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Biomedical subjects

K L Goetz

Publications and source records attributed to K L Goetz.

At least 37 records · Page 2Linked to original sources

Hemodynamic and renal effects of low-dose infusions of atrial peptide in awake dogs.

The effects of alpha-human atrial natriuretic peptide (alpha-hANP) on cardiovascular and renal function in conscious dogs were evaluated in two experimental protocols. In one protocol, alpha-hANP was infused intravenously at increasing rates of 50, 100, and 200 ng.min-1.kg-1 (stepup infusion) during successive 20-min periods. The greatest responses occurred during the final 20-min period of the stepup infusion when the plasma concentration of immunoreactive atrial natriuretic peptide (irANP) was increased by 44-fold over preinfusion values; pressures in the aorta and both atria were decreased at this time, whereas glomerular filtration rate, urine flow, and sodium excretion were increased. In a second protocol, alpha-hANP was infused for 1 h at constant rates of either 12.5, 25, or 50 ng.min-1.kg-1; these constant infusions increased plasma irANP by 3-, 7-, and 12-fold, respectively. Each infusion rate decreased left and right atrial pressures and increased urine flow and sodium excretion. The two lowest infusion rates elevated plasma irANP to levels that would be expected to occur only during unusual physiological, or perhaps pathophysiological, conditions. The two highest infusion rates decreased plasma renin activity. Nevertheless, the accompanying maximal increases in sodium excretion were modest (41-72%). These data imply that small changes in circulating atrial peptides that presumably occur under normal physiological conditions would not have a dominant effect on the regulation of sodium excretion; the peptides may, however, play a modulatory role on sodium excretion under these conditions. It remains to be determined whether the ability of atrial peptides to lower cardiac filling pressures is of physiological significance.

Animals↗

Ventricular receptors stimulate vasopressin release during hemorrhage.

These experiments were designed to investigate whether a reflex arising from ventricular receptors is capable of stimulating vasopressin secretion during hemorrhage. Three groups of conscious dogs (sham operated, cardiac denervated, and ventricular denervated) were hemorrhaged slowly until 30 ml blood/kg body wt had been removed. Hemorrhage produced comparable decreases in stroke volume, central venous pressure, and left atrial pressure in each group of dogs but produced a different pattern of heart rate response in each group. Plasma vasopressin concentrations before hemorrhage did not differ in the three groups of dogs. In sham-operated dogs plasma vasopressin increased from a control level of 2.4 +/- 0.3 to 6.2 +/- 1.7, 200.0 +/- 65.4, and 991.3 +/- 220.9 pg/ml after 10, 20, and 30 ml/kg of blood had been removed, respectively. In contrast, plasma vasopressin did not increase in either cardiac-denervated or ventricular-denervated dogs after 10 ml/kg of blood had been removed, and the increases in circulating vasopressin after 20 and 30 ml/kg hemorrhage were markedly attenuated by cardiac denervation and by ventricular denervation. The magnitude of the increase in plasma vasopressin in the cardiac-denervated and ventricular-denervated dogs did not differ significantly at comparable levels of hemorrhage. The results are consistent with the possibility that a reflex initiated by ventricular receptors is primarily responsible for stimulating the secretion of vasopressin during hemorrhage in conscious dogs.

Aldosterone↗

Natriuresis during atrial distension and a concurrent decline in plasma atriopeptin.

In the conscious dog, left atrial distension elicits a composite response that modulates both cardiovascular and renal function. The response to atrial distension may be mediated by the combined effects of neural reflexes and the release of atriopeptin. To assess the relative contributions of atrial reflex mechanisms and circulating atriopeptin to the renal response elicited by atrial distension, alpha-human atrial natriuretic peptide (alpha-hANP) was infused into conscious dogs at 50 ng.kg-1.min-1 for 60 min. Then the infusion was stopped abruptly, and left atrial pressure was increased 8 mmHg by inflating a balloon positioned above the mitral valve. Plasma atriopeptin decreased during the 40-min period of atrial distension, but urine flow and sodium excretion increased during this time. In another series of experiments, volume expansion was substituted for atrial distension. Saline (24 ml/kg) was infused intravenously for 5 min immediately after the 60-min period of alpha-hANP infusion. Urine flow and sodium excretion increased after administration of saline even though plasma atriopeptin decreased substantially during the same time period. These results provide evidence that circulating levels of atriopeptin do not play a dominant role in influencing sodium excretion either during atrial distension or in response to saline infusion.

Aldosterone↗

Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs.

