Individual renal clearances determined at renal vein catheterization.

Renal para-aminohippurate (PAH) clearances were predicted in 16 kidneys of eight hypertensive patients with renal artery stenosis, pyelonephritis, or obstructive nephropathy, without individual ureteral catheterization. Predictions of left or right kidney clearance (CL or CR) were based on roentgenographic renal frontal areas (A), on total PAH clearances (CT), and on individual PAH extractions (E) measured at renal vein catheterization according to the formula (formula: see text). When these patients underwent ureteral catheterization for diagnostic reasons, individual PAH clearances were measured and ranged from 22 to 286 cm3/min. After correction for differences in total PAH clearance on the two occasions, predicted and individually measured values corresponded closely along a line of identity. The 95% confidence limit (+/- 2 SEM) for predictions of individual PAH clearance was approximately +/- 38 cm3/min and for percet of total PAH clearance distributed to left or right kidney, +/- 6%. Individual renal PAH clearances can therefore be predicted at renal vein catheterization with acceptable error. Thus, the substantially invasive procedure of ureteral catheterization is not required to ascertain left and right kidney PAH clearance in patients already at risk from renal disease.

Permeability of dog lung endothelium to sodium, diols, amides, and water.

Bolus injection of T-1824-albumin, test indicator, and tritiated water into a jugular vein of the anesthetized dog and sequential sampling of blood from a carotid artery yielded multiple-indicator outflow patterns for the lung. Permeability-surface products of the test indicator for the lung endothelial barrier were obtained by comparison of test indicator with T-1824-albumin on the upslope of the test-indicator curve and correction for backdiffusion. The derived endothelial permeability coefficients, based on surface area/wet lung weight-500 cm2/g (mean +/- 2 SE, 10(-5) cm s(-1)), were: sodium ion, 2.9 +/- 0.8; ethylene glycol, 7.3 +/- 1.5; 1, 3-propranediol, 7.9 +/- 3.2; 1, 2-propanediol, 10 +/- 4; 1, 4-butanediol, 14 +/- 8; 1, 5-pentanediol, 21 +/- 6; 1, 6-hexanediol, 41 +/- 11; formamide, 16 +/- 9; acetamide, 13 +/- 4; propionamide, 31 +/- 12; butyramide, 42 +/- 24; valeramide, 79 +/- 12; tritiated water, 150 +/- 50. The backdiffusion correction varies from 8% for sodium to 75% for valeramide. A parallel-pathway model of blood-tissue passive exchange of small nonelectrolyte solutes is compatible with these results, with a lipid pathway through endothelial cells and an aqueous pathway possibly through interendothelial clefts.

Reflection coefficients of dog lung endothelium to small hydrophilic solutes.

Step additions of small hydrophilic solutes to the perfusate of isolated dog lungs produce weight changes (Vargas-Johnson). The product: (observed reflection coefficient) times (observed filtration coefficient) for the lung endothelial barrier is obtained from the initial weight slope per unit osmolality change. The observed filtration coefficient determined from the sustained constant weight slope per increment of pulmonary outflow pressure was 0.038 plus or minus 0.011 cm/s (assumed exchange area 500 cm2/g lung). Correction to average transcapillary pressure (32% upward) and for osmotic buffering by resident solute (25% upward) gave 0.063 plus or minus 0.018 cm/s. The observed reflection coefficients were (mean plus or minus 2 SE): sodium chloride, 0.30 plus or minus 0.11; urea, 0.30 plus or minus 0.12; glucose, 0.48 plus or minus 0.26; sucrose, 0.39 plus or minus 0.17; raffinose, 0.35 plus or minus 0.16; hypotonic response: interstitial solute, 0.26 plus or minus 0.10. The observed reflection coefficient of sodium chloride, corrected for the preceding filtration coefficient effects (65% downward) and for combined flow limitation and osmotic buffering effects (50% upward) was 0.27. Transcapillary gradients of small hydrophilic solutes produce substantial osmotic effects for short times (seconds). Passive exchanges and net fluxes across the endothelium of the lung capillaries have parameters similar to those of the endothelium of skeletal muscle.

Red cell permeability effect on the mean transit of an indicator transported through an organ by red cells and plasma.

When an indicator that permeates red blood cells with an equilibration time of the order of the mean transit time of the indicator through an organ is bolus injected solely into the plasma inflow to that organ, the mean transit time of the indicator is greater than it is when the indicator is injected preequilibrated between the plasma inflow and the red cell inflow. The mean transit time for equilibrated entry is in turn greater than that for indicator injected solely into the red cell inflow. A simplified method of calculation of this effect is given in the present paper; it requires only a model solution for the indicator steady state as distinguished from a more complicated time-dependent solution. The dependence of the effect on red cell membrane permeability allows this permeability to suitable indicators to be deduced. The method was applied to existing data on urea and thiourea passage through the dog kidney.

