Mixed Venous PO2 Research Articles

Effects of inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of ARDS.

Inhaling low concentrations of nitric oxide (NO) gas causes selective pulmonary vasodilation of ventilated lung regions. NO activates soluble guanylate cyclase, increasing guanosine 3',5'-cyclic monophosphate (cGMP). Inhibition of NO synthesis enhances hypoxic pulmonary vasoconstriction. Therefore we examined independent and combined effects of NO inhalation and infusion of NG-nitro-L-arginine methyl ester (L-NAME), an NO synthesis inhibitor, on pulmonary vascular pressure-flow relationships, gas exchange, and plasma cGMP levels in anesthetized and mechanically ventilated sheep with acute lung injury induced by bilateral lavage. After lavage, inhaling 60 ppm by volume of NO decreased pulmonary arterial pressure (PAP) and resistance without any systemic hemodynamic effects, increased arterial PO2, and decreased venous admixture (Qva/QT; all P < 0.05) without altering cardiac output (QT), mixed venous PO2, or O2 uptake, major determinants of intrapulmonary shunt. During NO inhalation, PAP-left atrial pressure gradient (PAP-LAP) and Qva/QT were reduced (both P < 0.05) independently of QT, which was varied mechanically. L-NAME infusion produced systemic and pulmonary vasoconstriction and increased PAP-LAP gradient across the entire range of QT, whereas Qva/QT, was not changed. NO inhalation after L-NAME infusion produced pulmonary vasodilation and decreased Qva/QT to the same degree as NO inhalation alone. Five to 10 min after inhalation of 60 ppm NO, before and after L-NAME infusion, arterial plasma cGMP levels were increased by 80% (both P < 0.05). With NO breathing after L-NAME, we measured a consistent transpulmonary cGMP arteriovenous gradient [31 +/- 8 and 33 +/- 7 (SE) pmol/ml at 5 and 10 min, respectively; both P < 0.05]. NO inhalation before or after L-NAME administration in this acute lung injury model reduced Qva/QT, most likely by increasing cGMP concentration in ventilated lung regions and causing selective pulmonary vasodilation.

Enhanced Oxygen Delivery by Perflubron Emulsion During Acute Hemodilution

A high-concentration 90% w/v perflubron (perfluorooctyl bromide [PFOB]) emulsion (Oxygent HT) is being evaluated as an oxygen carrier for use during surgery. This study was done to assess oxygen delivery by Oxygent HT during acute normovolemic hemodilution. Anesthetized mongrel dogs, instrumented with femoral and pulmonary artery catheters, were hemodiluted to a hematocrit of 25% with 3:1 (v/v) of Ringers-lactate (R-L). Dogs were then ventilated with 100% O2 and hemodiluted to a Hct approximately 11% with 1.5 (v/v) of colloid (autologous plasma and 5% albumin). Dogs then received either 3.3 mL/kg Oxygent HT (n = 5) or 3.3 mL/kg R-L (n = 4), and were monitored for 3 hours. Total oxygen delivery (DO2), blood oxygen content, cardiac output, mixed venous PO2, and mixed venous Hb saturation was higher in Oxygent HT treated dogs compared to the R-L controls. The percentage of total DO2 contributed by perflubron-dissolved oxygen was about 8-10% and accounted for 25-30% of total oxygen consumption (VO2). The percentage of VO2 contributed by Hb-carried oxygen was significantly higher in R-L controls (46 +/- 4%) than in the treated dogs (15 +/- 3%), indicating that the availability of the perflubron-dissolved oxygen allowed for a reserve of oxygen to remain available in the red blood cells.

Cardiac afferents attenuate the muscle metaboreflex in the rat.

