Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation. Results of a randomized, double-blind, controlled study

OBJECTIVE: To assess the effects of dobutamine at a rate of 5 micrograms/kg/min on hemodynamics and gastric intramucosal acidosis in patients with hyperdynamic septic shock treated with epinephrine. DESIGN: A prospective, interventional, clinical trial. SETTING: An adult, 16-bed medical/surgical intensive care unit of a university hospital. PATIENTS: Twenty septic shock patients with a mean arterial pressure of > 75 mm Hg and a cardiac index of > 3.5 L/min/m2. INTERVENTIONS: After baseline measurements (H0), each patient received dobutamine at a rate of 5 micrograms/kg/min. Baseline measurements included: hemodynamic parameters, tonometric parameters, arterial and mixed venous gases, and arterial lactate concentrations. These measurements were repeated after 1 (H1), 2 (H2), and 3 (H3) hrs. After H2 measurements, dobutamine was stopped. The patients were separated into two groups according to their PCO2 gap (tonometer PCO2-PaCO2). The increased PCO2 gap group was defined by a PCO2 gap > 8 torr (> 1.1 kPa) (n = 13), and the normal PCO2 gap group by a PCO2 gap < or = 8 torr (< or = 1.1 kPa)(n = 7). MEASUREMENTS AND MAIN RESULTS: Dobutamine at 5 micrograms/kg/min had no significant effects on mean arterial pressure, heart rate, cardiac index, systemic vascular resistance, oxygen delivery, and oxygen consumption in epinephrine-treated septic shock. No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia. During dobutamine infusion, arterial lactate concentration decreased from 5.1 +/- 0.4 in the increased PCO2 gap group and 4.2 +/- 0.4 in the normal PCO2 gap group to 3.9 +/- 0.3 and 3.5 +/- 0.3 mmol/L, respectively (p < .01). The PCO2 gap decreased and gastric intramucosal pH increased in the increased PCO2 gap group from 12 +/- 0.8 (1.6 +/- 0.1 kPa) to 3.5 +/- 0.8 torr (0.5 +/- 0.1 kPa) (p < .01) and from 7.11 +/- 0.03 to 7.18 +/- 0.02 (p < .01), respectively, and did not change in the normal PCO2 gap group. After stopping dobutamine infusion, the PCO2 gap and intramucosal pH returned to baseline values in the increased PCO2 gap group. CONCLUSION: The addition of 5 micrograms/kg/min of dobutamine added to epinephrine in hyperdynamic septic shock selectively improved the adequacy of gastric mucosal perfusion without modification in systemic hemodynamics.     

Liver injury as a model of uncontrolled hemorrhagic shock: resuscitation with different hypertonic regimens

OBJECTIVE: To study if metabolic stress modifies the thermogenic effect of dobutamine. DESIGN: Prospective, increasing dose, pharmacologic study. SETTING: Laboratory of the Department of Intensive Care Unit at a university hospital. SUBJECTS: Twelve normal volunteers. INTERVENTIONS: Dobutamine hydrochloride was infused to 12 healthy male volunteers starting at a dose of 2 micrograms/min/kg and gradually increased to 4 and 6 micrograms/min/kg. Each dose of dobutamine was infused for 20 mins. Metabolic stress was induced in six of the 12 volunteers using a triple hormone infusion (epinephrine, cortisol, and glucagon) before dobutamine, and was continued at a constant rate during the dobutamine infusion. The remaining six volunteers served as the control group and received only dobutamine. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2) was measured using a metabolic monitor. Arterial blood pressure was measured noninvasively, and cardiac output was monitored by Doppler echocardiography. Plasma concentrations of dopamine, norepinephrine, and epinephrine were measured in both groups. In the triple hormone group, blood was sampled to measure concentrations of insulin, glucagon, cortisol, free fatty acids, and glycerol to ensure the presence of a metabolic stress reaction. At the maximum dose, dobutamine induced a 19% increase (from 140 +/- 17 to 166 +/- 17 mL/min/m2) in VO2 in the control group and an 11% increase (from 167 +/- 10 to 184 +/- 13 mL/min/m2) in the triple hormone group (p < .05 between the two groups) compared with baseline. No change in the respiratory exchange ratio was seen. The triple hormone infusion alone induced hypermetabolism, a marked hemodynamic response, and increased lipolysis. CONCLUSIONS: Stress, induced by a triple hormone infusion, diminishes the thermogenic effect of dobutamine. In the clinical setting, a > 10% to 15% increase in VO2 in response to dobutamine may not be explained just by the thermogenic effect of the drug.     

