists between renin-angiotensin system activity and LV systolic performance in primary and secondary human hypertension, a possibility that merits further study.

Angiotensin II↗
PubMed1987

Liver function abnormalities in chronic heart failure. Influence of systemic hemodynamics.

To characterize the incidence and severity of liver function abnormalities in patients with congestive heart failure, we analyzed systemic hemodynamics and biochemical profiles in 133 patients with stable chronic congestive heart failure, secondary to a dilated cardiomyopathy. The patients were divided into three groups, based on the severity of the reduction in cardiac index (CI). The mean values of all liver function tests in groups 1 (n = 43; CI greater than or equal to 2.0 L/min/m2) and 2 (n = 48; CI greater than 1.5 and less than 2.0 L/min/m2) were essentially normal, except for minimally elevated alkaline phosphatase levels and slightly decreased albumin levels in both groups, and slight increases in levels of gamma-glutamyl transpeptidase and total bilirubin in group 2. In contrast, group 3 patients (n = 42; CI less than or equal to 1.5 L/min/m2) had the most severe heart failure, as assessed by the lowest CI and highest cardiac filling pressures, and significantly higher levels of aspartate aminotransferase (65 +/- 82 U/L), alanine aminotransferase (77 +/- 102 U/L), lactate dehydrogenase (282 +/- 91 U/L), and total bilirubin (29 +/- 14 mumol/L [1.7 +/- 0.8 mg/dL]). The percentage of patients in group 3 with these abnormalities ranged between 27% and 80%. Although linear regression analysis showed that the elevations in right atrial and pulmonary wedge pressures, and the decreases in CI, were significantly correlated with liver function abnormalities, the correlation coefficients were small. Thus, liver function abnormalities remain common in patients with congestive heart failure but are generally small in magnitude and not associated with clinically apparent hepatic disease. It is likely that reduced forward flow and passive backward congestion are both contributing factors in the pathogenesis of these biochemical abnormalities, although nonhemodynamic factors may also be important.

Adult↗
PubMed1987

The hemodynamics of calcium-channel antagonists in hypertension: vascular and myocardial responses.

Hemodynamic studies have indicated that the mechanism of the antihypertensive effect of calcium-channel antagonists is reduction of systemic vascular resistance. However, potential negative inotropic effects could have an adverse effect on myocardial performance. In this study, we evaluated the hemodynamic response to the prototypic calcium-channel antagonist, verapamil, in patients with moderate-to-severe hypertension. We gave incremental infusions of verapamil in subsystemic doses into the brachial artery of an isolated forearm preparation. The response to 10 micrograms/min/100 ml revealed a reduction in forearm vascular resistance from 55 to 21 units and an increase in forearm blood flow from 3.57 to 7.54 ml/min/100 ml (both p less than .01). Intravenous administration of verapamil as a bolus (0.15 mg/kg) and continuous infusion (1 or 2 mg/min) resulted in a significant decrease in mean arterial pressure and systemic vascular resistance as well as a significant increase in cardiac index and stroke volume index. This occurred without a significant increase in pulmonary wedge pressure. One week of oral therapy resulted in a significant reduction of mean arterial pressure and systemic vascular resistance both at rest and at peak exercise, associated with a significant increase in stroke volume index and no increase in pulmonary wedge pressure. These findings document the direct vasodilator effects of the prototypic calcium-channel antagonist verapamil in patients with moderate-to-severe hypertension. In addition, these data show that myocardial performance can improve during therapy, when myocardial reserve is sufficient, and the adverse effects of systemic vasoconstriction are reversed by therapy.

Adult↗
PubMed1986

Effect of nicardipine on rest and exercise hemodynamics in chronic congestive heart failure.

The hemodynamic response to vasodilation induced by the new calcium channel antagonist nicardipine was studied in 10 patients with severe, chronic congestive heart failure. Rest and exercise hemodynamics were evaluated in the baseline state and after 1 week of oral nicardipine therapy (30 mg 3 times daily). In addition, respiratory gas exchange and arteriovenous oxygen difference were measured to assess changes in oxygen utilization. The responses of the sympathetic nervous system were evaluated by measuring plasma norepinephrine concentrations at rest and during maximal exercise. At rest, nicardipine administration was associated with significant reductions in mean systemic arterial pressure, systemic vascular resistance, pulmonary artery wedge pressure and pulmonary arterial pressure, and significant increases in cardiac index and stroke volume index. These effects were maintained during exercise. In contrast to findings with other calcium channel antagonists, no negative inotropic effect of nicardipine was identified. Nicardipine administration was associated with reduction of arteriovenous oxygen difference. Nicardipine had no effect on plasma norepinephrine concentrations, suggesting absence of reflex sympathetic nervous activation. Thus, nicardipine-mediated vasodilation leads to significant improvements in both rest and exercise cardiac performance.

Adult↗
PubMed1986

Adverse influence of baroreceptor dysfunction on upright exercise in congestive heart failure.

