Search PubMed⌕ Search

Biomedical subjects

S R Goldsmith

Publications and source records attributed to S R Goldsmith.

At least 55 records · Page 3Linked to original sources
PubMed1988

Updated use of digitalis and nitrates in the elderly.

Myocardial ischemia may be produced by a wide variety of pathophysiologic scenarios. Currently, long-acting nitrates, beta blockers, and calcium blocking drugs are available to treat ischemia. Each class of therapy poses potential problems for the elderly, and therapy must be individualized. Long-acting nitrates are probably not the best choice of monotherapy since tolerance develops to their use over time. Congestive heart failure, a common sequela to myocardial infarction, is currently best treated by diuretics and vasodilating drugs. These therapies are generally well-tolerated by the elderly. Digitalis, which is not easily given to the elderly due to potential toxicity, is probably best avoided in this patient group unless needed to treat arrhythmia. Careful differential diagnosis of congestive heart failure is a critical pre-condition to starting any therapy for heart failure, particularly in the elderly patient.

Adrenergic beta-Antagonists↗
PubMed1987

Treatment of congestive heart failure. Pathophysiologic and pharmacologic concepts.

Congestive heart failure is a serious health problem in Western society. Understanding of both the basic pathophysiology and the design of rational and effective treatment of this syndrome has increased dramatically in the last ten years. However, congestive heart failure remains a highly lethal disease, which kills at a rate exceeding that of most cancers. Prevention is therefore of the utmost importance and has to come primarily from a reduction in the incidence and damage done from myocardial infarction. Improved understanding of the pathophysiology of idiopathic dilated cardiomyopathy is also needed. Through understanding of pathophysiologic principles, effective therapy based on interference with known mechanisms that are operative in the disease is now available but can be refined in the future.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Nonosmotic influences on osmotic stimulation of vasopressin in humans.

To study the influence of cardiopulmonary baroreceptor loading and unloading on the osmotic stimulation of arginine vasopressin (AVP) in normal humans, we gave 105-min 5% saline infusions (0.06 ml X kg-1 X min-1) to three groups of subjects under different cardiopulmonary baroreceptor loading conditions. Group A received only the infusion, with a consequent increase in central venous pressure (CVP) of 2.6 +/- 1.7 mmHg; group B had CVP held constant by continuous lower body negative pressure; and group C had CVP decreased by -3.3 +/- 1.4 mmHg, also with lower body negative pressure, for the duration of the infusion. Mean arterial pressure increased in group A by 6.6 +/- 3.7 mmHg, but did not change in groups B and C. On average, osmolality increased by the same amount in each of the three groups (11.6 +/- 3.3, 13.7 +/- 3.2, and 10.9 +/- 2.5 mosmol/kg, P = NS). The changes in AVP in the three groups were 3.6 +/- 2.0, 2.7 +/- 1.9, and 6.2 +/- 3.5 pg/ml, P less than 0.03, with group C different from group B and groups A and B not different by individual pairs testing. An independent effect of prolonged CVP reduction on AVP levels in group C was made unlikely by studies in four additional subjects in whom AVP did not change at constant osmolality during 105 min of CVP reduction comparable with that in group C. Thus modest loading of both cardiopulmonary and sinoaortic baroreceptors does not alter the osmotic stimulation of AVP in normal humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Arginine vasopressin and the renal response to water loading in congestive heart failure.

Previous studies have shown on the basis of isolated comparisons that plasma arginine vasopressin (AVP) levels are inappropriately increased for a given serum osmolality in patients with CHF. To explore further the osmoregulation of AVP in this condition, the response of plasma AVP to a 15- to 20-ml/kg oral water load was compared in 26 patients with CHF and 14 normal subjects. In the normal subjects, serum osmolality decreased from 289 +/- 5.0 to 282 +/- 5.0 mOsm/kg (p less than 0.001) and AVP from 3.6 +/- 1.1 to 2.1 +/- 0.78 pg/ml (p less than 0.001). In the patients with CHF, osmolality decreased from 289 +/- 7.0 to to 281 +/- 7.0 mOsm/kg and AVP from 7.1 +/- 3.6 to 5.8 +/- 3.4 pg/ml (p less than 0.001). As a percentage of the control value, the decrease in AVP was much greater in the normal group, 41 +/- 15% vs 18 +/- 10% (p less than 0.001). Urinary osmolality levels were measured before and after water loading in 11 patients and in 7 normal subjects. Normal subjects diluted from 812 +/- 130 to 133 +/- 26 mOsm/kg (p less than 0.001) and CHF patients from 599 +/- 218 to 253 +/- 170 mOsm/kg, a statistically significant (p less than 0.01) but smaller (p less than 0.05) level of suppression. There were, however, 2 distinct groups within the CHF population: one in which urine osmolality was appropriately decreased (from 594 +/- 269 to 144 +/- 37 mOsm/kg, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Hemodynamic effects of infused arginine vasopressin in congestive heart failure.