The influence of cardiac afferents on the muscle metaboreflex was examined in 16 rats instrumented with a Silastic-tipped catheter in the pericardial space and right atrium, Doppler ultrasonic flow probe and a pneumatic vascular occluder around the terminal aorta, and a Teflon catheter in the thoracic aorta. In protocol I (cardiac efferent and afferent blockade), the muscle metaboreflex was examined under three experimental conditions: 1) control, 2) cardiac autonomic efferent blockade [intrapericardial methylscopolamine (10 micrograms/kg) and propranolol (50 micrograms/kg)], and 3) combined cardiac autonomic efferent and afferent blockade (intrapericardial procainamide, 2%). In protocol II (blood volume expansion), the muscle metaboreflex was examined before and after 15% blood volume expansion. Mild treadmill exercise (9 m/min, 10% grade) increased heart rate (71 +/- 9.4 beats/min), mean arterial pressure (12 +/- 2.0 mmHg), and terminal aortic blood flow velocity (6 +/- 1.0 kHz). During exercise, a reduction of terminal aortic blood flow velocity (10.5 +/- 1.1%) reduced mixed venous PO2 18 +/- 6%. The gain of the muscle metaboreflex in the control condition was 14.6 +/- 2.9 mmHg/kHz. Efferent blockade reduced the gain 51 +/- 7%. However, combined cardiac efferent and afferent blockade increased the gain 207 +/- 64% above the efferent blocked condition and restored the gain to levels above those obtained in the control condition (18.3 +/- 4.6 mmHg/kHz). In addition, 15% blood volume expansion reduced the gain of the muscle metaboreflex regulation of mean arterial pressure and heart rate (44 +/- 9.5% and 41 +/- 12.0%, respectively). Thus cardiac afferents tonically inhibit the pressor response to a reduction in terminal aortic blood flow velocity during exercise.

Mechanisms of Impaired Arterial Oxygenation in Patients With Liver Cirrhosis and Severe Respiratory Insufficiency: Effects of Indomethacin

The mechanisms of impaired arterial oxygenation that occur in certain patients with chronic liver cirrhosis are still debated. In the present study, we investigated nine cirrhotic patients with severe respiratory disability (mean PaO2, 64 +/- 5 mm Hg), using the inert gas elimination technique to assess the distribution of ventilation-perfusion (VA/Q) ratios. We also determined shunt fraction during pure oxygen breathing, both in supine and sitting positions. To test the hypothesis that vasodilating prostaglandins could contribute to alter gas exchange in such patients with cirrhosis, we examined the hemodynamic and gasometric responses to indomethacin, 50 mg IV, in six of them. During baseline conditions, patients had high cardiac index (CI, 4.9 +/- 0.2 L/min/m2), and low pulmonary (PVR, 1.78 +/- 0.37 mm Hg/L/min/m2) or systemic (SVR, 17.7 +/- 1.15 mm Hg/L/min/m2) vascular resistances. Large intrapulmonary shunt fraction was documented in each patient with a mean value of 19.6 +/- 2.7 percent. Small perfusion in low VA/Q areas was associated with shunt in only three patients (2.5 to 5.3 percent of blood flow). Arterial PO2 was negatively related to shunt (p < 0.01) and to the dispersion of blood flow distribution (p < 0.02). There was no difference between measured and predicted PaO2. Shunt estimates from the inert gas and the 100 percent O2 breathing techniques were, respectively, 19.6 +/- 2.7 percent and 21.7 +/- 3.0 percent. During 100 percent oxygen breathing, changing from supine to sitting position decreased PaO2 from 401 +/- 50 to 333 +/- 64 mm Hg (p < 0.02), while O2 shunt remained unchanged, arteriovenous difference widened, and mixed venous PO2 decreased, from 61 +/- 3 to 47 +/- 4 mm Hg (p < 0.001). Indomethacin did not improve gas exchange or VA/Q distribution and did not affect systemic or pulmonary hemodynamics. The results show that in cirrhotic patients with severe respiratory disability, intrapulmonary shunting is the main determinant of impaired gas exchange, with no evidence of a defect in oxygen diffusion or an extrapulmonary shunt. Vasodilating prostaglandins do not appear to contribute to these alterations.

Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive lung disease.

