Decrease In Arterial Oxygen Tension Research Articles

Platelet-activating factor in porcine Pseudomonas acute lung injury

We investigated the role of platelet-activating factor (PAF) in acute septic lung injury by examining the effects of the selective PAF antagonist SRI 63-675 and by measuring PAF in lung tissue in the porcine model. Four groups of pigs (15–25 kg) were studied: saline control (C, n = 5); Pseudomonas (Ps, n = 9), given 5 × 10 8 CFU/ml at 0.3 ml/20 kg/min intravenously over 1 hr; SRI ( n = 3), given SRI 63-675 in a 40 mg/kg bolus; and SRI + Ps ( n = 5). Ps infusion produced a fulminant lung injury characterized by a threefold increase in pulmonary arterial pressure at 30 min and persistent pulmonary hypertension ( P < 0.05 vs C), a significant ( P < 0.05 vs C) decrease in arterial oxygen tension ( PaO 2) from 60 min, a significant ( P < 0.05 vs C) increase in extravascular lung water (EVLW) from 120 min, and a significant ( P < 0.05 vs C) increase in albumin flux determined scintigraphically as slope index at 150–180 min. Systemic arterial pressure and cardiac index (CI) decreased significantly ( P < 0.05) in the Ps group vs C at 60 and 180 min, respectively. Bolus injection of SRI 63-675 at the time of Ps infusion blocked the early pulmonary hypertension, attenuated the early and late fall in PaO 2, ameliorated the increase in EVLW, and prevented the late (150–180 min) increase in albumin flux. SRI 63-675 had minimal effects on Ps-induced hypotension or alterations in CI. The quantity of PAF bioactivity in lung tissue as determined by rabbit platelet serotonin release was significantly ( P < 0.05) greater in Ps-infused animals than in saline controls. Collectively these results suggest that PAF plays a major role in septic lung injury.

Hemodynamic responses to acute hypoxia, hypobaria, and exercise in subjects susceptible to high-altitude pulmonary edema

To verify the presence of the constitutional abnormality implicated in the pathogenesis of high-altitude pulmonary edema (HAPE), we evaluated the hemodynamic responses to hypoxia, hypobaria, and exercise in HAPE-susceptible subjects (HAPE-S). HAPE-S were five males with a history of HAPE. Five healthy volunteers who had repeated experiences of mountain climbing without any history of altitude-related problems served as controls. HAPE-S showed much greater increase in pulmonary vascular resistance index (PVRI) than the control subjects, resulting in a much higher level of pulmonary arterial pressure (Ppa), under both acute hypoxia of 15% O2 (Ppa = 29.0 +/- 2.8 vs. 17.8 +/- 0.3 Torr, P less than 0.05) and acute hypobaria of 515 Torr (32.3 +/- 2.8 vs. 19.1 +/- 0.8 Torr, P less than 0.05). Also, PVRI in HAPE-S exhibited a tendency to increase even during light exercise with supine bicycle ergometer (50 W), whereas PVRI in the control subjects significantly decreased, so that HAPE-S showed a greater increase in Ppa (delta Ppa = 16.0 +/- 1.5 vs. 4.9 +/- 1.1 Torr, P less than 0.001) and a greater decrease in arterial oxygen tension (17.8 +/- 4.7 vs. 5.6 +/- 1.7 Torr, P less than 0.05). We thus conclude that HAPE-S have a constitutional abnormality, which can be evaluated at low altitude, in the pulmonary circulatory responses to possible causative factors of HAPE such as hypoxia, hypobaria, and exercise.

High-volume, high-pressure pulsatile lavage during cemented arthroplasty.