Red cell membrane permeability deduced from bulk diffusion coefficients.

The permeability coefficients of dog red cell membrane to tritiated water and to a series of[(14)C]amides have been deduced from bulk diffusion measurements through a "tissue" composed of packed red cells. Red cells were packed by centrifugation inside polyethylene tubing. The red cell column was pulsed at one end with radiolabeled solute and diffusion was allowed to proceed for several hours. The distribution of radioactivity along the red cell column was measured by sequential slicing and counting, and the diffusion coefficient was determined by a simple plotting technique, assuming a one-dimensional diffusional model. In order to derive the red cell membrane permeability coefficient from the bulk diffusion coefficient, the red cells were assumed to be packed in a regular manner approximating closely spaced parallelopipeds. The local steady-state diffusional flux was idealized as a one-dimensional intracellular pathway in parallel with a one-dimensional extracellular pathway with solute exchange occurring within the series pathway and between the pathways. The diffusion coefficients in the intracellular and extracellular pathways were estimated from bulk diffusion measurements through concentrated hemoglobin solutions and plasma, respectively; while the volume of the extracellular pathway was determined using radiolabeled sucrose. The membrane permeability coefficients were in satisfactory agreement with the data of Sha'afi, R. I., C. M. Gary-Bobo, and A. K. Solomon (1971. J. Gen. Physiol. 58:238) obtained by a rapid-reaction technique. The method is simple and particularly well suited for rapidly permeating solutes.

Long-term kinetics of serum and xanthoma cholesterol radioactivity in patients with hypercholesterolemia.

In four patients with hypercholesterolemia (type II hyperlipoproteinemia) and xanthomatosis the decay of serum cholesterol specific activity was followed for 53-63 wk after pulse labeling. Specific activity of biopsied xanthoma cholesterol was measured four times in the course of the study. The xanthoma specific activity curve crossed and thereafter remained above the serum specific activity curve. The average ratio of xanthoma to serum specific activity was 4.7 at the end of the study. The final half-time of the xanthoma decay curves was significantly greater (average: 200 days) than the slowest half-time of serum specific activity decay (average: 93 days). The data were analyzed by input-output analysis and yielded the following results. The average value for the total input rate of body cholesterol (I(T)) (sum of dietary and biosynthesized cholesterol) was 1.29 g/day. The average size of the rapidly miscible pool of cholesterol (M(a)) was 55.7 g. and of the total exchangeable body mass of cholesterol (M) 116.5 g. The average value of M - M(a) (remaining exchangeable mass of cholesterol) was 60.8 g. The derived values for exchangeable masses of cholesterol, in the present patients with marked hypercholesterolemia, were significantly larger than in a group of patients with normal serum lipids in previous studies. One of the four patients died of a sudden acute myocardial infarction 53 wk after pulse labeling. Specific activity of aortic wall and atheroma cholesterol was 3.12 times that of serum. The ratio was close to 2 for adipose tissue and spleen, and was slightly above 1 or was close to unity in most other organs studied, with the exception of brain which showed a ratio of 0.19.

Long-term decay of serum cholesterol radioactivity: body cholesterol metabolism in normals and in patients with hyperlipoproteinemia and atherosclerosis.

After the intravenous injection of labeled cholesterol, the decay of specific radioactivity of total serum cholesterol was studied in 12 patients for 15-63 wk (average, 45 wk). In some, but not all of the patients studied, the slow slope of the decay curves suggested a deviation from monoexponential behavior, and the data of the slow period of the decay of specific activity were curve fitted by two exponentials. Six patients had serum lipid values regarded as normal and six had hyperlipoproteinemia. The data were analyzed by input-output analysis and yielded the following results. Values for the input rate of cholesterol (I(T)) (the sum of dietary and biosynthesized cholesterol) showed no difference between the normals and patients with hypercholesterolemia. The size of the rapidly miscible pool of cholesterol (M(a)) was significantly higher in the group of hypercholesterolemic patients partly due to increased serum cholesterol levels. The size of the total exchangeable body mass of cholesterol (M) was higher by an average of 49 g in the patients with hypercholesterolemia as compared to normals. The remaining exchangeable mass of cholesterol (M - M(a)) of the hypercholesterolemic subjects was higher by an average of 29 g as compared to normals. These differences were statistically significant.