Acute Plasma Volume Expansion Research Articles

Effect of unilateral renal denervation on bilateral renal response to saline loading in anteroventral third ventricle-lesioned rats

Our previous experiments demonstrated that lesions in the antdroventral third ventricle (AV3V) region of the brain attenuated natriuretic and diuretic response to saline loading in rats. To further assess if renal nerves are involved in this impaired response, we compared the effect of acute unilateral renal denervation on the response to saline loading in AV3V-lesioned and intact rats. Rats with electrolytic ablation in the AV3V region were prepared 4 weeks prior to experiments. The arterial blood pressure (BP) and bilateral renal responses to acute expansion of plasma volume by saline loading (0.388 ml/min for 1 h) were measured in rats under pentobarbital anesthesia. Saline loading before renal denervation induced a smaller increase in bilateral renal excretion of sodium and water in AV3V-lesioned rats than in control rats. Acute renal denervation produced ipsilateral natriuresis and diuresis without causing significant change in the excretory functions of the contralateral kidneys in both the lesioned and the control rats. BP and glomerular filtration rate of both groups of rats remained unaltered. The denervation-induced natriuretic and diuretic responses in the lesioned rats were not significantly different from those of the control rats. Subsequent saline loading bilateral renal excretion of sodium and water in both groups of rats. However, the previously obersrved attenuation of natriuretic and diuretic responses to saline loading in rats with AV3V lesions was abolished after renal denervation. These results suggest that the integrity of the AV3V region is necessary for normal regulation of sodium and water balance. Furthermore, there is a functional connection between the renal nerve and the AV3V region in modulating renal excretion during volume expansion.

Atrial natriuretic hormones--thirty years after the discovery of atrial volume receptors.

Twenty-five years after the discoveries of the existence of atrial granules and of volume receptors in the heart atria the search for natriuretic hormones has led to the isolation and identification of the atrial natriuretic factors (ANF) now considered as a hormonal system. These peptides are probably synthesized and stored in the Golgi apparatus of cardiac myocytes and are released in response to atrial wall stretch following acute plasma volume expansion and increased central blood volume, e.g., during head-out water immersion, in arterial hypertension, or increased left and/or right atrial pressure in cardiac failure, but also possibly in response to increased frequency of myocardial contractions, e.g. in paroxysmal tachycardia. The mechanisms of the renal action of these potent natriuretic hormones are not yet precisely known. Increased GFR may contribute to the initial rise in urinary sodium excretion and increased renal medullary blood flow to the later phase of natriuresis. The proximal tubule, the thin descending and the ascending limb of Henle's loop and especially the medullary collecting tubule were so far incriminated as tubular sites of action of ANF. Finally, recycling of sodium in medullary tissue and secretion of sodium via back-flux from the interstitium into the medullary collecting tubule are postulated to result in the hypernatric urine observed after ANF administration. Direct suppression of the secretion of renin, aldosterone, vasopressin, and vasopressin-stimulated cAMP synthesis may also contribute to its diuretic, natriuretic, and antihypertensive effects. The renal hemodynamic and tubular as well as the adrenal and systemic vascular effects are related to enhanced cGMP synthesis in medium-sized arterial vessels, in glomeruli and specific tubular segments, and in adrenal tissue, and may be calcium dependent. Specific ANF-binding sites were detected in these target organs. Although increased ANF release was observed in response to atrial distension in various disease states, which may contribute to renal sodium elimination in human hypertension and congestive heart failure, further studies are needed to identify its precise physiological and pathophysiological significance.

George E. Brown memorial lecture. Role of atrial peptides in body fluid homeostasis.