To determine the efficacy of high-volume, high-pressure pulsatile lavage in the prevention of cardiopulmonary dysfunction and fat embolism during cemented arthroplasty, we studied twenty-eight mongrel dogs that had had a bilateral cemented arthroplasty. Significant increases in pulmonary-artery pressure and pulmonary vascular resistance, accompanied by decreases in arterial oxygen tension and increases in intrapulmonary shunt fraction (Qs/Qt), characterized cardiopulmonary dysfunction after bilateral cemented arthroplasty when no lavage was used. Low-volume, low-pressure manual lavage did not significantly alter these physiological changes, but there was a significant reduction in the number of fat emboli that were demonstrated in the lungs as compared with the no-lavage group. High-volume, high-pressure pulsatile lavage of the intramedullary cavity after reaming significantly reduced the changes in pulmonary-artery pressure, pulmonary vascular resistance, arterial oxygen tension, and intrapulmonary shunt fraction (Qs/Qt). In the pulsatile-lavage group, the number of fat microemboli that were found in the lungs was reduced to 25.7 per cent of those found in the no-lavage group. We concluded that meticulous high-volume, high-pressure pulsatile lavage reduces both pulmonary physiological derangements and fat emboli during bilateral cemented arthroplasty in dogs.

Alterations in acid-base status and blood gas dynamics during progressive hyperkalaemia in neonatal calves

Alterations in acid-base status and blood-gas dynamics were studied during induced progressive hyperkalaemia in neonatal calves. The hyperkalaemia was associated initially with respiratory alkalosis in arterial blood when plasma K+ was increased to 6.08 +/- 1.02 mmol litre-1. The rise of plasma K+ above 6.08 +/- 1.02 mmol litre-1 led to the development of metabolic acidosis in arterial and venous blood. There was partial respiratory compensation. Plasma K+ concentrations at or above 11.03 +/- 0.34 mmol litre-1 were associated with a decrease in arterial oxygen tension and arterial oxygen saturation. The oxygen extraction ratio was increased during hyperkalaemia.

Capnography Is Not as Sensitive as Pulmonary Artery Pressure Monitoring in Detecting Marrow Microembolism

We studied several methods for detecting pulmonary embolic events in a model of fat and marrow microembolism during canine cemented arthroplasty procedures. The cardiopulmonary effects of bilateral cemented arthroplasty in this model include increased pulmonary artery pressure and pulmonary vascular resistance accompanying a decrease in arterial oxygen tension. We documented significant fat and marrow microembolism by postmortem quantitative morphometry of lung sections. Vessels occluded ranged in diameter from 0.5 to 190 microns. The acute increases in pulmonary artery pressure (PAP) (to 26.8 +/- 4.4 mm Hg from 15.3 +/- 3.3 mm Hg) after cemented arthroplasty were not detected by changes in continuously monitored end-tidal CO2 or in right atrial or arterial blood pressures. Although capnography is a useful intra-operative monitor, in this model it is less sensitive than PAP monitoring in detection of fat and marrow microemboli.

Minimal Positive End-Expiratory Pressure (PEEP) May be “Best PEEP”

In the absence of clinical trials, positive end-expired pressure (PEEP) has been accepted as efficacious for treatment of postoperative decreases in arterial oxygen tension (PaO2) from a variety of causes including adult respiratory distress syndrome (ARDS). PEEP is thought to increase PaO2 by alveolar recruitment, which in turn, has been hypothesized to play a decisive role in pulmonary recovery. One hundred and eighteen patients were followed prospectively, and after development of decreased PaO2, randomized to receive recruitive PEEP (determined by blood gas criteria) or supportive PEEP (the minimal PEEP required to maintain PaO2 above 60 mm Hg on .5 inspired O2 fraction (FIO2). No prognostic factors were significantly different between the two groups. Recruitive PEEP application in 22 patients yielded a significantly increased incidence of hypotension (55 percent), pneumothorax (20 percent), and death during treatment (27 percent) when compared to the 28 supportive PEEP patients who had no hypotension or pneumothorax and only one death during treatment (4 percent). After PEEP treatment, deaths in each group were similar (19 percent and 15 percent, respectively). We find no evidence that PEEP treatment promotes beneficial outcomes and conclude that recruitment attempts may be harmful.

