Effects of sodium nitroprusside on systemic and regional hemodynamics and oxygen utilization in the dog.
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Biomedical subjects
Publications and source records attributed to S Chien.
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The responses of alterations in regional hemodynamics and oxygen transport rate to hematocrit (Hct) were studied in 20 pentobarbitalized dogs. Hemodilution was carried out by isovolemic exchange with plasma in 12 dogs and the hemoconcentration with packed cells in 8 dogs. The cardiac output and regional blood flows were determined with the microsphere technique. In hemodilution, the increases of blood flow to the myocardium and the brain were out of proportion to the increase of cardiac output; the oxygen supply to the myocardium remained unchanged while that to the brain decreased only slightly. In hemoconcentration, vasodilation occurred in the myocardium and the brain to maintain constant oxygen supply. Splenic vessels had marked vasoconstriction with Hct alteration in either direction. Blood vessels in the liver, intestine, and kidney responded with a milder vasoconstriction and maintained a constant oxygen supply between Hct of 30-55%. Therefore, during Hct alteration, redistribution of blood flow to myocardium and brain occurred. The optimal Hct range for constant oxygen supply was different among various organs.
Twenty closed-chest dogs anesthetized with pentobarbital sodium were used for studying coronary hemodynamics and myocardial oxygen utilization during hemorrhagic hypotension, with the mean arterial pressure maintained constant at 50 mmHg. Variations of hematocrit (Hct) were achieved by exchange of blood with plasma or packed cells. Coronary blood flow (133Xe washout) varied inversely with Hct, whereas cardiac output (indicator dilution) showed a peak value at a Hct of approximately 25%. Coronary, systemic, and pulmonary flow resistances varied in the same direction with Hct, and the relationship was attributable to the change of blood viscosity with Hct. Analyses of vascular hindrance (= resistance/viscosity) suggested that during hemorrhagic hypotension, coronary vasodilation was maintained during variations of Hct. In systemic and pulmonary circulations, however, there were marked increases in vasoconstriction after hemodilution. The optimum Hct for maximum O2 transport was 25% for coronary circulatin and approximately 45% for systemic circulation. The O2 consumption (QO2) in the myocardium increased after hemodilution with a peak value at a Hct of approximately 25%. The QO2 in the total body was constant over a wide range of Hct between 25 and 45%, above and below which the QO2 decreased.
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In order to establish quantitative models of leukocyte functions, several morphometric parameters on individual white cells are needed. These include the diameter, volume, and membrane area of the cells and their nuclei in the undeformed state. A stereologic method was used to obtain these quantities from transmission electron microscopy of random sections through human white blood cells (neutrophils, lymphocytes, monocytes, and eosinophils). In order to estimate possible artifacts due to preparation of the cells for transmission electron microscopy, a detailed comparison with light microscopy was made. The results show that undeformed white cells in isotonic solution are spherical with many membrane foldings and have a significantly smaller diameter than that measured on blood smears. A method of chemical fixation was employed so that the shrinkage due to fixation of the cells is below the resolution of light microscopic measurements. Further, it was shown that all leukocytes, including lymphocytes, have much more membrane area than is needed to cover their volumes, and this membrane area remains constant when the cell is hypotonically swollen.
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The effects of surface hypothermia (25 degrees C) on arterial hematocrit value (by microcentrifuge) and plasma protein concentration (by refractometry) were studied in infants undergoing surface cooling for cardiac operations. To analyze in detail the mechanisms leading to the observed changes in patients, we performed parallel studies on normal dogs and permanently splenectomized dogs. In these dogs, measurements were also made of plasma volume (by 125I-albumin) and red cell volume (by 51Cr-erythrocytes). Arterial hematocrit value increased progressively during surface cooling in infants. Assuming that red cell volume remained constant and that the ratio of whole body red cell percentage to arterial hematocrit value during surface cooling in infants as in splenectomized dogs, we estimated percent changes in plasma volume in infants from arterial hematocrit data. The computed plasma volume decreased progressively as the body temperature was decreased. Since plasma protein concentration remained constant, the loss of plasma volume suggested a sequestration of whole plasma in portions of the circulatory bed and/or an extravasation of whole plasma into the interstitial space.
By using scanning electron microscopy (SEM) we were able to follow the sequence of ultrastructural alterations of the luminal surface which occurred when specimens of canine carotid artery were subjected to controlled transmural pressures. Specimens of carotid artery were removed from dogs following fixation at experimental pressures ranging from 0 mm Hg to 100 mm Hg. The endothelium of specimens fixed at 0 mm Hg has parallel longitudinal ridges formed by the contraction of the underlying internal elastic lamina. With increasing transmural pressure, the luminal surface undergoes a gradual flattening of the endothelial ridges so that at 100 mm Hg, these ridges have completely disappeared. The observed morphologic changes of the arterial endothelium indicate that SEM can provide good ultrastructural information on blood vessels subjected to controlled transmural pressure and that the pressure-dependent alterations must be considered in studies on vascular structure and function.
