Venous Oxygen Tension Research Articles

Effects of norepinephrine and phenylephrine on intestinal oxygen supply and mucosal tissue oxygen tension.

To investigate effects of intravenous norepinephrine (NE) and phenylephrine (PE) on intestinal oxygen supply in an autoperfused, innervated jejunal segment. Prospective, randomized animal study in an animal research laboratory. In 24 anesthetized and normoventilated pigs a segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension (PO2muc; Clark-type surface oxygen electrodes), microvascular hemoglobin oxygen saturation (HbO2, tissue reflectance spectrophotometry), and microvascular blood flow (perfusion units, PU; laser Doppler velocimetry), systemic hemodynamics, mesenteric-venous acid base and blood gas variables, and systemic acid base and blood gas variables were recorded after a resting period and at 20-min intervals during infusion of NE (0.01, 0.05, 0.1, 0.5, 1, 2 micrograms x kg-1 x min-1; n = 8) or PE (0.1, 0.5, 1, 2, 5, 10 micrograms x kg-1 x min-1; n = 8) and in controls (n = 8) without treatment. NE infusion led to significant tachycardia, an increase in cardiac output, and systemic oxygen delivery and consumption while PE progressively increased mean arterial pressure with only small effects on systemic blood flow. NE or PE infusion did not affect mesenteric venous oxygen tension (baseline: PE 53 +/- 5, NE, 52 +/- 4.2 mmHg), mesenteric oxygen extraction ratio (baseline: PE 0.29 +/- 0.08, NE 0.3 +/- 0.06), jejunal microvascular blood flow (baseline: PE 254 +/- 127, NE 282 +/- 72 PU), PO2muc (baseline: PE 31 +/- 9.1, NE 33 +/- 11 mmHg), and HbO2 (baseline: PE 52 +/- 9.6%, NE 58 +/- 11.6%). Despite major differences in systemic hemodynamics jejunal tissue oxygen supply is not affected by progressively increasing intravenous infusion of norepinephrine and phenylephrine.

K(ATP)(+) channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation.

The role of ATP-sensitive K(+) (K(ATP)(+)) channels, nitric oxide, and adenosine in coronary exercise hyperemia was investigated. Dogs (n = 10) were chronically instrumented with catheters in the aorta and coronary sinus and instrumented with a flow transducer on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous plasma concentrations using a previously tested mathematical model. Experiments were conducted at rest and during graded treadmill exercise with and without combined inhibition of K(ATP)(+) channels (glibenclamide, 1 mg/kg iv), nitric oxide synthesis (N(omega)-nitro-L-arginine, 35 mg/kg iv), and adenosine receptors (8-phenyltheophylline, 3 mg/kg iv). During control exercise, myocardial oxygen consumption increased ~2.9-fold, coronary blood flow increased ~2.6-fold, and coronary venous oxygen tension decreased from 19.9 +/- 0.4 to 13.7 +/- 0.6 mmHg. Triple blockade did not significantly change the myocardial oxygen consumption or coronary blood flow response during exercise but lowered the resting coronary venous oxygen tension to 10.0 +/- 0.4 mmHg and during exercise to 6.2 +/- 0.5 mmHg. Cardiac adenosine levels did not increase sufficiently to overcome the adenosine receptor blockade. These results indicate that combined inhibition of K(ATP)(+) channels, nitric oxide synthesis, and adenosine receptors lowers the balance between total oxygen supply and consumption at rest but that these factors are not required for local metabolic coronary vasodilation during exercise.

Insulin (GIK) Improves Central Mixed and Hepatic Venous Oxygenation in Clinical Cardiac Surgery

Objective - Insulin is a vasodilating agent and it was hypothesized that insulin (GIK) could improve systemic and regional oxygenation in cardiac surgery with cardiopulmonary bypass (CPB). Two questions were addressed: 1) Does insulin improve central mixed and hepatic venous oxygenation during CPB? and 2) Does this treatment reduce systemic levels of the proinflammatory mediators C3a and IL-6? Design - Prospective, randomized, controlled study at a university hospital. Thirty patients were included and 16 of these received an infusion of insulin, glucose and potassium (GIK) using an euglycemic clamp technique. The insulin infusion was started during hypothermia, 15 min before rewarming. Blood gases and hemodynamic parameters were measured during hypothermia (before the insulin infusion was started), during rewarming at 35°C, and 30 min after CPB was discontinued. Inflammatory markers were measured: preoperatively, during hypothermia and 2 h after CPB. Results - GIK was associated with reduced systemic vascular resistance ( p = 0.02 vs the control group), higher bypass pump flow ( p = 0.001), higher central mixed oxygen saturation ( p = 0.036) and oxygen tension ( p = 0.001) and higher hepatic venous oxygen saturation ( p = 0.04) and oxygen tension ( p = 0.006). C3a and IL-6 increased during surgery in both groups but there were no differences between the groups. Conclusion - 1) GIK infusion improved central mixed and hepatic venous oxygenation in patients undergoing heart surgery. 2) During the conditions of this study, this had no effect on the proinflammatory mediators C3a and IL-6.