To test the hypothesis that baroreceptor autoregulation is an important determinant of exercise performance, the hemodynamic responses to the gravitational stress of head-up tilt and upright exercise were assessed in 41 patients with severe chronic congestive heart failure. Three patterns of autonomic dysfunction during head-up tilt were identified. Group A patients had near-normal circulatory reflexes whereas Group B patients experienced orthostatic hypotension and Group C patients lacked the afferent stimulus of venous pooling. Group A patients had a significantly longer exercise duration than both Groups B and C (607 +/- 104 versus 330 +/- 86 and 365 +/- 53 seconds, respectively, p less than 0.05) and a significantly higher double product at peak exercise (17,779 +/- 956 versus 12,235 +/- 869 and 13,760 +/- 998, respectively, p less than 0.05). Thus, baroreceptor abnormalities in the autoregulatory response to postural change are important determinants of the cardiovascular responses required during exercise and influence exercise performance. These abnormalities may help clarify the discrepancies between supine and upright exercise performance and may influence the long-term efficacy of vasodilator therapy in chronic congestive heart failure.

Adult↗
PubMed1986

Regional blood flow and neurohormonal responses to milrinone in congestive heart failure.

We measured systemic hemodynamics, regional blood flow, and neurohormonal parameters in 13 patients with severe chronic congestive heart failure before and after 1 month of therapy with oral milrinone, a bipyridine cardiotonic agent. After milrinone there were significant reductions in pulmonary wedge pressure (27 +/- 2 to 19 +/- 3 mm Hg; P less than 0.02) and systemic vascular resistance (1866 +/- 152 to 1393 +/- 93 dyne X sec/cm5; P less than 0.05) that were associated with increases in cardiac index (1.85 +/- 0.15 to 2.47 +/- 0.20 L/min/m2; P less than 0.02). There was a marked improvement in forearm blood flow (1.98 +/- 0.14 to 3.02 +/- 0.16 ml/min/dl; P less than 0.01) and a reduction in forearm vascular resistance (45 +/- 3 to 30 +/- 3 U; P less than 0.01). Overall there was no significant change in renal blow flow, renal vascular resistance, or glomerular filtration rate. However, there was a heterogeneous response of renal blood flow and glomerular filtration rate, such that both were directly correlated with the magnitude of increase of cardiac index (r = 0.587 [P less than 0.05] and r = 0.721 [P less than 0.01], respectively). After milrinone there were no significant overall or subgroup changes in urinary sodium excretion, blood volume, plasma renin activity, urinary aldosterone levels, plasma or platelet vasopressin levels, or plasma norepinephrine levels. Thus 1 month of therapy with milrinone improves systemic and forearm hemodynamics, but its effects on renal blood flow and function were heterogeneous. These heterogeneous effects on regional blood flow may depend on the relative vasodilator and inotropic effects of milrinone.

Aged↗
PubMed1986

Conceptual and therapeutic approaches to inhibition of the renin-angiotensin system in chronic heart failure.

The renin-angiotensin system is activated in the majority of patients with chronic congestive heart failure. This may be part of the pathophysiology of the disease, a secondary phenomenon, or the result of intense diuretic therapy. Irrespective of the mechanism of renin-angiotensin activation, converting enzyme inhibitors are an effective form of therapy as well as a means to evaluate pathophysiologic mechanisms of congestive heart failure. Because of the activation of the renin-angiotensin system, angiotensin-mediated vasoconstriction and aldosterone-mediated sodium retention can be suppressed and, in some individuals, completely blocked by converting enzyme inhibitors. Improved forward cardiac flow and reduction of pulmonary congestion occur with reversal of vasoconstriction, so that relief of edema, due to enhanced sodium and water excretion, will occur. While it is easy to identify a close correlation between markers of renin-angiotensin activity and the initial response to converting enzyme inhibitors, it is more difficult to identify this response long-term. This may be due to changes in dietary sodium intake, intensity of diuretic therapy, or alteration in renal blood flow and function. Clinically, however, the response to converting enzyme inhibitors is favorable in the majority of people.

Angiotensin II↗
PubMed1986

The renin system and atrial natriuretic hormone in congestive heart failure.

The renin angiotensin system is activated in the majority of patients with chronic congestive heart failure of moderate to severe symptomatology. Renin release may result from one of several different stimuli: renal tubular sodium delivery and sensing by the macula densa, sympathetic nervous system activity, and baroreceptor to changes in renal blood flow. Difficulties arise with an analysis of renin angiotensin system activity due to the necessity for diuretic therapy in the majority of these patients. Despite the presence of diuretic therapy, however, there is a wide range of renin angiotensin system activity. In evaluating this activity the administration of a converting enzyme inhibitor will block the contribution of angiotensin mediated vasoconstriction, thereby confirming the importance of the renin angiotensin system activity as a mediator of the long-term consequences of heart failure. In situations of low plasma renin activity, vasoconstriction is mediated by an alternate mechanism. The mechanisms of this non-renin mediated vasoconstriction are less apparent, but may include calcium mediated vasoconstriction, and the effects of increased cytosolic content. This low renin group of patients appear to be very sensitive to reversal of vasoconstriction by calcium channel antagonists, especially when converting enzyme inhibitors are ineffective. In an analysis of the factors that may result in renin release, tubular delivery of sodium to the macula densa may emerge as the most important regulator of renin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