S. Simchon

Surface adsorption of dextrans on human red cell membrane

The adsorption isotherms of dextrans with molecular weights of 40,000 (Dx 40), 74,000 (Dx 70), and 450,000 (Dx 500) were studied on normal red blood cells (RBCs) and RBCs with surface charge depleted by neuraminidase treatment. The adsorption curves on neuraminidase-treated RBCs showed a two-step behavior with secondary adsorption commencing at a bulk concentration of approximately 5 g/100 ml. A plateau adsorption of approximately 9 × 10−14 g/RBC was attained with bulk concentrations between 12 and 20 g/100 ml. Normal RBCs showed similar adsorption curves as neuraminidase-treated RBCs in Dx 70, as well as in Dx 500, with bulk concentrations up to 5 g/100 ml. Further increases in bulk concentration of Dx 70 or Dx 500 caused greater adsorption on normal RBCs than on neuraminidase-treated RBCs, with a plateau concentration of approximately 15 × 10−14 g/RBC. Adsorption of Dx 40 on normal RBCs was higher than that on neuraminidase-treated RBCs at all bulk concentrations. These results on surface adsorption have been correlated with the aggregation behavior of the same cell systems. The data offer evidence in support of the hypothesis that surface adsorption of dextrans leads to RBC aggregation by bridging adjacent cell surfaces. The results also indicate that the adsorption of dextrans to RBC surface is a dynamic, reversible process in which the adsorbed molecules exchange readily with the molecules in the bulk or those attached to another cell surface. RBC aggregation is associated with an apparent decrease in surface adsorption as the opposing cell surfaces in the aggregate share their adsorption sites via the same dextran molecules.

Salt-induced hypertension in Dahl salt-sensitive rats. Hemodynamics and renal responses.

This study was performed with Dahi salt-sensitive (DS) and Dahi salt-resistant (DR) rats to detect differences hi cardiovascular hemodynamics and renal responses that might be involved hi initiating salt-induced hypertension hi DS rats. The effects of 4 weeks of 8% NaCl diet were studied hi conscious, male DR and DS rats hi which vascular and urinary catheters had been previously implanted. Results were compared with those obtained from control groups of DR and DS rats on 4 weeks of 1% NaCl diet. DR rats on 8% salt diet did not develop hypertension, and cardiac output and blood volume were unchanged; glomerular filtration rate, urinary flow, sodium excretion, and plasma atrial natriuretic factor (ANT) increased. DS rats on 8% salt diet developed hypertension, and cardiac output and blood volume increased; glomerular filtration rate, urinary flow, and sodium excretion did not change, despite an increase hi ANF. DS and DR rats on 1% NaCl diet were subjected to ANF infusion. After ANF infusion DR rats had a decreased blood volume and an increased glomerular filtration rate, urinary flow, and sodium excretion; DS rats showed no significant changes hi blood volume, glomerular filtration rate, urinary flow, or sodium excretion. ANF caused vasodilation hi all regions studied hi DR rats; DS rats showed vasodilation hi all regions except the kidney. After acute volume expansion, although both DR and DS rats responded by an increase hi cardiac output, only DS rats developed prolonged hypertension. This finding suggests an inadequate vasodilatory mechanism in DS rats. In response to acute volume expansion, renal resistance decreased hi DR rats but not hi DS rats. It is concluded that the primary hemodynamic disturbance hi DS rats with salt-Induced hypertension is an increase hi cardiac output caused by blood volume expansion hi the absence of any vasodilation. Comparison of the responses of DS and DR rats to high salt diets, ANF infusion, and acute volume expansion indicates that the salt-induced hypertension in DS rats is initiated by a diminished renal response to ANF.

3. Effects of changes in systemic hemodynamic parameters on pulpal hemodynamics

Summary Changes in systemic hemodynamic parameters have a profoundeffect on pulpal hemodynamics. The optimum Hct range for the transport rate of O 2 to the pulp is between 35% and 55%. The pulpal circulation has relatively lower resistance and higher flow in comparison with the systemic circulation on a per unit weight basis. Pulpal blood flow is sensitive to sympathetic nerve activity which causes vasoconstriction.

