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Biomedical subjects

R J Grekin

Publications and source records attributed to R J Grekin.

At least 37 records · Page 2Linked to original sources
PubMed1988

Effect of vasopressors on atrial natriuretic factor and hemodynamic function in humans.

To assess the effects of vasopressors on plasma levels of immunoreactive atrial natriuretic factor (ANF), 13 normal men were studied on two occasions. On the experimental day, subjects received sequential 15-minute intravenous infusions of angiotensin II in doses of 4, 8, and 16 pmol/kg/min. Following a 30-minute recovery period, subjects received sequential 15-minute infusions of phenylephrine in doses of 0.4 and 0.8 micrograms/kg/min. Right atrial pressure, mean pulmonary capillary wedge pressure, pulmonary artery pressure, mean systemic arterial pressure, and plasma levels of renin activity, aldosterone, angiotensin II, and immunoreactive ANF were obtained sequentially throughout the protocol. During the control day, vehicle was infused and plasma samples were obtained for hormone measurements. Infusion of angiotensin II and phenylephrine increased mean systemic arterial pressure in a stepwise fashion. Both right atrial pressure and pulmonary capillary wedge pressure increased significantly during both doses of phenylephrine, but only the highest dose of angiotensin II significantly increased atrial pressures. Plasma levels of immunoreactive ANF increased parallel with the changes in right atrial pressure and pulmonary capillary wedge pressure, with significant increases occurring only at the highest dose of both pressors. Angiotensin II and aldosterone levels increased and renin activity decreased during infusion of angiotensin II. There were no significant changes in plasma levels of immunoreactive ANF during the control day. These studies demonstrate that infusion of vasopressors increases plasma levels of ANF, but only when the vasopressor effect is associated with significant increases in right atrial and pulmonary capillary wedge pressures. Atrial stretch is the most likely mediator of the increase in plasma levels of immunoreactive ANF during vasoconstriction.

Adult↗
PubMed1987

Atrial natriuretic hormone secretion in patients with renal failure.

To study the effects of volume overload and renal failure on plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH), we measured levels of this hormone in normal subjects, in patients with advanced chronic renal failure (CRF) with and without clinically evident volume overload, and in patients with end-stage renal disease (ESRD) treated with chronic hemodialysis. The levels were 13 +/- 2 pmol/l in normal volunteers, 77 +/- 24 pmol/l in patients with CRF without volume overload, and 219 +/- 50 pmol/l in patients with CRF and clinically evident volume overload (analysis of variance, p less than 0.001, alpha = 0.05 compared to normals). In patients with ESRD, the levels of IR-ANH were 145 +/- 46 pmol/l before dialysis and decreased to 87 +/- 31 after dialysis (p less than 0.025). No correlation was found between the decrease in IR-ANH levels and the decrease in weight during dialysis. A significant positive correlation was found between the IR-ANH levels and blood urea nitrogen in patients with CRF (r = 0.658, p less than 0.01). Volume overload appears to be the most important stimulatory factor for ANH secretion in renal failure patients but other mechanisms, especially a decrease in metabolic clearance, may also contribute to elevated plasma levels. The increased secretion of ANH in patients with renal failure may be an important adaptive response to volume overload and hypertension.

Adult↗
PubMed1987

Atrial natriuretic hormone is not elevated during dopamine induced natriuresis.

To evaluate the possibility that atrial natriuretic hormone (ANH) is involved in dopamine induced natriuresis and diuresis, we studied five normal male volunteers. Each was studied on two occasions. During the first two hours of each study, normal saline, 25 ml/hr, was infused. During the second two hours either normal saline, 25 ml/hr, or dopamine, 4 micrograms/kg/min, in normal saline, was infused. Dopamine infusion caused prominent and significant natriuresis and diuresis but plasma levels of immunoreactive ANH levels did not change. We conclude that the ANH is not involved in dopamine induced natriuresis and that dopaminergic stimulation is not responsible for ANH secretion.

Adult↗
PubMed1987

Suppression of plasma renin activity in a boy with chronic hyperkalemia.