Extracts of mammalian atria, but not ventricles, induce marked diuresis, natriuresis, and reduction in blood pressure when infused systemically in rats and dogs. These extracts also inhibit aldosterone biosynthesis and renal renin release. Natriuretic peptides, 21 amino acids and longer, have been isolated from atria of rodents and man, and share a nearly homologous amino acid sequence at the carboxyterminus. Natriuretic activity resides in a 17-amino acid ring formed by a disulfide bridge, and the C-terminal Phe-Arg appears necessary for full biological potency. The deoxyribonucleic acid-encoding atrial natriuretic peptides have been cloned and the gene structure elucidated. Reduction of the diuretic and natriuretic responses to an acute volume load by right atrial appendectomy first suggested a role for atrial peptides in the physiological response to plasma volume expansion. Subsequently, release of peptides with natriuretic and spasmolytic properties from isolated heart preparations in response to right atrial distension was demonstrated by bioassay and radioimmunoassay. The presence of these peptides in normal rat and human plasma in concentrations of 20-100 pM, and the findings of increased levels in response to acute and chronic plasma volume expansion, rapid atrial tachyarrhythmias, systemic hypertension, congestive heart failure, and renal insufficiency imply that they play an important role in body fluid homeostasis. The mechanisms by which atrial peptides increase renal salt and water excretion are as yet unclear. Renal vascular effects have been consistently demonstrated, and limited evidence for direct actions on tubule ion transport has also been reported recently. In vitro, these peptides cause precontracted vascular and nonvascular smooth muscle to relax, mediated by a direct action on smooth muscle cells. Specific receptors for these peptides have been characterized in crude membranes prepared from whole kidney homogenates and adrenal glomerulosa cells, in intact glomeruli and cultured glomerular mesangial cells, and in intact bovine aortic smooth muscle and endothelial cells. Natriuretic peptides stimulate cyclic guanosine monophosphate accumulation in target tissues, and augment particulate guanylate cyclase activity in membrane fractions, suggesting that cyclic guanosine monophosphate is the second messenger mediating their cellular action.

Idiopathic hypovolemia.

Eleven patients with orthostatic intolerance had, for no detectable reason, a marked reduction in blood volume (73 +/- 2.29% [SE] of normal). Head-up tilt caused a pronounced increase in heart rate (+ 39 +/- 6 beats/min); one patient had a vasovagal episode after the initial tachycardia. Extensive diagnostic study excluded pheochromocytoma, hypoaldosteronism, or any obvious cause for hypovolemia (total plasma catecholamines, 372 +/- 53 ng/L; plasma aldosterone level, 14.5 +/- 2.56 ng/100 mL; plasma cortisol level, 18.5 +/- 2.4 ng/100 mL). The supine hemodynamic pattern (decreased cardiac output and increased total peripheral resistance with normal ejection fraction and mean transit time) was markedly different from that of hyperbeta adrenergic states. Acute plasma volume expansion (+ 11 +/- 2%) in ten patients using human serum albumin improved both their symptoms and heart rate response to tilt. After long-term blood volume expansion with florinef (E.R. Squibb, Princeton, New Jersey), 0.1 mg twice a day, and a high-salt diet, the head-up tilt test was repeated in five patients. The response was normal in four patients. These observations outline a syndrome of marked idiopathic hypovolemia with symptomatic labile hypertension and intolerance to head-up tilt, alleviated by volume expansion.

Vasoactive factors in the mechanism of renal sodium handling in cirrhotics: The effect of acute plasma expansion

