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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adaptations of the method of Takahashi et al. (1966. J. Gen. Physiol. 50:317-333) were used to test the validity of the one-dimensional diffusion equation for O2 in the resting excised frog sartorius muscle. This equation is: (formula: see text) where x is the distance perpendicular to the muscle surface. t is time, P(x, t) is the partial pressure of O2,D and alpha are the diffusion coefficient and solubility for O2 in the tissue, and Q is the rate of O2 consumption. P(O, t), the time-course of PO2 at one muscle surface, was measured by a micro-oxygen electrode. Transients in the PO2 profile of the muscle were induced by two methods: (a) after an equilibration period, one surface was sealed off by a disc in which the O2 electrode was embedded; (b) when PO2 at this surface reached a steady state, a step change was made in the PO2 at the other surface. With either method, the agreement between the measured P(O, t) and that predicted by the diffusion equation was excellent, making possible the calculation of D and Q. These two methods yielded statistically indistinguishable results, with the following pooled means (+/- SEM): (formula: see text) At each temperature, D was independent of muscle thickness (range, 0.67-1.34 mm). The activation energy (EA) for diffusion of oxygen in muscle was -3.85 kcal/mol, which closely matches the corresponding value in water. Together with absolute values of D in water taken from the literature, the present data imply that (Dmuscle/DH2O) is in the range 0.59-0.69. This value, and that of EA, are in agreement with the theory of Wang (1954, J. Am. Chem. Soc. 76:4755-4763), suggesting that with respects to the diffusion of O2, to a useful approximation, frog skeletal muscle may be considered simply as a homogeneous protein solution.
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PMID:Diffusion and consumption of oxygen in the resting frog sartorius muscle. 30 46

The effect of 10 cm H2O of positive end-expiratory pressure (PEEP) on pulmonary extravascular water volume (PEWV) was measured in an animal model of noncardiogenic pulmonary edema. Three groups of animals were studied: (1) controls, (2) those given a saline infusion plus alloxan, and (3) those which received saline infusion plus alloxan and PEEP. All animals were ventilated with a constant volume ventilator. Mean PEWV (+/- SEM) in milliliters per gram of dry lung weight was 4.00 +/- 0.21 for group 1, 6.01 +/- 0.70 for group 2, and 5.77 +/- 0.83 for group 3. Mean PEWV increased significantly in both alloxan groups (groups 2 and 3) as compared to the control group (for both, p less than 0.05); however, PEWV did not differ significantly in the group that received PEEP, as compared to the group ventilated without PEEP. Arterial PO2 and airway pressure required to deliver a constant tidal volume did not change significantly in the experimental groups as compared to the control group. It was concluded that PEEP does not decrease lung water content in pulmonary edema caused by damage to fluid-exchanging vessels.
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PMID:Failure of positive end-expiratory pressure to decrease lung water content in alloxan-induced pulmonary edema. 38 15