Endothelin is a recently discovered vasoconstrictor peptide that is synthesized in certain vascular endothelial cells. We have identified the cardiovascular, renal, and hormonal responses that can be elicited in conscious dogs by intravenous administration of endothelin at rates of 10 and 30 ng.kg-1.min-1 for 60 min (0.24 and 0.72 nmol.kg-1/1-h infusion). Each dose of endothelin increased total peripheral resistance, arterial pressure, and left atrial pressure and decreased heart rate and cardiac output. Hematocrit increased by 4.8% (NS) and 22.9% (P less than 0.01) in response to the lower and higher infusion rates, respectively. Urinary sodium excretion, urine osmolality, and osmolar clearance decreased and free water clearance increased. The lower dose of endothelin decreased plasma norepinephrine and increased plasma atriopeptin. The higher dose increased plasma levels of vasopressin, renin, aldosterone, norepinephrine, epinephrine, and atriopeptin. The higher infusion rate of the peptide caused one or more brief vomiting episodes in four of five dogs. Although it is not yet known whether endothelin is a circulating hormone, it is clear that this peptide is capable of causing profound cardiovascular, renal, and endocrine alterations in conscious dogs. The possible relevance of these observations to physiological processes and to pathological conditions such as hypertension remains to be established.

Angiotensin II↗

Effect of hemorrhage on plasma atriopeptin levels in conscious dogs.

An increase in atrial pressure has been shown to cause an increase in the concentration of atrial peptides (atriopeptin) in plasma. We therefore hypothesized that a reduction in atrial pressure would decrease the concentration of atriopeptin in plasma. In formulating this hypothesis we assumed that changes in the concentration of other circulating hormones or changes in cardiac nerve activity during hemorrhage would not affect the secretion of atriopeptin. To test the hypothesis, we bled sham-operated conscious dogs at a rate of 0.8 ml.kg-1.min-1 to decrease right and left atrial pressures. Hemorrhage was continued until a total of 30 ml of blood per kilogram body weight had been removed. Identical experiments were performed on conscious cardiac-denervated dogs. The concentration of plasma atriopeptin was decreased in each group of dogs after 10 ml of blood per kilogram of body weight had been removed, but the decrease achieved statistical significance only in the cardiac-denervated dogs. Further hemorrhage, however, produced no further decreases in circulating atriopeptin in either group even though atrial pressures continued to decline as more blood was removed. A comparison of the atriopeptin response to hemorrhage revealed no significant difference between the sham-operated and cardiac-denervated dogs, thus providing no evidence for a specific effect of cardiac nerves on atriopeptin secretion during hemorrhage. Our results demonstrate that the relationship between atrial pressure and plasma atriopeptin that has been observed repeatedly during atrial stretch is not evident during relatively slow, prolonged hemorrhage. There is, however, a small decline in circulating atriopeptin during the initial stage of hemorrhage that could be of biological significance.

Animals↗

A high-salt meal produces natriuresis in humans without elevating plasma atriopeptin.

The effects of a high-sodium meal on plasma atrial natriuretic peptide (atriopeptin) and renal sodium excretion were studied in eight normal human subjects. As expected, sodium excretion and urine osmolality increased following the meal. Plasma atriopeptin levels did not increase, however, after the high-sodium meal. In a control experiment, consumption of a low-sodium meal by six of the same subjects did not increase either urinary sodium excretion or plasma atriopeptin concentration. We conclude that the natriuresis elicited by a high-salt meal is not mediated by the atrial peptides.

Adult↗

Plasma atrial peptide concentration during acute changes in cardiac filling pressure induced by a contrast agent.

Left ventricular end-diastolic pressure and the concentration of atrial peptides in plasma were measured before and after the administration of contrast material into the left ventricle of 12 patients during cardiac catheterization. A positive relationship between changes in left ventricular end-diastolic pressure and the circulating level of atrial peptides was found in all 12 patients. Increases in plasma atrial peptide levels were detected within less than one minute after injection of the contrast agent. We conclude that the release of atrial peptides in the human is modulated rapidly by changes in atrial pressure. The rapid release of peptides from the atria in response to an increase in atrial pressure, coupled with evidence that atrial peptides reduce cardiac filling pressure, is consistent with the possibility that the atrial peptides may serve as part of a negative feedback system that enables the heart to influence its own filling pressure.

Adult↗

Augmented pressor response to vasopressin in awake dogs after cardiac denervation.

