Acute myocardial infarction with normal coronary arteries during septic shock from Neisseria meningitidis

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (?^·V_A/?^·Q) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and?^·V_A/?^·Qdistributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO₂) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal?^·V_A/?^·Qratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal?^·V_A/?^·Qrelationships.     

Effect of aerosolized prostacyclin and inhaled nitric oxide on experimental hypoxic pulmonary hypertension

Objective: To compare the effect of different concentrations of inhaled nitric oxide and doses of nebulized prostacyclin on hypoxia-induced pulmonary hypertension in pigs.¶Design: Prospective, controlled animal study.¶Setting: Animal research facilities of an university hospital.¶Interventions: After reducing the fraction of inspired oxygen (FIO₂) from 1.0 to 0.1, two groups of five pigs each were submitted to inhalation of three concentrations of nitric oxide (5, 10 and 20 ppm) or three doses of prostacyclin (2.5, 5, 10 ng × kg^–1× min^–1).¶Results: All doses of prostacyclin and concentrations of nitric oxide resulted in a decrease in mean pulmonary arterial pressure and pulmonary vascular resistance when compared to hypoxic ventilation (p < 0.001) which was independent of the dose or concentration of either drug used. While inhalation of nitric oxide caused a reduction in mean pulmonary arterial pressure back to values obtained during ventilation with FIO₂ 1.0, values achieved with prostacyclin were still significantly higher when compared to measurements prior to the initiation of hypoxic ventilation. However, direct comparison of the effect of 20 ppm nitric oxide and 10 ng × kg^–1× min^–1 prostacyclin on mean pulmonary arterial pressure revealed no differences between the drugs. All other hemodynamic and gas exchange parameters remained stable throughout the study.¶Conclusions: Inhalation of clinically used concentrations of nitric oxide and doses of prostacyclin can decrease elevated pulmonary arterial pressure in an animal model of hypoxic pulmonary vasoconstriction without impairing systemic hemodynamics or gas exchange.     

Effect of inhaled nitric oxide in combination with almitrine on ventilation-perfusion distributions in experimental lung injury

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (V˙._A/Q˙) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and V˙._A/Q˙ distributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO₂) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal V˙._A/Q˙ ratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal V˙._A/Q˙ relationships.     

The role of endothelin-1 in pressure autoregulation of cerebral blood flow in rats

Objective: To investigate the role of the endothelin system in pressure autoregulation of cerebral blood flow (CBF) in rats.¶Design: We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure–intracranial pressure) with norepinephrine (0.08 μg · kg^?1· min^?1 for 30 min) twice in ten anesthetized normocapnic rats. The first test was performed without (control test) and the second test after administration of the combined endothelin ET_A/B receptor antagonist, bosentan, i. v. (30 mg/kg; drug test). CBF was measured by the hydrogen clearance technique.¶Results: During the control test, norepinephrine infusion increased CPP by 21 ± 2 (23 ± 2 %) mmHg (mean ± SEM; p < 0.001) and CBF by 3.6 ± 3.1 (6 ± 8 %) ml/100 g/min (p = 0.5, Fig. 1); during the drug test, norepinephrine infusion increased CPP by 18 ± 1 (20 ± 2 %) mmHg (p < 0.001) and CBF by 15.8 ± 4.1 (46 ± 13 %) ml/100 g/min (p = 0.004). Mean arterial pressure was not affected by bosentan infusion (p = 0.2). PaC0₂ levels were stable during the tests (40.2 ± 1.4 mmHg).¶Conclusions: The endothelin system is involved in cerebral pressure autoregulation in a rodent model in vivo. The role of this system under pathophysiologic conditions such as subarachnoid hemorrhage, where basal vascular tone and its regulation may be altered, remains to be defined.     