Oxygen delivery and uptake relationships in patients with aortic stenosis

Previous studies have reported finding supply-dependent O2 uptake (VO2) in patients with the adult respiratory distress syndrome, sepsis, chronic obstructive lung disease, sleep apnea, and other cardiopulmonary diseases. A common element among these diverse conditions is the potential to reduce systemic O2 delivery (QO2 = cardiac output.arterial O2 content). The aim of the present study was to determine whether patients with aortic stenosis also exhibit increases in VO2 when O2 delivery is increased after valvuloplasty. Fifty-six patients were studied while breathing room air in the supine position. Expired gases for determination of O2 uptake (VO2 [measured]), cardiac output (thermodilution), arterial and mixed venous blood gases, and hemodynamic measurements were obtained immediately before and within 30 min after aortic valvuloplasty. After valvuloplasty, VO2 (measured) increased from 3.03 +/- 0.51 to 3.24 +/- 0.62 ml/min/kg (p < 0.0001). However, O2 extraction ratio did not change from baseline levels (32.16 +/- 10.1%) after valvuloplasty (32.21 +/- 8.25%, p = not significant). These results could have occurred only if O2 delivery had also increased. Accordingly, Fick-derived Q and corresponding QO2 (Fick) both increased significantly, suggesting the presence of O2 supply-dependent VO2. However, neither Q (thermodilution) nor QO2 (thermodilution) changed significantly, and regression of VO2 (measured) against QO2 (thermodilution) failed to detect a relationship. We conclude that patients with aortic stenosis exhibit increases in O2 delivery and uptake after valvuloplasty, although this may or may not reflect covert tissue hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decisions about enteral tube feeding among the elderly

OBJECTIVE: To characterize the acute actions and physiologic dose profile of epinephrine, as a single inotrope, in patients with septic shock. DESIGN: Prospective clinical study. The relationship between epinephrine dose and cardiovascular variables was analyzed using repeated-measures analysis of variance. SETTING: ICU in a university teaching hospital. PATIENTS: Eighteen patients with septic shock, mean age 64 +/- 8 (SD) yrs, and with a mean admission Acute Physiology and Chronic Health Evaluation (APACHE II) score of 23 (range 14 to 35). INTERVENTIONS: Initial volume loading and the measurement of a baseline hemodynamic profile were followed by the administration of an epinephrine infusion at 3 microgram/min with subsequent increments of 3 micrograms/min and the determination of a hemodynamic profile after each dose increment. Therapy was titrated to clinical goals of perfusion and restoration of premorbid systolic arterial BP. MEASUREMENTS AND MAIN RESULTS: After volume loading, mean hemodynamic indices were as follows: mean arterial pressure (MAP) 62 +/- 7 mm Hg; cardiac index 3.8 +/- 1.1 L/min/m2; left ventricular stroke work index 25 +/- 11 g.m/m2; oxygen delivery (Do2) index 460 +/- 168 mL/min/m2; and oxygen consumption (VO2) index 165 +/- 64 mL/min/m2. In the dose range of 3 to 18 microgram/min, epinephrine produced linear increases in average heart rate, MAP, cardiac index, left ventricular stroke work index, stroke volume index, VO2, and DO2. No effect was noted on pulmonary artery occlusion pressure (PAOP), mean pulmonary arterial pressure, or systemic vascular resistance index. CONCLUSIONS: Epinephrine increases DO2 in septic shock by increasing cardiac index without an effect on systemic vascular resistance index or PAOP.     