Twenty cirrhotic patients with ascites, divided into two groups of 10 each, according to their daily urinary sodium excretion (sodium retainers and sodium excretors) and given a diet of 75 mEq of sodium daily, underwent acute plasma volume expansion with 1,000 ml of 10% dextran in saline, infused through a catheter located in the right atrium. Even if a significant increase in sodium excretion was observed in both groups (p less than 0.001 in sodium excretors and p less than 0.05 in sodium retainers), plasma expansion did not reverse sodium retention in sodium retainers. A significant increase in creatinine clearance was found only in sodium retainers (p less than 0.02). Basal plasma renin activity and plasma aldosterone were elevated only in a few patients of both groups. The renin-angiotensin-aldosterone system was highly responsive to plasma expansion. Sodium retainers, who showed an ineffective natriuretic response after expansion, were able to suppress both plasma renin activity and plasma aldosterone in an analogous manner to the sodium-excreting group. This result lends strong support to the concept that the elevated aldosterone level in cirrhosis is not the major determinant of sodium retention. The kallikrein-kinin system was responsive to volume stimulus, since a decrease in kallikrein excretion was noted. It was significant in sodium retainers (p less than 0.05). Plasma PGE1,2 levels were significantly higher in sodium retainers than in controls. This may suggest that there is an activation of the intrarenal prostaglandin system, which could play a protective role against renal ischaemia. After volume expansion, PGE1,2 increased, but not significantly. Octopamine appeared unrelated to sodium excretion and unresponsive to volume stimulus. Endotoxins did not seem to be involved in renal sodium handling. Plasma volume expansion seemed effective in inducing a reduction of vasoconstrictor and sodium-retaining factors, such as the renin-angiotensin-aldosterone system. It is possible to suggest that volume expansion could increase PGE1,2. Plasma volume expansion produced different rates of sodium excretion in the two groups of patients and this suggests that impaired sodium handling in cirrhosis could, to some extent, be independent of effective plasma volume.

Blood volume and hemoglobin concentration as determinants of maximal aerobic power

Changes in blood volume (BV) and hemoglobin concentration ( [Hb] ) were induced in five healthy young men. After acute hypovolemic anemia was achieved by blood withdrawal, VO2max values decreased, while the same [Hb] due to acute plasma volume expansion (6% dextran) did not alter VO2max. After reinfusion of red blood cells, leading to hypervolemia and increased [Hb], VO2max increased. Plasma volume expansion in this situation, leading to hypervolemia at normal [Hb], resulted in a slight reduction in VO2max, which, however, remained elevated (approximately 4%) above control values. Physical performance, measured as time to exhaustion, corresponded to the changes in VO2max except for the hypervolemic anemic situation, where it decreased. Changes in peak heart rate were inversely related to BV changes, but were also influenced by [Hb]. The results point to a significant influence of the total amount of Hb rather than the blood hemoglobin concentration for obtaining a high maximal aerobic power. Thus, a reduced [Hb], concomitantly with an elevated blood volume (plasma volume), may result in an unchanged VO2max, but reduced performance time.

Acute albumin‐induced plasma volume expansion and heat exposure: Effects on hormonal periodicity in men

Abstract To determine the effects of acute plasma volume expansion and heat exposure on the periodic oscillations of selected hormones, two doses of albumin were administered intravenously followed by exposure to heat stress (37°C, 25–30% RH). Plasma volume was previously established by a dye dilution technique using indocyanine green. During heat exposure blood samples were taken from antecubital catheters at 1, 3, 6, 9, 12, and 24 hours following completion of albumin or saline (control) infusion, and the plasma analyzed. No significant effects of heat stress or albumin administration were noted on circulating cortisol concentrations or on the diurnal/nocturnal periodicity of cortisol and aldosterone levels. There did occur a significant reduction in plasma levels of aldosterone as a result of albumin‐induced plasma volume expansion. We concluded that the duration and intensity of heat stress used in these studies had no effects on plasma hormonal levels and periodicities, but plasma volume expansion el...

Acute albumin-induced plasma volume expansion and exercise in the heat: effects on hormonal responses in men.