Inert gas rebreathing: the effect of haemoglobin based pulmonary shunt flow correction on the accuracy of cardiac output measurements in clinical practice

Background: Cardiac output (CO) is an important cardiac parameter, however its determination is difficult in clinical routine. Non‐invasive inert gas rebreathing (IGR) measurements yielded promising results in recent studies. It directly measures pulmonary blood flow (PBF) which equals CO in absence of significant pulmonary shunt flow (Q_S). A reliable shunt correction requiring the haemoglobin concentration (c_Hb) as only value to be entered manually has been implemented. Therefore, the aim of the study was to evaluate the effect of various approaches to Q_S correction on the accuracy of IGR. Methods: Cardiac output determined by cardiac magnetic resonance imaging (CMR) served as reference values. The data was analysed in four groups: PBF without correcting for Q_S (group A), shunt correction using the patients’ individual c_Hb values (group B), a fixed standard c_Hb of 14·0 g dl^?1 (group C) and a gender‐adapted standard c_Hb for male (15·0 g dl^?1) and female (13·5 g dl^?1) probands each (group D). Results: 147 patients were analysed. Mean CO_CMR was 5·2 ± 1·4 l min^?1, mean CO_IGR was 4·8 ± 1·3 l min^?1 in group A, 5·1 ± 1·3 in group B, 5·1 ± 1·3 l min^?1 in group C and 5·1 ± 1·4 l min^?1 in group D. The accuracy in group A (mean bias 0·5 ± 1·1 l min^?1) was significantly lower as compared to groups B, C and D (0·1 ± 1·1 l min^?1; P<0·01). Conclusion: IGR allows a reliable non‐invasive determination of CO. Since PBF significantly increased the measurement bias, shunt correction should always be applied. A fixed c_Hb of 14·0 g dl^?1 can be used for both genders if the exact c_Hb value is not known. Nevertheless, the individual value should be used if any possible.     

Dobutamine reverses the vasopressin-associated impairment in cardiac index and systemic oxygen supply in ovine endotoxemia

Introduction

Arginine vasopressin (AVP) is increasingly used to treat sepsis-related vasodilation and to decrease catecholamine requirements. However, AVP infusion may be associated with a marked decrease in systemic blood flow and oxygen transport. The purpose of the present study was to evaluate whether dobutamine may be titrated to reverse the AVP-related decrease in cardiac index (CI) and systemic oxygen delivery index (DO₂I) in an established model of ovine endotoxemia.

Methods

Twenty-four adult ewes were chronically instrumented to determine cardiopulmonary hemodynamics and global oxygen transport. All ewes received a continuous endotoxin infusion that contributed to a hypotensive-hyperdynamic circulation and death of five sheep. After 16 hours of endotoxemia, the surviving ewes (n = 19; weight 35.6 ± 1.5 kg (mean ± SEM)) were randomized to receive either AVP (0.04 Umin^-1) and dobutamine (n = 8) or the vehicle (normal saline; n = 6) and compared with a third group treated with AVP infusion alone (n = 5). Dobutamine infusion was started at an initial rate of 2 μg kg^-1min^-1 and was increased to 5 and 10 μg kg^-1 min^-1 after 30 and 60 minutes, respectively.

Results

AVP infusion increased mean arterial pressure (MAP) and systemic vascular resistance index at the expense of a markedly decreased CI (4.1 ± 0.5 versus 8.2 ± 0.3 l min^-1 m^-2), DO₂I (577 ± 68 versus 1,150 ± 50 ml min^-1 m^-2) and mixed-venous oxygen saturation (S_vO₂; 54.5 ± 1.8% versus 69.4 ± 1.0%; all p < 0.001 versus control). Dobutamine dose-dependently reversed the decrease in CI (8.8 ± 0.7 l min^-1 m^-2 versus 4.4 ± 0.5 l min^-1 m^-2), DO₂I (1323 ± 102 versus 633 ± 61 ml min^-1 m^-2) and S_vO₂ (72.2 ± 1.7% versus 56.5 ± 2.0%, all p < 0.001 at dobutamine 10 μg kg^-1 min^-1 versus AVP group) and further increased MAP.

Conclusion

This study provides evidence that dobutamine is a useful agent for reversing the AVP-associated impairment in systemic blood flow and global oxygen transport.     

CO assessment by suprasternal Doppler in critically ill patients: comparison with thermodilution