Salutary effects of the prostacyclin analogue CG 4203 in lethal endotoxemia in rats

In pentobarbitone anesthetized rats infusion of E. coli endotoxin (0.42 mg·kg −1·min −1 for 4 hours) produced 96% lethality within 6 hours. Transient decrease in mean arterial blood pressure, thrombocytopenia, leukopenia, loss of plasma fibrinogen, fibrin deposits in renal glomeruli, hemolysis and decrease in arterial oxygen tension and pH were observed. Infusion of the prostacyclin analogue CG 4203 (0.464 and 1.0 μg·kg −1·min −1 for 6 hours), starting concomitantly with the endotoxin infusion, improved the survival rate to 95 and 100%. Blood pressure during endotoxemia was slightly lower in CG 4203 treated rats than in vehicle controls. CG 4203 infusion marginally attenuated thrombocytopenia and obviously inhibited leukopenia, but did not effect fibrinogen consumption in endotoxemic rats. Incidence of glomerular fibrin deposits was dose dependently and significantly reduced by CG 4203. The lower dose reduced and the higher dose completely prevented the occurence of hemolysis. Acidotic changes were not observed in CG 4203 treated endotoxin-shocked rats. Also with treatment starting 1 hour after the onset of endotoxemia CG 4203 in the same doses significantly inhibited the endotoxin-induced lethality. As protective mechanisms against lethal rat endotoxemia the prostacyclin-like hemodynamic, fibrinolytic, rheological and membrane stabilizing properties of CG 4203 are discussed.

Vasodilator Properties of Prostacyclin After Coronary Artery Bypass Surgery

The vasodilatory properties of prostacyclin were studied in 12 intubated patients who underwent coronary artery bypass surgery. When infused in doses of 2.5, 5, 10, and 20 ng/kg/min, prostacyclin produced a dose-dependent decrease in systemic vascular resistance from 2,702 +/- 143 to 1,654 +/- 106 dynes/cm5/m2 (p less than 0.05). Heart rate, right atrial pressure, and pulmonary arterial and capillary wedge pressures did not change. Cardiac function was improved, since stroke volume index increased from 29.5 +/- 1.4 to 35.5 +/- 2.0 ml/min/m2 (p less than 0.05) and the rate pressure product decreased from 13.3 +/- 1.3 to 10.9 +/- 0.9 X 10(3) mm Hg/beats/min (p less than 0.05), while stroke work index remained unchanged. These hemodynamic changes were associated with a dose-dependent decrease in arterial oxygen tension which occurred from 278 +/- 25 to 133 +/- 22 mm Hg; however, oxygen transport increased as a result of the prostacyclin-induced increase in cardiac index. This study demonstrates that prostacyclin is a potent arterial vasodilator that may be of interest in the treatment of postoperative vasoconstriction occurring after coronary artery bypass surgery.

Biocompatibility of haemoperfusion.

To evaluate the influence of haemoperfusion on haemodynamics, complement system, leucocyte and thrombocyte concentration, a controlled study was performed in three groups of five dogs each. During the first 30 min of haemoperfusion with columns containing cellulose-coated activated charcoal, a significant decrease of mean aortic pressure, cardiac output and stroke volume was observed, while heart rate and total systemic resistance decreased. A comparable phenomenon, although to a much lesser extent, was observed during perfusion using columns containing polystyrene resin. Perfusion with columns containing cellulose-coated activated charcoal caused a significant decrease in total haemolytic complement, indicating activation of the complement system. A significant decrease in the leucocyte and thrombocyte concentration due to sequestration of granulocytes and thrombocytes in the columns was observed during the first 30 min of perfusion in both groups. Pulmonary leucostasis, without decrease of arterial oxygen tension, occurred during perfusion with columns containing cellulose-coated activated charcoal. Both the simultaneous occurrence and the transient character of the haemodynamic changes, complement activation and sequestration of granulocytes and thrombocytes in the perfusion column suggest a relationship between these various changes. The results stress the importance of close monitoring of the haemodynamic parameters of the intoxicated patient, particularly during the early phase of haemoperfusion.

