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Biomedical subjects

C W Gottschalk

Publications and source records attributed to C W Gottschalk.

At least 19 recordsLinked to original sources

History of the science of dialysis.

Thomas Graham (1805-1869), who is credited with seminal work on the nature of the diffusion of gases and of osmotic forces in fluids, can properly be called the father of modern dialysis. His apparatus to study the behavior of biological fluids through a semipermeable membrane clearly presaged the artificial kidney in clinical use today. In 1913, John Abel and coworkers reported the first application of the principles of diffusion to remove substances from the blood of living animals. Unaware of Abel's work, Georg Haas (1886-1971) performed the first human dialysis in the German town of Giessen in 1924. But it was not until 1945 that Willem Johan Kolff, working under extremely difficult wartime conditions in The Netherlands, achieved the first clinically successful hemodialysis in a human patient.

Animals↗

Alexander Schumlansky's De structura renum.

The overall structural organization of the kidney, its vasculature and its excretory units, the nephrons, was the subject of intense study and disagreement for hundreds of years. In 1783, Schumlansky received a doctoral degree with the dissertation De structura renum, in which he presented a detailed and comprehensive description of the major blood vessels of the kidney, the blood vessels of the medulla and pyramids of Ferrein and the malpighian glandula. He concluded the dissertation with a description of 3 experiments on a pig kidney, deducing a connection between the glomerulus and the uriniferous tubule, though his illustration of it was far from convincing. It was only 59 years later that Bowman proved Schumlansky to be correct.

Anatomy↗

Elucidation of kidney function by micropuncture: an historical perspective.

An understanding of the fundamental mechanisms of kidney function awaited the advent of micropuncture techniques. The initial micropuncture study by Wearn and Richards in 1924 presented the first direct evidence that the initial step in urine formation was the process of ultrafiltration at the glomerulus and that certain solutes were reabsorbed in the renal tubules. Subsequent micropuncture studies and the development by Burg and colleagues for in vitro perfusion of surviving tubular segments have provided an enormous amount of information about glomerular function and the transport characteristics of all nephron segments in the normal and diseased kidney.

History, 20th Century↗

Effects of chronic renal denervation in conscious restrained rats.

Sodium (Na), calcium (Ca), inorganic phosphate (Pi) and water excretion were measured in nondiuretic (ND) and extracellular fluid (ECF) volume expanded (VE) conscious restrained rats four weeks after denervation or sham-denervation of the left kidney. On the day of the study the animals were lightly anaesthetized with ether and the femoral vessels on one side were catheterized. Urine was collected from both kidneys. The animals were allowed to recover for 3 hours and studied in a restraining chamber. In ND animals isotonic saline containing inulin and para-amino-hippuric acid (PAH) were given at a rate of 0.067 +/- 0.002 (SE) ml/min/kg body weight (BW). In VE animals the infusion rate was 0.24 +/- 0.04 ml/min/kg BW. Kidney catecholamine content was measured after the experiments. Clearances of PAH and of inulin (GFR) were the same in both kidneys. Urine volume (V), sodium excretion (UNa V/GFR), inorganic phosphate excretion (UPi V/GFR) and calcium excretion (UCa V/GFR) were significantly higher in the denervated kidneys. Values in sham denervated kidneys were not greater than those of the right kidney. Denervation was proven by demonstrating absent or very low catecholamine content in the kidneys. The results demonstrate that: chronic renal denervation in rats leads to diuresis and natriuresis even in the conscious state, thus confirming previous results from our laboratory; such changes occur independently of the state of the ECF volume and of renal haemodynamic changes; the increased excretion of Ca++ and Pi after denervation demonstrates that renal nerves affect the reabsorption of these ions either independently or by way of their effect on sodium reabsorption. These data allow us to suggest that a renal tubular dysfunction, which was proved in anaesthetized denervated animals, can also be observed in the conscious state.

Animals↗

Prostaglandin blockade impairs denervation diuresis and natriuresis in the rat.

Acute unilateral renal denervation of control rats produced an ipsilateral diuresis (5.5 +/- 0.8 to 10.0 +/- 1.0 microliter/min, P less than 0.01) and natriuresis (579 +/- 202 to 2,668 +/- 225 neq/min, P less than 0.01) without a significant change in glomerular filtration rate or effective renal plasma flow. Inhibition of prostaglandin synthesis with indomethacin or meclofenamate (4 mg/kg iv) after acute unilateral denervation eliminated the diuresis (13.3 +/- 1.6 to 5.0 +/- 0.9 microliter/min, P less than 0.01) and attenuated the natriuresis (3,098 +/- 462 to 1,097 +/- 163 neq/min, P less than 0.01). Denervation diuresis and natriuresis were significantly impaired to the same extent when denervation was performed after inhibition of prostaglandin synthesis (3.2 +/- 0.3 to 4.9 +/- 0.4 microliter/min, NS; and 490 +/- 154 to 1,036 +/- 274 neq/min, P less than 0.05 vs. control, respectively). These results indicate that the natriuresis and diuresis seen after acute unilateral denervation in anesthetized rats are highly dependent upon prostaglandins and cannot be initiated or maintained when prostaglandin synthesis is impaired by indomethacin or meclofenamate.

Animals↗

Glomerular ultrafiltration dynamics: historical perspective.