Hemodynamic responses to varying intravenous infusion rates of vasopressin were studied in two groups of dogs; one group was cardiac denervated and the other sham operated. Vasopressin given at 200, 1,000, and 5,000 fmol X kg-1 X min-1 produced increases in aortic pressure that were significantly greater in cardiac-denervated dogs than in sham-operated dogs. The augmented pressor response in cardiac-denervated dogs was associated with greater increases in total peripheral resistance in this group; decreases in cardiac output were similar in the two groups of dogs. Vasopressin decreased heart rate significantly in each group, but the magnitude of the decrease was significantly smaller in cardiac-denervated dogs. In contrast to these results, the intravenous infusion of phenylephrine or angiotensin II in other experiments on the same dogs produced comparable increases in aortic pressure in each group. These results are consistent with earlier evidence indicating that vasopressin elicits more effective reflex mechanisms to attenuate the increases in blood pressure caused by its direct vasoconstrictor action than do other vasoconstrictor agents, such as angiotensin II and phenylephrine. Since the infusion of vasopressin produced a greater increase in arterial blood pressure in cardiac-denervated dogs than it did in sham-operated control dogs, it appears that at least part of the unique action of vasopressin may be mediated by the potentiation of a peripheral vasodepressor reflex arising from cardiac receptors.

Angiotensin II↗

Elevated atrial natriuretic factor in neonates with respiratory distress syndrome.

Atrial natriuretic factor (ANF) plasma concentrations were measured in 16 healthy term newborn infants and in 18 preterm infants with respiratory distress syndrome during the first 4 postnatal days. Changes in the plasma concentration of ANF were then correlated with postnatal age, severity of respiratory distress, and water and sodium balance. The plasma ANF concentration in healthy term infants increased during the first 2 days of life. Similar values were observed among preterm infants requiring hood oxygen. The plasma ANF concentrations were substantially higher in preterm infants receiving positive pressure ventilation. All infants had negative water and sodium balance during the period of study. No correlation was found, however, between absolute plasma ANF concentrations and urinary flow rate, sodium excretion, or fractional sodium excretion, suggesting that ANF did not exert a dominant role in the excretion of sodium in these infants.

Adult↗

Computerized axial tomography scans and subtypes of schizophrenia. A review of the literature.

Since the initial reports of ventricular enlargement in schizophrenics, attempts have been made to define a subgroup of patients with brain atrophy on computerized axial tomography (CAT) scans. The authors reviewed this literature for clinical, biochemical, and environmental correlates of lateral and third ventricular enlargement as well as cortical and cerebellar atrophy and brain density. It is concluded that CAT abnormalities are useful markers in delineating a group of schizophrenics characterized predominantly by neuropsychological impairment, poor premorbid adjustment, global monoamine disturbance, poor treatment response to neuroleptics, lack of positive symptoms, and predominance of negative symptoms. A proposal for further classification of these patients is given both in terms of the dopamine hypothesis and Kraepelin's dementia praecox.

Atrophy↗

Effects of atriopeptin infusion versus effects of left atrial stretch in awake dogs.

We infused synthetic atriopeptin III intravenously into 10 conscious dogs while monitoring renal function and systemic hemodynamics. The results obtained from these infusion experiments were compared with results from other experiments in which left atrial distension was performed in the same dogs. Both atriopeptin infusion and left atrial distension caused significant increases in urine flow, sodium excretion, potassium excretion, and free water reabsorption and a significant decrease in renal blood flow. On the other hand, the pattern of systemic hemodynamic responses to atriopeptin infusion were quite different from the hemodynamic responses elicited by left atrial distension. However, there was a striking concordance between the renal effects of atriopeptin and those of left atrial distension. We therefore hypothesize that the renal response to left atrial distension in the conscious dog is mediated largely by the release of natriuretic peptides from the atria.

Aldosterone↗

Canine renal responses to atrial stretch or intravenous saline are not attenuated at night.

Primates develop a diuresis and natriuresis in response to stimuli that increase central blood volume. However, the renal response is markedly attenuated when these same experimental stimuli are applied at night. The purpose of the present study was to determine whether a quadruped, specifically the dog, also demonstrates attenuated renal responses to similar stimuli given at night. Two experimental protocols were performed on conscious dogs at night: 1) left atrial distension by partial mitral valve obstruction and 2) intravenous saline administration. Results from these experiments were compared with results from comparable experiments performed on the same dogs during the day. Each experimental intervention produced increases in urine flow and sodium excretion and decreases in urine osmolality during both day and night experiments (all P less than 0.05). The responses obtained during the night did not differ significantly from those obtained during the day. Thus the dog does not demonstrate an attenuated renal response to central volume expansion during the night. This contrasts with the adaptive response in primates that serves to minimize fluid loss when the intrathoracic blood pool is increased during prolonged recumbency at night. Presumably quadrupeds, with trunks horizontal both day and night, do not require nocturnal adaptive mechanisms to conserve body fluids.