The hemodynamic effects of exogenously administered arginine vasopressin were assessed in 11 patients with chronic congestive heart failure. Infusion rates of 0.1 to 0.8 pmol/kg per min increased plasma arginine vasopressin from 6.5 +/- 2.7 (SD) pg/ml at control to 63 +/- 39 pg/ml at the highest infusion rate. There were progressive decreases in cardiac output and stroke volume, with increases in systemic vascular resistance and pulmonary capillary wedge pressure, but only minimal changes in heart rate and blood pressure. Changes in cardiac output, stroke volume and systemic resistance were evident from the first infusion rate, which increased plasma arginine vasopressin from 6.5 +/- 2.7 to 9.9 +/- 4.6 pg/ml. A paired analysis of baseline hemodynamic data with those measured during infusions producing an arginine vasopressin level averaging 15 +/- 2.6 pg/ml yielded the following changes: cardiac output decreased from 4.6 +/- 1.2 to 4.2 +/- 0.96 liters/min (p less than 0.01), stroke volume decreased from 60 +/- 19 to 54 +/- 16 ml (p less than 0.005) and systemic vascular resistance increased from 1,329 +/- 396 to 1,443 +/- 395 dynes X s X cm-5 (p = 0.01). Thus, small increases in circulating arginine vasopressin cause modest but significant adverse circulatory effects in patients with congestive heart failure. A fall in cardiac output, probably as a result of increased afterload, is seen at levels of arginine vasopressin within the basal range found in congestive heart failure. These data demonstrate that circulating arginine vasopressin in physiologic concentrations is capable of influencing hemodynamics in patients with congestive heart failure and suggest that therapy for this condition directed at inhibition of the vascular effect of arginine vasopressin may be potentially useful.

Adult↗
PubMed1985

Response of plasma vasopressin to ethanol in congestive heart failure.

Plasma arginine vasopressin (AVP) levels are frequently increased in patients with congestive heart failure (CHF). Further, AVP does not respond normally to certain osmotic and nonosmotic manipulations in this condition. As a test of the central suppressibility of AVP in CHF, an oral ethanol challenge was given (0.7 ml/kg body weight) to 10 patients with CHF and 10 normal control subjects, and the response of AVP, osmolality, heart rate and blood pressure was measured over the next 2 hours. In the CHF group, AVP was 9.6 +/- 3.9 pg/ml (+/- standard deviation) at control and remained unchanged throughout the protocol. In the normal group, AVP was 6.9 +/- 2.9 pg/ml at control and declined significantly to 4.9 +/- 2.0 pg/ml at 20 minutes (p less than 0.05). Osmolality and blood ethanol changes were similar in the 2 groups, as were those in mean arterial pressure. The administration of ethanol therefore did not result in an acute decrease in plasma AVP in patients with CHF, but did so in normal subjects. Differences in the response of blood pressure and osmolality do not explain the abnormality; hence, a defect in the central control of AVP release may exist in CHF. This observation may have implications for the mechanisms involved in the generation or maintenance of elevated AVP levels in patients with this disease.

Arginine Vasopressin↗
PubMed1985

Relative attenuation of sympathetic drive during exercise in patients with congestive heart failure.

Patients with congestive heart failure have been considered to have augmented sympathetic drive both at rest and during dynamic exercise. The augmentation observed during exercise may be related to the state of near exhaustion experienced by patients with heart failure at relatively low work loads. To compare the response of the sympathetic nervous system to exercise in normal subjects and patients with heart failure when they are working in a comparable physiologic frame of reference, the data for both groups can be expressed as percent peak oxygen consumption achieved (percent peak VO2) rather than as a function of absolute oxygen consumption (VO2). Ten healthy control subjects and 31 patients with chronic clinical class II and III heart failure were studied during upright maximal bicycle exercise. Eighteen of the 31 patients had primary cardiomyopathy and 13 had ischemic cardiomyopathy. The average ejection fraction at rest was 24 +/- 10% (+/- SD) in the group with heart failure. Heart rate, systolic blood pressure, VO2 and plasma norepinephrine levels were measured at rest and throughout exercise. When the data were expressed as a function of percent peak VO2 achieved, patients with heart failure demonstrated a flatter slope (p = 0.004) than normal in the response of plasma norepinephrine to exercise, indicating a relative blunting of sympathetic drive. This was accompanied by attenuated heart rate (p = 0.001) and blood pressure (p less than 0.001) responses. These differences were not apparent when the data are expressed as a function of absolute VO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Reflex control of osmotically stimulated vasopressin in normal humans.