Characterization of a Hypoxia-inducible Factor (HIF-1α) from Rainbow Trout: ACCUMULATION OF PROTEIN OCCURS AT NORMAL VENOUS OXYGEN TENSION

The mammalian hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that controls the induction of several genes involved in glycolysis, erythropoiesis, and angiogenesis when cells are exposed to hypoxic conditions. Until now, the expression and function of HIF-1alpha have not been studied in fish, which experience wide fluctuations of oxygen tensions in their natural environment. Using electrophoretic mobility shift assay, we have ascertained that a hypoxia-inducible factor is present in rainbow trout cells. We have also cloned the full-length cDNA (3605 base pairs) of the HIF-1alpha from rainbow trout with a predicted protein sequence of 766 amino acids that showed a 61% similarity to human and mouse HIF-1alpha. Polyclonal antibodies against the N-terminal part (amino acids 12-363) and the C-terminal part (amino acids 330-730) of rainbow trout HIF-1alpha protein recognized rainbow trout and chinook salmon HIF-1alpha protein in Western blot analysis. Also, the human and mouse HIF-1alpha proteins were recognized by the N-terminal rainbow trout anti-HIF-1alpha antibody but not by the C-terminal HIF-1alpha antibody. The accumulation of HIF-1alpha was studied by incubating rainbow trout and chinook salmon cells at different oxygen concentrations from 20 to 0.2% O(2) for 1 h. The greatest accumulation of HIF-1alpha protein occurred at 5% O(2) (38 torr), a typical oxygen tension of venous blood in normoxic animals. The protein stability experiments in the absence or presence of a proteasome inhibitor, MG-132, demonstrated that the inhibitor is able to stabilize the protein, which normally is degraded via the proteasome pathway both in normoxia and hypoxia. Notably, the hypoxia response element of oxygen-dependent degradation domain is identical in mammalian, Xenopus, and rainbow trout HIF-1alpha proteins, suggesting a high degree of evolutionary conservation in degradation of HIF-1alpha protein.

Jugular venous oximetry and oxygen tension during hypothermic cardiopulmonary bypass