Animals↗

Atrial stretch increases sodium excretion independently of release of atrial peptides.

The effects of atrial distension on plasma atrial natriuretic factor and renal salt and water excretion were studied in normal dogs and in cardiac-denervated dogs. In five conscious normal dogs, elevation of left atrial pressure (7.8 Torr) consistently increased plasma concentrations of radioimmunoassayable atrial natriuretic factor (riANF), urine flow, and sodium excretion. Elevation of right atrial pressure (3.5 Torr) in the same five dogs also consistently increased riANF, but sodium excretion and urine flow did not increase. In four conscious cardiac-denervated dogs, elevation of left atrial pressure (9.2 Torr) consistently increased riANF, but urine flow and sodium excretion did not increase. Because atrial distension increased plasma riANF in each of the three types of experiments, but urine flow and sodium excretion increased in only one type, we conclude that atrial natriuretic peptides are not responsible for the diuretic and natriuretic responses elicited by left atrial distension. It is conceivable, of course, that atrial peptides released during atrial distension may act synergistically with other changes evoked by atrial distension and thereby contribute to the natriuresis elicited by left atrial stretch. However, the increase in plasma riANF during atrial distension appears to be incapable of independently increasing salt and water excretion in the conscious dog.

Animals↗

Blood pressure of sinoaortic-denervated dogs is not increased by cardiac denervation.

Although blood pressure rises markedly after acute sinoaortic denervation, animals with chronic sinoaortic denervation have normal or only slightly elevated mean arterial pressures. The present study was performed to determine whether reflexes from cardiac receptors exert antihypertensive effects and thereby lower blood pressure in animals with chronic sinoaortic denervation. We made multiple measurements of blood pressures in dogs with chronic sinoaortic denervation before and after their hearts were denervated surgically. Mean arterial pressure after cardiac denervation (100.3 +/- 4.2 mm Hg) was not significantly different from the mean pressures recorded before cardiac denervation in these sinoaortic-denervated dogs (104.8 +/- 3.1 mm Hg). Also, mean heart rate after cardiac denervation (107.4 +/- 5.5 beats/min) did not differ significantly from the mean heart rate recorded before cardiac denervation (107.2 +/- 5.9 beats/min). Cardiac denervation did, however, appear to reduce the lability of both blood pressure and heart rate in sinoaortic-denervated dogs. We conclude that cardiac receptors are not responsible for maintaining arterial pressure within essentially normal limits in animals with chronic sinoaortic denervation.

Animals↗

Plasma vasopressin, renin activity, and aldosterone responses to maximal exercise in active college females.

The effect of maximal treadmill exercise on plasma concentrations of vasopressin (AVP); renin activity (PRA); and aldosterone (ALDO) was studied in nine female college basketball players before and after a 5-month basketball season. Pre-season plasma AVP increased (p less than 0.05) from a pre-exercise concentration of 3.8 +/- 0.5 to 15.8 +/- 4.8 pg X ml-1 following exercise. Post-season, the pre-exercise plasma AVP level averaged 1.5 +/- 0.5 pg X ml-1 and increased to 16.7 +/- 5.9 pg X ml-1 after the exercise test. PRA increased (p less than 0.05) from a pre-exercise value of 1.6 +/- 0.6 to 6.8 +/- 1.7 ngAI X ml-1 X hr-1 5 min after the end of exercise during the pre-season test. In the post-season, the pre-exercise PRA was comparable (2.4 +/- 0.6 ngAI X ml- X hr-1), as was the elevation found after maximal exercise (8.3 +/- 1.9 ngAI X ml- X hr-1). Pre-season plasma ALDO increased (p less than 0.05) from 102.9 +/- 30.8 pg X ml-1 in the pre-exercise period to 453.8 +/- 54.8 pg X ml-1 after the exercise test. In the post-season the values were 108.9 +/- 19.4 and 365.9 +/- 64.4 pg X ml-1, respectively. Thus, maximal exercise in females produced significant increases in plasma AVP, renin activity, and ALDO that are comparable to those reported previously for male subjects. Moreover, this response is remarkably reproducible as demonstrated by the results of the two tests performed 5 months apart.

Adult↗