To assess the responses of fluid regulatory and stress hormones to acute expansion of plasma volume and exercise in the heat, 50 g of albumin dissolved in 200 ml normal saline or 200 ml saline alone was administered intravenously to 7 adult, male test subjects followed by exercise (40% VO2 max) in the heat (Tdb = 45 degrees C, Twb = 25 degrees C). Blood samples were obtained after sitting in the heat for 1 h, 1 h after completion of infusion which itself required approximately 1.5 h, after standing for 30 min, and 15, 30, 45, and 60 min after commencing exercise. Plasma cortisol levels were generally unaffected by these treatments. Responses of plasma aldosterone levels to postural change and exercise in the heat were attenuated in the albumin trial, and growth hormone levels were unaffected by albumin administration. Angiotensin I levels' were significantly decreased at several sampling intervals during the albumin trial, but unaffected by exercise. We concluded from these studies that plasma volume expansion by intravascular albumin administration had no effect on stress hormone responses during exercise in the heat, while regulatory hormone levels were lower in several instances during the albumin trial.

The effects of positive end-expiratory pressure on right and left ventricular performance.

The cardiovascular effects of positive end-expiratory pressure (PEEP) were studied in mechanically ventilated, vagotomized, Beta-blocked, anesthetized dogs. To compensate for the effect of PEEP on decreasing systemic venous return, acute plasma volume expansion was accomplished returning stroke volume and cardiac output to control values. Left and right ventricular filling pressures (LVFP and RVFP) and aortic pressure were measured relative to pressure (transmural pressure). Ventricular performance was assessed by comparing the transmural ventricular filling pressures at similar stroke volumes. Studies were performed on individual dogs with increasing LVFP produced by Beta-blockade, volume expansion, and obstruction of the descending thoracic aorta. Utilizing these methods we observed that for a given cardiac output, transmural LVFP was higher on PEEP compared to a control state with both normal and elevated control LVFP. On the right side, for a given cardiac output, RVFP was elevated only when the control LVFP was elevated. Our results suggest a nonneuronal adverse effect of PEEP on both left and right ventricular performance. This effect is probably due to mechanical heart-lung interaction since left ventricular (LV) dp/dt showed no change.

Human cardiovascular adjustments to exercise and thermal stress.

Human cardiovascular adjustments to exercise and thermal stress.

Renal Response in Sepsis

A significant diuresis was associated with early sepsis in dogs allowed food and water at will, even though water intake was below or near control levels. This occurred at a time of fever (39.9 C) and of increased fluid losses in the region of inflammation. Acute plasma volume expansion with dextran 75 (Dextran 6%) in normal saline before and after sepsis resulted in a higher peak urine flow 193μl/min/kg) in the septic state than under control conditions (147μl/min/kg). Administration of vasopressin injection during acute plasma volume expansion resulted in a reduction in the diuresis during sepsis (84μl/min/kg), but not under control conditions. Acute pretreatment of animals with desoxycorticosterone acetate (DOCA) was ineffective in dampening the diuresis of sepsis (218μl/min/kg), whereas, chronic treatment (eight days) with DOCA augmented the peak diuresis seen in sepsis (258μl/min/kg) during acute plasma volume expansion. Thus, in this laboratory model, sepsis resulted in an early diuresis, a phenomenon that may be related to a disturbance in the antidiuretic hormone system.

Dynamics of glomerular ultrafiltration in the rat. IV. Determination of the ultrafiltration coefficient.

Pressures and flow rates were measured in accessible surface glomeruli of mutant Wistar rats under conditions deliberately designed to prevent achievement of filtration pressure equilibrium, that is, the equalization of transcapillary hydrostatic and oncotic pressures by the efferent end of the glomerulus as typically observed in the normal hydropenic rat. Disequilibrium was obtained at elevated levels of glomerular plasma flow (GPF) brought about by acute expansion of plasma volume with a volume of rat plasma equal to 5% of body weight. Glomerular hydrostatic and oncotic pressures measured at high GPF were used to calculate the ultrafiltration coefficient, K(f), the product of effective hydraulic permeability and surface area. GPF was then either lowered (by aortic constriction) or raised (by carotid occlusion) in order to examine the dependence of K(f) on GPF. The value of K(f) per glomerulus, 0.08 nl/(s.mm Hg), was found not to vary over an approximately twofold range of GPF. This finding, taken together with data from previous studies from this laboratory, leads us to conclude that plasma-flow dependence of glomerular filtration rate (GFR) results primarily from flow-induced changes in mean ultrafiltration pressure, rather than large changes in K(f).