Introduction. In patients undergoing cardiopulmonary bypass (CPB), jugular bulb desaturation may be associated with postoperative neurocognitive dysfunction. We examined jugular bulb oximetry (SjvO2) and oxygen tension (PjvO2) in patients undergoing CPB with pH-stat perfusion management.Methods. Jugular bulb catheters were inserted in 12 patients undergoing hypothermic CPB for coronary artery bypass. Jugular bulb temperature was monitored continuously. Jugular venous blood was sampled at intervals during cooling, rewarming, and after bypass. SjvO2 was measured by cooximeter (AVOX System 4000). PjvO2 was measured by gas analyzer (Nova Stat Profile Ultra) and recorded both uncorrected at 37°C (stat) and temperature corrected (pH-stat).Results. SjvO2 decreased as jugular bulb temperature increased. However, only 2 patients demonstrated jugular bulb desaturation (<50%) during rewarming, both when jugular venous temperature exceeded 37.5°C. Desaturation during rewarming was not consistently associated with low PjvO2 values (<27 mm Hg). During cooling and hypothermia, PjvO2 (pH-stat values) were lower than PjvO2 (stat values) and may reflect a more accurate measure of brain oxygenation.Conclusions. During CPB, SjvO2 decreased as jugular bulb temperature increased, with desaturation noted during hypothermia. Therefore, brain oxygenation may be jeopardized in the presence of marked hypothermia. We also noted that, during cooling and hypothermia, PjvO2 measured with pH-stat technique was much lower than that measured with a stat technique. The significance of this finding requires further investigation. [1Croughwell N. Newman M. Blumenthal J. et al.Ann Thor Surg. 1994; 58: 1702-1708Abstract Full Text PDF PubMed Scopus (214) Google Scholar]Issues. Suboptimal brain oxygenation during hypothermia: stat versus pH-stat blood gases. Introduction. In patients undergoing cardiopulmonary bypass (CPB), jugular bulb desaturation may be associated with postoperative neurocognitive dysfunction. We examined jugular bulb oximetry (SjvO2) and oxygen tension (PjvO2) in patients undergoing CPB with pH-stat perfusion management. Methods. Jugular bulb catheters were inserted in 12 patients undergoing hypothermic CPB for coronary artery bypass. Jugular bulb temperature was monitored continuously. Jugular venous blood was sampled at intervals during cooling, rewarming, and after bypass. SjvO2 was measured by cooximeter (AVOX System 4000). PjvO2 was measured by gas analyzer (Nova Stat Profile Ultra) and recorded both uncorrected at 37°C (stat) and temperature corrected (pH-stat). Results. SjvO2 decreased as jugular bulb temperature increased. However, only 2 patients demonstrated jugular bulb desaturation (<50%) during rewarming, both when jugular venous temperature exceeded 37.5°C. Desaturation during rewarming was not consistently associated with low PjvO2 values (<27 mm Hg). During cooling and hypothermia, PjvO2 (pH-stat values) were lower than PjvO2 (stat values) and may reflect a more accurate measure of brain oxygenation. Conclusions. During CPB, SjvO2 decreased as jugular bulb temperature increased, with desaturation noted during hypothermia. Therefore, brain oxygenation may be jeopardized in the presence of marked hypothermia. We also noted that, during cooling and hypothermia, PjvO2 measured with pH-stat technique was much lower than that measured with a stat technique. The significance of this finding requires further investigation. [1Croughwell N. Newman M. Blumenthal J. et al.Ann Thor Surg. 1994; 58: 1702-1708Abstract Full Text PDF PubMed Scopus (214) Google Scholar] Issues. Suboptimal brain oxygenation during hypothermia: stat versus pH-stat blood gases.

Feedforward sympathetic coronary vasodilation in exercising dogs.

The hypothesis that exercise-induced coronary vasodilation is a result of sympathetic activation of coronary smooth muscle beta-adrenoceptors was tested. Ten dogs were chronically instrumented with a flow transducer on the circumflex coronary artery and catheters in the aorta and coronary sinus. During treadmill exercise, coronary venous oxygen tension decreased with increasing myocardial oxygen consumption, indicating an imperfect match between myocardial blood flow and oxygen consumption. This match was improved after alpha-adrenoceptor blockade with phentolamine but was significantly worse than control after alpha + beta-adrenoceptor blockade with phentolamine plus propranolol. The response after alpha-adrenoceptor blockade included local metabolic vasodilation plus a beta-adrenoceptor vasodilator component, whereas the response after alpha + beta-adrenoceptor blockade contained only the local metabolic vasodilator component. The large difference in coronary venous oxygen tensions during exercise between alpha-adrenoceptor blockade and alpha + beta-adrenoceptor blockade indicates that there is significant feedforward beta-adrenoceptor coronary vasodilation in exercising dogs. Coronary venous and estimated myocardial interstitial adenosine concentrations did not increase during exercise before or after alpha + beta-adrenoceptor blockade, indicating that adenosine levels did not increase to compensate for the loss of feedforward beta-adrenoceptor-mediated coronary vasodilation. These results indicate a meaningful role for feedforward beta-receptor-mediated sympathetic coronary vasodilation during exercise.