Effectiveness of nitric oxide inhalation in septic ARDS

STUDY OBJECTIVE: To evaluate the percentage of nitric oxide (NO) responders in septic shock patients with ARDS. Additionally, to investigate long-term NO effects on cardiac performance and oxygen kinetic patterns in NO responders vs nonresponders. DESIGN: Prospective cohort study. SETTING: ICU of a university hospital. PATIENTS: Twenty-five consecutive patients with a diagnosis of septic shock and established ARDS requiring inotropic and vasopressor support. INTERVENTIONS: After diagnosis of ARDS, NO was administered at 18 or 36 ppm. Patients demonstrating a NO-induced rise of arterial oxygen tension of 20% or more and/or a fall in mean pulmonary artery pressure of 15% or more were grouped as NO responders; others were grouped as nonresponders. MEASUREMENTS AND RESULTS: Ten patients (40%) were NO responders, while 15 patients (60%) were nonresponders. Mortality was 40% in NO responders and 67% in nonresponders (NS). NO responders developed a significantly lower mean pulmonary artery pressure (28 +/- 6 vs 33 +/- 6 mm Hg; p < 0.05), lower pulmonary vascular resistance (PVR: 258 +/- 73 vs 377 +/- 163 dyne.s.cm-5.m-2; p < 0.05), and higher PaO2/FIO2 ratio (192 +/- 85 vs 144 +/- 74 mm Hg; p < 0.05) within the study period. In responders, NO-induced afterload reduction resulted in increased right ventricular ejection fraction (RVEF: 40 +/- 7 vs 35 +/- 9%; p < 0.05), significantly higher cardiac index (CI: 4.5 +/- 1.1 vs 4.0 +/- 1.2 L.min-1.m-2; p < 0.05) and oxygen delivery (DO2: 681 +/- 141 vs 599 +/- 160 mL.min-1.m-2; p < 0.05) compared with nonresponders. In NO nonresponders, RVEF was correlated with PVR, CI, DO2, mixed venous oxygen saturation (SvO2), and oxygen extraction ratio (O2ER) (r = +/- 0.60 to +/- 0.69; p < 0.05). No significant correlation between RVEF and any of these parameters was observed in responders. SvO2 (75 +/- 7 vs 69 +/- 8%; p < 0.05) and O2ER (0.24 +/- 0.06 vs 0.27 +/- 0.06; p < 0.05) were significantly different between responders and nonresponders, while no difference in oxygen consumption was observed (161 +/- 41 vs 153 +/- 43 mL.min.m-2). CONCLUSIONS: Inhaled NO is effective in only a subgroup of septic ARDS patients, with a higher, but insignificantly different percentage of survivors in the responder group. NO responders were characterized by increased RVEF accompanied by higher CI, DO2, and lower O2ER. In nonresponders, RVEF remained depressed, with a close correlation between RVEF and CO as well as DO2 and O2ER. Thus, nonresponders seem to suffer from impaired cardiac reserves and correspondingly lower oxygen transport variables.     

Oxygen transport pattern in burned patient with sepsis under inotropic support

Hemodynamic and oxygen-kinetic data of 16 burn patients with sepsis were analysed to explore relationship between oxygen transport pattern and clinical outcome after dopamine and dobutamine therapy. Two patterns of oxygen transport were shown in the 16 patients. Of them, ten (62.5%) had optimal DO2 and VO2 values (model I), and six (37.5%) had lower DO2 and VO2 values than the optimal (model II). All of 6 patients with model II developed lactic acidosis, septic shock and MOF and died. Two of 10 patients in model I developed MOF, only one died. The results indicate that, in burn patient with sepsis, the decreased response of DO2 and VO2 to inotropic therapy suggests failure of tissue perfusion, oxygen extraction and utilization, and may possibly predict the outcome.     

The effects of prostacyclin on gastric intramucosal pH in patients with septic shock

OBJECTIVE: To investigate whether infusing prostacyclin (PGI2) in patients with septic shock improves splanchnic oxygenation as assessed by gastric intramucosal pH (pHi). DESIGN: Interventional clinical study. SETTING: Surgical ICU in a university hospital. PATIENTS: 16 consecutive patients with septic shock according to the criteria of the ACCP/SCCM consensus conference all requiring norepinephrine to maintain arterial blood pressure. INTERVENTIONS: All patients received PGI2 (10 ng/kg x min) after no further increase in oxygen delivery could be obtained by volume expansion, red cell transfusion and dobutamine infusion. The results were compared with those before and after conventional resuscitation. The patients received continuous PGI2 infusion for 33-32 days. MEASUREMENTS AND RESULTS: O2 uptake was measured directly in the respiratory gases, pHi was determined by tonometry. Baseline O2 delivery, O2 uptake and pHi were 466 +/- 122 ml/min.m2, 158 +/- 38 ml/min.m2, and 7.29 +/- 0.09, respectively. While O2 uptake remained unchanged, infusing PGI2 increased O2 delivery (from 610 +/- 140 to 682 +/- 155 ml/min.m2, p < 0.01) and pHi (from 7.32 +/- 0.09 to 7.38 +/- 0.08, p < 0.001) beyond the values obtained by conventional resuscitation. While 9 of 11 patients with final pHi > 7.35 survived, all patients with final pHi < 7.35 died (p < 0.01). CONCLUSIONS: Infusing PGI2 in patients with septic shock increases pHi probably by enhancing blood flow to the splanchnic bed and thereby improves splanchnic oxygenation even when conventional resuscitation goals have been achieved.     