Disproportional changes in hematocrit, plasma volume, and proteins during exercise and bed rest.

The interrelationships between the changes in plasma volume, hematocrit, and plasma proteins during muscular exercise and bed rest were investigated. Proportionally, the changes in hematocrit are always smaller than the changes in plasma volume. For this reason changes in the concentration of blood constituents can only be quantitated on the basis of plasma volume changes. During short periods of intensive exercise, there was a small loss of plasma proteins. With prolonged submaximal exercise there was a net gain in plasma protein, which contributes to stabilization of the vascular volume. Prolonged bed rest induced hypoproteinemia; this loss of plasma protein probably plays an important role in recumbency hypovolemia.

Studies in clinical shock and hypotension

Left ventricular end diastolic (LVEDP) and mean right atrial (RAP) pressures were recorded simultaneously in 30 patients with shock (14 acute myocardial infarction, 10 acute pulmonary embolism or severe bronchopulmonary disease, and 6 sepsis). Myocardial infarction was characterized by a predominant increase in LVEDP, pulmonary disease by a predominant increase in RAP, and sepsis by a normal relationship between LVEDP and RAP. In all three groups a significant positive correlation was noted between RAP and LVEDP, with the regression line in cor pulmonale deviated significantly toward the RAP axis and the regression line in myocardial infarction exhibiting a zero RAP intercept at an elevated LVEDP.Low cardiac outputs with elevated LVEDP in myocardial infarction indicated severe left ventricular failure. Low outputs with elevated RAP in cor pulmonale were consistent with right ventricular overload. Although cardiac outputs often were normal in sepsis, low outputs with elevated cardiac filling pressures in some patients were consistent with a hemodynamic or humoral-induced generalized depression of cardiac performance.Vasoconstrictor and inotropic drugs often produced a functional disparity between the two ventricles, with the gradient between LVEDP and RAP increasing, apparently because of an increase in left ventricular work or an inadequacy of left ventricular oxygen delivery. Acute plasma volume expansion with dextran in patients with pulmonary vascular disease resulted in a somewhat more rapid rise in RAP than in LVEDP. In septic and myocardial infarction shock, however, LVEDP and RAP usually rose proportionally, with the absolute rise of LVEDP surpassing that of RAP. Although the absolute level of the central venous pressure thus may not be a reliable indicator of left ventricular function in shock, changes in venous pressure during acute plasma volume expansion should serve as a fairly safe guide to changes in LVEDP.

Study on alterations of blood flow and blood viscosity under hemorrhagic shock and effects of plasma expander.

Experiments were performed in 48 dogs subjected to a shock produced by hemorrhage after the modified Wiggers' method. Dogs were infused 90 minutes after hemorrhage with one of six test substances; shed blood, 5% glucose solution, or four kinds of dextran ( mw. 75,000, 47,000, 29,000 and 12,000 ). Infusion of dextran with mw. 29,000 produced the most remarkable increase in femoral arterial blood flow above the prehemorrhagic level. This flow improvement was thought to be more attributable to reduction in blood viscosity than an increase in blood volume. INTRODUCTION The development of shock is a complicated phenomenon not necessarily causally related to any one factor. The shock may be resulted from a multiplicity of influences such as hormonal, neural, circulatory and so onn. Hemorrhage, if it is significant in amount, may cause irreversible responses of the circulatory system. Maintenance of blood volume and blood pressure is necessary, but there is no guarantee to restore capillary circulation even with an adequate blood replacement. The circulatory conditions after hemorrhage are accompanied by cellular aggregation or sludging, increased blood viscosity and venular stasis of cells11 41 • Cellular aggregation, if uncorrected, may reduce nutritive capillary blood flow and result in hypoxic damages of the parenchymatous organs. A failure of capillary circulation is related to a principal cause of a fatal process. Reversal of cellular aggregation with return toward normal circulation is seen after the administration of low molecular weight dextran (LMWD )215)-91. The hemodynamic changes induced by the LMWD administration have been studied, both in terms of acute plasma volume expansion and in terms of blood flow increase attributed to the viscosity altering effects101 131 • Many studies216171 101 121 emphasize the relationship of viscosity alterations to the microcirculatory changes in the disturbed circulatory states and the usefulness of LMWD for Received for publication December 12, 1967. ~7l<rr'frl