In Vitro Model for Cardiac Function under Xenon Anesthesia

ProfessorProfessor: Departments of Anesthesiology and Physiology: Medical College of WisconsinPostdoctoral Research FellowAssistant ProfessorPostdoctoral Research Fellow: Department of Anesthesiology: Medical College of Wisconsin: Milwaukee, WisconsinProfessor and ChairmanDepartment of AnesthesiologyUniversity of UlmUlm, Germanyzbosnjak@mcw.eduIn Reply:—We appreciate the interest expressed by Drs. Schroth, Reyle-Hanh, and Rossaint with regard to our recent article. First, using a Marquette Gas Analyzer (Model 1100; Marquette Gas Analysis Corp., St. Louis, MO), we verified that the oxygen and nitrogen fractions were approximately 20 and 40%, respectively, and 20 and 0%, respectively, to give estimated xenon fractions of 40 and 80%, respectively, in the gas reservoir bags. In addition, effective xenon concentrations in solutions were verified by placing the samples and xenon standards into sealed 1-ml vials and conducting a head-space analysis using the H-P 5989 MS-ENGINE Mass Spectrometer (Hewlett-Packard, Palo Alto, CA).The second concern was that the hearts might become hypoxic with 20% oxygenated perfusate solution, despite the presence of approximately 2.8 g hemoglobin/100 ml perfusate. Most Langendorff preparations that are not perfused with crystalloid solutions are perfused with washed erythrocytes obtained from other species. As the authors pointed out, the venous oxygen tension and p H do not suggest hypoxia. Oxygen consumption of Langendorff hearts is approximately 50–70% of in vivo hearts, and lactate is not produced with carbogen equilibrated in crystalloid perfusate. This is caused in part by the lack of kinetic (stroke) work and decreased potential (isometric) work. Nevertheless, in our erythrocyte-perfused hearts, we conducted a control experiment suggested by the authors; that is, erythrocyte perfusion of hearts with 95% and 5% CO2before switching to the reservoirs containing 20% O2. The change from 95% to 20% O2produced no appreciable change in left ventricular pressure, and so we doubt that the hearts became hypoxic. However, we believe that the use of erythrocyte solution might result in a lower left ventricular pressure because of buffering of the calcium in the solution. A small increase in viscosity may also contribute to somewhat lower left ventricular pressure.

Role of nitric oxide and adenosine in control of coronary blood flow in exercising dogs.

Inhibition of nitric oxide (NO) synthesis results in very little change in coronary blood flow, but this is thought to be because cardiac adenosine concentration increases to compensate for the loss of NO vasodilation. Accordingly, in the present study, adenosine measurements were made before and during NO synthesis inhibition during exercise. Experiments were performed in chronically instrumented dogs at rest and during graded treadmill exercise before and during inhibition of NO synthesis with N(omega)-nitro-L-arginine (L-NNA, 35 mg/kg IV). Before inhibition of NO synthesis, myocardial oxygen consumption increased approximately 3.7-fold, and coronary blood flow increased approximately 3.2-fold from rest to the highest level of exercise, and this was not changed by NO synthesis inhibition. Coronary venous oxygen tension was modestly reduced by L-NNA at all levels of myocardial oxygen consumption. However, the slope of the relationship between myocardial oxygen consumption and coronary venous oxygen tension was not altered by L-NNA. Inhibition of NO synthesis did not increase coronary venous plasma or estimated interstitial adenosine concentration. During exercise, estimated interstitial adenosine remained well below the threshold concentration necessary for coronary vasodilation before or after L-NNA. NO causes a modest coronary vasodilation at rest and during exercise but does not act as a local metabolic vasodilator. Adenosine does not mediate a compensatory local metabolic coronary vasodilation when NO synthesis is inhibited.

Pulmonary artery perfusion with protective solution reduces lung injury after cardiopulmonary bypass

Background. The inflammatory response and higher temperature of lung tissue during cardiopulmonary bypass can result in lung injury. This study was to evaluate the protective effect of pulmonary perfusion with hypothermic antiinflammatory solution on lung function after cardiopulmonary bypass.Methods. Twelve adult mongrel dogs were randomly divided into two groups. The procedure was carried out through a midline sternotomy, cardiopulmonary bypass was established using cannulas placed in the ascending aorta, superior vena cava, and right atrium near the entrance of the inferior vena cava. After the ascending aorta was clamped and cardioplegic solution infused, the right lung was perfused through a cannula placed in the right pulmonary artery with 4°C lactated Ringer’s solution in the control group (n = 6) and with 4°C protective solution in the antiinflammation group (n = 6). Antiinflammatory solution consisted of anisodamine, l-arginine, aprotinin, glucose-insulin-potassium, and phosphate buffer. Plasma malondialdehyde, white blood cell counts, and lung function were measured at different time point before and after cardiopulmonary bypass; lung biopsies were also taken.Results. Peak airway pressure increased dramatically in the control group after cardiopulmonary bypass when compared with the antiinflammation group at four different time points (24 ± 1, 25 ± 2, 26 ± 2, 27 ± 2 cm H2O versus 17 ± 2, 18 ± 1, 17 ± 1, 18 ± 1 cm H2O; all p < 0.01). Pulmonary vascular resistance increased significantly in the control group than in the antiinflammation group at 5 and 60 minutes after cardiopulmonary bypass (1,282 ± 62 dynes · s · cm−5 versus 845 ± 86 dynes · s · cm−5 and 1,269 ± 124 dynes · s · cm−5 versus 852 ± 149 dynes · s · cm−5, p < 0.05). Right pulmonary venous oxygen tension (PvO2) in the antiinflammation group was higher than in the control group at 60 minutes after cardiopulmonary bypass (628 ± 33.3 mm Hg versus 393 ± 85.9 mm Hg, p < 0.05). The ratio of white blood cells in the right atrial and the right pulmonary venous blood was lower in the antiinflammation group than in the control group at 5 minutes after the clamp was removed (p < 0.05). Malondialdehyde were lower in the antiinflammation group at 5 and 90 minutes after the clamp was removed (p < 0.01 and p < 0.05, respectively). Histologic examination revealed that the left lung from both groups had marked intraalveolar edema and abundant intraalveolar neutrophils, whereas the right lung in the control group showed moderate injury and the antiinflammation group had normal pulmonary parenchyma.Conclusions. Pulmonary artery perfusion using hypothermic protective solution can reduce lung injury after cardiopulmonary bypass.