Previous studies have shown that in normal humans plasma arginine vasopressin (AVP) does not increase in response to unloading of cardiopulmonary and sinoaortic baroreceptors produced by lower body negative pressure (LBNP) unless hypotension occurs. To assess whether prior osmotic stimulation of AVP might bring out latent sensitivity to nonosmotic control mechanisms in humans we studied the response of plasma AVP to graded LBNP after a 105-min infusion of 5% saline in a group of eight normal individuals. During the infusion and before LBNP, serum osmolality increased from 288 +/- 9 to 300 +/- 10 mosmol/kg, and plasma AVP increased from 4.4 +/- 1.7 to 8.0 +/- 2.5 pg/ml. Neither osmolality nor AVP changed significantly during two stages of LBNP that first reduced central venous pressure alone and then reduced central venous pressure with accompanying tachycardia and narrowing of the pulse pressure. Time control studies performed in five individuals subjected to central venous catheterization and an identical hypertonic saline infusion failed to show significant spontaneous changes in AVP during a comparable interval after the infusions but without LBNP. Thus osmotic stimulation with hypertonic saline did not render AVP more sensitive to nonhypotensive unloading of cardiopulmonary and sinoaortic baroreceptors in normal humans.

Arginine Vasopressin↗
PubMed1985

Effect of head-down tilt on basal plasma norepinephrine and renin activity in humans.

The effects of loading cardiopulmonary baroreceptors on basal norepinephrine and renin activity were studied in six normal subjects. Loading of cardiopulmonary baroreceptors was accomplished by a 60-min 30 degrees head-down tilt with small supplemental saline infusions. Central venous pressure was measured continuously by intrathoracic catheter; arterial pressure was measured indirectly by cuff. During the tilt, central venous pressure increased from 5.1 +/- 1.3 to 8.9 +/- 1.7 mmHg (P less than 0.001), whereas arterial pressure was unchanged. Plasma norepinephrine (185 +/- 85 pg/ml) and plasma renin activity (3.9 +/- 5.7 ng . ml-1 . h-1) did not change. Moderate sustained loading of cardiopulmonary baroreceptors is therefore without effect on unstressed plasma norepinephrine and renin activity in normal humans, suggesting that the tonic inhibitory effects of these receptors on these neurohumoral control systems are not readily increased in the basal state.

Adult↗
PubMed1985

Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis.

Hemodynamic and neurohumoral responses to acute diuretic therapy were measured in 15 patients with severe chronic heart failure given intravenous furosemide, 1.3 +/- 0.6 (SD) mg/kg body weight. Left ventricular pump function deteriorated by 20 minutes, as indicated by a fall in stroke volume index (27 +/- 8 to 24 +/- 7 mL/min X m2 body surface area, p less than 0.01) and an increase in left ventricular filling pressure (28 +/- 7 to 33 +/- 9 mm Hg, p less than 0.01). Increases occurred in heart rate (87 +/- 13 to 91 +/- 16 beats/min, p less than 0.01), mean arterial pressure (90 +/- 15 to 96 +/- 15 mm Hg, p less than 0.01), systemic vascular resistance (1454 +/- 394 to 1676 +/- 415 dynes X s X cm-5, p less than 0.01), plasma renin activity (9.9 +/- 8.5 to 17.8 +/- 16 ng/mL X h, p less than 0.05), plasma norepinephrine level (667 +/- 390 to 839 +/- 368 pg/mL, p less than 0.01), and plasma arginine vasopressin level (6.2 +/- 1.3 to 8.3 +/- 2.0 pg/mL, p less than 0.01). During the next 3.5 hours the patients had diuresis (2085 +/- 1035 mL) and the expected fall in filling pressure (28 +/- 7 to 22 +/- 10 mm Hg, p less than 0.01). Neurohumoral indicators also returned toward the control levels. Intravenous furosemide, in patients with severe chronic heart failure, is associated with acute pump dysfunction temporally related to activation of the neurohumoral axis.

Adult↗
PubMed1984

Effect of increased intracardiac and arterial pressure on plasma vasopressin in humans.

The effects of loading cardiopulmonary and sinoaortic baroreceptors on plasma arginine vasopressin (AVP) levels were examined in 18 healthy young adults after a mild water restriction. Cardiopulmonary receptors were acutely loaded by volume expansion which increased central venous pressure (CVP) from 4.7 +/- 1.9 to 7.3 +/- 2.2 mmHg but did not change mean arterial blood pressure (MAP). Both receptor groups were acutely loaded by applications of lower body positive pressure, which induced a comparable increase in CVP and, in addition, raised MAP from 85 +/- 6.7 to 93 +/- 6.8 mmHg (P less than 0.001). There was evidence of reflex activation as forearm blood flow and heart rate increased during volume expansion while the increase in heart rate was blocked during lower body positive pressure. Neither intervention significantly altered the control AVP level of 4.6 +/- 1.4 pg/ml. An investigation of more prolonged stimulation of cardiopulmonary receptors was carried out using 1 h of head-down tilt. Again, despite increases in CVP (5.1 +/- 1.3 to 9.0 +/- 1.4 mmHg, P less than 0.005), AVP (5.7 +/- 2.4 pg/ml) did not decrease. MAP did not change during head-down tilt. There were no changes in osmolality throughout any of the studies. AVP levels in humans are therefore not responsive to moderate isosmotic loading of the cardiopulmonary and sinoaortic baroreceptors under conditions of mild water restriction.