Chronic hyperkalemia (6.8 mmol/L [6.8 mEq/L]) was discovered in a boy, aged 13 years 7 months, with short stature, delayed puberty, and normal blood pressure. Additional studies revealed hyperchloremic metabolic acidosis (serum values: sodium ion, 139 mmol/L [139 mEq/L]; chloride, 113 mmol/L [113 mEq/L]; bicarbonate, 18 mmol/L [18 mEq/L]), a normal glomerular filtration rate, a subnormal renal threshold for bicarbonate reabsorption, and normal serum thyroxine, growth hormone, and cortisol values. Renal excretion of potassium ion was subnormal for the prevailing serum concentration of potassium ion but was increased normally by infusion of sodium sulfate. The serum aldosterone concentration was appropriate for a normokalemic subject, despite marked suppression of plasma renin activity (PRA) (supine/upright: aldosterone, 140/580 pmol/L [5/21 ng/dL]; PRA, 0.0/0.03 ng/L X s [0.0/0.1 ng/mL/h]). Treatment with chlorothiazide and sodium chloride resulted in correction of the abnormal electrolyte concentrations and an increase in linear growth velocity. Serum aldosterone concentrations did not change significantly during treatment, even though the PRA had increased (supine/upright: aldosterone, 110/920 pmol/L [4/33 ng/dL]; PRA, 0.89/2.17 ng/L X s [3.2/7.8 ng/mL/h]). In this patient, we conclude that (1) hyperkalemia was due to inadequate renal excretion of potassium ion; (2) the serum potassium ion concentration was the major stimulus to aldosterone secretion before treatment; (3) suppression of PRA was more likely due to hyperkalemia than to extracellular volume expansion.

Acidosis↗
PubMed1987

Epinephrine increases plasma immunoreactive atrial natriuretic hormone levels in humans.

Six normal human subjects each underwent sequential 80-min infusions of saline and epinephrine (EPI) at 0.55 and 2.75 micrograms X min-1 X m-2 to determine the role of EPI in the control of atrial natriuretic hormone (ANH) in humans. Plasma immunoreactive-ANH (IR-ANH) levels nearly doubled in response to the infusion of EPI at 0.55 microgram X min-1 X m-2 (P less than 0.05) and then plateaued; heart rate accelerated significantly (P less than 0.01) with increasing plasma EPI levels, whereas systolic blood pressure increased only with higher plasma EPI levels (P less than 0.05). To determine whether beta-adrenergic mechanisms mediate the EPI-induced increase in IR-ANH, six additional subjects each received infusions on two separate days of saline for 240 min and the beta-adrenergic antagonist propranolol followed by propranolol plus EPI at 2.75 micrograms X min-1 X min-2 each for 80 min. Neither saline nor propranolol plus EPI caused a significant increase in plasma IR-ANH. We conclude that EPI increases plasma IR-ANH through beta-adrenergic mechanisms in humans. beta-Adrenergic-mediated increases in plasma IR-ANH levels appear to be unrelated to changes in the heart rate.

Atrial Natriuretic Factor↗
PubMed1987

Centrally administered atrial natriuretic factor increases renal water excretion.

The effects of intracerebroventricular (ICV) infusion of atrial natriuretic factor (ANF; atriopeptin III) on renal function, plasma concentrations of antidiurectic hormone, aldosterone, and plasma renin activity (PRA) were examined in anesthetized rats and sodium-depleted conscious sheep. The results were compared with those obtained by intravenous infusion of the same dose of ANF. In both rats and sheep, urine volume was increased four- to sixfold over basal values by ICV infusion of ANF. The response was not associated with increased excretion of sodium or potassium. However, urine osmolality was decreased, and free water clearance increased. Intravenous infusion of the same dose of ANF was without effect. Neither mean arterial blood pressure nor heart rate was changed by the ICV infusion of ANF. In the sheep, renal plasma flow showed no significant changes and glomerular filtration rate was unaltered with the exception of a single experimental period out of four periods of ICV ANF infusion. Plasma concentration of ADH was decreased and PRA increased, whereas aldosterone levels remained unchanged as a function of ICV ANF. In the rat, the diuretic response to ANF was prevented by continuous intravenous infusion of a subpressor dose of ADH. These results suggest that ANF within the central nervous system inhibits secretion of ADH.

Aldosterone↗
PubMed1987

Hormonal responses to cardiac tamponade: inhibition of release of atrial natriuretic factor despite elevation of atrial pressures.