It is known that theophylline reduces cerebral blood flow in humans. To quantitatively assess the possible adverse effect of theophylline on brain tissue oxygen tension (PO2) due to decreased cerebral blood flow, two sets of experiments were conducted in mildly hypoxaemic patients with chronic obstructive lung disease. Firstly, internal jugular venous PO2 (PjO2) was measured simultaneously with arterial and mixed venous blood PO2 (PaO2 and PvO2) during right heart catheterisation in 10 subjects (mean PaO2 73 mm Hg; conversion factor: 10 mm Hg = 1.33 kPa)) before and after intravenous infusion of aminophylline (6 mg/kg). The PjO2 and PvO2 were considered to reflect the average tissue PO2 for the brain and for the whole body respectively. Secondly, the relation between PaO2 and PjO2 over a wide range, with the PaCO2 similar to that in the first study, was investigated in a different group of 12 subjects by stepwise changes in inspiratory gas composition. The mean PjO2 decreased by as much as 6 mm Hg 15 minutes after an infusion of aminophylline, whereas PaO2 stayed at the same level and PvO2 showed only a small decrease. The low PjO2 value of 29 (SD 6) mm Hg with aminophylline in the first study was similar to the PjO2 value of 30 (2) mm Hg obtained during severe hypoxia (PaO2 45 mm Hg) in the second study. The coefficient of oxygen delivery for the brain decreased by 29% with aminophylline treatment, but did not change significantly during severe hypoxic challenge. These data suggest that an infusion of aminophylline lowers brain tissue PO2 appreciably when given to mildly hypoxaemic patients with chronic obstructive lung disease.

Cephalic Jugular Venous Blood Gas Measurement during Neonatal Venoarterial Extracorporeal Membrane Oxygenation

Cannulation of the cephalic portion of the right internal jugular vein during extracorporeal membrane oxygenation (ECMO) allows for increased venous return flow to the circuit. This procedure also allows access to venous drainage from the brain. We reviewed data from simultaneous blood gases obtained from the cephalic jugular vein and the mixed venous return in 5 neonates during venoarterial ECMO. Cephalic venous pO2 values were significantly lower than mixed venous pO2 values (P &lt; .001). The values for pH and pCO2 did not vary between the sites. Our experience with 34 infants using cephalic jugular drainage is reviewed. Since the institution of right jugular venous drainage, the intracranial hemorrhage rate in neonates undergoing ECMO at our center has decreased from 34% to 6% (p &lt; .01).

Septic shock in patients with cirrhosis

To examine the hemodynamic and metabolic characteristics and ICU outcome of septic shock in patients with cirrhosis. Prospective, comparative study. Measurements performed in the first 24 hrs of septic shock. A general hospital ICU. Twelve patients with cirrhosis and 23 patients without cirrhosis admitted for septic shock. Arterial pressure was measured using an arterial catheter. Pulmonary arterial and right atrial pressures were measured by using a pulmonary artery catheter. Cardiac output was determined by using the thermodilution method. Pulmonary arterial L-lactate plasma concentrations were measured using an automated spectrophotometer, and blood temperature was measured using a cardiac output computer. Arterial and mixed venous PO2, PCO2, and pH values were measured by using specific electrodes. Oxygen saturations and hemoglobin concentrations were measured using a hemoximeter. Patients with cirrhosis had decompensated liver disease (grade C of the Child-Pugh classification). The number of Gram-negative infections and therapeutic interventions were similar in both groups. Patients with cirrhosis had higher cardiac indices (5.14 +/- 0.52 [SE] vs. 3.91 +/- 0.30 L/min/m2, p less than .05), plasma lactate concentrations (9.0 +/- 2.0 vs. 5.2 +/- 0.7 mmol/L, p less than .05) and ICU mortality rates (100% vs. 43%, p less than .05), and lower blood temperatures (35.5 +/- 0.6 vs. 37.6 +/- 0.2 degrees C, p less than .05) than patients without cirrhosis. Systemic vascular resistance, arterial pressure, pulmonary arterial pressure, oxygen delivery and consumption, and arterial and mixed venous acid-base status were not significantly different between the two groups. In patients with cirrhosis, septic shock was characterized by severe liver dysfunction, low blood temperature, marked increases in cardiac index and lactic acidemia, and a 100% ICU mortality rate. These findings should be taken into account if patients with cirrhosis are to be included in controlled studies on septic shock.