Hypoxic pulmonary vasoconstriction in man: effects of hyperventilation.

The pulmonary vasoconstriction response to hypoxia was studied in eight anaesthetized supine subjects. One lung was made hypoxic while the other was ventilated with 100% oxygen. This was achieved by separating the tidal gas-distribution to the lungs by means of a double-lumen tracheal catheter. The hypoxic pulmonary vasoconstriction (HPV) response was estimated from the blood flow diversion away from the hypoxic lung. Blood flow distribution between the lungs was calculated from the regional expired carbon dioxide production, assuming regional carbon dioxide production to be proportional to blood flow. The subjects were studied during six different conditions. Firstly, when ventilated with 100% oxygen to both lungs at a PaCO2 of about 6 kPa. Secondly, with 100% oxygen to the left lung and 5% oxygen in nitrogen to the right (test) lung. The ratio between carbon dioxide output from right and left lung was calculated. These measurements were repeated during two states of hyperventilation (PaCO2 of about 4.5 kPa and 3.5 kPa, respectively) with and without hypoxia (conditions 3-6). During normoventilation, blood flow distribution between the lungs was equal. During hypoxia, blood flow distribution to the hypoxic lung decreased by 35% of the pre-hypoxic value. Furthermore, a decrease in arterial oxygen tension from 51.5 +/- 4.5 to 11.5 +/- 2.1 kPa was observed. During excessive hyperventilation (PaCO2 3.2 +/- 0.2 kPa), blood flow distribution to the hypoxic right lung decreased by only 10% of its pre-hypoxic value. A further decrease in arterial oxygen tension to 8.5 +/- 1.8 kPa was observed. This decrease in PaO2 was possibly due to an increased venous admixture caused by an abolished HPV response. It is concluded that hyperventilation counteracts hypoxic pulmonary vasoconstriction in man.

Effects of molsidomine on hemodynamics and blood gases in acute myocardial infarction with left heart failure

We studied the effects of molsidomine on hemodynamic properties and blood gas levels in eight patients with acute myocardial infarction and left heart failure. One hour after an 8 mg intravenous bolus injection, pulmonary wedge pressure and right atrial pressure decreased, respectively, from 30 ± 9 to 23 ± 12 mm Hg ( p < 0.01) and from 10.4 ± 3.6 to 7.8 ± 4.0 mm Hg ( p < 0.05) without significant changes in heart rate, cardiac index, or systemic blood pressure. There was a mild decrease in arterial oxygen tension (from 61 ± 15 to 56 ± 6 mm Hg), but it was not significant. The drug induced no adverse effects. Intravenous bolus injection of molsidomine rapidly relieves pulmonary congestion in patients with acute myocardial infarction.

Serum angiotensin-converting enzyme increases during hemodialysis. Evidence for injury of the pulmonary vascular endothelium?

In 19 patients hemodialysis was associated with significant decreases in arterial oxygen tension and leukocyte count. After 240 min of dialysis serum angiotensin-converting enzyme (ACE) corrected for hemoconcentration increased 14.3% (p less than 0.001) indicating injury of the vascular endothelium during hemodialysis. It is suggested that the increase in serum ACE is due to a complement-mediated sequestration of leukocytes in the pulmonary vasculature leading to injury of the vascular endothelium with interstitial edema and pulmonary dysfunction. Furthermore, it is suggested that serum ACE analysis may prove a new method to assess biocompatibility of materials used in devices for extracorporeal circulation.