Cardiac and renal hyperresponsiveness to acute plasma volume expansion in hypertension

Cardiac and renal hyperresponsiveness to acute plasma volume expansion in hypertension

PROTECTION AGAINST ACUTE TRAUMA AND TRAUMATIC SHOCK BY VASODILATORS

The effects of hydralazine and Dibenzyline, agents which induce vasodilatation by different mechanisms, on the development of shock were studied in rats subjected to two levels of trauma in a Noble–Collip drum. Hydralazine effectively reduced the incidence of acute traumatic deaths (those occurring during or within 15 minutes after completion of the period of trauma), but it protected against late, shock deaths and improved over-all survival only among animals subjected to relatively mild trauma. Dibenzyline completely eliminated all late, shock deaths and increased over-all survival at both levels of trauma. The total incidence of early deaths was unaltered, but among Dibenzyline-treated animals a higher percentage of these occurred during the period of trauma, indicating some increased susceptibility to the immediate effects of acute trauma. The drug also caused some increase in the incidence of intraperitoneal hemorrhage due to rupture of the liver or spleen. Vascular engorgement of these organs, which increased during the drumming period in both control and Dibenzyline-treated animals, was not altered by the drug. The results of combined administration of hydralazine or polyvinylpyrrolidone (PVP) and Dibenzyline were qualitatively and quantitatively the same as those obtained with Dibenzyline alone. These data indicate that vasodilatation induced by inhibition of sympathetic vasoconstriction provides effective protection against death from shock, but may increase susceptibility to the immediate deleterious effects of acute trauma. A drug such as hydralazine, which can increase cardiac output, and acute expansion of plasma volume by PVP may sustain the circulation, particularly the cerebral circulation, during acute trauma, but do not effectively increase ultimate survival.

PROTECTION AGAINST ACUTE TRAUMA AND TRAUMATIC SHOCK BY VASODILATORS

The effects of hydralazine and Dibenzyline, agents which induce vasodilatation by different mechanisms, on the development of shock were studied in rats subjected to two levels of trauma in a Noble–Collip drum. Hydralazine effectively reduced the incidence of acute traumatic deaths (those occurring during or within 15 minutes after completion of the period of trauma), but it protected against late, shock deaths and improved over-all survival only among animals subjected to relatively mild trauma. Dibenzyline completely eliminated all late, shock deaths and increased over-all survival at both levels of trauma. The total incidence of early deaths was unaltered, but among Dibenzyline-treated animals a higher percentage of these occurred during the period of trauma, indicating some increased susceptibility to the immediate effects of acute trauma. The drug also caused some increase in the incidence of intraperitoneal hemorrhage due to rupture of the liver or spleen. Vascular engorgement of these organs, which increased during the drumming period in both control and Dibenzyline-treated animals, was not altered by the drug. The results of combined administration of hydralazine or polyvinylpyrrolidone (PVP) and Dibenzyline were qualitatively and quantitatively the same as those obtained with Dibenzyline alone. These data indicate that vasodilatation induced by inhibition of sympathetic vasoconstriction provides effective protection against death from shock, but may increase susceptibility to the immediate deleterious effects of acute trauma. A drug such as hydralazine, which can increase cardiac output, and acute expansion of plasma volume by PVP may sustain the circulation, particularly the cerebral circulation, during acute trauma, but do not effectively increase ultimate survival.