Effects of acid-base status on acute hypoxic pulmonary vasoconstriction and gas exchange.

To investigate the relationship between hypoxic pulmonary vasoconstriction and respiratory and metabolic acidosis and respiratory alkalosis, the pulmonary gas exchange and pulmonary hemodynamic responses were measured in anesthetized, paralyzed, and mechanically ventilated dogs in two sets of experiments (series A, n = 6; series B, n = 10). The animals were treated with acute hypoxia, CO2 inhalation, hyperventilation, and dinitrophenol in various combinations. Multiple regression analysis indicated that mean pulmonary arterial pressure (Ppa) was significantly correlated with end-tidal PO2, mixed venous PO2, and the mean pulmonary capillary pH (average of arterial and mixed venous pH) as independent variables [series A: r = +0.999, standard error of estimate (SEE) = 0.4 mmHg; series B: r = +0.98, SEE = 1.4 mmHg]. Similar analyses of mean values published by other authors from an acute study on humans with exercise at sea level and simulated altitudes of 10,000 and 15,000 ft also indicated a good relationship (n = 14, r = +0.98, SEE = 2.1 mmHg). The mean data (n = 19) obtained in Operation Everest II at various exercise loads and simulated altitudes gave a correlation of r = +0.87, SEE = 6.1 mmHg. These empirical analyses suggest that variations in the rise of Ppa with hypoxia can be accounted for in vivo by the superimposed acid-base status. Furthermore, ventilation-perfusion inhomogeneity, as estimated in the dogs from end-tidal and arterial O2 and CO2 differences and assuming no true shunt or diffusion impairment, was highly correlated with Ppa and mean pulmonary capillary pH (r = +0.999 in series A, r = +0.77 in series B). The human data from the above studies also showed significant correlations between Ppa and directly measured ventilation-perfusion (standard deviation of perfusion obtained from inert gas measurements). These observations indicate that the beneficial effects of hyperventilation during hypoxia may be related to the marked alkalosis that serves to reduce Ppa and improve pulmonary gas exchange efficiency.

Ventilation-Perfusion Matching during Exercise

In normal subjects, exercise widens the alveolar-arterial PO2 difference (P[A-a]O2) despite a more uniform topographic distribution of ventilation-perfusion (VA/Q) ratios. While part of the increase in P(A-a)O2 (especially during heavy exercise) is due to diffusion limitation, a considerable amount is caused by an increase in VA/Q mismatch as detected by the multiple inert gas elimination technique. Why this occurs is unknown, but circumstantial evidence suggests it may be related to interstitial pulmonary edema rather than to factors dependent on ventilation, airway gas mixing, airway muscle tone, or pulmonary vascular tone. In patients with lung disease, the gas exchange consequences of exercise are variable. Thus, arterial PO2 may increase, remain the same, or fall. In general, patients with advanced chronic obstructive pulmonary disease (COPD) or interstitial fibrosis who exercise show a fall in PO2. This is usually not due to worsening VA/Q relationships but mostly to the well-known fall in mixed venous PO2, which itself results from a relatively smaller increase in cardiac output than VO2. However, in interstitial fibrosis (but not COPD), there is good evidence that a part of the fall in PO2 on exercise is caused by alveolar-capillary diffusion limitation of O2 transport; in COPD (but not interstitial fibrosis), a frequent additional contributing factor to the hypoxemia of exercise is an inadequate ventilatory response, such that minute ventilation does not rise as much as does CO2 production or O2 uptake, causing arterial PCO2 to increase and PO2 to fall.

