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Biomedical subjects

J G Porush

Publications and source records attributed to J G Porush.

At least 19 recordsLinked to original sources

Failure of atrial natriuretic peptide to induce natriuresis in aortocaval fistula dogs.

Creation of an aortocaval fistula (ACF) in dogs induces salt and water retention, activation of the renin-angiotensin and adrenergic nervous systems and renal papillary ischemia associated with high levels of circulating atrial natriuretic peptide (ANP). The effects of intrarenal ANP (1.2 micrograms/min) infusion on systemic and renal hemodynamics, renal excretory function, renal output of renin and norepinephrine (NE) and papillary plasma flow (PPF) were studied in both normal and ACF dogs. ANP did not alter systemic hemodynamics in either group, but led to a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V), sodium excretion (UNaV) and fractional excretion of sodium (FENa), and a significant decrease in renal vascular resistance (RVR) and urine osmolality (UOsm) in normal dogs. GFR, RBF, RVR, V, UNaV, FENa and UOsm remained unchanged, however, in ACF dogs. In ACF dogs, both renal renin and NE output were significantly greater during baseline and remained significantly greater following ANP infusion, associated with a significantly lower PPF compared with normal dogs. These data suggest that ACF dogs are resistant to the renal effects of ANP, which can neither mitigate the hormonal mediators of sodium retention nor reverse the papillary ischemia observed in this model.

Animals

Reversal of Na+ retention in chronic caval dogs by verapamil: contribution of medullary circulation.

The effects of verapamil on papillary plasma flow (PPF) and Na+ excretion were studied in anesthetized chronic caval dogs with low cardiac output and Na+ retention. Infusion of verapamil into the left renal artery (5 and 10 micrograms.kg-1.min-1) caused a dose-dependent ipsilateral increase in renal blood flow and Na+ excretion (from 10 +/- 2 to 171 +/- 32 and 225 +/- 35 mu eq/min, respectively). PPF in the left kidney was 26.6 +/- 4.4 and was significantly greater than that measured in the contralateral kidney (13.3 +/- 2.4 ml.min-1.100 g-1) (P < 0.01). The natriuresis occurred independent of changes in cardiac output and peripheral vascular resistance. In a separate group of caval dogs in which stimulation of the renin-angiotensin and adrenergic systems was intensified with a tighter caval constriction, verapamil failed to induce renal vasodilation or natriuresis and PPF was not altered. Despite the disparate hemodynamic responses, verapamil stimulated renal production of both renin and prostaglandin E2 in both groups of caval dogs. We conclude that the ability of verapamil to induce papillary vasodilation may contribute to the natriuresis seen in the caval dog, in which the site of Na+ retention includes the loop of Henle.

Animals

Hypertension and renal insufficiency: recognition and management.

The incidence of end-stage renal disease among hypertensive patients is increasing. Early recognition of renal insufficiency is critically important, since reversible causes of renal failure, such as urinary tract obstruction and renal artery stenosis, may be identified and corrected. Control of hypertension slows the progression of renal failure. Once renal failure develops, special attention must be given to diet and drug therapy.

Humans

Effective hypertension control in inner city blacks.

A clinic for patients with "resistant" hypertension was established and patients were followed by one physician, nurse, and secretary. The records of 105 randomly chosen patients out of 700 were reviewed. In 86 of 105 (82%), diastolic blood pressure was controlled (less than 90 mm Hg) (group I), but in 19 patients, after 54 +/- 6 (mean +/- standard error) months, it remained greater than 90 mm Hg (group II) with substantial improvement in 53% (10 of 19 patients). The two groups were similar in age (57 +/- 1 vs 54 +/- 3 years), race (84% vs 74% blacks), and sex (75% vs 86% female). The entry blood pressures in groups I and II were similar, 170 +/- 3/101 +/- 1 and 167 +/- 6/105 +/- 3 mm Hg, respectively. Last visit blood pressure was 130 +/- 1/79 +/- 1 in group I, lower than 156 +/- 5/94 +/- 2 in group II (p less than 0.05). At entry into the clinic and at the last visit, dosing and type of medications were similar in both groups. Although patient visits averaged 6.7/yr in both groups, patients in group II missed 1.7 +/- 0.3 compared with 0.9 +/- 0.1 visits/year for group I (p less than 0.01). Group II patients were also less compliant with medications, primarily because of psychosocial problems. Medications, however, were more available to this group, since 16 of 19 (84%) were Medicaid recipients, compared with 46 of 86 (53%) in group I (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents

Renal medullary circulation: hormonal control.