Objective: Comparison of suprasternal Doppler (SST) and thermodilution (TD) for the measurement of cardiac output (CO) in critically ill patients.¶Design: Prospective study.¶Setting: Intensive care unit of a university hospital.¶Patients and participants: 65 consecutive critically ill patients requiring a pulmonary artery catheter.¶Interventions: Paired CO measurements were made simultaneously using SST and TD by two independent operators. The time to obtain a CO value by SST was measured. Correlation coefficients and the linear regression equation were determined. A Bland and Altman diagram was plotted. A Bland and Altman diagram was also plotted for the level of cardiac index (CI) values (low: CI < 2.5 l min^–1 m^–2; normal: 2.5 ≤ CI ≤ 4.5 l min^–1 m^–2; high: CI > 4.5 l min^–1 m^–2).¶Measurements and results: In seven patients SST failed to measure CO. In the remaining 58 patients 314 paired CO measurements were performed. The mean time to measure CO by SST was 73 ± 45 s. The equation of linear regression was: SST_CO = 0.84 TD_CO + 1.39. The correlation coefficient was 0.84. The bias between SST and TD was –0.2 ± 1.4 l min^–1. Biases were –0.23 ± 0.50, –0.20 ± 0.68, and 0.25 ± 0.92 l min^–1 m^–2 for low, normal, and high levels of CI, respectively.¶Conclusion: SST does not accurately measure CO but allows a rapid assessment of CI level in critically ill patients.     

Role of alpha-adrenoceptor subtypes mediating sympathetic vasoconstriction in human digits

Abstract. The effects of intra-arterial administration of alpha-1 and alpha-2 adrenoceptor agonists and antagonists on human digital blood flow were studied before and during reflex sympathetic vasoconstriction in normal subjects. Total finger flow was measured by venous occlusion air plethysmography and capillary flow by the disappearance rate of a radioisotope from a local injection in a fingerpad. Intra-arterial phenylephrine (0·2–1·3 μg min^-1) and clonidine (0·12–0·48 μg min^-1) produced dose-related decreases in finger blood flow and increases in vascular resistance. Clonidine was the more potent vasoconstrictor. Prazosin (0·48 μg min^-1) effectively blocked the vasoconstrictor effect of phenylephrine but not clonidine, while yohimbine (30–70 μg min^-1) blocked the effect of clonidine but not phenylephrine. In a 20°C room, prazosin (0·4–13·2 μg min^-1) caused no significant changes in finger blood flow (7·7 ± 2·1 to 11·7 ± 3·3 ml min^-1) 100 ml^-1) or vascular resistance (30·9 ± 8·8 to 28·1 ± 8·7 mmHg ml^-1 min^-1 100 ml^-1). In the 20°C room, yohimbine (30–70 μg min^-1) produced a significant increase in finger blood flow (7·8 ± 2·8 to 23·4 ± 6·8 ml, P>0·01) and decrease in vascular resistance (20·5 ± 5·7 to 6·0 ± 2·2 units, P>0·01). No significant changes occurred in finger capillary flow with prazosin or yohimbine infusions. It is concluded that alpha-1 and alpha-2 adrenoceptors are present in human digital vasculature and that alpha-2 adrenoceptors are more important than alpha-1 adrenoceptors in sympathetic neural vasoconstriction. Since capillary blood flow was unaffected by yohimbine infusions during reflex sympathetic vasoconstriction, the alpha-2 adrenoceptors predominantly influence arteriovenous shunts in the finger.     

Intensity of Nordic Walking in young females with different peak O2 consumption

The purpose of this cross‐sectional study was to determine the physiological reaction to the different intensity Nordic Walking exercise in young females with different aerobic capacity values. Twenty‐eight 19–24‐year‐old female university students participated in the study. Their peak O₂ consumption (VO₂ peak kg^?1) and individual ventilatory threshold (IVT) were measured using a continuous incremental protocol until volitional exhaustion on treadmill. The subjects were analysed as a whole group (n = 28) and were also divided into three groups based on the measured VO₂ peak kg^?1 (Difference between groups is 1 SD) as follows: 1. >46 ml min^?1 kg^?1 (n = 8), 2. 41–46 ml min^?1 kg^?1 (n = 12) and 3. <41 ml min^?1 kg^?1 (n = 8). The second test consisted of four times 1 km Nordic Walking with increasing speed on the 200 m indoor track, performed as a continuous study (Step 1 – slow walking, Step 2 – usual speed walking, Step 3 – faster speed walking and Step 4 – maximal speed walking). During the walking test expired gas was sampled breath‐by‐breath and heart rate (HR) was recorded continuously. Ratings of perceived exertion (RPE) were asked using the Borg RPE scale separately for every 1 km of the walking test. No significant differences emerged between groups in HR of IVT (172·4 ± 10·3–176·4 ± 4·9 beats min^?1) or maximal HR (190·1 ± 7·3–191·6 ± 7·8 beats min^?1) during the treadmill test. During maximal speed walking the speed (7·4 ± 0·4–7·5 ± 0·6 km h^?1) and O₂ consumption (30·4 ± 3·9–34·0 ± 4·5 ml min^?1 kg^?1) were relatively similar between groups (P > 0·05). However, during maximal speed walking, the O₂ consumption in the second and third groups was similar with the IVT (94·9 ± 17·5% and 99·4 ± 15·5%, respectively) but in the first group it was only 75·5 ± 8·0% from IVT. Mean HR during the maximal speed walking was in the first group 151·6 ± 12·5 beats min^?1, in the second (169·7 ± 10·3 beats min^?1) and the third (173·1 ± 15·8 beats min^?1) groups it was comparable with the calculated IVT level. The Borg RPE was very low in every group (11·9 ± 2·0–14·4 ± 2·3) and the relationship with VO₂and HR was not significant during maximal speed Nordic Walking. In summary, the present study indicated that walking is an acceptable exercise for young females independent of their initial VO₂ peak level. However, females with low initial VO₂ peak can be recommended to exercise with the subjective ‘faster speed walking’. In contrast, females with high initial VO₂ peak should exercise with maximal speed.     