Our knowledge of the structure and function of the renal glomerulus is reviewed in a historical context. The glomerular corpuscles were first described by Malpighi in 1666. Subsequent injection studies led to conflicting claims concerning a glomerular-tubular connection. This connection was accepted only after the convincing demonstration of the anatomical relationship essentially as we now know it by Bowman in 1842. Ludwig was the first to propose that the mechanism of separation of fluid in the glomeruli was by ultrafiltration. Estimates of the ultrafiltration forces in mammals led to conflicting speculation as to whether or not filtration-pressure equilibrium was reached in glomerular capillaries. Results of direct determinations in some Munich-Wistar rats indicate filtration pressure equilibrium, an ultrafiltration coefficient (Kf) of 0.08 nl X s-1 X mmHg-1, and a strong influence of plasma flow on filtration rate (GFR). In contrast, evidence has been presented that filtration dynamics in other Munich-Wistar rats and several other strains of rats are characterized by filtration disequilibrium, a Kf of 0.04 nl X s-1 X mmHg-1, and a weak dependence of GFR on plasma flow. In conscious and anesthetized rats, kidney GFR is usually relatively stable in the presence of renal vasodilation. Filtration disequilibrium is reported in the dog and equilibrium in the squirrel monkey. Although predictions for humans suggest filtration disequilibrium, final conclusions await an in-depth analysis of direct measurements.

Animals↗

Role of renal nerves in maintaining sodium balance in unrestrained conscious rats.

This study was designed to investigate the effects of bilateral renal denervation on sodium and water balance, the renin-angiotensin system, and systemic blood pressure in unrestrained conscious rats maintained on a normal- or low-sodium diet. Renal denervation was proven by chemical and functional tests. Both bilaterally denervated rats (n = 18) and sham-denervated rats (n = 15) maintained positive sodium balance while on a normal sodium intake. Both groups were in negative sodium balance for 1 day after dietary sodium restriction was instituted but were in positive sodium balance for the following 9 days. Systolic blood pressure was higher in sham-denervated (115 +/- 3 mmHg) than in denervated rats (102 +/- 3 mmHg) while on a normal diet (P less than 0.05) and remained so during sodium restriction. Plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were significantly diminished in the denervated rats during normal sodium intake (P less than 0.05). After dietary sodium restriction, PRC increased in both groups but remained significantly lower in the denervated rats (P less than 0.05). Following dietary sodium restriction, PAC also increased significantly to levels that were similar in both groups of rats. These results demonstrate that awake unrestrained growing rats can maintain positive sodium balance on a low sodium intake even in the absence of the renal nerves. However, efferent renal nerve activity influenced plasma renin activity in these animals.

Aldosterone↗

Glomerular ultrafiltration dynamics: euvolemic and plasma volume-expanded rats.

With the use of micropuncture techniques, glomerular dynamics were characterized in euvolemic Munich-Wistar (Chapel Hil) rats. Single nephron glomerular filtration rate (SNGFR) and plasma flow (SNGPF) averaged 31 nl/min and 100 nl/min, respectively. Efferent effective ultrafiltration pressure (PUF) was greater than zero in each animal (7 mmHg, P less than 0.001), indicating filtration pressure disequilibrium. Mean PUF (PUF) was 15 mmHg and specific glomerular filtration coefficient (Kf) values averaged 0.033 nl/(s x mmHg). Similar experiments were performed on Munich-Wistar rats from B.M. Brenner's colony. Filtration pressure equilibrium was reached in rats with SNGPF < 112 nl/min; disequilibrium existed when SNGPF was > 168 nl/min. Overall, PUF (15 mmHg) was similar to that in Chapel Hill rats, SNGFR (49 nl/min) was greater, as was specific Kf (0.066 nl/(s.mmHg)). These observations document important Kf differences in the two colonies. In other experiments on Chapel Hill rats, plasma volume expansion produced increases in SNGPF and renal plasma flow (RPF). However, SNGFR (33 nl/min) and GFR (1.2 ml/(min x g kidney wt)) were unchanged, as were SNGFR/GFR and SNGPF/RPF ratios. SNGFR was relatively insensitive to increased plasma flow because of the relatively low Kf and filtration pressure disequilibrium during euvolemia. In additional experiments, GFR was also only weakly dependent on RPF in conscious rats.

Animals↗

Functional evidence for renorenal reflexes in the rat.

Acute left renal denervation in anesthetized volume-expanded rats produced an ipsilateral diuresis and natriuresis in 19 animals. A simultaneous decrease of glomerular filtration rate, p-aminohippurate clearance, urinary volume (P < 0.002), and percentage of filtered sodium excreted (4.0 +/- 0.6 (SE) vs. 1.9 +/- 0.4%, P < 0.003) occurred in the right innervated kidney in 10 rats. Prior denervation of the right kidney in the other nine rats prevented the renal hemodynamic changes and the fall of urinary volume and of sodium excretion (3.9 +/- 0.6 vs. 4.3 +/- 0.5%) by the right kidney after left renal denervation. Nerve traffic to the right kidney was measured in six other animals after left renal denervation and was found to increase to a mean value 33.8 +/- 6.3% above control levels (P < 0.007) 0-30 min after denervation, with a further significant increase to 66.2 +/- 16.1% above control levels (P < 0.025) 30-60 min after denervation. These results indicate that the functional changes in the right kidney after contralateral renal denervation in volume-expanded rats are caused by a reflex increase in nerve traffic to the right kidney, possibly as a consequence of an interruption of afferent nerve activity originating in the left kidney.

Animals↗