Effects of Sodium Nitroprusside on Systemic and Regional Hemodynamics and Oxygen Utilization in the Dog

The effects of sodium nitroprusside (SNP) on the systemic and regional circulation, as well as on oxygen utilization, were studied in anesthetized dogs. A solution of SNP was infused intravenously to lower the blood pressure first to 75 per cent and then to 50 per cent of control. Seven of 15 dogs demonstrated resistance to SNP: SNP infusion rates ranging from 25 to 120 μg/kg/min were necessary in this group (resistant, or R, group) to bring blood pressure to 50 per cent of control, whereas less than 7 µg/kg/min SNP were needed to lower the blood pressure to 50 per cent of control in the other eight dogs, which were more sensitive to SNP (sensitive or S, group). In the control state, there was no apparent difference between the two groups in hemodynamic functions, oxygen transport, or oxygen utilization. In the R group, after blood pressure was lowered to 50 per cent of control, cardiac output increased to 150 per cent as a result of increased myocardial contractility, blood flows increased markedly in the myocardium (250 per cent) and brain (145 per cent) and decreased in the liver (hepatic artery, 40 per cent), kidney (50 per cent) and spleen (30 per cent), and myocardial oxygen consumption increased to 250 per cent of control. In the S group, corresponding values remained more or less constant throughout the period of hypotension. These findings may have significant implications in administering SNP to patients who are not responsive to SNP and who have hepatic or renal dysfunction, and/or coronary insufficiency.

A Double Isotope Technique to Determine Regional Albumin Permeability: Effects of Anesthesia

Abstract The transvascular leakage of albumin in various organs and tissues was studied with a double isotope technique in rats anesthetized with sodium pentobarbital, given intraperitoneally or intravenously, and in unanesthetized (conscious) rats. 125I-labeled albumin and 131I-labeled albumin were injected into the tail vein 1 hr apart. The albumin permeability index in tissues and organs is indicated by the local ratio (Xa/Ya)/(Xb/Yb), where (Xa/Ya) is the ratio of 125I/131I-albumin activities per g of tissue and (Xb/Yb) is the ratio of 125I/131I-albumin activities per g of blood. If there is no passage of albumin across the capillary membrane over the 1-hr period of study, the permeability index will be equal to one. In unanesthetized rats, the liver, lung, kidney, femoral muscle, and femoral skin were regions with a high albumin permeability index (above 2). In these organs, intraperitoneal and intravenous anesthesia caused a decrease or no significant change of the albumin permeability index. There was no significant albumin leakage over 1-hr period (index not significantly different from 1) in the mesentery, abdominal muscle, abdominal skin, cremaster, heart, and brain of unanesthetized rats. Intraperitoneal anesthesia caused the albumin permeability index to increase to approximately 4 in the mesentery, abdominal muscle, and the abdominal skin, but not in the cremaster, heart, or brain. These results demonstrate that pentobarbital anesthesia when given into the peritoneal cavity causes a significant increase in albumin leakage in the abdominal region.

Effects of blood viscosity on renin secretion

The effects of alterations in blood and plasma viscosities on plasma renin activity (PRA) were studied in dogs anesthetized with pentobarbital. Blood viscosity was altered by changing the hematocrit (Hct) level by isovolemic exchange using packed red blood cells or plasma. Plasma viscosity was elevated by isovolemic exchange using Hct-matched blood with high molecular weight dextran (Dx, mean m.w. approximately 450,000) dissolved in plasma. Following control measurements of plasma and blood viscosities, plasma [Dx], PRA, Hct and hemodynamic functions, the dog was subjected to isovolemic exchange transfusions to either alter the Hct or administer the Dx. Various measurements were repeated 40-60 min after each exchange. Arterial pressure and renal blood flow remained relatively constant after exchanges; increases in plasma and blood viscosities were accompanied by a decrease in renal vascular hindrance (vasodilation) to keep the renal flow resistance at control level. PRA rose with increases in plasma [Dx] and viscosity, and the rise in PRA was best correlated with the decrease in renal hindrance. The changes in PRA and renal hindrance have the same regression line whether blood viscosity was altered by Hct variation or Dx administration. The results indicate that increases in viscosity cause a compensatory vasodilation of renal vessels to cause renin secretion.