To determine whether acute chloride depletion per se stimulates renin, we produced selective chloride depletion without sodium depletion in rats by peritoneal dialysis (PD) against 0.15 M NaHCO3 or 0.15 M NaNO3. Control rats were dialyzed against 0.15 M NaCl. Plasma renin activity (PRA) was measured before (PRA1) and 105 minutes after (PRA2) PD. Plasma volume was expanded after PD by infusion of salt-free albumin and was measured immediately after PRA2 by [131I]albumin. In experiment 1, rats were prepared on a normal diet. PRA2 (7.0 +/- 1.0 ng/ml per hr, mean +/- SEM) was increased (P less than 0.05) over PRA1 (4.7 +/- 0.7 ng/ml per hr) in Cl-depleted but not in control rats (PRA1 = 5.3 +/- 0.7, PRA2 = 6.1 +/- 0.7, P = NS). In experiment 2, to produce greater chloride depletion, all rats were prepared for 2 weeks on a low salt diet. PRA2 (47 +/- 5 ng/ml per hr) was increased as compared to PRA1 (24 +/- 2 ng/ml per hr, P less than 0.005) in the Cl-depleted group but not in the control group (PRA1 = 24 +/- 3, PRA2 = 27 +/- 6 ng/ml per hr, P = NS). Serum potassium and final plasma volume were slightly but not significantly lower than controls in these Cl-depleted rats. To exclude an additive effect of these two stimuli for renin, in experiment 2a we infused chloride-depleted rats with three times as much albumin as controls and with KHCO3, 100 mEq/liter. Despite volume expansion and potassium loading, PRA2 (41 +/- 6 ng/ml per hr) was significantly elevated as compared to PRA1 (25 +/- 4 ng/ml per hr, P less than 0.01). Since acute metabolic alkalosis also was present in all Cl-depleted renin-stimulated rats, an additional group (2b) was dialyzed against 0.15 M NaNO3; final plasma arterial pH (7.43) was not different from controls (7.42). Nevertheless, PRA2 levels again were higher (36 +/- 6 ng/ml per hr, P less than 0.05) as compared to PRA1 (23 +/- 4 ng/ml per hr). In all experiments, arterial blood pressure, glomerular filtration rate, and filtered sodium load were not different. Free water reabsorption was lower in Cl-depleted than in control rats. We conclude that acute selective chloride depletion per se is a potent stimulus for renin release.
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PMID:Stimulation of renin by acute selective chloride depletion in the rat. 42 74

Six patients with chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second, 1.01 +/- 0.08 L [mean +/- SEM] ) were given either 1 mL of 100% alcohol per kilogram of body weight in an aqueous solution or a similar volume of water in a crossover design on consecutive days. All subjects became intoxicated and the peak alcohol concentration was 137 +/- 11 mg/dL, 40 minutes after ingestion. No significant difference was found in either PaO2 or PaCO2 between the alcohol and control period. A significant decrease in arterial pH occurred following alcohol (P less than .05), and represented a mild metabolic acidosis. Alcohol ingestion resulted in an increase in oxygen consumption (P less than .05) and carbon dioxide production (P less than .05) but no change in respiratory rate. It appears that small to moderate amounts of alcohol will not cause marked changes in oxygen tension or alveolar hypoventilation in patients with severe COPD who do not have marked hypercapnia. Nevertheless, other effects of alcohol on the cardiopulmonary system and the concomitant use of sedatives have to be considered before condoning the use of alcohol.
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PMID:Moderate alcohol dose and chronic obstructive pulmonary disease: not a cause of hypoventilation. 43 97

Administration of dichloroacetate (DCA) to normal rats resulted in a fall in serum glucose and triglycerides and a rise in ketone bodies. Insulin and cholesterol levels were unchanged. The effects of DCA on lipid metabolism were examined in isolated rat hepatocytes. At 10 mM DCA, the incorporation of tritiated water into fatty acids (saponifiable lipids) was inhibited by 33 +/- 4% (mean +/- SEM, N = 5). No effect on incorporation into cholesterol (measured as nonsaponifiable lipids) was observed. DCA inhibited the incorporation of 14C-glucose into lipid but had no effect on glucose oxidation. Fatty acid oxidation was increased by 76 +/- 7% (mean +/- SEM, N = 6). However, DCA had no effect on the recovery of newly synthesized lipid. Thus, inhibition of tritiated water incorporation into fatty acids represents decreased synthesis rather than increased turnover. DCA did not affect the incorporation of 14C-palmitate into triglycerides or phospholipids. Cell viability, as assessed by incorporation of 3H-isoleucine into protein and trypan blue exclusion, was not affected by DCA. These results suggest that DCA lowers serum triglycerides through inhibition of fatty acid synthesis and stimulation of fatty acid oxidation by liver.
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PMID:Effects of dichloroacetate on lipid metabolism in isolated rat liver cells. 43 64