Influence of combined intravenous and oral glucose administration on splanchnic glucose uptake in man

Summary. The influence of intravenous plus oral glucose administration on splanchnic glucose handling was examined in healthy young individuals by combining the hepatic vein catheterization technique with the double glucose tracer method. After 1 h of steady state hyperglycaemia (11·7 Itim ) induced by intravenous glucose alone (hyperglycaemic clamp technique), subjects ingested 89 ± 1 g of glucose, and the hyper-glycaemic plateau was maintained for the subsequent 4 h by adjusting the exogenous glucose infusion rate. Over the 4-h absorptive period, only 51 ± 4 g of oral glucose (i.e. 58 ±4% of the ingested load) appeared in the systemic circulation, while 193 ± 15 g (1·072±0·083 mol) of glucose had to be infused exogenously to sustain the hyperglycaemia. Endogenous glucose production was suppressed by over 60%. Net splanchnic glucose balance switched from a positive value (i.e. net uptake) of 506 ± 2–56 uniol min^-1kg^-1with intravenous glucose alone (0·60 min) to a negative one (i.e. net output) of 12·50 ± 2·44 u. mol min^-1kg^-1during 4 h (60–300 min) of intravenous+oral glucose. The mean rate of splanchnic glucose uptake was estimated to be 6·39 ±4·67 ixmol min^-1kg^-1with intravenous glucose alone, and 8·83 ±4·28 u. mol min^-1kg^-1with intravenous+oral glucose. In either case, the large majority (80–90%) of the glucose appearing in the systemic circulation was disposed of by extrasplanchnic tissues. These results indicate that pre-existing hyperglycaemia and/or hyperinsulinaemia inhibit gastrointestinal glucose absorption, and that oral glucose administration does not result in a major redistribution of intravenous glucose between splanchnic and extrasplanchnic tissues.     

Reference Fitness Values in the Untrained Spinal Cord Injury Population

ObjectiveEstablish reference values of cardiorespiratory fitness applicable to the general, untrained spinal cord injury (SCI) population.DesignData were retroactively obtained from 12 studies (May 2004 to May 2012).SettingAn institution-affiliated applied physiology research laboratory.ParticipantsA total of 153 men and 26 women (age, 18–55y) with chronic SCI (N=179) were included. Participants were not involved in training activities for 1 or more months before testing and were able to complete a progressive resistance exercise test to determine peak oxygen consumption (Vo₂peak).InterventionsNot applicable.Main Outcome MeasurePercentile ranking (poor<20%; fair; 20%–40%; average, 40%–60%; good, 60%–80%; excellent, 80%–100%) used to establish reference values.ResultsReference cardiorespiratory fitness values based on functional classification as paraplegic or tetraplegic were established (paraplegic: median, 16.0mL·kg⁻¹·min⁻¹; range, 1.4–35.2mL·kg⁻¹·min⁻¹; tetraplegic: median, 8.8mL·kg⁻¹·min⁻¹; range, 1.5–21.5mL·kg⁻¹·min⁻¹) for untrained men and women. For the primary outcome measure (Vo₂peak), persons with paraplegia had significantly higher values than did persons with tetraplegia (P<.001). Although men had higher values than did women, these differences did not reach significance (P=.256). Regression analysis revealed that motor level of injury was associated with 22.3% of the variability in Vo₂peak (P<.001), and an additional 8.7% was associated with body mass index (P<.001). No other measure accounted for additional significant variability.ConclusionsEstablished reference fitness values will allow investigators/clinicians to stratify the relative fitness of subjects/patients from the general SCI population. Key determinants are motor level of injury and body habitus, yet most variability in aerobic capacity is not associated with standard measures of SCI status or demographic characteristics.     