Cardiovascular and pulmonary effects of morphine in conscious pigs

Cardiovascular and pulmonary effects of morphine (1 mg/kg bolus iv) were investigated in conscious chronically instrumented pigs, a species exhibiting an excitable response. Control animals received an equivalent volume (less than 2 ml) of normal saline. Morphine induced an immediate but small increase in cardiac output and substantial increases in heart rate, mean systemic and pulmonary arterial pressure, left and right ventricular work, hematocrit, and hemoglobin concentration, but did not change stroke volume or systemic vascular resistance. Morphine administration also led to a gradual increase in ventilatory rate and rapid increases in tidal volume, expired and alveolar ventilation, ventilation-perfusion ratio, and shunt fraction. In addition, morphine administration produced substantial decrements in arterial and mixed venous PO2, hemoglobin saturation and mixed venous O2 content; no change in arterial O2 content; and a widening of the arteriovenous O2 difference. Arterial O2 transport was increased slightly. Finally, it produced substantial increments in arterial and mixed venous PCO2 and substantial decrements in arterial and mixed venous pH. It was concluded that arterial O2 delivery did not adequately rise to meet tissue O2 demand, in part because an appropriate increase in cardiac output was attenuated by morphine, and in part because morphine impaired pulmonary gas exchange.

Cardiovascular Actions of Desflurane in Normocarbic Volunteers

The cardiovascular actions of three concentrations of desflurane (formerly I-653), a new inhalation anesthetic, were examined in 12 unmedicated normocapnic, normothermic male volunteers. We compared the effects of 0.83, 1.24, and 1.66 MAC desflurane with measurements obtained while the same men were conscious. Desflurane caused a dose-dependent increase in right-heart filling pressure and a decrease in systemic vascular resistance and mean systemic arterial blood pressure. As measured by echocardiography, left ventricular end-diastolic area did not change except for a small increase at 1.66 MAC desflurane, and systolic wall stress was less at all concentrations of desflurane than during the conscious state. Desflurane did not change cardiac index or left ventricular ejection fraction. Heart rate did not change at 0.83 MAC, but progressively increased with deeper desflurane anesthesia. Stroke volume index was less at all concentrations of desflurane than while the men were conscious, but desflurane did not alter the velocity of ventricular circumferential fiber shortening. Mixed venous blood PO2 and oxyhemoglobin saturation were higher during all concentrations of desflurane anesthesia than during the conscious state. No volunteer developed a metabolic acidosis. We conclude that desflurane with controlled ventilation and constant PaCO2 causes cardiovascular depression, as indicated by the increased cardiac filling pressure and decreased stroke volume index and by no change in the velocity of circumferential fiber shortening in the presence of decreased systolic wall stress. However, cardiac output is well maintained, and heart rate does not increase at light levels of anesthesia. The cardiovascular actions of 0.83 and 1.66 MAC desflurane were also reexamined in 6 of the 12 men during the seventh hour of anesthesia. Prolonged desflurane anesthesia resulted in lesser cardiovascular depression than was evidenced during the first 90 min. The measures of cardiac filling (central venous pressure and left ventricular end-diastolic cross-sectional area) did not differ between the early and late periods of anesthesia. Systemic vascular resistance decreased further during the late period, but systolic wall stress did not differ between the two time periods. During the seventh hour of desflurane anesthesia, heart rate and cardiac index were higher at both anesthetic concentrations than during the first 90 min of anesthesia. Left ventricular ejection fraction and velocity of fiber shortening did not change with duration of desflurane anesthesia. Oxygen consumption, oxygen transport, the ratio of the two, mixed venous PO2, and mixed venous oxyhemoglobin saturation (SO2) increased late in the anesthetic in comparison with the first 90 min.

Transition from Exercise to Rest: Ventilatory and Arterial Blood Gas Responses

The mechanisms leading to rapid changes in arterial blood gas values soon after exercise ends have not been well established. To further study these phenomena, we exercised seven normal male volunteers to exhaustion on a cycle ergometer with a 25-W/min ramped protocol measuring arterial blood gas values, and breath-by-breath gas exchange from rest to exercise and through 15 minutes of recovery. Arterial PO2 (PaO2) increased from 108 mm Hg at peak exercise to 125 mm Hg at 2 minutes of recovery. There was a smaller rise in calculated alveolar PO2 (PAO2) from 121 to 128 mm Hg over the same period. Arterial PCO2 (PaCO2) fell from 35.0 mm Hg to 31.9 mm Hg. The gas exchange ratio R rose from 1.21 to 1.52, after having peaked at 1.68 at 1 minute. The alveolar-arterial O2 gradient (P[A-a]O2) fell from 12.3 mm Hg at peak exercise to 3.2 mm Hg at 2 minutes. Following exercise, the rise in R is related to a more rapid fall in O2 uptake than in CO2 output, and the fall in P(A-a)O2 is probably related to improved V/Q relationships and to a rise in mixed venous PO2. We conclude that the rise in PaO2 in the recovery period after progressive nonsteady state exercise is due to several factors, including a fall in P(A-a)O2 and a rise in PAO2 due primarily to an elevation of R and also to a fall in PaCO2.

