Adjuvant use of warm butyl alcohol vapor in experimental pulmonary edema.

Studies were done to determine if warm n-butyl alcohol vapor might be effective for the destruction of respiratory tract foam bubbles and for alleviation of the arterial hypoxemia accompanying severe acute pulmonary edema. In vitro studies showed that warm butyl alcohol vapors made from 5% and 7% butyl alcohol solutions at 39 degrees C were much more effective in antifoam activity against synthetic foam bubbles than ethyl alcohol vapors, made from 20% and 30% ethyl alcohol at 22 degrees C. Warm butyl alcohol vapor also slowly destroyed in vitro the fine foam bubbles of alveolar lining origin made in rabbit lung post mortem. Evolving lung edema was induced in anesthetized rabbits by aspiration of 1.1 ml/kg of 1.2 molal sorbitol/0.14 molal sodium chloride/0.01 molal hydrochloric acid solution of pH 2.0. After established severe arterial hypoxemia and in the absence of overt foam, inhalation of warm butyl alcohol/H2O vapor-air mixture, made by air humidification from 7% butyl alcohol at 39 degrees C, alleviated promptly the hypoxemia. The improvement was progressive over the first 45 minutes of continued vapor therapy. The lessened hypoxemia occurred without concurrent improvement in the amount of formed lung edema fluid. Control inhalations of warm 100% H2O vapor-air mixture did not improve the hypoxemia. The only noted side effects of warm butyl alcohol vapor treatments were slight hypotension and slight metabolic acidosis which developed very slowly. The results suggest that warm butyl alcohol vapor might prove to be an effective adjuvant agent to lessen critically severe hypoxemia in selective cases of acute pulmonary edema in man.

Effect of indomethacin on modest pressure natriuresis in chloralose-anesthetized, non-laparotomized dogs.

To determine if indomethacin (indo) would attenuate the effects of changed renal perfusion pressure on sodium excretion as reported by others, we performed clearance studies in chloralose-anesthetized dogs without the major stress of laparotomy. Mean renal arterial pressure was varied by a balloon-tipped catheter indwelling the aorta suprarenally. With pressure decreases to mean values above 85 mm Hg during isotonic saline infusion, sodium output decreased only by 10.7 +/- 2.4% per 10 mm Hg pressure decrease without indo pre-treatment but decreased by 22.0 +/- 3.8% per 10 mm Hg pressure decrease with indo pre-treatment. The greater, rather than lesser, pressure effect on excretory function after indo in these experiments with chloralose anesthesia suggest that renal prostaglandin (PG) activity does not mediate normally pressure natriuresis. Instead, the data suggest that, in the absence of major stress, the renal pressure effects on excretory function may become more sensitive after indo. In addition, we postulate that the normal acute pressure natriuresis may be modest and may average no more than 20% change for each 10 mm Hg change in mean pressure above 90 mm Hg when stress is minimal and when vasoactive preglomerular autoregulation is nearly perfect. This is a phenomenon which keeps intrarenal tissue pressure and urine output relatively constant with arterial pressure elevations.

Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results.

L-Arginine may be a conditionally essential amino acid in children and adolescents with sickle cell disease, particularly as required substrate in the arginine-nitric oxide pathway for endogenous nitrovasodilation and vasoprotection. Vasoprotection by arginine is mediated partly by nitric oxide-induced inhibition of endothelial damage and inhibition of adhesion and activation of leukocytes. Activated leukocytes may trigger many of the complications, including vasoocclusive events and intimal hyperplasias. High blood leukocyte counts during steady states in the absence of infection are significant laboratory risk factors for adverse complications. L-Citrulline as precursor amino acid was given orally twice daily in daily doses of approximately 0.1 g/kg in a pilot Phase II clinical trial during steady states in four homozygous sickle cell disease subjects and one sickle cell-hemoglobin C disease patient (ages 10-18). There soon resulted dramatic improvements in symptoms of well-being, raised plasma arginine levels, and reductions in high total leukocyte and high segmented neutrophil counts toward or to within normal limits. Continued L-citrulline supplementation in compliant subjects continued to lessen symptomatology, to maintain plasma arginine concentrations greater than control levels, and to maintain nearly normal total leukocyte and neutrophil counts. Side effects or toxicity from citrulline were not experienced. Oral L-citrulline may portend very useful for palliative therapy in sickle cell disease. Placebo-controlled, long-term trials are now indicated.

Modest pressure natriuresis and autoregulation during water diuresis in dogs.

