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S E Curtis

Publications and source records attributed to S E Curtis.

At least 37 records · Page 2Linked to original sources
PubMed1995

Role of the vascular endothelium in O2 extraction during progressive ischemia in canine skeletal muscle.

O2 extraction during progressive ischemia in canine skeletal muscle, J. Appl. Physiol. 79(4): 1351-1360, 1995.--O2 uptake (VO2) is defended during decreased O2 delivery (QO2) by an increase in the O2 extraction ratio (O2ER, VO2/QO2), presumably by recruitment of capillaries. This study tested the hypothesis that activity of the microvascular endothelium plays a necessary role in achievement of maximal O2ER. We pump perfused the vascularly isolated hindlimbs of 24 anesthetized and paralyzed dogs at progressively lower flows over a 90-min period. In eight dogs, hindlimb vascular endothelium was removed by injection of deoxycholate (DOC) into the perfusing artery before the ischemic challenge. DOC treatment resulted in loss of normal in vivo and in vitro endothelium-dependent dilatory responses to acetylcholine, but endothelium-independent vascular smooth muscle responses were intact. Eight other dogs were pretreated with nitro-L-arginine methyl ester plus indomethacin (L+I group) to block the synthesis of the vasodilators nitric oxide and prostacyclin. L+I and DOC treatment were associated with increases in hindlimb vascular resistance of 168 +/- 17 and 63 +/- 12%, respectively. O2ER at critical QO2 (QO2 at which VO2 begins to decrease) was 81 +/- 2% in eight control dogs, 66 +/- 6% in L+I, and 42 +/- 4% in DOC, indicating a significant O2 extraction defect in the two treatment groups. These data suggest that products of the vascular endothelium play an important role in the matching of O2 supply to demand during supply limitation in skeletal muscle.

Acetylcholine↗
PubMed1995

ATP-sensitive K+ channel blockade impairs O2 extraction during progressive ischemia in pig hindlimb.

Tissues maintain O2 consumption (VO2) when blood flow and O2 delivery (DO2) are decreased by better matching of blood flow to meet local cellular O2 demand, a process that increases extraction of available O2. This study tested the hypothesis that ATP-sensitive K+ channels play a significant role in the response of pig hindlimb to ischemia. We pump perfused the vascularly isolated but innervated right hindlimb of 14 anesthetized pigs with normoxic blood while measuring hindlimb DO2, VO2, perfusion pressure, and cytochrome aa3 redox state. In one-half of the pigs, the pump-perfused hindlimb was also infused with 10 micrograms.min-1.kg-1 of glibenclamide, a potent blocker of ATP-sensitive K+ channels. Control animals were infused with 5% glucose solution alone. Blood flow was then progressively reduced in both groups in 10 steps at 10-min intervals. Glibenclamide had no effect on any preischemic hindlimb or systemic measurements. Hindlimb VO2 and cytochrome aa3 redox state began to decrease at a significantly higher DO2 in glibenclamide-treated compared with control pigs. At this critical DO2, the O2 extraction ratio (VO2/DO2) was 53 +/- 4% in the glibenclamide group and 73 +/- 5% in the control group (P < 0.05). Hindlimb vascular resistance increased significantly with ischemia in the glibenclamide group but did not change in the control group. We conclude that ATP-sensitive K+ channels may be importantly involved in the vascular recruitment response that tried to meet tissue O2 needs as blood flow was progressively reduced in the pig hindlimb.

Adenosine Triphosphate↗
PubMed1995

Effects of nitric oxide synthase inhibition on regional hemodynamics and oxygen transport in endotoxic dogs.

Nitric oxide synthase (NOS) inhibition has been used to increase blood pressure in humans with septic shock despite a lack of data regarding its effects on O2 delivery (QO2). We studied the effects of NG-nitro-L-arginine methyl ester (L-NAME) on systemic, gut, and hindlimb circulations of endotoxic dogs. Twelve dogs were infused with 2 mg/kg of LPS over 1 h followed by 60 mL/kg of 6% dextran over 2 h. Six dogs also received 20 mg/kg of L-NAME, LPS caused mean arterial pressure (MAP), flow and QO2 to whole body, hindlimb and gut to decrease, but O2 uptake (VO2) did not change. Dextran resuscitation alone produced a hyperdynamic state with increased blood flow to or above baseline. With L-NAME, systemic and regional resistances increased twofold and MAP returned to near baseline. Late in the study, these dogs had significantly lower blood flow and QO2 to the gut but maintained VO2 by increasing oxygen extraction to near critical levels. These data suggest that in acute endotoxicosis, L-NAME may significantly improve blood pressure but may markedly encroach on O2 transport reserves to the gut.