Insulin sensitivity in alcoholic cirrhosis

The amount-of-substance rate of glucose metabolism and its sensitivity to the concentration of insulin was quantified in 10 non-diabetic patients with alcoholic cirrhosis of varying severity, using the ‘glucose clamp technique’. Fasting glucose and insulin were 5.4±0.3 mmol/1 and 187±50 μmol/1 (mean ± SEM), respectively. During the hyperglycaemic clamp (blood glucose at 12.5 mmol/1) the glucose metabolic rate (divided by body mass) was 27± 4 μmol·min^?1·kg^?1 at an insulin concentration of 998± 158 pmol/1. Thus the insulin sensitivity of the tissue glucose metabolism was 22±7 m³·min^?1·kg^?1. During the euglycaemic clamp exogenous insulin was given to a concentration of 574± 72 pmol/1. The resulting glucose metabolic rate was 20± 4 μmol·min^?1·kg^?1 and the insulin sensitivity the same as during hyperglycaemia. The calculated systemic delivery rate of insulin (divided by body surface area) was 783± 172 pmol·min^?1·m^?2. Fasting glucagon was 32± 5 pmol/ and only partly depressed by glucose or insulin. In comparison with stated relevant control groups cirrhotics exhibit glucose intolerance characterized by decreased sensitivity to insulin, hyperinsulinaemia due to increased release, and hyperglucagonaemia with decreased suppressibility. There was no relation between clinical or biochemical data of the patients and the above results, suggesting that the abnormal glucose metabolism does not depend directly on the decreased liver function but on a disturbed pancreatic-hepatic-peripheral axis.     

Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer

Summary. Fasting is generally accompanied by a decrease in energy metabolism and hormones. On the other hand, indirect evidence has suggested that the response to adrenergic agonists may be maintained or even increased in malnutrition. The present study evaluated whether weight-losing patients with and without cancer have increased plasma concentrations of catecholamines and different responses to intravenously infused adrenaline compared to weight-stable individuals. Eight malnourished cancer and 10 non-cancer patients (11% weight loss) were compared to seven well-nourished and weight-stable patients. Adrenaline was infused i.v. at a rate of 0·005 μg min^-1 kg^-1 body weight during 40 min followed by a 40 min rest period (without infusion) and then a final 40 min period with i.v. adrenaline infusion (0·02 μg min^-1 kg^-1 body weight). Plasma glycerol concentration at fast was higher in weight-losing patients compared to weight-stable individuals. Whole body oxygen uptake, carbon dioxide production, heart rate and plasma concentrations of free fatty acids (FFA) increased while the mean arterial pressure decreased significantly in response to adrenaline infusion at 0·02 μg kg^-1 min^-1 in both weight-losing and weight-stable patients. Adrenaline at 0·005 μg kg^-1 min^-1 increased plasma FFA levels by 19% (P<0·05) in weight-losing patients while no significant alteration was observed in well-nourished patients. Adrenaline infusion at 0·02 μg kg^-1 min^-1 decreased the mean arterial blood pressure and stimulated respiratory gas exchange and heart rate significantly more in weight-losing than in weight-stable patients. The slopes for oxygen uptake, carbon dioxide production, heart rate, plasma FFA and plasma glycerol vs. plasma adrenaline and noradrenaline were all significantly steeper (P<0·05–0·01) in malnourished patients than in well-nourished controls. The present study suggests an increased sensitivity to adrenaline in weight-losing patients compared to matched controls with normal nutritional state and stable weight.     