Multiple cases of life-threatening adenovirus pneumonia in a mental health care center

Eighteen cases of pneumonia developed during an outbreak of adenovirus infection in a chronic psychiatric care facility. The six patients most severely affected were admitted to the intensive care unit (ICU) at our institution. Four of these patients developed septic shock. We report the presentation, disease progression, and response to treatment of these patients. Clinical features consisted of high fever, nonproductive cough, and dense lower lobe infiltrates. Laboratory abnormalities included transient fall in white blood cell and platelet counts, and elevations of transaminases, lactate dehydrogenase (LDH), and creatinine phosphokinase (CPK). Five patients were intubated for hypoxemia and four developed the acute respiratory distress syndrome (ARDS) and septic shock (mean cardiac output, 14.1 +/- 1.3 L/min; cardiac index, 6.4 +/- 0.4 L/min/min2; systemic vascular resistance, 326 +/- 107 dyne cm/s2). All patients recovered and were discharged back to the chronic care facility except for one patient with chronic renal failure who died 2 mo after admission. Adenovirus (serotype 35) was isolated from the respiratory secretions of five patients and antibody titers increased 6-fold in the other. These patients constitute the largest series of patients with ARDS and septic shock caused by adenovirus pneumonia and the first outbreak of multiple cases of adenovirus pneumonia in immunocompetent civilian adults occurring from a single source.     

Dobutamine as a countermeasure for reduced exercise performance of rats exposed to simulated microgravity

Post-spaceflight results and findings from humans and rodents after conditions of bed rest or simulated microgravity indicate maximum exercise performance is significantly compromised. However, the chronic administration of dobutamine (a synthetic adrenomimetic) to humans in relevant experiments improves exercise performance by mechanisms that prevent the decline in peak O2 consumption (VO2peak) and reduce the concentration of lactic acid measured in the blood. Although dobutamine restores maximum VO2 values in animals participating in simulated microgravity studies, it is unknown whether injections of this alpha 1-, beta 1-, and beta 2-adrenoceptor agonist in rats will enhance exercise performance. To investigate this, adult male rats were assigned to three experimental groups: caged control receiving saline; head-down, tail-suspended (HDS) receiving saline (HDS-S); and an HDS group receiving dobutamine hydrochloride injections (1.8 mg/kg twice daily per rat). Treadmill tests were performed before suspension, at 14 days, and after 21 days. VO2peak, run time, and the rate of rise in colonic temperature (heating index) were evaluated after 14 days, whereas at 21 days, hemodynamic responses (heart rate, systolic blood pressure, and double product) were determined during submaximal exercise with blood pH, blood gases, and lactic acid concentration values obtained during maximal exercise. In contrast to the results for the HDS-S rats, dobutamine administration did restore VO2peak and "normalized" lactic acid concentrations during maximal exercise. However, daily injections were unable to enhance exercise performance aspects associated with treadmill run time, the mechanical efficiency of running, the heating index, or the retention of muscle and body mass. These simulated microgravity findings suggest that dobutamine's potential value as a countermeasure for postflight maximal performance or for egress emergencies is limited and that other countermeasures must be considered.     