Atrial distension, rather than change in intra-atrial pressure, has been suggested as a principal mediator of release of atrial natriuretic factor (ANF). During cardiac tamponade, atrial pressures rise whereas transmural pressures and atrial stretch may not be affected. The roles of atrial pressure and atrial distension were investigated in six open-chest dogs subjected to cardiac tamponade and rapid volume expansion as disparate means of affecting intra-atrial pressures and atrial stretch. Hemodynamic measurements, immunoreactive ANF (ir-ANF), plasma renin activity, antidiuretic hormone, epinephrine, and norepinephrine were monitored before, during, and after three interventions: (1) tamponade, (2) rapid volume loading followed by tamponade, and (3) volume loading during tamponade. Volume expansion increased right atrial pressure and caused a significant rise in ir-ANF. Elevations of right atrial pressure caused by tamponade were comparable to those induced by volume infusion, but an increase in ir-ANF was not elicited during tamponade, and the ir-ANF response to volume loading was abolished when performed during tamponade. The relation between the change in ANF concentration and change in right atrial pressure were highly significant in the absence of tamponade, when atrial stretch was freely responsive to volume expansion (r = .73, p less than .0001), but not when stretch was inhibited (r = -.16, p = NS). These observations underscore the importance of considering the modulating effects of atrial compliance, transmural pressure, and atrial stretch on the relation between atrial pressures and ANF release.

Animals↗
PubMed1987

Central dopaminergic regulation of aldosterone secretion in sheep.

Central dopaminergic mechanisms involved in the regulation of plasma aldosterone concentration were investigated in 16 conscious sheep following Na depletion with intramuscularly administered furosemide. Intracerebroventricular infusion of dopamine (20 micrograms/min) decreased plasma aldosterone significantly to 52 +/- 8% of basal level and increased plasma renin activity (PRA) significantly to 172 +/- 25% of basal level in this animal model. In addition, intracerebroventricular infusion of the dopamine antagonist metoclopramide (20 micrograms/min) in artificial cerebrospinal fluid vehicle significantly increased aldosterone levels to 144 +/- 14% of basal level and decreased PRA to 62 +/- 5% of basal value. Neither intracerebroventricular infusion of the vehicle nor intravenous infusions of metoclopramide or dopamine at the same doses changed aldosterone or PRA levels. Intracerebroventricular bolus injections of metoclopramide (20 micrograms/kg in 0.4 ml of vehicle) were also effective, increasing aldosterone levels to 266 +/- 22% of basal level and decreasing PRA to 70 +/- 12% of basal level. Intravenous bolus injections of the same dose of metoclopramide were ineffective. Dopamine was infused intracerebroventricularly into two uniadrenalectomized sheep with the remaining adrenal transplanted to the neck. Aldosterone levels were decreased to 49 +/- 10% of basal level, and PRA was increased to 157 +/- 10% of basal value. None of the infusions or injections changed arterial or intracranial pressure, or plasma K, Na, and cortisol levels. These data indicate that endogenous or exogenous dopamine may act on central dopamine receptors to decrease plasma aldosterone concentration by an unknown humoral mechanism. The known aldosterone regulators, plasma Na, K, angiotensin II, and adrenocorticotropic hormone, are not involved in the regulation.

Adrenal Glands↗
PubMed1987

Functional and scintigraphic evaluation of the silent adrenal mass.

Seven patients with unilateral and one patient with bilateral and asymmetric (R greater than L) incidentally discovered adrenal mass abnormalities depicted by computed tomography (CT) were studied by 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy. There was marked lateralization of NP-59 uptake to the side of the mass lesion in the seven patients with unilateral masses and prominent asymmetric, (R greater than L) bilateral uptake in the patient with bilateral masses despite the fact that there were no obvious abnormalities of adrenocortical or adrenomedullary function as determined from peripheral blood and 24-hr urinary hormone measurements. Simultaneous bilateral adrenal vein catheterization (AVC) was employed to measure the levels of hormone effluent from the adrenal cortex and medulla and in all instances the cortisol concentrations were greatest from the side of the mass lesion in those patients with unilateral masses and from the larger of the two adrenals in the patient with bilateral adrenal masses. Thus, there was congruence between the anatomic (CT) and functional (NP-59 scintigraphy and AVC) investigations that depicted asymmetry of the adrenal glands which were not associated with abnormalities of overall adrenal function or hypothalamic-pituitary-adrenal axis integrity.

Adosterol↗
PubMed1986

The scintigraphic localization of mineralocorticoid-producing adrenocortical carcinoma.

I-131-6 beta-iodomethylnorcholesterol (NP-59) was used to localize mineralocorticoid-secreting adrenocortical carcinomas in two patients and functioning metastases in a third patient studied after the removal of the primary tumor. The presence of sufficient NP-59 activity within these lesions for discernable imaging is unusual and would not have been expected based on previous experience with other functioning and nonfunctioning carcinomas of the adrenal cortex. These cases serve to illustrate the variable spectrum of iodocholesterol uptake into adrenocortical malignancies and suggest that scintigraphic studies, preoperatively for localization and postoperatively to confirm the presence of recurrence or metastases, might be useful to identify and characterize these rare neoplasms.