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Individual populations of AA and SS erythrocytes were fractionated according to cell density by centrifugation, and the fractions analysed for intracellular pH (PHi), the mole ratio of 2,3-diphosphoglycerate to haemoglobin (DPG:Hb), and cell concentration of haemoglobin (MCHC). The pHi of SS erythrocytes was consistently lower than that of AA erythrocytes throughout the density range, and the lowest pHi of both cell types (AA and SS) was found in cells with the highest density. As the highest density AA and SS erythrocytes are characterized by the lowest DPG:Hb values, their relatively low pHi cannot be ascribed to intracellular organic phosphate. Instead we propose that a redistribution of hydrogen ions across the membrane of both AA and SS erythrocytes is the ultimate result of progressive alterations in these membranes in vivo.
In 17 pentobarbitalized dogs, the shunting of 15-micrometer and 9-micrometer microspheres was studied in the brain, myocardium, kidney, intestine, and lung. The veins of these organs were catheterized for constant blood withdrawal for 2 min by direct venipuncture. The ratio of microsphere radioactivity in the venous blood to that in the arterial blood gave the shunting of microspheres by the venous sampling technique. The 15-micrometer microspheres showed 2% or less shunting for all organs studied, whereas the 9-micrometer microspheres had shunting ranging from 3% in the coronary sinus to 24% in the portal vein. The shunting of 9-micrometer microspheres was also calculated from direct tissue counting, where the 15-micrometer spheres were considered to be completely entrapped. The results of direct tissue counting indicate that the 2-min venous sampling underestimates microsphere shunting. CO2 administration increased significantly the shunting of 9-micrometer spheres, whereas the shunting of 15-micrometer spheres determined by venous sampling remained less than 2%. Consideration of shunting indicates that the 15-micrometer microspheres might be more appropriate for regional organ blood flow measurements, including the myocardium.
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Duchenne erythrocytes showed increased osmotic fragility as compared to controls (p less than 0.01), but individual values overlapped with controls, and only half of the Duchenne erythrocyte values were abnormal. When the effect of the smaller mean corpuscular volume of Duchenne erythrocytes was taken into account, there was no significant difference from controls in membrane deformability, as determined by microsieving or flow channel measurements. The increased osmotic fragility suggests minor changes in erythrocyte membrane properties in Duchenne muscular dystrophy.
Studies of 16 adults with nephrotic edema reveal a spectrum of disease, the extremes of which suggest two different pathophysiologic forms. Patients with the "classic" form--vasoconstriction or hypovolemic nephrosis--have high renin and aldosterone levels that are stimulated rather than suppressed by salt-loading but become lower before steroid diuresis. These patients have minimal lesion disease and, perhaps from diffuse capillary damage, tend to have hypovolemia with renin-induced vasoconstriction. Patients with the second, and heretofore undescribed, form--hypervolemic or overfilling nephrosis--have low renin and aldosterone values that rise normally after sodium depletion. Hypertension, mild renal insufficiency, hypervolemia, and steroid resistance with chronic glomerulonephritis are seen histologically. This form appears volume overloaded from impaired renal sodium excretion. In remission of either type, renin system deviations tend towards normal, but one form does not convert to the other. Renin-sodium profiling may help reveal the two forms and predict steroid responsiveness.
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The deformation of a portion of erythrocyte during aspirational entry into a micropipette has been analyzed on the basis of a constant area deformation of an infinite plane membrane into a cylindrical tube. Consideration of the equilibrium of the membrane at the tip of the pipette has generated the relation between the aspirated length and the dimensionless time during deformational entry as well as during relaxation after the removal of aspiration pressure. Experimental studies on deformation and relaxation of normal human erythrocytes were performed with the use of micropipettes and a video dimension analyzer which allowed the continuous recording of the time-courses. The deformation consisted of an initial rapid phase with a membrane viscosity (range 0.6 x 10(-4) to 4 x 10(-4) dyn.s/cm) varying inversely with the degree of deformation and a later slow phase with a high membrane viscosity (mean 2.06 x 10(-2) dyn.s/cm) which was not correlated with the degree of deformation. The membrane viscosity of the recovery phase after 20 s of deformation (mean 5.44 x 10(-4) dyn.s/cm) was also independent of the degree of deformation. When determined after a short period of deformation (e.g., 2 s), however, membrane viscosity of the recovery phase became lower and agreed with that of the deformation phase. These results suggest that the rheological properties of the membrane can undergo dynamic changes depending on the extent and duration of deformation, reflecting molecular rearrangement in response to membrane strain.
Hemodynamic functions and blood viscosity changes in hypothermia (core approximately 25 degrees C) were studied in 14 pentobarbital-anesthetized dogs subjected to surface cooling. The viscosity of blood (eta B) increased progressively to 173% of that at 37 degrees C when body temperature was lowered to 25 degrees C. The increase in blood viscosity was caused by: a) the direct effect of low temperature on plasma viscosity, b) hemoconcentration as a result of plasma loss, and c) the low-flow (low-shear) state induced by hypothermia. A larger portion of the increased viscosity was caused by the low-flow state in hypothermia. The systemic flow resistance (SFR) increased to 271% of control, and this was attributable about equally to the increases in blood viscosity and systemic vascular hindrance (SFR/eta B). Similarly, the viscosity of blood contributed significantly to raising the pulmonary flow resistance. The relative constancy of mixed venous O2 saturation suggests that the cardiac output at low body temperature is generally adequate to meet the metabolic needs.