pH dependence of corneal oxygen consumption

PURPOSE: To determine whether corneal acidosis, which occurs during contact lens wear, alters corneal O2 consumption (QO2) and if so, whether increased ion transport activity could contribute to altered QO2 during acidosis. METHODS: PO2 was measured, using the phosphorescence quenching of Pd-meso-tetra-(4-carboxyphenyl) porphine, in an airtight chamber that held a trephined rabbit cornea. The rate of change in chamber PO2 was used as a measure of QO2. QO2 was measured at pH 7.5 and then at either pH 6.7, 7.1, or 7.3. Measurements of QO2 at pHs 7.5 and 6.7 were repeated in the presence of 0.5 mM amiloride and 0.5 mM ouabain. RESULTS: When pH was changed from 7.5 to 6.7, 7.1, or 7.3, O2 consumption increased by a factor of 1.80+/-0.11 (+/-SE), 1.65+/-0.12, and 1.44+/-0.06, respectively. Amiloride (0.5 mM) and ouabain (0.5 mM) inhibited 50% and 65%, respectively, of the increase in QO2 at pH 6.7. CONCLUSIONS: Corneal acidosis leads to increased QO2 in a dose-dependent manner. The increased QO2 is in part secondary to the activation of pH regulatory mechanisms, including Na+/H+ exchange, which then stimulates Na+/ K+-ATPase activity. These findings indicate that contact lens-induced acidosis can exacerbate corneal hypoxia and related complications.     

Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome. The NO Almitrine Study Group

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.     

Pressure support ventilation in adult respiratory distress syndrome: short-term effects of a servocontrolled mode

PURPOSE: To assess the short-term effects of pressure support ventilation in adult respiratory distress syndrome (ARDS), we studied 17 patients with moderate to severe ARDS using mandatory rate ventilation (MRV), a servocontrolled mode of PSV having respiratory rate as the targeted parameter. MATERIALS AND METHODS: Based on the duration of ARDS, the patients were divided into two groups: Group 1, early ARDS (duration up to 1 week), 10 patients; Group 2, intermediate ARDS (duration between 1 and 2 weeks). The patients were initially ventilated with assisted mechanical ventilation then with MRV, and finally with controlled mechanical ventilation. After a 20-minute period allowed for stabilization in each mode, ventilatory variables, gas exchange, hemodynamics, and patient's inspiratory effort were evaluated. RESULTS: During MRV blood gases, airway pressures and hemodynamic variables remained within acceptable limits in all patients. Compared with assisted mechanical ventilation, during MRV, patients of group 1 decreased their VT and V (from 0.64 +/- 0.04 to 0.42 +/- 0.03 L/sec) and increased their TI/TT (from 0.39 +/- 0.03 to 0.52 +/- 0.03). f did not change. PAO2 - PaO2 and QS/QT decreased (from 306 +/- 16 to 269 +/- 15 mm Hg, and from 20.2 +/- 1.4 to 17.5 +/- 1.1, respectively), while PaCO2 increased (from 44 +/- 3 to 50 +/- 3 mm Hg). On the contrary, patients of group 2 increased their VT (from 0.69 +/- 0.02 to 0.92 +/- 0.09 L), decreased their f (from 22.3 +/- 0.5 to 19.3 +/- 0.3 b/min), although they did not change their V and TI/TT. PAO2 - PaO2 and QS/QT remained stable. PaCO2 diminished (from 39 +/- 3 to 34 +/- 3 mm Hg). Pressure support level was higher in group 2 than in group 1 (29.4 +/- 3.0 v 19.8 +/- 2.9 cm H2O). CONCLUSIONS: We conclude that (1) PSV delivered by MRV may adequately ventilate patients with moderate to severe ARDS, preserving gas exchange and hemodynamics, at least for the short period tested; (2) early and intermediate ARDS respond in a different manner to MRV in terms of breathing pattern, gas exchange, and level of pressure assistance; and (3) patients with early ARDS are those who have an improvement in intrapulmonary oxygenation probably due, at least in part, to alveolar recruitment augmented by active diaphragmatic contraction.     