Effects of Fasting on Plasma Volume and Fluid and Sodium Exchanges in Male Rabbits

Summary Daily determinations or fluid exchanges, urinary Na+ excretion, and plasma volume, Na+, K+, protein, and os-molality were made using 13 adult male rabbits during periods of ad libitum feeding, food deprivation for 4 days (water available), and 1 day of refeeding. Significant increases in urinary Na+ excretion and volume occurred after 24 hr of deprivation, and a significant increase in drinking took place after 2 days; maximal values were obtained by Day 3 for all three parameters. The plasma volume was significantly reduced from 33.4 to 29.3 ml/kg, coincident with the changes in urinary volume and Na+ excretion after 1 day of deprivation, and remained at this reduced level. Plasma osmo-lality was decreased after 1 day of deprivation and continued to decline. Plasma concentrations of Na+, K+, and protein did not change. In a second group of rabbits deprived of food and water, a marked natri-uresis was induced despite the expected reduction in urine volume. In a third group of rabbits, plasma glucose concentration was decreased after 24 hr of fasting but returned to the control level by Day 2 of fasting. The data substantiate the assumption that the fasting-induced natriuresis and increased urine flow in the rabbit are accompanied by a reduction in plasma volume. The diuresis and natriuresis persist in fasting male rabbits with no further change in plasma volume after the first day of fasting. The natriuresis is clearly independent of the increased urine flow and fluid intake. The polydipsia is secondary to the reduction in plasma volume and enhances the increased urine flow to produce a marked polyuria. The authors thank Mr. John Hegmann for his excellent technical assistance.

Effect of verapamil on splanchnic haemodynamics in a portal hypertensive rat model

Abstract To elucidate the effects of verapamil on splanchnic haemodynamics in rats with portal hypertension, verapamil was given at a low dose (0.2 mg/kg) and a high dose (2 mg/kg) to the rat model after portal vein ligation. Approximately 10% decrease in arterial pressure was caused by the low dose of verapamil, with significant decreases in cardiac output and portal venous inflow as well as reduced portal pressure; these were all indicative of a rise in portal vascular resistance. In contrast, the marked fall in both arterial pressure and cardiac output in the high dose, accompanied by a significant decrease in the portal pressure and the unchanged portal venous inflow, suggested a reduction in portal vascular resistance. This study shows that the acute effects of verapamil on portal hypertension may vary with the dosage used. These results also demonstrate that, since the therapeutic efficacy and safety of verapamil is only in a very limited range of dose, caution should be taken in its clinical use in the treatment of cirrhosis with portal hypertension.

Analysis of the renin-angiotensin system during fasting in adult male rabbits.

Summary Caloric deprivation for 3 days in adult male rabbits induced significant increases in daily urinary Na+ excretion, urinary volume and fluid intake as previously reported. These changes were accompanied by: (a) a significant reduction in plasma renin concentration; (b) an unchanged plasma renin activity; (c) a marked increase in the plasma angiotensinogen concentration; (d) a significant reduction in plasma angiotensin I; and (e) a significant increase in plasma angiotensin II. In a separate group of adult male rabbits, 3 days of caloric deprivation significantly increased the amount of converting enzyme in pulmonary parenchymal tissue. These findings correlate with the previously reported enhancement of mineralocortical hormone secretion and limiting effect of the latter on the natriuresis of caloric withdrawal. Since the increased mineralocortical hormone secretion does not prevent the natriuresis, the possibility that these striking changes in the components of the renin-angiotensin system during caloric deprivation may exert intrarenal effects is discussed. The authors wish to thank Dr. R. O. Soffer, Albert Einstein College of Medicine, for his helpful suggestions and for providing us with a preprint of his method for determining the pulmonary converting enzyme. We also thank Mr. John Hegmann for his excellent technical assistance.

Electrochemical and Macromolecular Interactions at Red Blood Cell Surface

Red blood cells aggregate to form rouleaux in the presence of macro-molecules. Neutral and charged macromolecules were used to induce RBC aggregation quantified by microscopic observation. Variations of cell surface potential were achieved by the removal of RBC surface charge with neuraminidase treatment or by changing the ionic composition of the fluid medium. RBC aggregation by neutral polymer dextran is enhanced by removal of RBC surface charge and decreased by reduction of ionic strength. RBC aggregation by heparin requires the presence of sialic acids at cell surface and enhanced by reduction of ionic strength. It is concluded that the surface charge of RBCs plays a significant role in cell-to-cell interactions.