Adult↗
PubMed1984

The neurohumoral axis in congestive heart failure.

The incidence of congestive heart failure is increasing in the United States. This common syndrome is characterized not only by impaired ventricular function but also by an increase in some endogenous vasoconstrictor substances, including norepinephrine, angiotensin II, and arginine vasopressin. Although activation of the systems that release these substances is presumed to be compensatory (to maintain perfusion pressure during inadequate flow), the sympathetic nervous system, renin-angiotensin-aldosterone system, and arginine vasopressin may contribute to the pathogenesis of the syndrome. The excessive vasoconstriction present in heart failure likely produces a further burden on the failing myocardium. New strategies in therapy are being developed to counteract the activation of vasoconstrictor forces in congestive heart failure. Data indicate that selective blockade of the renin-angiotensin system is useful. Preliminary data suggest that inhibition of the sympathetic nervous system may be helpful, and inhibition of vasopressin in animals with heart failure is being studied. New and more selective therapy for heart failure may come from these studies.

Animals↗
PubMed1984

Free and conjugated plasma catecholamines in patients with congestive heart failure.

Conjugation is an important mechanism in the deactivation process of circulating catecholamines, because most of the circulating catecholamines are found in the conjugated rather than the free form. To determine whether a defect in conjugation might account for some of the elevated free plasma norepinephrine in patients with CHF, we measured free and conjugated circulating catecholamines in 12 patients with chronic CHF. These measurements were also obtained in eight age-matched control subjects without clinical heart disease. The data demonstrate that the free plasma norepinephrine in patients with heart failure (566 +/- 227 (SD) pg/ml) is significantly greater than the free plasma norepinephrine in normal age-matched control subjects (337 +/- 148 pg/ml, p less than 0.05). The amount of free circulating epinephrine in the patients with heart failure (51 +/- 25 pg/ml) is similar to that in the control population (46 +/- 50 pg/ml), whereas the free circulating dopamine content is greater in the heart failure population (36 +/- 21 pg/ml) compared with normal (17 +/- 15 pg/ml, p less than 0.05). Although the absolute conjugated catecholamines are also increased in patients with heart failure, the percent conjugation of norepinephrine in heart failure (73%) did not vary from control values (71%). The percent conjugation of epinephrine in the group with heart failure (81%) was similar to that in the control group (76%), as was the percent conjugation of dopamine in the two groups (99%). Therefore, it is unlikely that a defect in conjugation of catecholamines is contributing to the excessive free plasma norepinephrine found in patients with congestive heart failure.

Adult↗
PubMed1983

The acute response of plasma norepinephrine, renin activity, and arginine vasopressin to short-term nitroprusside and nitroprusside withdrawal in patients with congestive heart failure.

Activation of the sympathetic nervous system, manifested by an increase in heart rate and circulating plasma norepinephrine, can occur in normal subjects when they are given vasodilators. The extent to which this activation occurs in patients with congestive heart failure (CHF) and whether this activation could account for the hemodynamic rebound sometimes observed following abrupt withdrawal of nitroprusside in such patients are unclear. We prospectively and retrospectively studied the effects of nitroprusside on plasma norepinephrine in 38 patients with CHF to determine if acute vasodilator therapy activates this vasoconstrictor system during or following such treatment. Thirty-six of these patients also had plasma renin activity (PRA) measured and plasma arginine vasopressin was measured in 12 patients. Baseline supine plasma norepinephrine (714 +/- 72 pg/ml, +/- SEM), PRA (15 +/- 2 ng/ml/hr), and arginine vasopressin (10 +/- 1 pg/ml) were increased at least twofold in the CHF patients. Nitroprusside (96 +/- 11 micrograms/min) was infused for 63 +/- 5 minutes after achieving an optimal hemodynamic response: cardiac index increased (2.01 +/- 0.08 to 2.67 +/- 0.1 L/min/m2, p less than 0.001), pulmonary artery wedge pressure decreased (25 +/- 1 to 16 +/- 1 mm Hg, p less than 0.001), mean arterial pressure decreased (83 +/- 1 to 72 +/- 1 mm Hg, p less than 0.001), and heart rate was unchanged. Plasma norepinephrine (632 +/- 43 pg/ml), PRA (18 +/- 3 ng/ml/hr), and arginine vasopressin (11 +/- 1 pg/ml) did not change significantly for the group during peak effect of the vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