Neither dopamine nor dobutamine corrects mesenteric blood flow depression caused by positive end-expiratory pressure in a rat model of acute lung injury

OBJECTIVE: To determine if either dopamine or dobutamine would counteract the deleterious effect that positive end-expiratory pressure (PEEP) has on cardiac output and mesenteric blood flow in a rat model of acute lung injury. DESIGN: Prospective, randomized, controlled trial in a clinically relevant model of acute lung injury. SETTING: Microcirculation research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The animals were anesthetized with pentobarbital (30 mg/kg) by intraperitoneal injection. They underwent tracheostomy, jugular and femoral vein cannulation, femoral artery cannulation, carotid artery thermistor placement, and bowel preparation for in vivo video microscopy. Acute lung injury was created by administering 0.1 N hydrochloric acid (1 mL/kg) via the tracheostomy. Dopamine or dobutamine (2.5 or 12.5 microg/kg/min), followed by two intravenous fluid boluses, was administered to rats ventilated with 5, 10, 15, and 20 cm H2O of PEEP. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, thermodilution cardiac output, mesenteric arteriolar diameter, and red blood cell velocity were measured and mesenteric blood flow was calculated. Cardiac output was depressed in rats exposed to 20 cm H2O of PEEP by 32+/-2%. The corresponding values for cardiac output depression at 20 cm H2O of PEEP in rats receiving 2.5 and 12.5 microg/kg/min of dopamine and 2.5 and 12.5 microg/kg/min of dobutamine were 31+/-1%, 21+/-1%, 29+/-0%, and 24+/-2%, respectively. Mesenteric blood flow was depressed in rats ventilated with 20 cm H2O of PEEP by 74+/-3%, while the corresponding values in rats exposed to 20 cm H2O of PEEP and receiving 2.5 or 12.5 microg/kg/min of dopamine or 2.5 or 12.5 microg/kg/min of dobutamine were 86+/-3%, 77+/-3%, 73+/-3%, and 66+/-3%, respectively. Fluid boluses did not correct the deficits in cardiac output or mesenteric blood flow caused by the combination of acute lung injury and PEEP. CONCLUSIONS: The higher doses of dopamine and dobutamine partially, but insignificantly, corrected the cardiac output depression caused by PEEP in a model of acute lung injury. Neither dose of dopamine nor dobutamine was able to improve PEEP-induced mesenteric blood flow depression.     

Cardiovascular and metabolic costs of forward, backward, and lateral motion

PURPOSE: The purpose of this study was to compare the metabolic and cardiovascular responses of movement in forward (FM), backward (BM), and lateral (LM) directions. METHODS: Thirteen athletes with the following characteristics (mean +/- SD) were evaluated: age 21+/-3 yr, height 172.0+/-9.0 cm, weight 62.92+/-9.05 kg, and VO2max 54.13+/-7.42 mL x kg(-1) x min(-1). Subjects were evaluated at 80.45 and 134.08 m x min(-1). A repeated measures ANOVA was used for statistical analysis (P < 0.05). RESULTS: At 80.45 m x min(-1), the following respective VO2 mL x kg(-1) x min(-1) and heart rate (HR) beats x min(-1) responses were: FM = 12.42+/-2.29, 113+/-10; BM = 15.95+/-2.45, 132+/-16; and LM = 22.10+/-4.76, 140+/-15. Both VO2 and HR were significantly different between conditions: LM > BM > FM. At 134.08 m x min(-1), the following respective VO2 and HR responses were: FM = 27.15+/-2.51, 146+/-7; BM = 31.33+/-5.77, 168+/-11; and LM = 32.58+/-5.74, 169+/-10. At 134.08 m x min(-1) neither HR or VO2 were significantly different between LM or BM (LM, BM, > FM). Stride length and stride frequency were also significantly different between conditions. These results indicate the variation in the energy cost of FM, BM, and LM.     

Improved walking economy in patients with peripheral arterial occlusive disease

The effect of exercise rehabilitation on the oxygen cost of ambulation in patients with peripheral arterial occlusive disease (PAOD) was evaluated with specific emphasis on the effects of exercise rehabilitation on the slow component of VO2. Because the slow component of VO2 represents an increase in VO2 despite constant-intensity exercise, it can profoundly affect the relative energy cost of exercise in individuals with a low functional capacity. Twenty-six patients with intermittent claudication performed treadmill walking at 2.0 mph/0% grade for 20 min or until maximal claudication pain before and after 4 months of rehabilitation. The slow component of VO2 during the treadmill test was defined as the difference between the end-exercise VO2 and the VO2 observed at minute 3. Ankle/brachial systolic pressure index (ABI) was measured before and immediately following the exercise test. Rehabilitation consisted of 3 d x wk(-1) of treadmill walking for 15-30 min at 60-70% of VO2peak. The slow component of VO2 and end-exercise VO2 at pretraining (0.75 +/- 0.90 and 11.12 +/- 2.10 mL x kg[-1] x min[-1]) were significantly reduced after 4 months of exercise rehabilitation (-0.07 +/- 1.11 and 10.07 +/- 1.80 mL x kg[-1] x min[-1]; P < 0.05). Exercise rehabilitation also significantly (P < 0.05) increased the post-exercise ABI (pre-rehabilitation = 0.36 +/- 0.26, post-rehabilitation = 0.43 +/- 0.25). These data suggest that 4 months of exercise rehabilitation: 1) improves walking economy in PAOD patients because of a decreased slow component of VO2, and 2) increases post-exercise ABI.     