The effect of acute NH4C1-induced metabolic acidemia on renal electrolyte excretion was examined in nine healthy subjects during steady state water diuresis. Following oral NH4C1, venous pH and bicarbonate concentration declined significantly (p less than 0.01) while inulin and PAH clearances remained unchanged. Mean sodium excretion (UNaV) increased from 142 +/- 16 mueq/min (mean +/- SEM) to 310 +/- 49 mueq/min (p less than 0.01) at 8 hr without change in plasma aldosterone or renin levels. Urine flow remained unchanged while CH2O/(CH2O + CCl) declined significantly, suggesting that acute metabolic acidemia inhibits sodium transport in the distal nephron. Similar results were observed in two subjects with central diabetes insipidus. Three subjects restudied following the ingestion of an equivalent amount of chloride administered as NaCl, failed to demonstrate a significant rise in UNaV. UKV fell acutely from 91 +/- 13 to 45 +/- 5 mueq/min (p less than 0.001) despite an increase in serum potassium concentration. No change in plasma insulin was observed. UCaV rose from 66 +/- 15 to 143 +/- 18 microgram/min and fractional excretion of calcium increased from 0.55 +/- 0.13 to 1.24 +/- 0.21% (p less than 0.001). Total serum calcium fell slightly, but ionized calcium rose from 3.99 +/- 0.05 to 4.30 +/- 0.03 mg/dl (p less than 0.001). No change in nephrogenous cyclic (cAMP) excretion was observed. In conclusion, acute metabolic acidemia in man (1) inhibits sodium reabsorption in the distal nephron independent of changes in plasma aldosterone concentration, filtered chloride load, or volume expansion; (2) inhibits potassium excretion despite a rise in serum potassium concentration; and (3) inhibits tubular calcium reabsorption independetn of changes in parathyroid hormone (as reflected by urinary cAMP).
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PMID:Effect of acute metabolic acidemia on renal electrolyte transport in man. 45 20

In healthy volunteers, the effects of intravenously administered glucagon on small intestinal function was investigated. Bolus doses resulting in plasma glucagon concentrations of greater than 800 pg/ml (5 min after injection) abolished jejunal contractions for 4.4 +/- 0.4 (SEM) min after a latency period of 49 +/- 4 sec. During continuous intravenous glucagon infusion, jejunal dilatation and increase in mean transit time (MTT) occurred at plasma levels greater than 720 pg/ml, while inhibition of water and electrolyte absorption was observed only with plasma glucagon concentrations of 1760 +/- 114 pg/ml. Under these conditions, the propulsion of fasting intestinal contents was slowed without change in flow rate. The observed effects cannot be attributed to the simultaneously occurring rise in plasma insulin and glucose concentrations. Short-term increases in circulating glucagon concentration inhibit intestinal tone, contractions, and propulsion with only a minor effect on water and electrolyte absorption limited to a narrow concentration range of plasma glucagon. Neither effect occurs at glucagon levels likely to occur under physiologic concentrations. The latency period preceding the abolition of jejunal contractions suggests that glucagon does not act directly on intestinal smooth muscle cells.
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PMID:Glucagon effects on the human small intestine. 45 37

The pharmacokinetics of morphine and its derived metabolite, morphine 3-monoglucuronide, were studied in normal and bile-cannulated dogs. High doses (7.2-7.7 mg/kg iv) caused renal and biliary shutdowns and time lags in urinary drug and metabolite excretion and in biliary secretion of the hepatically formed conjugate. Intermediate doses (0.41-0.47 mg/kg iv) inhibited urine flow but not renal clearance. Low doses (0.019-0.07 mg/kg iv) had no apparent effect. Dose-related effects on the total, metabolic, and biliary clearances imply saturable enzymes and/or dose-inhibited hepatic flows, accounting for the major elimination half-lives of 83 +/- 8 and 37 +/- 13 min at the high and low doses, respectively. The slow terminal phase in plasma morphine and metabolite elimination and urinary accumulation is due apparently to the enterohepatic metabolite recirculation after biliary excretion, gastrointestinal hydrolysis, and hepatic first-pass reconjugation. Bile-cannulated dogs showed no fecal drug and no slow terminal plasma and urine elimination phases. Intravenous morphine 3-monoglucuronide was eliminated only renally and showed neither biliary excretion nor prolonged hepatically formed glucuronide elimination. Hepatic morphine clearances at normal therapeutic doses parallel hepatic blood flow and explain the lack of oral morphine bioavailability by anticipating complete first-pass liver metabolism. Renal morphine and morphine conjugate clearances were 85 (+/- 9 SEM) and 41 (+/- 4 SEM) ml/min, respectively, indicating glomerular filtration for the latter and glomerular filtration plus tubular secretion for the former. Urinary morphine and morphine conjugate excretion accounted for approximately to 83% of the dose. Biliary secretion accounted for 11-14% of the dose. Morphine showed dose-independent plasma protein binding of 36 (+/- 1 SEM) % and a red cell-plasma water partition coefficient of 1.11 +/- 0.04 SD. New equations were developed to model the discontinuous morphine and morphine metabolite pharmacokinetics.
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PMID:Pharmacokinetics of morphine and its surrogates. III: Morphine and morphine 3-monoglucuronide pharmacokinetics in the dog as a function of dose. 45 81