EXERCISE TESTING IN THE EVALUATION OF DIFFUSE INTERSTITIAL LUNG DISEASE

Abstract:The cardio‐pulmonary response to incremental and steady‐state bicycte exercise was measured in a group of 22 patients with diffuse interstitial lung disease (DILD). In most patients the lung volumes were less than 80% of their predicted normal value. In 19 patients the uptake of carbon monoxide was less than 60% of the value predicted for the observed lung volume.Maximum working capacity (wmax) was reduced in 20 patients. Eight patients stopped exercising before they achieved their predicted maximum heart rate. In all patients ventilation (VE) was increased in relation to oxygen consumption. The increase in VE resulted from an increased frequency of breathing.Exercise induced a decrease in arterial oxygen tension in 11 patients. When 60% oxygen was inspired during exercise the endurance time at 80% Wmax increased from 8.0 ± 5.5 to 13.9 ± 8.7 min. The increase in endurance time related to the extent of desaturation during exercise with air breathing. Oxygen breathing did not improve Wmax.We conclude that exercise testing in patients with DILD is useful for determining the severity of disease and provides additional information in relation to gas exchange.

EXERCISE TESTING IN THE EVALUATION OF DIFFUSE INTERSTITIAL LUNG DISEASE

The cardio-pulmonary response to incremental and steady-state bicycle exercise was measured in a group of 22 patients with diffuse interstitial lung disease (DILD). In most patients the lung volumes were less than 80% of their predicted normal value. In 19 patients the uptake of carbon monoxide was less than 60% of the value predicted for the observed lung volume. Maximum working capacity (Wmax) was reduced in 20 patients. Eight patients stopped exercising before they achieved their predicted maximum heart rate. In all patients ventilation (VE) was increased in relation to oxygen consumption. The increase in VE resulted from an increased frequency of breathing. Exercise induced a decrease in arterial oxygen tension in 11 patients. When 60% oxygen was inspired during exercise the endurance time at 80% Wmax increased from 8.0 +/- 5.5 to 13.9 +/- 8.7 min. The increase in endurance time related to the extent of desaturation during exercise with air breathing. Oxygen breathing did not improve Wmax. We conclude that exercise testing in patients with DILD is useful for determining the severity of disease and provides additional information in relation to gas exchange.

Determinants of oxygenation during hemodialysis and related procedures. A report of data acquired under varying conditions and a review of the literature.

A decrease in arterial oxygen tension during hemodialysis has been attributed to a number of factors. In order to more completely define these factors, we studied respiratory gas exchange, arterial blood gases and pH, and dialyzer flux of CO2 during pure ultrafiltration, three types of acetate dialysis, and sorbent regenerated bicarbonate dialysis in which the dialysate concentration of bicarbonate varies. Changes due to position and extracorporeal circulation of a 300-ml volume of blood (sham dialysis) were studied for any effect contributing to the hypoxemia noted with circulation through the membrane and variation in dialysate. Alveolar oxygen tension (PAO2) is calculated by the equation PAO2 = PIO2-PaCO2 (FIO2 + 1-FIO2/RE). RE is the ratio of CO2 excretion by the lung (VCO2) to oxygen consumption (VO2). RE equals RQ (metabolic quotient) when no extrapulmonary CO2 losses occur. Normals in a lounge chair had no change in RE and PAO2. RE decreased to 0.75 during sham dialysis and PAO2 decreased. During pure ultrafiltration RE decreased due to a decrease in VO2 and VCO2 with proportionately greater decrease in VCO2. PAO2 decreased accordingly. Acetate dialysis produced an increase in oxygen consumption without a proportional increase in CO2 excretion and both RQ and RE decreased. When PAO2 decreased during any of these procedures, arterial oxygen tension (PaO2) decreased without a change in A-aO2 gradient. No changes in PaCO2 were noted. RQ did not change during bicarbonate dialysis. At high bicarbonate dialysate concentrations, however, PaCO2 increased and PAO2 decreased. The major reason for hypoxemia during acetate dialysis is a decrease in alveolar oxygen tension due to changes in metabolism and a decrease in pulmonary CO2 excretion when CO2 is lost from the dialyzer. The increasing pH may contribute to the metabolic change during acetate dialysis and the hypoventilation during bicarbonate dialysis. There is little evidence to support an effect of pulmonary capillary obstruction or changes in oxyhemoglobin association on the decrease in arterial oxygen tension observed.

Determinants of oxygenation during hemodialysis and related procedures.