Differential regional hemodynamic effects of corticotropin in conscious sheep

The regional hemodynamic effects of 5 days of intravenous infusion of corticotropin (ACTH) (5 micrograms/kg per day) were examined in conscious sheep (n = 8). Mean arterial pressure increased from 81 +/- 2 to 93 +/- 3 mm Hg (P < .001) on day 2 of ACTH and remained at this level during the infusion. Cardiac output increased from 5.13 +/- 0.19 to 6.06 +/- 0.33 L/min (P < .01) because of an increase in stroke volume from 65 +/- 4 to 79 +/- 8 mL per beat (P < .01); heart rate remained unchanged. ACTH did not alter total peripheral conductance but had differential effects on regional conductances. Mesenteric conductance fell from 5.8 +/- 0.2 to a minimum of 4.9 +/- 0.3 (mL/min)/mm Hg (P < .05), and renal conductance increased from 3.5 +/- 0.3 to 4.6 +/- 0.3 (mL/min)/mm Hg (P < .001). There was a small increase in iliac conductance (P < .05) and no change in coronary conductance. Mesenteric and iliac conductances fell progressively over 24 to 48 hours, whereas renal conductance increased rapidly after 3 hours of ACTH, reaching a maximum after 6 hours. Renal blood flow was increased during ACTH infusion from 278 +/- 18 to 403 +/- 23 mL/min (P < .001); mesenteric blood flow was unchanged; there was a small increase in iliac blood flow (P < .01); and coronary blood flow increased (P < .05), paralleling the change in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estrogen receptor alpha and beta expression in upper gastrointestinal tract with regulation of trefoil factor family 2 mRNA levels in ovariectomized rats

STUDY OBJECTIVE: To investigate the effect of short-term inhalation of nitric oxide (NO) on transpulmonary angiotensin II formation in patients with severe ARDS. DESIGN: Prospective, clinical study. SETTING: Anesthesiology ICU of a university hospital. PATIENTS: Ten ARDS patients who responded to inhalation of 100 ppm NO by decreasing their pulmonary vascular resistance (PVR) by at least 20 dyne x s x cm(-5) were included in the study. INTERVENTIONS AND MEASUREMENTS: In addition to standard treatment, the patients inhaled 0, 1, and 100 ppm NO in 20-min intervals. Fraction of inspired oxygen was 1.0. Hemodynamics were measured and recorded online. Mixed venous (pulmonary arterial catheter) and arterial (arterial catheter) blood samples were taken simultaneously for hormonal analyses at the end of each inhalation period. RESULTS: Pulmonary arterial pressure decreased from 33+/-2 mm Hg (0 ppm NO, mean+/-SEM) to 29+/-2 mm Hg (1 ppm NO, p<0.05), and to 27+/-2 mm Hg (100 ppm NO, p<0.05, vs 0 ppm). PVR decreased from 298+/-56 (0 ppm NO) to 243+/-45 dyne x s x cm(-5) (1 ppm NO, not significant [NS]), and to 197+/-34 dyne x s x cm(-5) (100 ppm NO, p<0.05, vs 0 ppm). Arterial oxygen pressure increased from 174+/-23 mm Hg (0 ppm NO) to 205+/-26 mm Hg (1 ppm NO, NS), and to 245+/-25 mm Hg (100 ppm NO, p <0.05, vs 0 ppm). Mean plasma angiotensin II concentrations were 85+/-20 (arterial) and 57+/-13 pg/mL (mixed venous) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary plasma angiotensin II concentration gradient (=difference between arterial and mixed venous blood values) was 28+/-8 pg/mL (range, 0 to 69) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary angiotensin II formation (transpulmonary angiotensin II gradient multiplied with the cardiac index) was 117+/-39 ng/min/m2 (range, 0 to 414) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean arterial plasma cyclic guanosine monophosphate concentration was 11+/-2 pmol/mL (0 ppm NO), did not change during 1 ppm NO, and increased to 58+/-8 pmol/mL (100 ppm NO, p<0.05). Arterial plasma concentrations of aldosterone (142+/-47 pg/mL), atrial natriuretic peptide (114+/-34 pg/mL), angiotensin-converting enzyme (30+/-5 U/L), and plasma renin activity (94+/-26 ng/mL/h of angiotensin I) did not change. CONCLUSION: The decrease of PVR by short-term NO inhalation in ARDS patients was not accompanied by changes in transpulmonary angiotensin II formation. Our results do not support any relationship between transpulmonary angiotensin II formation and the decrease in PVR induced by inhaled NO.     