Effects of Ventilation on Lung Function after Normothermic Ischemia

The effects of atelectasis and hyperinflation were compared on immediate postischemic lung function and architecture, following normothermic ischemia. Thirty Sprague-Dawley rats were divided into 3 groups; 2 groups were subjected to 60 minutes of normothermic ischemia. The lungs were atelectatic in 10 (group A), they were hyperinflated to a pressure of 10 cm H2O in 10 (group B), and 10 rats served as nonischemic controls (group C). After 5 minutes of reperfusion, left pneumonectomies were performed and the lungs were examined histopathologically. There were no statistically significant differences in pulmonary venous blood oxygen tension or pH in the 3 groups. There was a significant difference between the compliance data of groups A and B (p &lt; 0.05) and a highly significant difference between the compliance data of groups A and C (p &lt; 0.001). Alveolar edema, perivascular edema, peribronchiolar edema, vascular congestion, and intrapulmonary hemorrhage were more frequent and more severe in the atelectatic group than in the hyperinflated group. The results indicate that postischemic injury occurred at an early stage in atelectatic lungs before any change in blood gas values and that superior postischemic preservation was achieved in lungs maintained in a hyperinflated state.

Cardiopulmonary effects of a two hour medetomidine infusion and its antagonism by atipamezole in horses and ponies

The cardiopulmonary effects of an intravenous (iv) medetomidine injection (5 μg/kg) followed 5 min later by its infusion at 3.5 μg/kg/h for 115 rnin were studied in 9 horses and ponies. Five minutes after the end of infusion 60 μg/kg atipamezole were given. Physiological data during infusion were compared with pre-sedation values. Stroke volume was reduced significantly 5 min after initial medetomidine injection. Cardiac index was reduced significantly and systemic vascular resistance increased significantly for the first 20 min, but returned towards pre-sedation values after this time. Arterial blood pressures were reduced significantly from 30 min until the end of the procedure (minimum MAP was 102.4 ± 9.61 mmHg). Mixed venous oxygen tension was reduced significantly during the infusion. Respiratory rate fell and PaCO 2 - rose significantly from 40 min onward. Other variables showed no significant changes. The horses recovered rapidly after atipamezole was injected. Arterial blood pressures remained significantly lowered, but other cardiovascular variables returned towards pre-sedation values. It is concluded that the infusion of medetomidine at 3.5 μg/kg/h causes minimum cardiopulmonary depression once the effects of an initial 5 μg/kg injection have waned, and so could prove suitable as part of an anaesthetic technique in equidae.

Effect of endotracheal suctioning on cerebral oxygenation in traumatic brain-injured patients.

In patients with severe head injuries, brain damage occurs not only from the primary trauma but also secondarily from a reduction in cerebral oxygenation as a result of brain swelling, ischemia, and elevated intracranial pressure (ICP). However, routine interventions designed to maintain oxygenation, such as endotracheal suctioning (ETS), also may negatively affect the cerebrovascular status by increasing the ICP. The purpose of this study was to determine whether ETS influences cerebral oxygenation in patients with traumatic brain injury. Descriptive, prospective, with repeated assessments within each patient. Ten-bed trauma intensive care unit in a university Level I trauma center. Nineteen patients who were 16 yrs or older, had acute head injury, a Glasgow Coma Scale score < or =8; external ventricular drain and arterial pressure devices in place, and were intubated and mechanically ventilated. ETS protocol consisting of administration of four ventilator-delivered breaths at 135% of the patients' actual tidal volume, 100% F(IO)2, before and after suctioning with a standardized catheter at a 16-L flow rate. This study examined cerebrovascular responses as measured by the traditional measures of ICP and cerebral perfusion pressure, as well as middle cerebral artery velocity and jugular venous oxygen tension that occurred during ETS in head-injured adults. The results of this study show that both ICP and cerebral perfusion pressure are increased during ETS. In the majority of patients (84%), the ICP returned to baseline values within 2 mins. The increase in jugular venous oxygen tension associated with increases in middle cerebral artery velocity and mean arterial pressure suggests that cerebral oxygen delivery was maintained during ETS. Cerebral changes associated with ETS using the described protocol are consistent with the preservation of cerebral oxygenation.