Animals↗
PubMed1994

[Intestinal mucosa injury during experimental endotoxin-induced shock].

To ascertain tissue oxygenation during conversion from hypo to hyperdynamic state with vascular volume expansion, venous outflow from a segment of ileum was isolated in anesthetized and pump-ventilated endotoxic dogs to measure gut oxygen uptake (VO2), lactate metabolism, intramucosal PCO2 and tissue PO2 (PtiO2). Tissue PO2 was measured by multipoint surface Mehrdraht Dortmund Oberfläche electrodes placed on mucosal and serosal surfaces of gut. Six dogs were infused with 2 mg.kg-1 E. coli lipopolysaccharide (LPS) in one hour followed by a two hour 0.5 mL.kg-1.min-1 dextran infusion. Two dogs were used as controls and received dextran infusion in order to assess time and hemodilution-dependent effects. LPS infusion resulted in an hypodynamic sepsis with supply limited VO2, increased arterial lactate and increased lactate output by gut. Resuscitation resulted in an hyperdynamic sepsis with improvement of whole-body VO2. In the gut, VO2 remained low and intramucosal PCO2 as well as lactate output remained high, despite increased flow. Gut PtiO2 results suggested blood flow maldistribution with tissue hypoxia in the mucosa despite increased total flow to the gut. Gut VO2, lactate flux, intramucosal PCO2, and tissue PO2 were consistent with regulatory responses that shut down mucosal perfusion and oxygenation in spite of increased blood flow to gut.

Animals↗
PubMed1994

Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation.

There is indirect evidence that tissue hypoxia occurs in human sepsis and surface measures of muscle tissue PO2 (PtiO2) in hypodynamic endotoxic animals are decreased. This study assessed systemic and regional tissue oxygenation in a more relevant model of hyperdynamic endotoxicosis. We isolated venous outflow from the left hindlimb and a segment of ileum in six anesthetized dogs to measure muscle and gut O2 delivery and uptake (VO2) and lactate flux, gut intramucosal pH (pHi) by tonometry, and PtiO2 by multi-point surface electrodes placed on mucosal and serosal surfaces of gut and on muscle. We then infused Escherichia coli lipopolysaccharide (LPS; 2 mg/kg) over 1 h followed by a 2-h infusion of dextran (0.5 ml.kg-1.min-1). LPS infusion significantly decreased systemic and gut VO2, cardiac output (Q), and blood pressure and increased arterial lactate and gut lactate flux. Resuscitation increased Q to above baseline and restored systemic VO2. In response to LPS and then resuscitation, muscle PtiO2 distribution did not change, suggesting little microcirculatory disturbance, although mean PtiO2 first decreased and then increased. In contrast, gut VO2 and pHi remained low and lactate output remained high, despite restoration of gut blood flow. Gut VO2, lactate flux, pHi, and PtiO2 histograms were consistent with a marked redistribution of blood flow within the gut wall, away from the mucosa and toward the muscularis. These data show that, in hyperdynamic acute endotoxemia, skeletal muscle PtiO2 and VO2 are well maintained, but blood flow within the gut is significantly disturbed with mucosal hypoxia.

Animals↗
PubMed1994

Canine hindlimb blood flow and O2 uptake after inhibition of EDRF/NO synthesis.

The nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was used to determine whether the decrease in canine hindlimb blood flow (QL) with NOS inhibition would limit skeletal muscle O2 uptake (VO2). Arterial inflow and venous outflow from the hindlimb were isolated, and the paw was excluded from the circulation. Pump perfusion from the right femoral artery kept the hindlimb perfusion pressure near the auto-perfused level. Six anesthetized dogs received L-NAME (20 mg/kg i.v.), whereas another group of five dogs received the stereospecific enantiomer N omega-nitro-D-arginine methyl ester (D-NAME 20 mg/kg i.v.). Efficacy of NOS inhibition was tested with intra-arterial boluses of acetylcholine. QL was measured continuously, and whole body and hindlimb VO2 were measured 60 and 120 min after L-NAME or D-NAME. Whole body VO2 remained at control levels, but cardiac output decreased from 117 +/- 17 to 57 +/- 7 ml.kg-1.min-1 60 min after L-NAME (P < 0.05) and remained at that level for the duration of the experiment. Cardiac output was significantly higher in the D-NAME group than in the L-NAME group at 60 min. After L-NAME, QL fell 24% but VO2 increased from 5.2 +/- 0.4 to 7.4 +/- 0.6 ml.kg-1.min-1 (P < 0.05). No change in QL or VO2 occurred after D-NAME. NOS inhibition did not limit hindlimb VO2, despite decreases in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Hypoxic vasodilation does not require nitric oxide (EDRF/NO) synthesis.

Our question was whether inhibition of nitric oxide [endothelium-derived relaxing factor (EDRF)/NO] production in an in situ vascularly isolated but innervated canine hindlimb would prevent hypoxic vasodilation or interfere with O2 extraction during ischemic (IH) or hypoxic hypoxia (HH). After a control period, we gave NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.v.) to two of four groups of six dogs before a 30-min period of IH or HH. In IH, arterial inflow from a pump-membrane oxygenator system was lowered from 65 to 35 ml.min-1.kg-1 with PO2 maintained at approximately 110 Torr. In HH, PO2 was lowered from 107 to 28 Torr with flow at 78 ml.min-1.kg-1. Total O2 delivery was lowered to approximately 5 ml.min-1.kg-1 in all groups during hypoxia. Hindlimb vascular resistance (LVR) increased from 1.11 +/- 0.09 to 2.21 +/- 0.25 peripheral resistance units (PRU; P < 0.05) after L-NAME infusion and hindlimb O2 uptake increased from 3.9 +/- 0.2 to 4.5 +/- 0.3 ml.min-1.kg-1 (P < 0.05). In controls, LVR decreased from 1.10 +/- 0.06 to 0.63 +/- 0.04 PRU with HH (P < 0.05) and from 1.03 +/- 0.06 to 0.82 +/- 0.02 PRU (P = NS) with IH. In L-NAME-treated dogs, LVR decreased from 2.38 +/- 0.37 to 1.07 +/- 0.13 PRU with HH (P < 0.05) and from 2.04 +/- 0.29 to 1.41 +/- 0.13 PRU (P = NS) with IH. There were no differences in O2 extraction ratio (0.72) or in O2 uptake between groups during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Central and peripheral prostaglandins are involved in sickness behavior in birds.

Many of the behavioral manifestations of mammals and birds following infection are now recognized as important mechanisms for maintaining homeostasis and promoting recovery. To investigate the role of prostaglandins (PGs) in the behavioral and physiological effects of lipopolysaccharide (LPS) in birds, chickens were injected with indomethacin (Ind) peripherally (IP, 5 mg) or centrally (ICV, 100 micrograms) and their behavior and body temperature following a challenge IP injection of LPS (2.5 mg) were assessed at 1 and 2 h, respectively. Pretreatment with Ind IP or ICV completely inhibited the hyperthermia caused by LPS. Ind injected IP but not ICV significantly attenuated the LPS-induced anorexia. The drowsiness caused by LPS was completely inhibited by Ind injected IP and partially inhibited by Ind administered ICV. These results are interpreted to indicate that LPS induces hyperthermia in the chicken by activating a PG system in the brain. Peripheral PGs appear to be involved in the anorectic response to LPS, whereas drowsiness caused by LPS may involve both peripheral and central PGs. These data are consistent with the hypothesis that multiple PG systems are activated during the acute-phase response, which may explain the dissociation between mechanisms controlling the behavioral and physiological responses to infection.

Animals↗
PubMed1993

Sickness behavior in birds caused by peripheral or central injection of endotoxin.