19-Iodocholesterol↗
PubMed1986

Plasma levels of immunoreactive atrial natriuretic factor increase during supraventricular tachycardia.

A significant diuretic and natriuretic response occurs during paroxysmal supraventricular tachycardia (SVT). Although the diuresis may be secondary to suppression of vasopressin secretion, the etiology of the natriuresis remains unexplained. To determine if atrial natriuretic factor (ANF) could contribute to the polyuric response during SVT, 10 patients were studied: five during spontaneous SVT and five during simulated SVT produced by rapid simultaneous atrial and ventricular pacing. Plasma immunoreactive ANF (IR-ANF) levels measured by radioimmunoassay were obtained at baseline (before and/or 24 to 48 hours after SVT) and after at least 15 minutes of SVT in all patients. During spontaneous and simulated SVT, IR-ANF was significantly elevated (mean +/- SE; 275 +/- 68 pmol/L) compared to baseline (28 +/- 7 pmol/L; p = 0.0036). Similar increases in IR-ANF were noted during both simulated and spontaneous SVT. To determine if this IR-ANF release was related to the increase in heart rate or the rise in right atrial pressure during SVT, IR-ANF levels were also measured in five patients with sinus tachycardia and in six patients with congestive heart failure. IR-ANF was significantly related to right atrial pressure (r = 0.93; p = 0.0009) but not to heart rate (r = 0.46). Thus, IR-ANF is elevated during SVT and may contribute to the natriuretic response. The stimulus to IR-ANF secretion during SVT appears to be related to the rise in right atrial pressure rather than to the increase in heart rate.

Adult↗
PubMed1986

The role of endorphins and vasopressin in canine endotoxin shock.

Chemical antagonists were used to assess the role of beta-endorphin and arginine-vasopressin (AVP) in canine endotoxin shock. Fifteen awake dogs were given Escherichia coli endotoxin IV. Within 5 min, CO decreased to 28%, LV dP/dt to 46%, and MAP to 52% baseline. Fifteen minutes after endotoxin, five dogs each received naloxone, AVP antagonist, or no treatment. Control (untreated) animals exhibited persistent cardiovascular depression, with CO 49%, LV dP/dt 69%, and MAP 91% of baseline after 45 min. Naloxone improved CO to 69%, LV dP/dt to 94%, and MAP to 91% by 30 min after treatment. AVP blockade improved CO to 105%, LV dP/dt to 107%, and MAP to 95% of baseline by 30 min after treatment, and caused significant tachycardia. Plasma cortisol and AVP increased markedly in all groups after endotoxin administration. AVP antagonist treatment increased mean survival from 1.4 to 4 days. These data suggest that abnormally elevated AVP contributes to cardiovascular depression in canine endotoxin shock and that AVP blockade is therapeutic in the animal model studied.

Animals↗
PubMed1986

Plasma levels of immunoreactive atrial natriuretic hormone in patients with diabetes mellitus.

In order to determine whether atrial natriuretic hormone (ANH) secretion is altered in diabetic patients with autonomic neuropathy, plasma immunoreactive ANH (IR-ANH) levels were measured in 23 patients with insulin-dependent diabetes mellitus, 12 of whom had definite cardiac autonomic neuropathy determined by noninvasive maneuvers. Levels were also measured in 31 healthy control subjects. Whereas only one of the 11 diabetics without cardiac autonomic neuropathy had elevated IR-ANH levels, four of the 12 diabetics with cardiac autonomic neuropathy had elevated IR-ANH levels (P = 0.03 compared to control subjects). 24-h urinary sodium excetion was not different among the groups. There was no significant correlation between IR-ANH levels and diabetes control and any of the parameters of autonomic nervous system activity nor between IR-ANH levels and plasma norepinephrine or epinephrine levels. Furthermore, no relationship was observed in the diabetic subjects between IR-ANH levels and left ventricular ejection fraction determined by radionuclide ventriculography. Thus, elevated IR-ANH levels occur with greater frequency in diabetic patients with autonomic neuropathy. These elevations do not appear to be due to alterations in dietary sodium intake or left ventricular dysfunction.

Adult↗
PubMed1986

The relationship between plasma levels of immunoreactive atrial natriuretic hormone and hemodynamic function in man.