Ranitidine or dobutamine alone or combined has no effect on gastric intramucosal-arterial PCO2 difference after cardiac surgery

Objective: To test the hypothesis that ranitidine, either alone or in combination with dobutamine, modifies the gastric intramucosal-arterial PCO₂ difference.¶Design: Full factorial design (double-blinded for ranitidine).¶Setting: Intensive Care Unit of a university hospital.¶Patients: Sixty-four haemodynamically stable coronary artery bypass surgery patients.¶Interventions: Ranitidine (150 mg preoperatively per os and 50 mg intravenously postoperatively) and dobutamine (4 μ g · kg^–1· min^–1 for 3 h postoperatively) were administered in four randomised groups of patients: preoperative and postoperative ranitidine, either alone (n = 15) or in combination with dobutamine (n = 17), dobutamine alone (n = 15) or neither ranitidine nor dobutamine (n = 17).¶Measurements and results: Gastric intramucosal-arterial PCO₂ difference was measured during the first 5 postoperative hours. No differences in the postoperative pattern of gastric intramucosal-arterial PCO₂ difference were found among the groups.¶Conclusions: Ranitidine and dobutamine have no effect on the gastric tonometry results on intramucosal-arterial PCO₂ difference after uncomplicated cardiac surgery. Hence, the routine use of H₂-antagonists for gastrointestinal tonometry is not warranted. Our results must be limited to results obtained by tonometry; they do not allow any conclusions on the effects of these drugs on splanchnic blood flow or its distribution.     

Plasma lipid and lipoprotein profiles in pre- and post-menopausal middle-aged runners

Summary. Plasma lipid and lipoprotein profiles were compared in middle-aged trained and untrained women before and after menopause. Subjects were assigned to one of four groups: (1) pre-menopausal trained (Pre-T: n= 17, aged 42 ±5 years, body fat 19±5%, training distance 53 ±20 km week^-1, V?o_2max 49 ±4 ml kg^-1 min^-1, mean±SD); (2) pre-menopausal untrained (Pre-UT: n= 26, 42 ±5 years, 24 ±7%, 34 ±6 ml kg^-1 min^-1); (3) post-menopausal trained (Post-T: n= 16, 54 ±3 years, 20 ±4%, 43 ±19 km week^-1, 41 ±5 ml kg^-1 min^-1); and (4) post-menopausal untrained (Post-UT: n= 15, 55 ±3 years, 25 ±6%, 31 ±3 ml kg^-1 min^-1). There were no significant differences in total cholesterol (range 173–194 mg dl^-1), triglyceride (56–72 mg dl^-1), and HDL-cholesterol (HDLC: 76–85 mg dl^-1) among the four groups. LDL-cholesterol (LDLC) in the post-menopausal women (Post-T: 96 ±32 mg dl^-1; Post-UT: 104 ±23 mg dl^-1) tended to be higher than in the premenopausal women (Pre-T: 86 ± 25 mg dl^-1, Pre-UT: 81 ± 23 mg dl^-1). LDLC/HDLC ratio in Post-UT (1·42 ±0·38 unit) was higher than in the pre-menopausal women (Pre-T: 1·03±0·31 unit, P<0·01; Pre-UT: 1·10±0·38 unit, P<0·05), whereas the ratio in Post-T (1·20 ±0·38 unit) was not different from those of the pre-menopausal groups. These results suggest that endurance running protects against the increase in LDLC/HDLC ratio that frequently occurs after menopause.     

Mitigation of endotoxin-induced acute lung injury in ventilated rabbits by surfactant and inhaled nitric oxide

Objective: To evaluate the efficacy of surfactant and inhaled nitric oxide (iNO) in endotoxin-induced acute lung injury (ALI).¶Design: Prospective, randomised, controlled experimental study.¶Setting: A medical university hospital research laboratory.¶Intervention: Twenty-nine adult rabbits (2.4–3.4 kg) were given two doses of intravenous endotoxin (Escherichia coli) (0.01 mg/kg and, 12 h later, 0.1 mg/kg), and then subjected to mechanical ventilation. After 8 h these animals were allocated to four treatment groups: (1) control, (2) iNO at 20 ppm (NO), (3) surfactant at 100 mg/kg (Surf) and (4) both surfactant and iNO as in groups 2 and 3 (SNO), and ventilated for a further 6 h followed by broncho-alveolar lavage (BAL), analysis of surfactant contents in BAL fluid and histological examination of the lungs.¶Measurements and results: All the animals had developed ALI with respiratory failure 8 h after the second dose of endotoxin as evidenced by a decrease of PaO₂/FIO₂ from 520 ± 30 to 395 ± 19 mmHg and dynamic compliance (Cdyn) from 1.20 ± 0.11 to 0.73 ± 0.05 ml/cmH₂O × kg, and an increase of intrapulmonary shunting (Qs/Qt) from 7.5 ± 0.8 % to 12.9 ± 1.0 % (all measurements p < 0.01 versus baseline). In the SNO group, values for PaO₂/FIO₂, Cdyn and Qs/Qt after 6 h were 301 ± 15 mmHg, 0.67 ± 0.05 ml/cmH₂O × kg and 16.5 ± 0.8 %, compared to 224 ± 26 mmHg, 0.53 ± 0.04 ml/cmH₂O × kg and 24.1 ± 2.0 %, respectively, in the control group (all measurements p < 0.01). Both Surf and NO groups showed intermediate levels of these parameters. In both Surf and SNO groups, the minimum surface tension of BAL fluid was lower, and the content of disaturated phosphatidylcholine/total protein higher, than in the control and NO groups (p < 0.01). Histological features of lung injury were less prominent and wet/dry lung weight ratio lower in the NO, Surf and SNO groups. Decreased surfactant protein A (SP-A) and its mRNA expression were found in all endotoxin-exposed groups, but the SP-A content of the SNO group was moderately improved in comparison to the control group. Surfactant aggregate size was not affected.¶Conclusion: Early application of surfactant and iNO moderately mitigated ALI as reflected by improvement of lung mechanics, pulmonary perfusion and morphology.     