Recent evidence indicates that many of the physiologic, metabolic, and behavioral responses that accompany infection in mammals are important for maintaining homeostasis and promoting recovery. In the present report, we have extended this concept to birds by demonstrating that LPS injected IP reduces feed intake, increases somnolence, decreases plasma [Fe] and [Zn], increases plasma [Cu], and elevates plasma corticosterone. To determine if any of these effects could be mediated centrally, LPS was injected intracerebroventricularly (ICV). Whereas peripheral injection of LPS caused a modest increase in body temperature, the hyperthermic effect of LPS injected ICV was intense and long lasting. This hyperthermia following ICV injection of LPS was accompanied by only a transient reduction in food intake and elevation in somnolent activity, with no change in plasma [Fe] or [Zn]. Both peripheral and central injections of LPS increased plasma corticosterone, but the increase caused by peripherally administered LPS was sixfold higher than that caused by LPS injected centrally. Collectively, these data show that chickens respond to both peripheral and central injections of endotoxin by reducing food consumption, increasing somnolence, becoming febrile, and elevating plasma corticosterone. However, the magnitude of these responses depends upon whether LPS acts at central or peripheral sites.

Animals↗
PubMed1993

Prognostic value of the dobutamine test in patients with sepsis syndrome and normal lactate values: a prospective, multicenter study.

OBJECTIVES: To determine the oxygen supply (DO2) and uptake (VO2) responses to a 60-min dobutamine infusion in critically ill septic patients without circulatory shock and with normal blood lactate concentrations. Also, to determine whether these responses would predict outcome. DESIGN: Prospective, cohort study. SETTING: Five intensive care units in university-affiliated, city hospitals. PATIENTS: Fifty critically ill patients with sepsis syndrome were studied from April 1990 to August 1991. INTERVENTIONS: Pulmonary artery catheterization; fluid loading if pulmonary artery occlusion pressure was < 10 mm Hg; and 10 micrograms/min/kg dobutamine infusion for 60 mins. MEASUREMENTS AND MAIN RESULTS: Cardiac index, DO2, VO2, and oxygen extraction ratio were determined immediately before and 1 hr after the onset of the dobutamine test. Using receiver operating characteristic curves, responders to the dobutamine infusion were identified by a > 15% increase in VO2 from the time immediately before to 1 hr after the onset of the dobutamine test. We identified 23 responders and 27 nonresponders. Groups differed significantly in age (responders 46 yrs vs. nonresponders 55 yrs) and associated chronic disease (responders one cancer vs. nonresponders six cancers). Significant changes in responders were: a) cardiac index increased 42.9%; b) systemic vascular resistance decreased 20.7%; and c) DO2 increased 39.1% while VO2 increased 40.8%, with no changes in oxygen extraction or blood lactate concentration. Significant changes in nonresponders were: a) cardiac index increased 14.2%; b) DO2 increased 13.2% and c) oxygen extraction decreased from 0.26 to 0.22. Lactate concentration increased significantly by 25.1% in nonresponders. The mortality rate in responders (8.7%) was significantly less than that rate in nonresponders (44.4%). CONCLUSIONS: Most of these septic patients without shock or hyperlactatemia responded to dobutamine infusion in one of two ways: with little increase in DO2 and no increase in VO2, or with significant increases in both DO2 and VO2. The latter response is typical of healthy volunteers given dobutamine. Because of the calorigenic effect of dobutamine, our results imply nothing about the presence or absence of oxygen supply limitation. Still, patients who had increases in DO2 and VO2 had a much higher survival rate than patients who did not. We speculate that the inability of some patients to respond to dobutamine and the associated higher mortality rate may be related to beta-adrenoreceptor dysfunction.

Adult↗
PubMed1993

Role of angiotensin and adrenoceptors in hemodynamic response to aortic cross-clamping.

An earlier study has shown that angiotensin and catecholamines were responsible for the vasoconstriction observed in the isolated hindlimb preparation during aortic cross-clamping. That study also demonstrated that when vasoconstriction was blocked with an alpha-adrenergic antagonist, phenoxybenzamine, vasodilation was elicited by aortic cross-clamping. The present study tested the hypothesis that this vasodilation was mediated via beta-adrenergic receptors. Eighteen dogs had their hindlimb denervated, vascularly isolated, and pump perfused with blood drained from the inferior vena cava, after passing through a gas-exchanging membrane where oxygen and carbon dioxide tensions were normalized. Left and right thoracotomies were performed, and the aorta and inferior vena cava were cross-clamped. The cross-clamping was associated with 29-37% increase in limb vascular resistance in control dogs (n = 6), in animals pretreated with propranolol (2 mg/kg, n = 6), and in dogs pretreated with a combination of phenoxybenzamine (3 mg/kg) and propranolol (2 mg/kg, n = 6). In animals pretreated with a combination of phenoxybenzamine, propranolol, and enalaprilat (2 mg/kg, n = 6), an angiotensin-converting enzyme inhibitor, limb vascular resistance did not change. This study has confirmed that aortic cross-clamping is associated with vasoconstriction induced by angiotensin and activation of alpha-adrenoceptors and has further demonstrated that vasodilation is attributable to beta-adrenoceptor activation.