To evaluate the relationship between plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH) and different hemodynamic parameters in man, we studied 34 patients undergoing right heart catheterization. Plasma levels of IR-ANH in blood samples withdrawn from the femoral vein (n = 28), right ventricle (n = 27), and left ventricle (n = 17) were determined by radioimmunoassay. Right atrial pressure, pulmonary arterial wedge pressure, heart rate, and mean arterial pressure were found to be independent and significant predictors of IR-ANH plasma levels. The closest correlations were between right atrial pressure and either right ventricular IR-ANH levels (r = .78, p greater than .001) or femoral vein IR-ANH levels (r = .52, p less than .006). Five patients with isolated left ventricular failure had elevated IR-ANH levels out of proportion to their right atrial pressure levels. Pulmonary arterial wedge pressure also correlated with right ventricular IR-ANH levels (r = .46, p less than .002) and with femoral vein IR-ANH levels (r = .58, p less than .002). A single patient with isolated right heart failure had markedly elevated IR-ANH levels despite normal pulmonary arterial wedge pressure. Right ventricular levels were twice femoral vein levels and were closely correlated (181 +/- 40 vs 90 +/- 20 pmol/liter; r = .90, p less than .001). Right ventricular and left ventricular levels were almost identical (155 +/- 46 vs 146 +/- 43 pmol/liter; r = .99, p less than .001). Patients with volume overload states had elevated IR-ANH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Immunoreactive atrial natriuretic hormone levels increase in deoxycorticosterone acetate-treated pigs.

Extensive evidence reported here and elsewhere indicates a hormonal role for atrial natriuretic factor. In the light of this evidence, it appears that atrial natriuretic hormone is a more appropriate term for these peptides than atrial natriuretic factor. Plasma levels of immunoreactive atrial natriuretic hormone were measured daily in seven pigs before and 1 week after subcutaneous implantation of deoxycorticosterone acetate (DOCA). Nine other animals underwent daily measurements of mean arterial pressure and central venous pressure during similar treatments. Plasma immunoreactive atrial natriuretic hormone levels rose progressively during the first 3 days after implantation, from a basal level of 60 +/- 9 pmol/L to a peak level of 159 +/- 21 pmol/L (p less than 0.05), and they remained significantly elevated throughout the rest of the 7-day observation period. In two animals that were restudied 6 weeks after DOCA implantation, plasma immunoreactive atrial natriuretic hormone had returned to preimplantation levels. The rise in plasma hormone levels after DOCA implantation closely paralleled the previously reported time course of mineralocorticoid escape. Whether atrial natriuretic hormone plays an important part in the escape phenomenon remains to be determined.

Animals↗
PubMed1986

Ectopic prolactinoma in a patient with hyperparathyroidism and abnormal sellar radiography.

In a patient with hyperparathyroidism and chronic renal failure due to polycystic kidney disease, a finding of destroyed sellar and parasellar structures and hyperprolactinemia suggested the diagnosis of invasive pituitary prolactinoma. At surgery no tumor was found, and pathological examination of the sphenoid bone revealed a parathyroid bone lesion (brown tumor) as well as ectopic prolactinoma in the clivus. This patient demonstrates that a tumor may develop in ectopic pituitary tissue. The combination of radiographically abnormal sellar structures with pituitary hormone hypersecretion should not be regarded as absolute proof of a pituitary adenoma.

Choristoma↗
PubMed1986

Acromegaly due to ectopic growth hormone (GH)-releasing hormone (GHRH) production: dynamic studies of GH and ectopic GHRH secretion.

Dynamic studies of GH and GH-releasing hormone (GHRH) secretion were performed in a man with a GHRH-producing carcinoid tumor and acromegaly. Insulin hypoglycemia stimulated and metoclopramide inhibited both GH and GHRH acutely. Bromocriptine suppressed GH both acutely and chronically without altering circulating GHRH levels and also blunted the GH response to exogenous GHRH. TRH acutely stimulated GH, but not GHRH, secretion, and iv bolus doses of synthetic GHRH-(1-40) stimulated GH release acutely. Somatostatin infusion decreased both GH and GHRH concentrations and blunted the GH responses to TRH and GHRH-(1-40). We conclude that prolonged exposure of the pituitary gland to high concentrations of GHRH is associated with chronic GH hypersecretion and may be accompanied by a preserved acute GH response to exogenous GHRH; a paradoxical response of GH to TRH may be mediated at the pituitary level, consequent to prolonged pituitary exposure to GHRH; bromocriptine suppression of GH in acromegaly is due to a direct pituitary effect of the drug; and somatostatin inhibits both ectopic GHRH secretion as well as GH responsiveness to GHRH in vivo. Since GH secretory responses in patients with somatotroph adenomas are similar to those in this patient, augmented GHRH secretion may play a role in development of the "classic" form of acromegaly.

Acromegaly↗