Forearm metabolism during infusion of adrenaline: comparison of the dominant and non‐dominant arm

Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain‐gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured by the local ¹³³Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a‐v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0·3 nmol kg^?1 min^?1. No difference in the metabolic information obtained in the fasting state could be demonstrated. During infusion of adrenaline, blood flow and lactate output increased significantly more in the non‐dominant arm (8·12 ± 1·24 versus 6·45 ± 1·19 ml 100 g^?1 min^?1) and (2·99 ± 0·60 versus 1·83 ± 0·43 μmol 100 g^?1 min^?1). Adrenaline induced a significant increase in oxygen uptake in the non‐dominant forearm (baseline period: 4·98 ± 0·72 μmol 100 g^?1 min^?1; adrenaline period: 6·63 ± 0·62 μmol 100 g^?1 min^?1) while there was no increase in the dominant forearm (baseline period: 5·69 ± 1·03 μmol 100 g^?1 min^?1; adrenaline period: 4·94 ± 0·84 μmol 100 g^?1 min^?1). It is concluded that the two forearms do not respond equally to adrenaline stimulation. Thus, when comparing results from different studies, it is necessary to know which arm was examined.     

Acute effects of vitamin A on the kinetics of endotoxin in conscious rabbits

Background: Vitamin A reduces the pathophysiological effects of endotoxin in animals, but the mechanism and the lowest effective dose are not clear.¶Methods: An intravenous bolus of endotoxin 20 μg · kg^–1 was given to 30 rabbits. In 10 of them, 1000 IE · kg^–1 retinyl palmitate was injected intravenously 1 h before the endotoxin and in another 10 rabbits 1 h after the endotoxin. A one-compartment open model was fitted to the time-concentration profile of endotoxin in plasma.¶Results: The half-life of endotoxin was half as long when vitamin A was given for prophylaxis (median 35 min) and for treatment (33 min) than in the controls (67 min; p < 0.004). The plasma concentrations of immunoglobulin G and M endotoxin-core antibodies, the leucocyte count and the acid-base balance did not differ between the groups during the experiment, but the pyrogenic reaction was more pronounced in the controls.¶Conclusion: A fairly low dose of vitamin A reduced the half-life of endotoxin.     

Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study

Introduction

Recent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements.

Methods

We enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 μg·kg^-1·h^-1), vasopressin (.03 U·min^-1) or norepinephrine (15 μg·min^-1; n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA.

Results

There were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of.03 U of vasopressin or 15 μg·min^-1 of norepinephrine, 1.3 μg·kg^-1·h^-1 of terlipressin allowed a marked reduction in catecholamine requirements (0.8 ± 1.3 and 1.2 ± 1.4 vs. 0.2 ± 0.4 μg·kg^-1·min^-1 at 48 hours; each P < 0.05) and was associated with less rebound hypotension (P < 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 ± 2.8 and 2.8 ± 2.5 vs. 0.9 ± 0.3 mg·dL^-1; each P < 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P < 0.001 48 hours vs. BL).

Conclusions

The present study provides evidence that continuous infusion of low-dose terlipressin – when given as first-line vasopressor agent in septic shock – is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements.

Trial registration

ClinicalTrial.gov NCT00481572.