The effects of renal arterial pressure change on renal output of sodium and volume were measured during water diuresis in 25 chloralose-anesthetized dogs. Conditions included a minimal invasive stress, limited sodium administration, and mean renal arterial pressures varied suprarenally, by aortic balloon inflation to lowermost levels of 82-106 mm Hg. Group A dogs received no aldosterone; group B, C and D dogs were given aldosterone. Dogs of group C also received (1-Sar, 8-Ile)-angiotensin II. Group D dogs received phenylephrine which elevated arterial and right atrial pressures moderately without decrease in renal blood flow. In groups A, B and C, mean changes in sodium output, volume output, fractional excretions and free water clearances were not detectable with mean renal arterial pressure reductions, which averaged 29 +/- 2.9, 22 +/- 2.8 and 27 +/- 5.2 mm Hg, respectively. Right atrial pressures, effective renal blood flows and glomerular filtration rates did not change with the renal arterial pressure changes in these groups. In the group D dogs, during the larger pressure reductions of 54 +/- 6.6 mm Hg from higher values of 158 +/- 7.0 mm Hg, mean urine flow and effective renal blood flow remained constant while glomerular filtration rate and sodium output decreased only slightly. Output efficiency ratios related to perfusion pressure were calculated. With no more than modest pressure-induced excretory changes, it is concluded that excretory sodium and urinary volume autoregulation in concert with nearly perfect circulatory autoregulation were demonstrated with regionally varied mean renal arterial pressure. The same preglomerular myogenic responses to transvascular pressure, which restrict glomerular and transcapillary pressures, are viewed dominantly responsible for both circulatory and excretory autoregulation under normal conditions of minimal stress and low fractional sodium excretions. Homeostatic implications are discussed concerning likely relevance to the Guyton-Coleman theory for the long-term control of arterial blood pressure.

Photometry of inulin and polyfructosan by use of a cysteine/tryptophan reaction.

Described are a macromethod for measuring 2 to 30 mug of polyfructoside in sample volumes of 0.5 ml and a micromethod for measuring 40 to 400 ng in 10-mul samples. The absorptivity of the cysteine/tryptophan color product is 2.5-to 10-fold those found with use of five other colorimetric methods for inulin. The method is highly specific for alkali-stable polyfructoside. Color, measured at 515 nm, was maximal on development at 56 degrees C for 25 min in dilute (57-58% by vol) sulfuric acid, after the addition of the combined cysteine hydrochloride/tryptophan reagent. Analytical recoveries of inulin and polyfructosan from plasma and urine were complete. With initial alkaline heating, the endogenous blank inulinoid values averaged 0.6 +/- 0.47 (SD) mg/liter for plasma and 0.05 +1- 0.024 mg/min for urine. The coefficient of variation of the macromethod was less then 3%; that for the micromethod ranged from 1.3 to 6.3%. The micromethod appears adaptable to the determination of nanogram quantities of polyfructoside in nanoliter volumes of biological fluids.

Potential use of warm butyl alcohol vapor as adjunct agent in the emergency treatment of sea water wet near-drowning.

The short-term course of sea water wet near-drowning was studied in anesthetized rabbits breathing spontaneously. Therapeutic trials were incorporated using warm n-butyl alcohol vapor both in inspired air and in inspired oxygen. The purpose was to determine if butyl alcohol vapor might alleviate the hypoxemia of sea water aspiration, possibly by a defoaming action on the fine foam bubbles of alveolar origin in the lung edema even without tracheal foam being present. The findings from 20 rabbits without overt tracheal foam, that had aspirated 2.05 mL/kg of sea water and were placed 10-minutes postaspirationally into four different inhalational treatment groups, showed remarkable differences. Warm butyl alcohol vapor made by humidification of 7.5% solution at 31 degrees C alleviated the hypoxemia. With vapor treatment for 15 minutes, mean arterial oxygen tension (PaO2) was not significantly changed in the water vapor-air group, but increased significantly to 50.5 +/- 4.6, 70.0 +/- 8.9, and 146.7 +/- 40.7 mm Hg in the butanol/water vapor-air, water vapor-oxygen, and butanol/water vapor-oxygen groups, respectively. With treatment for 30 minutes, mean PaO2 increased to 248.3 +/- 38.0 mm Hg with butanol/water vapor-oxygen inhalations, but only to 91.2 +/- 9.8 mm Hg with 100% water vapor-oxygen inhalations. Thus, the inspired vapor of butanol was much more effective in elevation of arterial blood oxygen pressures when combined with oxygen therapy over the values found when 100% water vapor-oxygen treatments were given. Respiratory and cardiac depressant effects from inspired butanol were not evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Absence of renal circulatory autoregulation during perfusion with paraffin oil.