Training effects of short and long bouts of brisk walking in sedentary women

This study compared the effects of short and long bouts of brisk walking in sedentary women. Forty seven women aged 44.4 +/- 6.2 yr (mean +/- SD) were randomly assigned to either three 10-min walks per day (short bouts), one 30-min walk per day (long bouts) or no training (control). Brisk walking was done on 5 d x wk(-1), at 70 to 80% of maximal heart rate, typically at speeds between 1.6 and 1.8 m x s(-1) (3.5 and 4.0 mph), for 10 wk. Subjects agreed not to make changes to their diet. Twelve short-bout walkers, 12 long-bout walkers, and 10 controls completed the study. Relative to controls, VO2max (short-bout, +2.3 +/- 0.1 mL x kg(-1) x min(-1); long-bout, +2.4 +/- 0.1 mL x kg(-1) x min(-1); controls, -0.5 +/- 0.1 mL x kg(-1) x min[-1]) and the VO2 at a blood lactate concentration of 2 mmol x L(-1) increased in walkers (both P < 0.05), with no difference in response between walking groups. Neither heart rate during standard, submaximal exercise nor resting systolic blood pressure changed in a different way in walkers and controls. The sum of four skinfold thicknesses decreased in both walking groups (P < 0.05) but body mass (short-bout, -1.7 +/- 1.7 kg; long-bout, -0.9 +/- 2.0 kg; controls, +0.6 +/- 0.7 kg) and waist circumference decreased significantly only in short-bout walkers. Changes in anthropometric variables did not differ between short- and long-bout walkers. Thus short bouts of brisk walking resulted in similar improvements in fitness and were at least as effective in decreasing body fatness as long bouts of the same total duration.     

Anaerobic threshold and maximal aerobic power for three modes of exercise

Alterations in selected respiratory gas exchange parameters have been proposed as sensitive, noninvasive indices of the onset of metabolic acidosis (anaerobic threshold (AT) during incremental exercise. Our purposes were to investigate the validity and feasibility of AT detection using routine laboratory measures of gas exchange, i.e., nonlinear increases in VE and VCO2 and abrupt increases in FEO2. Additionally, we examined the comparability of the AT and VO2 max among three modes of exercise (arm cranking, leg cycling, and treadmill walk-running) with double determinations obtained from 30 college-age, male volunteer subjects. The AT's for arm cranking, leg cycling, and treadmill walk-running occurred at 46.5 +/- 8.9 (means +/- SD), 63.8 +/- 9.0, and 58.6 +/- 5.8% of VO2 max, respectively. No significant difference was found between the leg exercise modes (cycling and walk-running) for the AT while all pairwise arm versus leg comparisons were significantly different. Using nine additional subjects performing leg cycling tests, a significant correlation of r = 0.95 was found between gas exchange AT measurements (expressed as % VO2 max) and venous blood lactate AT measurements (% VO2 max). We conclude that the gas exchange AT is a valid and valuable indirect method for the detection of the development of lactic acidosis during incremental exercise.     

Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts

OBJECTIVES: The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. BACKGROUND: Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. METHODS: The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. RESULTS: Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 +/- 1.26 to 5.37 +/- 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vo2 (from 0.22 +/- 0.08 to 0.27 +/- 0.09 ml O2, p < 0.05) and PVA-independent Vo2 (from 0.019 +/- 0.019 to 0.091 +/- 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p < 0.05). CONCLUSIONS: These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.