Effects of isosorbide dinitrate on electrocardiography, hemodynamics, and ventilation in patients with exercise-induced elevation of pulmonary artery wedge pressure.

The mechanisms underlying exertional hyperpnea in patients with coronary artery disease and transient left ventricular dysfunction are still not fully understood. The study was undertaken to investigate whether the ventilatory response to exercise reflects the effects of acute medical treatment of exercise-induced left ventricular dysfunction, and to evaluate mechanisms relevant to excessive exertional ventilation. In 11 male patients, aged 65.2 +/- 6.0 years, all with pulmonary artery wedge pressure (PAWP) > 25 mmHg and ST depression > 2 mm during moderate supine exercise, ventilation (V), oxygen uptake (VO2), hemodynamics, electrocardiogram (ECG), and arterial and mixed venous blood gases were examined during supine rest and exercise, before and at hourly intervals after peroral intake of 30 mg isosorbide dinitrate (ISDN). Six similar patients were examined with the same protocol without ISDN administration and comprised a control group. Before administration of ISDN, exercise PAWP was 35.3 +/- 5.9 mmHg, ECG showed 2.77 +/- 1.06 mm ST depression, and V/VO2 was 31.8 +/- 4.8 l/l. One h after ISDN administration, exercise mean PAWP was 11.0 +/- 2.5 mmHg (p < 0.001), ST depression 0.59 +/- 0.8 mm (p < 0.001), whereas V/VO2 was unchanged, 30.1 +/- 5.3 l/l. Two h later, PAWP remained reduced and there were only minor ST depressions, while V/VO2 remained high. Exercise cardiac index (CI) and mixed venous oxygen tension (PvO2), initially 4.7 +/- 0.67 l/min/m2 and 3.54 +/- 0.35 kPa, respectively, remained at the same low level throughout the study. In the six nontreated patients, there were no significant changes in ST depression, exercise PAWP, or exertional ventilation. Isosorbide dinitrate treatment markedly improved exercise-induced left heart dysfunction, whereas excessive ventilatory response was unaffected, even after 3 h. Thus, measurements of the exercise hyperpnea did not properly reflect effective reduction of myocardial ischemia.

Effects of inhaled nitric oxide 10 ppm in spontaneously breathing horses anaesthetized with halothane

Inhaled nitric oxide, a selective pulmonary vasodilator, is known to improve arterial oxygenation after cardiopulmonary bypass and during acute respiratory distress syndrome in humans. During general anaesthesia with spontaneous ventilation, healthy adult horses develop large alveolar-arterial oxygen tension differences. In this study, we have determined the effects of inhaled nitric oxide (10 parts per million (ppm)) on venous admixture and pulmonary haemodynamics in horses anaesthetized with halothane. Seven adult horses were studied twice in random sequence. After premedication with romifidine 100 micrograms kg-1, anaesthesia was induced with ketamine 2.2 mg kg-1 and maintained with 1.1 MAC (0.95%) of halothane in oxygen. Horses breathed spontaneously. After 65 min, each horse had nitric oxide 10 ppm added to the inspired gas for 20 min (procedure HA + NO) or anaesthesia was continued with halothane in oxygen (procedure HA). Cardiac output, minute ventilation, arterial and mixed venous oxygen and carbon dioxide tensions, and mean pulmonary and carotid arterial pressures were measured for 100 min. Shunt fraction and pulmonary and systemic vascular resistances were calculated. Shunt fraction (SF) and mean pulmonary artery pressure (PPA mean) were not different between the two groups after 65 min of general anaesthesia (HA: SF 0.20 (SD 0.06), PPA mean 45 (8) mm Hg; HA + NO: SF 0.21 (0.04), PPA mean 44 (7) mm Hg) or after 85 min (HA: SF 0.22 (0.07), PPA mean 45 (8) mm Hg; HA + NO: SF 0.20 (0.03), PPA mean 43 (7) mm Hg). There were no significant effects of time or nitric oxide inhalation on any other variable. There was a significant correlation (r = 0.80, P < 0.05) between calculated shunt fraction 65 min after induction of anaesthesia and body weight.