A decrease in arterial oxygen tension during hemodialysis has been attributed to a number of factors. In order to more completely define these factors, we studied respiratory gas exchange, arterial bl

Effect of Inhibition of Prostaglandin Synthesis on Platelet Count, Platelet Aggregates and Arterial Oxygen Tension during Hemodialysis

20 chronic hemodialysis patients were studied during two successive dialyses. Before the second dialysis patients ingested 320 mg acetylsalicylic acid (ASA). Hemodialysis was associated with a decrease in arterial oxygen tension, leukocyte and platelet counts. These changes were unaffected by pretreatment with ASA. In 8 of the patients platelet aggregate ratio (PAR) was measured during dialysis. As a reflection of an increase in circulating platelet aggregates PAR was found to decrease after 30 and 60 min of dialysis. This decrease was prevented by pretreatment with ASA. We conclude that circulating platelet aggregates do not seem to be a major contributing factor to hemodialysis-induced arterial hypoxemia.

CARDIORESPIRATORY RESPONSES TO AN I.V. INFUSION OF DOBUTAMINE IN THE INTACT ANAESTHETIZED DOG

The cardiorespiratory responses to an i.v. infusion of dobutamine hydrochloride were assessed in eight anaesthetized, mechanically ventilated dogs. As the rate of infusion of dobutamine was increased from 2 to 30 microgram kg-1 min-1, there was a progressive decrease in arterial pressure, pulmonary wedge pressure and arterial pH. There was a significant decrease in arterial oxygen tension at the greater doses of dobutamine (15 and 30 microgram kg-1 min-1) from initial control values. Carbon dioxide output, arterial carbon dioxide tension, venous admixture and oxygen consumption increased during the infusion of dobutamine. However, oxygen supply increased further so that the oxygen consumption; supply ratio decreased. It is concluded that dobutamine may decrease arterial oxygen tension, but that the increased cardiac output and decreased arterial pH produced by dobutamine may increase oxygen supply to the tissues in spite of this.

Intravenous Injections of Tissue Thromboplastin and Phospholipase C in Sheep

SummaryTo gain further information about the protective effect of phospholipase C (PLC) against intravascular coagulation, we have carried out studies in sheep. Thromboplastin infusions gave a dose-dependent increase in pulmonary platelet-bound 11 inactivity and a dose-dependent decrease in arterial oxygen tension, factor VIIIc activity, fibrinogen level and platelet count. All these parameters were significantly correlated when doses of 0.4 – 0.5 ml bovine thromboplastin/kg/min were given. The model therefore seemed suitable for testing the effect of PLC in preventing intravascular coagulation elicited by infusion of thromboplastin. Our experiments show that PLC may have a certain protective effect against pulmonary microembolism caused by thromboplastin infusion, but there was no normalization of the pulmonary 111In-radioactivity from labelled platelets, arterial oxygen tension, coagulation factors or platelet count in contrast to earlier observations in rats. Protection was observed against the effect of lethal doses of thromboplastin, but although small doses of PLC were used, both sheep eventually died of PLC toxicity.

Pulmonary response of massive steroids in seriously injured patients.

The effects of massive steroids on pulmonary function after hypovolemic shock were tested in 114 injured patients who received an average of 13 transfusions, 760 ml plasma, and 11.7 L crystalloid solution; by random selection, 54 patients received methylprednisolone (1 g in operating room plus 3,578 mg average during the next three days). The patients who received steroids had a significant increase in central venous pressure and a decrease in arterial oxygen tension (PaO2) compared with control patients. The inspired oxygen concentration was similar for both groups; the FiO2/PO2, therefore, was significantly deranged (P = less than 0.05) in steroid patients (0.45 +/- 0.05 SE vs 0.37 +/- 0.02 SE). The patients who received steroids has an insignificantly increased pulmonary shunt (25 vs 22%), number of days on a volume ventilator (5.1 vs 3.0 days), and number of deaths (seven vs two), Massive steroids neither prevent nor ameliorate pulmonary failure after shock; indeed, steroids may aggravate pulmonary failure after shock.