Angiotensin II↗
PubMed1993

Effects of NG-substituted arginines on coronary vascular function after endotoxin.

We investigated the responses of canine coronary rings to endothelium-derived relaxing factor-nitric oxide- (EDRF-NO) dependent agonists and NO synthase (NOS) inhibitors 3 h after endotoxic shock was induced in dogs by lipopolysaccharide infusion (LPS; 2 mg/kg). EDRF-NO-dependent relaxation to thrombin [control maximum response produced after administration of thrombin (Emax) was -85.2 +/- 7.0% of the constrictor response produced by the thromboxane analogue U-46619], acetylcholine (control Emax -88.4 +/- 3.4%), or bradykinin (control Emax -80.5 +/- 2.2%) was not inhibited by LPS (Emax thrombin -75.9 +/- 9.5%; Emax acetylcholine -90.2 +/- 2.4%; Emax bradykinin -91.6 +/- 3.4%). The NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) (10(-6)-3 x 10(-4) M) caused constriction of rings with endothelium (Emax 36.3 +/- 5.6%), an effect that was greater after LPS (Emax 59.2 +/- 4.1%; P < 0.05). D-NMMA had no effect in control, but it increased tension after LPS (Emax 20.8 +/- 9.7%). Contrary to expectations, L- and D-NMMA relaxed endothelium-denuded rings (-30.4 +/- 8.7% L-NMMA; -45.1 +/- 11.7% D-NMMA; P < 0.05). However, neither agent caused relaxation after in vivo LPS (10.2 +/- 3.4% L-NMMA; 8.9 +/- 5.2% D-NMMA). N omega-nitro-L-arginine-methylester (L-NAME) and nitro-L-arginine (10(-6)-3 x 10(-4) M) increased tension (Emax 82.3 +/- 23.9 and 73.1 +/- 8.8%, respectively) but only when endothelium was present, and the increases were no greater in LPS-treated groups than in controls (with LPS: Emax L-NAME 87.3 +/- 16.5%; Emax nitro-L-arginine 65.7 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

Partial liquid breathing with perflubron improves arterial oxygenation in acute canine lung injury.

Tidal liquid breathing with perfluorocarbon liquid improves lung mechanics and gas exchange in surfactant-deficient lambs. We asked whether an intratracheal dose of perflubron equal to liquid functional residual capacity (FRC) or less (partial liquid breathing) would alter gas exchange in gas-ventilated, anesthetized, and oleic acid (OA)-injured dogs. We gave eight dogs perflubron in six aliquots, each equal to one-sixth of liquid FRC [sequential dose (SEQ) group], starting 90 min after OA. Two other groups of eight dogs each received a liquid FRC dose of perflubron (60-70 ml/kg) either just before (P-Pre) or 90 min after (P-Post) OA, and eight control (CON) dogs received OA but no perflubron. In CON, SEQ, and P-Post dogs, OA caused a significant decrease in static respiratory system compliance (Crs) (1.50 +/- 0.05 to 1.15 +/- 0.06 ml.cmH2O-1.kg-1) and arterial PO2 (508 +/- 10 to 113 +/- 16 Torr) by minute 90. In P-Pre, P-Post, and after the third dose of perflubron (50% FRC) in SEQ dogs, arterial PO2 was significantly higher than that in the CON dogs but was similar to that in the CON dogs after perflubron removal. Perflubron doses less than two-thirds of liquid FRC were associated with increased Crs compared with CON dogs, but further lung filling caused a decrease in Crs. Lung histology showed widespread edema and hemorrhage and was similar in perflubron and CON dogs. O2 delivery and uptake were well maintained in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