Autoregulation of vascular flow as a function of arterial pressure was studied in isolated dog and rat kidneys, perfused serially with an oxygenated aqueous colloidal medium and with oxygenated paraffin oil. Square wave elevations in arterial pressure eleicited autoregulatory adjustments in flow within the first few seconds of elevated pressure during colloidal perfusion but not during oil perfusion of the same kidneys. Before oil perfusion, the steady state autoregulatory efficiency ratios (% flow change/% pressure change) over pressures ranging from 95 to 180 mm Hg averaged 0.37 +/- 0.13 and 0.51 +/- 0.16 (mean +/- SD) in dog and rat kidneys, respectively. During oil perfusion, the autoregulatory efficiency ratios exceeded 1.0 in every instance. Following oil perfusion, vasoactive autoregulation of colloidal perfusate flow returned, at very low organ flows. Our results do not confirm the previous findings of LEICHTWEISS, SCHRODER, and WEISS [Pflügers Arch. ges. Physiol. 293: 303 1967] concerning the presence of autoregulation during oxygenated renal oil perfusion. Our findings suggest that renal circulatory autoregulation is either primarily myogenic or else primarily dependent upon a rapidly acting tubulovascular feedback mechanism.

Reusable tubular membrane oxygenator for isolated organ hemoperfusion.

A reusable tubular membrane oxygenator is described for hypotraumatic hemoperfusion of isolated organs in physiological studies. The constructed oxygenator was of approximately 0.24-m2 effective surface area and contained 450 silicone rubber capillaries of 0.51-mm nominal ID, 34.9 cm long, fixed by conical-shaped, plastic blood headers at manifolds made from Dow-Corning MDX-4-4210 silicone elastomer. During ex vivo hemoperfusions in dogs at inlet hemoglobin saturations near 67%, oxygen transfer rates of the oxygenator increased serially, from 16.6 +/- 1.7 ml/min per m2 (mean +/- SD) at blood flows of 100 ml/min to 34.1 +/- 3.8 ml/min per m2 at flows of 500 ml/min. The oxygenator was thromboresistant and of much loss priming blood volume and wall compliance than the nonresuable Travenol membrane oxygenator of 0.26-m2 effective surface area. The tubular oxygenator was easily cleaned and reassembled, with reproducible oxygen transfer rates. It should prove useful for hemoperfusion studies in organs of moderate size, such as the isolated canine kidney, stomach, and pancreas.

Vagal afferents inhibit the antidiuresis and antinatriuresis secondary to bilateral carotid occlusion in the chloralose-anesthetized dog.

It has been reported that bilateral carotid occlusion (BCO) does not alter renal excretory function in conscious dogs on a high-salt diet with intact vagi provided renal perfusion pressure (RPP) is held constant. In contrast, low carotid sinus pressures in chloralose-anesthetized dogs with severed vagi elicit significant reductions in renal excretory function which were mediated by renal sympathetic nerves. The purpose of the present study was to investigate the influence of BCO on renal function in chloralose-anesthetized, volume expanded dogs with and without intact cervical vagi and with RPP held constant. A total of 10 dogs, volume expanded with hypotonic saline, were prepared to measure systemic arterial pressure (SAP), carotid sinus pressure (CSP), RPP, and urine flow. With the cervical vagi intact, BCO elicited an increase in SAP from 132 +/- 4 mm Hg to 172 +/- 5 mm Hg (p less than 0.01). This was associated with significant and paradoxical increases in urine flow (+35%), sodium excretion (+63%), osmolar clearance (+32%), and free water clearance (+33%). These changes were also accompanied by small but significant increases in ERBF (+11%) and GFR (+12%). Bilateral cervical vagotomy alone (Vx) increased SAP (129 +/- 6 mm Hg to 146 +/- 5 mm Hg, p less than 0.05). Urine flow and free water clearance were decreased but sodium excretion and osmolar clearance were increased. No change in ERBF or GFR was measured. BCO after Vx elicited a greater increase in SAP as compared to BCO alone (194.5 +/- 6.2 mm Hg) which was accompanied by significant decreases in urine flow (-60%), sodium excretion (-55%), osmolar clearance (-43%), ERBF (-13%), and GFR (-19%). Therefore, the results of this study demonstrate that the contrasting influences of BCO on renal function reported previously in conscious and anesthetized animal models may be due to the presence or absence of the inhibitory influences of afferent fibers contained in the cervical vagi, probably cardiac in origin.