Gas exchange abnormalities in asthma

There has been considerable interest over the last years in gas exchange abnormalities that occur in patients with bronchial asthma, particularly during an acute attack. These are essentially characterized by moderate to severe hypoxemia and hypocapnia caused by considerable ventilation-perfusion (VA/Q) mismatch. Using the multiple inert gas elimination technique, the baseline pattern of VA/Q distribution reveals a bimodal bloodflow distribution of VA/Q ratios but no shunt. Inhaled salbutamol seems to be an efficient and safe therapeutic approach, owing to the lack of deleterious effect on VA/Q inequality. Following intravenous salbutamol there is development of further VA/Q mismatch for the same degree of bronchodilation, the resulting deleterious effect on PaO2 being offset by the improvement in mixed venous PO2 due to increased cardiac output.

Effects of Propranolol on Arterial Oxygenation and Oxygen Transport to Tissues in Patients with Cirrhosis

Patients with cirrhosis may show ventilation-perfusion (VA/Q) inequality in the absence of any intrinsic heart or lung disease. However, the high cardiac output of cirrhosis generally prevents or minimizes the appearance of a severe degree of arterial hypoxemia. Propranolol has been used to reduce cardiac output and portal pressure in these patients. We wondered whether it might alter arterial oxygenation and reduce O2 transport to tissues. We studied eight patients (three women) 54 +/- 3 (SEM) yr of age before and after intravenous propranolol (0.1 mg/kg followed by 2 mg/h). Cardiac output (QT) fell from 7.8 +/- 0.7 to 6.0 +/- 0.7 L/min (p less than 0.05), and portal pressure was reduced (22 +/- 2 to 19 +/- 2 mm Hg, p less than 0.01). Arterial PO2 did not change (88 +/- 4 to 89 +/- 5 mm Hg) because the fall in mixed venous PO2 (43 +/- 1 to 40 +/- 1 mm Hg, p less than 0.01) that followed the lower QT was counterbalanced by a lower intrapulmonary shunt (multiple inert gas technique) (4 +/- 2 to 2 +/- 1%, p less than 0.05) and a shift of the VA/Q distributions toward a higher VA/Q ratio. Paralleling the fall in QT, oxygen transport to tissues (QO2) was reduced (19 +/- 2 to 14 +/- 1 ml/min/kg, p less than 0.01). However, O2 uptake (VO2) remained constant (3.4 +/- 0.2 to 3.6 +/- 0.2 ml/min/kg) because O2 extraction by the tissues increased appropriately (22 +/- 2 to 28 +/- 1%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Constant‐flow ventilation during experimental left ventricular failure