An index of permeability of the alveolar-capillary membrane was derived from the relative extraction from the lung into arterial blood of 2 tracers, 125I-antipyrine and 51Cr-ethylenediaminetetraacetate. The effect on this index of aspirating 2 ml of isotonic saline, distilled water, or 10(-1) M hydrochloric acid per kg of body weight was studied in 3 groups of rabbits. The severity and time course of changes in the permeability index were correlated with changes in lung mechanics, gas exchange, serial chest roentgenograms, ratio of extravascular lung water to dry weight, and histologic findings. Aspiration of saline produced no change in the permeability index; aspiration of water produced a large mean +/- SEM increase in the index, from a baseline of 0.025 +/- 0.002 to 1,050 +/- 0.054 (P less than 0.001), but this value returned to baseline 15 min later. After hydrochloric acid, the permeability index increased from a baseline of 0.027 +/- 0.003 to 1.068 +/- 0.098 (P less than 0.005), with no evidence of resolution after 60 min. Changes in lung mechanics, gas exchange, and roentgenograms were smallest after aspiration of distilled water and greatest after aspiration of hydrochloric acid. The functional changes after aspiration of water and saline recovered at a rate proportional to the known clearance rates of these liquids from the lung. The changes after hydrochloric acid either showed no tendency toward recovery or, in the case of the roentgenograms, worsened with time. There were no detectable histologic abnormalities or an increase in the ratio of extravascular lung water to dry weight after aspiration of water or saline, but there were extensive histologic abnormalities and a 70 per cent increase in lung water after acid. The increase in the permeability index after aspiration of water was too transient to exert a deleterious effect. In contrast, the persistence of the increase in the permeability index after hydrochloric acid was associated with persistent functional changes attributable to the considerable increase in lung water.
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PMID:Alveolar-capillary membrane permeability. Correlation with functional, radiographic, and postmortem changes after fluid aspiration. 47 59

In order to quantitatively investigate the usefulness of intraosseous fluid and drug administration as a resuscitative modality, we studied the infusion flow rates of crystalloid solutions obtainable at varying infusion pressures into the bovine tibial medullary cavity and time to initial as well as 90% of maximal effect of intraosseously administered vasoactive drugs. Mean infusion rates +/- SEM (n = 6) at 300, 200, and 100 torr and atmosphere + 81 cm H2O were 41 +/- 2, 32 +/- 1, 27 +/-2, and 10 +/- 1 ml/min, respectively. The mean time (+/- SEM) to initial effect of intraosseous injections (n = 6) of either 0.5 mg epinephrine or 50 mg ephedrine was 17 +/- 3 seconds and mean time to 90% of maximal effect was 45 +/- 5 seconds. These results provide a quantitative basis for resuscitation by fluid and drug administration via the tibial malleolar intraosseous route and suggest that when performed in appropriate situations, the technique may have clinical utility.
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PMID:Intraosseous infusion: pressure-flow relationship and pharmacokinetics. 49 Jun 93


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