It is now becoming apparent that the medullary circulation in the kidney can be regulated separately from overall renal blood flow. This characteristic of the medullary circulation plays an important role in the kidney's ability to excrete a dilute or concentrated urine in concert with changes in water and sodium transport in the distal nephron secondary to the action of vasopressin, prostaglandins, the renal nerves, and other hormones without significant other renal hemodynamic changes. There is strong evidence that renal autocoids such as angiotensin II and prostaglandins uniquely affect regional blood flow in the inner medulla because of the special structure and organization of the microvasculature in this region. There is also evidence that this regional blood flow is in part regulated by circulating hormones, such as vasopressin and atrial natriuretic peptide, which are released in response to changes in extracellular fluid volume or osmolality. In addition, data are emerging to suggest that the kallikrein-kinin system, acetylcholine, the renal nerves and adenosine participate in this regulation. In addition to the role of the medullary circulation in the urinary concentrating operation, there are data to suggest that the medullary circulation either directly (by changes in physical forces) or indirectly (by regulating medullary toxicity) may influence sodium excretion in a variety of conditions. In this regard, activation of the renin-angiotensin system locally reduces blood flow in the papilla which may be necessary before sodium retention is fully expressed in salt retaining states. Future research looking at the microvasculature of the medulla and papilla and those factors that control the contractility of these vessels are necessary before a clearer picture emerges. Nevertheless, from the data already available it seems reasonable to suggest that the medullary circulation may be as important to kidney function during physiological and pathophysiological states as is the cortical circulation.

Acetylcholine

Low-dose heparin in routine hemodialysis monitored by activated partial thromboplastin time.

To evaluate the use of the activated partial thromboplastin time (APTT), as measured by the Coag-A-Mate semi-automatic unit, in lowering the dosage of heparin in stable chronic hemodialysis patients, four protocols for anticoagulation were utilized. Ten patients were dialyzed five times with each protocol. In protocol I, clotting time was performed baseline, 2 and 4 hours and in protocol II, baseline and every 30 minutes, with heparin administered by bolus to keep the clotting time at 2-2 1/2 times normal. In protocols III and IV the APTT was performed every 30 minutes, with heparin given by bolus in protocol III and infusion in protocol IV, to keep the APTT 1 1/2-2 times normal. Protocol I required 6000 +/- 543 U of heparin with the dose decreasing significantly to 3694 +/- 158 U in protocol II, 2634 +/- 139 U in protocol III and 2013 +/- 117 U in protocol IV (P less than 0.05- less than 0.001). Three episodes of clotting occurred, one in protocol III and two in protocol IV. There was no bleeding, and clearances of urea, creatinine, phosphate and uric acid at 1 and 5 hours were similar in all protocols. APTT, as measured by the Coag-A-Mate unit, provides a simple means of lowering heparin requirements in routine dialysis patients.

Blood Coagulation

Infusion intravenous pyelography and renal function. Effects in patients with chronic renal insufficiency.

Acute renal failure (ARF) following infusion intravenous pyelography (IVP) has been reported in patients with chronic renal insufficiency, particularly diabetics. Renal function was evaluated before and after infusion IVP in 40 patients with chronic renal insufficiency. In 11 of 12 (92%) diabetics and 17 of 28 (61%) nondiabetics, a 25% or greater increase in serum creatinine values and/or decrease in creatinine clearance was noted after IVP despite adequate hydration in all patients. The maximum decrease in kidney function occurred within three days and usually returned to or near pre-IVP levels in seven to ten days. At least 70% of the patients had hypertension and/or evidence of vascular disease. The data suggest that preexisting vascular disease in the kidney, possibly associated with the known vasoconstricting effects of contrast media, may be an important factor in the ARF following infusion IVP.

Creatinine

Effects of acetazolamide on proximal tubule C1, Na, and HCO3 transport in normal and acidotic dogs during distal blockade.

It has been suggested that the establishment of a tubular fluid to plasma chloride gradient in the late proximal tubule by the reabsorption of bicarbonate (and other anions) in the early proximal tubule is responsible for a significant part of sodium chloride and water reabsorption in the proximal tubule. In the present study the effects of acetazolamide on proximal tubule water and electrolyte excretion were examined in 6 normal dogs and 10 chronic ammonium chloride-loaded dogs during distal blockade produced by ethacrynic acid and chlorothiazide administration. During distal blockade control urine/plasma osmolality and urine/plasma sodium were close to unity in all experiments. Urine/plasma chloride and urine/plasma bicarbonate were 1.21+/-0.02 and 0.75+/-0.07 in normal and 1.24+/-0.01 and 0.04+/-0.01 in acidotic dogs, respectively. After the administration of acetazolamide (20 mg/kg i.v.), there was a significant increase in urine flow, absolute and fractional excretion of sodium, bicarbonate, and chloride in all animals. Associated with these effects, urine/plasma osmolality and urine/plasma sodium remained unchanged but urine/plasma chloride decreased significantly to 1.15+/-0.01 in normal and to 1.19+/-0.01 in acidotic dogs. In acidotic dogs there was a significant correlation between the increase in bicarbonate, sodium, or chloride excretion after acetazolamide and the plasma bicarbonate level (range 6.8-12.5 meq/liter). These data demonstrate a significant effect of acetazolamide on bicarbonate, sodium, and chloride reabsorption in the proximal tubule even in the face of severe acidosis. Moreover, the data suggest that the decrease in chloride reabsorption (and accompanying sodium) after acetazolamide is related to the decrease in bicarbonate reabsorption and the associated decrease in the transtubular chloride gradient.