Effect of Hyperoxia and Hypoxia on Subcutaneous Tissue Gases and pH

The effect of different fractions of inspired oxygen on subcutaneous oxygen tension, carbon dioxide tension and pH in relation to arterial and mixed venous blood gases and pH and hemodynamic variables was evaluated in 13 domestic pigs. Subcutaneous, arterial and mixed venous oxygen tensions were closely correlated (r = 0.94). A minor significant increase in subcutaneous carbon dioxide tension was noted during hyperoxia (p < 0.05). A major increase (33%) was noted during the last step of hypoxia, when arterial and mixed venous carbon dioxide tensions increased only 12 and 17%, respectively. A minor decrease in subcutaneous pH was noted during hyperoxia (p < 0.05) and a major decrease during hypoxia (p < 0.05). Measurements of subcutaneous tissue gases and pH are indicators of oxygen utilization during hyper- and hypoxia.

Mimicry in primary rat hepatocyte cultures of the in vivo perivenous induction by phenobarbital of cytochrome P-450 2B1 mRNA: role of epidermal growth factor and perivenous oxygen tension.

Treatment of male rats with phenobarbital (PB) results in a perivenous and mid-zonal pattern of cytochrome P-450 (CYP)2B1 mRNA expression within the liver acinus. The mechanism of this zonated induction is still poorly understood. In this study sinusoidal gradients of oxygen and epidermal growth factor (EGF) besides those of the pituitary-dependent hormones growth hormone (GH), thyroxine (T4), and triiodothyronine (T3) were considered to be possible determinants for the zonated induction of the CYP2B1 gene in liver. Moreover, heme proteins seem to play a key role in oxygen sensing. Therefore, the influence of arterial (16% O2) and venous (8% O2) oxygen tension (pO2), and of the heme synthesis inhibitors CoCl2 and desferrioxamine (DSF) on PB-dependent CYP2B1 mRNA induction as well as the repression by EGF and, for comparison, by GH, T4, and T3, of the induction under arterial and venous pO2 were investigated in primary rat hepatocytes. Within 3 days, phenobarbital induced CYP2B1 mRNA to maximal levels under arterial pO2 and to about 40% of maximal levels under venous pO2. CoCl2 annihilated induction by PB under both oxygen tensions, whereas desferrioxamine and heme abolished the positive modulation by O2, suggesting that heme is a necessary component for O2 sensing. EGF suppressed CYP2B1 mRNA induction by PB only under arterial but not under venous pO2, whereas GH, T4, and T3 inhibited induction under both arterial and venous pO2. Thus, in hepatocyte cultures, an O2 gradient in conjunction with EGF mimicked the perivenous induction by PB of the CYP2B1 gene observed in the liver in vivo.

Plasma Endothelin-1 Level in Chronic Obstructive Pulmonary Disease: Relationship with Natriuretic Peptide

Background and Objective: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the vascular endothelium. The purpose of this study was to elucidate the pathophysiological role of ET-1 in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD). Method: We measured plasma ET-1 levels during right heart catheterization both at rest and during exercise on room air and while breathing oxygen in patients with COPD. In addition, we simultaneously measured plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Results: Plasma ET-1 levels at rest were significantly higher in 21 patients with COPD than in 16 control subjects (p < 0.001). For COPD patients, there was no correlation between the plasma ET-1 level and pulmonary arterial pressure or pulmonary vascular resistance at rest. On the other hand, there was a significant negative correlation between plasma ET-1 level and mixed venous oxygen tension (r = –0.503, p < 0.05). Also, the plasma ET-1 level was positively correlated with those of ANP (r = 0.540, p < 0.05) and BNP (r = 0.533, p < 0.05) at baseline. Oxygen administration significantly decreased plasma ET-1 levels at rest (p < 0.05). Plasma ET-1 levels did not change significantly with exercise despite the progression of pulmonary hypertension and hypoxemia. In contrast, plasma ANP and BNP levels both increased markedly with exercise (p < 0.01). Conclusion: We conclude that in patients with COPD, the plasma ET-1 level is not affected by acute progression of pulmonary hypertension and hypoxemia during exercise, and persistent hypoxemia may be associated with an increase in the plasma ET-1 level. In addition, our findings suggest that ANP and BNP may modulate the pulmonary vascular tone by interacting with ET-1 in these patients.

