Transient pulmonary platelet sequestration during endotoxemia in dogs.

We evaluated the time-course of regional platelet sequestration, following a bolus dose of endotoxin in anesthetized dogs. Autologous indium 111 labeled platelets, representing less than 1% of the circulating platelets, were injected 35-60 min prior to administering endotoxin intravenously to dogs. A gamma camera was used to monitor the distribution of these platelets within the thorax and abdomen. Alterations in the circulating blood platelet count paralleled the changes in blood radioactivity, enabling us to use external imaging to evaluate platelet kinetics. Marked hypotension and thrombocytopenia occurred within 6 min after administering endotoxin. The platelet pool in the lungs peaked at 9 min and was temporally related to the decrease in circulating platelet count, hypotension and increase in liver size. Translocation of platelets from the lungs to the circulating platelet pool occurred during the subsequent hour with sequestration occurring in the liver and possibly other organs. During this phase there was a recovery in platelet count to 35% of baseline levels but without significant recovery in mean arterial pressure. Based on these results we propose that endotoxin-induced thrombocytopenia results from pulmonary and hepatic sequestration of platelets, but that sequestration of platelets in the lungs is only transient. The mechanism and significance of subsequent translocation of platelets from the lungs to other sites, particularly the liver and the circulating platelet pool, remain to be investigated.

Spectral characterization and attenuation measurements in ultrasound.

Various means of characterizing ultrasonic attenuation in tissue are reviewed. A simple method for estimating frequency-dependent attenuation via measurement of the zero crossing density of the signal is presented and validated. Both the effects of the frequency dependence of scatter and stochastic variability of the measurement are considered and discussed. Results of measurements made in phantoms, animals and humans are presented and compared to the theoretical model. The technique is shown to be technically feasible.

Spectral variations in tissues and phantoms.

This paper is concerned with the characterization of attenuation in tissue. A simple method for measuring frequency dependent attenuation is demonstrated. The effects of frequency dependent scatter on the measurement of attenuation are also considered in order to determine the theoretical and practical ramifications of this interfering effect. Finally, a means of placing definitive error bounds on the statistical reliability of the measurement is discussed.

Pressure-flow relationships and pathological changes during renal preservation.

The renal pedicle of one kidney from each of four dogs was ligated for one hour. The contralateral kidney served as a control. Both kidneys were removed and perfused using the "Belzer" technique. Pressure-flow relationships were determined and biopsy samples taken. The vasculature was then injected with silicone rubber. Perfusion resistance, vascular filling with silicone rubber and observations made by electron microscopy were compared.

Functional adaptation of nephrons in dogs with acute progressing to chronic experimental glomerulonephritis.

Although a diminished fractional excretion of sodium (FENa) is the hallmark of acute proliferative glomerulonephritis (APGN), an enhanced natriuresis per glomerular filtration rate (GFR) in the chronic phases of this disease has been reported. We studied this adaptive response utilizing two different split-bladder dog models with unilateral, and a third group of dogs with bilateral Masugi's nephritis. Group I. Six dogs with unilateral nonaccelerated APGN studied a mean of 6 days after induction had a mean base-line APGN/intact kidney GFR of 31/50 ml/min (P less than 0.005) and FENa of 0.2/0.75% (P less than 0.005). Acute volume expansion caused a smaller absolute increase in FENa from the APGN kidney, 1.6%, than from the intact kidney, 4.0%, (P less than 0.01). Maximum tubular secretion of rho-aminohippuric acid/GFR (TmPAH/GFR) measured in three dogs was higher in the APGN kidney than intact kidney, 13.1 vs. 9.3 mg/dl. Subsequent studies on three of the six dogs when the disease had become chronic demonstrated a reversal in the pattern of sodium excretion in response to volume expansion. Group II. Six dogs with accelerated unilateral APGN (dogs presensitized to antibody source) studied a mean of 5 days after induction had a mean base-line APGN/intact kidney GFR of 16/57 ml/min and FENa of 0.22/0.12% (P less than 0.1). Contrary to group I, volume expansion caused a greater absolute increase in FENa from the APGN kidney, 5.8%, than from the intact kidney, 2.9% (P less than 0.05). TmPAH/GFR studied in four dogs was similar for both kidneys, 17.9 and 18.5 mg/dl for the APGN kidney and intact kidney, respectively. Group III. Sequential studies were performed on seven dogs with bilateral nonaccelerated APGN. Initially each demonstrated sodium retention and a smaller absolute increase in FENa in response to volume expansion compared to a predisease control study. With disease progression, volume expansion induced a greater absolute increase in FENa than in the control study. We concluded that (a) the fractional excretion of sodium from the APGN kidney will be less or greater than the contralateral intact kidney or control study depending on the severity and/or chronicity of the disease, possibly as the result of morphologic alterations; (b) the degree of extracellular fluid volume expansion is an important variable influencing similarity of glomerulotubular balance between the APGN and contralateral intact kidney; and (c) the "intact nephron hypothesis" applies in a limited fashion to kidneys with APGN in the absence of volume expansion just as it does for kidneys with chronic glomerulonephritis or pyelonephritis.

Self-hemodialysis. The optimal mode of dialytic therapy.

Maintenance hemodialysis is presently the mainstay of treatment for the majority of patients with end-stage renal disease. There has been disagreement, however, as to what form the delivery of dialysis should take-self-dialysis, at home, or in-center, as opposed to in-center, limited-care dialysis. This review of the recent literature strongly supports self-dialysis as the optimal form of therapy, since the cost is less, and survival and rehabilation are better than with limited-care dialysis. We conclude that a greater effort should be expended to encourage and even direct patients toward this form of therapy.

Disproportionate inhibition of sodium reabsorption in the unilaterally diseased kidney of dog and man after an acute saline load.

Clearance studies were performed on 49 split-bladder dogs with a unilateral pyelonephritic or remnant kidney and three patients with unilateral kidney disease to examine the effects of an acute saline load on the diseased kidney (DK) as opposed to a simultaneously studied, contralateral control kidney (CK), which also served to maintain a nonuremic environment. Before saline loading, base line studies in many of the dogs and the three humans were in agreement with previously published data. However, in dogs with a severe pyelonephritic lesion, a greater difference in DK vs. CK fractional excretion of sodium (FE(Na)) and water was noted, whose magnitude was inversely correlated with the level of glomerular filtration rate (GFR) and maximum urine osmolality of DK compared to CK. An acute saline load (75 ml/kg) resulted in an inhibition of fractional sodium and water reabsorption in the diseased dog kidney which was disproportionately greater than in the simultaneously studied CK, regardless of the type or severity of the lesion. While mean DK GFR for all dogs increased 15% more than CK GFR, failure of FE(Na) to increase after induction of a disproportionate increase in DK GFR with parathyroid hormone suggested that the saline-induced disproportionate increase in GFR was not solely responsible for the exaggerated inhibition of fractional sodium and water reabsorption in the diseased dog kidney. Studies in the three patients after saline loading (25 ml/kg) revealed a similar disproportionate resetting of glomerulotubular balance.Thus, regardless of base line function before expansion, the unilaterally diseased kidney of dog and man possesses unique characteristics in the absence of uremia which render it more reactive to the stimuli produced by acute saline loading. This suggests that the intrarenal environment of the kidney with a reduced nephron population may under some circumstances serve as a determinant of its function.