Acetazolamide

Shipboard dialysis.

With better understanding of the pathophysiology of uremia, the development of more efficient dialysis techniques and more portable machinery, a larger number of patients on maintenance dialysis are not stable enough to undertake travel to places where a regular hemodialysis center may not be availabel or to travel on a ship for a relatively long period of time. Ten stable patients were taken on a 7 day cruise utilizing the relatively lightweight and portable REDY Dialysis System. The medical team consisted of 2 nurses, 2 technicians and 1 physician. The ship's infirmary was converted to a 4 bed hemodialysis unit. Complications were minimal and easily handled by the medical staff.

Adult

Treatment of idiopathic membranous nephropathy.

In a retrospective study of the effect of treatment in biopsy-proved idiopathic membranous nephropathy, 91 adults and 12 children were followed for periods up to 29 years after clinical onset (mean, 6.5 years). Forty-four were treated with corticosteroids, 15 with corticosteroids and immunosuppressants; 44 had no treatment and served as a control group. Clinical cure and improvement were significantly greater in the treated than in the nontreated group (P less than 0.01). The recurrence rate, occurrence of renal failure and probability of death were significantly greater in the nontreated group, although some of these patients eventually showed improvement. Prognosis was better in patients who responded to therapy. These data strongly suggest that steroid therapy is beneficial in patients with membranous nephropathy.

Adolescent

Effects of alpha-adrenergic blockade on sodium excretion in normal and chronic salt retaining dogs.

The alpha-adrenergic blocking agent phenoxybenzamine (PBA) was administered intravenously (10 mug kg-1 min-1) during a steady state water diuresis under pentothal anesthesia to six normal dogs, six dogs with chronic throacic inferior vena cava constriction and ascites (caval dogs) and seven dogs chronically salt depleted by sodium restriction and furosemide administration. In normal dogs urinary sodium excretion increased significantly from 265+/56 (SEM) to 370+/65 muequiv./min, whereas no increase in sodium excretion was noted in either caval dogs or salt depleted animals after PBA. In all three groups urine volume, fractional free water clearance and distalsodium load did not change significantly. In normal dogs, tubular sodium reabsorption decreased significantly from 73.4+/2.8% to 63.1+/4.0%, whereas no change was noted in caval or salt depleted dogs. Blood pressure and renal hemodynamics were not significantly altered by PBA administration in any group. These data demonstrate a natriuretic effect of alpha-adrenergic blockade in normal dogs with the major effect in the water clearing segment of the nephron. The absence of any effect in chronic caval or salt depleted dogs suggests that increased alpha-adrenergic activity does not play a significant role in the sodium retention of these animals.

Adrenergic alpha-Antagonists

Evidence for enhanced distal tubule sodium reabsorption in chronic salt-depleted dogs.

In order to assess the renal tubular site(s) at which sodium reabsorption is enhanced in chronic sodium-depletion, seven normal dogs, six salt-depleted dogs, and three normal dogs receiving aldosterone were studied during a steady-state water diuresis under Pentothal anesthesia and during progressive hypotonic saline diuresis. For both maintenance of the water diuresis and progressive hypotonic saline diuresis 0.45% NaCl was used. During the steady state water diuresis delivery of sodium to the diluting segment of the nephron as approximated by solute-free water clearance + sodium clearance/glomerular filtration rate (CH2O + CNa/GFR) was significantly lower in salt-depleted dogs compared to normal dogs with or without aldosterone. During progressive hypotonic saline infusion fractional free water excretion (CH2O/GFR) was similar in all three groups as CH2O + CNa/GFR increased up to 12-14 ml/min-100 ml GFR. Thereafter, CH2O/GFR continued to rise in virtually a straight line in salt-depleted dogs but leveled off in normal dogs with or without aldosterone. These data demonstrate that enhanced sodium reabsorption in the diluting segment of the nephron is an important determinant of the renal sodium retention in chronic extracellular volume contraction in dogs in addition to confirming the presence of increased proximal tubule sodium reabsorption in these animals.

Aldosterone