Improvement of Rat Lung Structure and Function after Preservation with Celsior

Ischemia/reperfusion-induced increase in pulmonary microvascular permeability was shown to be reduced after preservation with Celsior. We investigated reimplantation-induced lung injury in isolated, reperfused rat lungs after preservation via the pulmonary artery with Celsior, Celsior + prostacyclin, and reduced-potassium (40 mmol) Euro-Collins solution (40 ml/kg/body wt each) followed by 2 h of cold ischemia. Arterial and veneous oxygen tensions were recorded during 50 min ofin vitroreperfusion after which the lungs (10 right lungs per experimental group) were fixed by vascular perfusion. The tissue was further processed for microscopy, and histological changes were quantified stereologically. Lung preservation with Celsior resulted in a significantly higher volume of air-filled alveolar space with a large proportion of widely distended alveoli compared with the other groups. In the Euro-Collins group the fraction of atelectatic alveoli exceeded that observed in Celsior-preserved lungs. In accordance, the difference between arterial and venous oxygen tensions was significant among Euro-Collins- and Celsior-protected lungs, with improved oxgenation values in the Celsior group. In contrast, addition of prostacyclin to Celsior treatment resulted in rather variable structural as well as functional data. There were no differences in the volumes of intraalveolar edema among the groups tested. However, the volume of alveolar tissue was increased in the Euro-Collins group. In conclusion, compared with Euro-Collins and Celsior + prostacyclin solutions, preservation with Celsior resulted in improved structural characteristics which in combination with improved oxygenation parameters supports the prospective advantage of Celsior in clinical organ preservation.

A method for collecting right coronary venous blood samples from conscious dogs.

This report describes for the first time a technique to collect right coronary venous blood samples from conscious dogs. Catheters, prepared from Micro-Renathane tubing, were surgically implanted in right ventricular superficial veins of three anesthetized dogs. Also implanted were an arterial catheter, a right coronary flow transducer, and a right coronary artery constrictor. The coronary catheter was introduced at a venous bifurcation so that its side holes were positioned above the bifurcation; both ends of the catheter were exteriorized. Heparinized saline was continuously infused through the venous catheter by a battery-powered pump. The dogs were maintained for 10-13 days after surgery, and all catheters remained patent. Multiple right coronary venous samples were collected from each dog. These samples were analyzed for venous oxygen tension (PvO2) under baseline conditions, with right coronary pressure reduced to 50 mmHg, and during the reactive hyperemia after release of the right coronary artery constriction. PvO2 was 27.7 +/- 1.0 mmHg at baseline, 23.4 +/- 1.0 mmHg during coronary artery constriction, and 34.3 +/- 1.5 mmHg during reactive hyperemia. These data and the position of the catheter at autopsy demonstrated that coronary venous blood had been sampled.

A physiology simulator: validation of its respiratory components and its ability to predict the patient's response to changes in mechanical ventilation

We aimed to validate the mathematical validity and accuracy of the respiratory components of the Nottingham Physiology Simulator (NPS), a computer simulation of physiological models. Subsequently, we aimed to assess the accuracy of the NPS in predicting the effects of a change in mechanical ventilation on patient arterial blood-gas tensions. The NPS was supplied with the following measured or calculated values from patients receiving intensive therapy: pulmonary shunt and physiological deadspace fractions, oxygen consumption, respiratory quotient, cardiac output, inspired oxygen fraction, expired minute volume, haemoglobin concentration, temperature and arterial base excess. Values calculated by the NPS for arterial oxygen tension and saturation (PaO2 and SaO2), mixed venous oxygen tension and saturation (PvO2 and SvO2), arterial and mixed venous carbon dioxide tension (PaCO2 and PvCO2) and arterial pH were accurate compared with measured values. Subsequently, arterial gas responses to changes in minute volume of FiO2 were measured in 31 patients and were compared with the NPS prediction for each response. The 95% limits of agreement in predicting the magnitude of change were: arterial oxygen tension -2.07 to 2.47 kPa; PaCO2 -0.33 to 0.67 kPa; and pH -0.023 to 0.033. This investigation has validated respiratory components of the NPS. We recommend the NPS as a clinical tool for predicting the effects of alterations in mechanical ventilation in stable patients in the intensive care unit.