The efficacy of constant-flow ventilation (CFV) was investigated in dogs with normal heart function (control phase, n = 8) and after development of left ventricular failure (LVF phase, n = 8). Heated, humidified and oxygen-enriched air (inspired oxygen fraction (Fio2) = 0.4) was continuously delivered via two catheters positioned within each mainstem bronchus at two flow rates (1.2 and 1.6 l/kg/min). Conventional mechanical ventilation (CMV) with positive end-expiratory pressure (PEEP) of 0.5 kPa was used as reference ventilation. During control, neither CMV with PEEP nor CFV revealed severe impairment of cardiopulmonary performance. Alveolo-arterial PO2 difference (P(A-a)O2) increased significantly during CFV1.2 and CFV1.6, indicating a higher degree of ventilation-perfusion (VA/Q) inhomogeneity. Acute left ventricular failure (LVF) was induced by proximal occlusion of the left anterior descending (LAD) coronary artery. Cardiac output (CO), maximum velocity of pressure development (dP/dtmax) and mixed venous PO2 decreased (P less than or equal to 0.05), whereas left ventricular end-diastolic pressure (LVEDP) and pulmonary capillary wedge pressure (PCWP) increased (P less than or equal to 0.05). Extravascular lung water (EVLW), as determined by thermal-dye technique, increased from 10.1 ml/kg to 20.9 ml/kg (P less than or equal to 0.01). Oxygenation, but not CO2 elimination, deteriorated in the LVF phase. There were no haemodynamic differences between CMV with PEEP and CFV1.2, but cardiopulmonary performance deteriorated with CFV1.6. Gas exchange was significantly more impaired during CFV1.2 and CFV1.6 due to increased VA/Q mismatching. However, there were no significant differences for P(A-a)O2 values between CFVControl and CFVLVF.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Opposite Changes in Cardiac Output and Arterial Po2on the Relationship between Mixed Venous Po2and Oxygen Transport

"Effect of Opposite Changes in Cardiac Output and Arterial Po2 on the Relationship between Mixed Venous Po2 and Oxygen Transport." American Review of Respiratory Disease, 141(3), p. 800

Pentoxifylline Improves Pulmonary Gas Exchange

Pentoxifylline is a xanthine derivative with hemorrheologic and vascular properties that may improve gas exchange in patients with chronic obstructive pulmonary disease (COPD). We tested this hypothesis in 12 patients with COPD (mean FEV1 = 40 percent predicted; mean DCO, 8.6 ml/min/mm Hg) randomly divided into a treatment and control group and six healthy volunteers. Following establishment of baseline DCO and maximum expiratory flow volume (MEFV) curve values, each subject in the treatment and healthy groups took 400 mg of pentoxifylline three times a day for 12 weeks. Weekly DCO and MEFV curves were measured before treadmill exercise in both COPD groups and before and after exercise in the healthy group. The MEFV curve parameters from the final three weeks of therapy did not differ significantly from baseline values. During this time, however, the treatment COPD group's resting DCO rose by 8.2 +/- 2.4 percent over baseline level (p less than 0.01). Treadmill walk time increased from 17.7 +/- 2.9 minutes to 23.2 +/- 2.9 minutes (p less than 0.02). This was accompanied by improved exercise oxygen saturation measured by oximetry (SoxiO2). Premedication SoxiO2 fell from 92.8 +/- 1.2 percent to 88.6 +/- 2.5 percent during exercise, and from 94.4 +/- 1.1 percent to only 91.8 +/- 1.0 percent after 12 weeks of medication (p less than 0.05). No such improvement was noted in the control COPD group. Although the healthy group's resting SoxiO2 and DCO did not change during treatment, their exercise DCO increased significantly from 36.3 +/- 3.1 ml/min/mm Hg to 41.8 +/- 3.5 ml/min/mm Hg (p less than 0.001). These data demonstrate that pentoxifylline improves gas exchange, possibly by increasing cardiac output, and/or by raising mixed venous PO2, and/or by improving blood flow to underperfused alveoli.

Prostacyclin for the Treatment of Pulmonary Hypertension in the Adult Respiratory Distress Syndrome

Nine patients who had developed pulmonary artery hypertension during the adult respiratory distress syndrome (ARDS) were treated with an infusion of prostacyclin (PGI2) (12.5-35.0 ng.kg-1.min-1). Whether PGI2 might decrease the pulmonary capillary pressure (PCP) obtained by analysis of the pulmonary artery occlusion pressure decay curve and improve systemic oxygen delivery was examined. Gas exchange alterations induced by PGI2 were analyzed by using the multiple inert gas elimination technique. PGI2 reduced the pulmonary artery pressure from 35.6 to 28.8 mmHg (P less than 0.001) and the PCP from 22.9 to 19.7 mmHg (P less than 0.01) without changing the contribution of the pulmonary venous resistance to the total pulmonary vascular resistance. The cardiac index increased from 4.2 to 5.7 1.min-1.m-2 (P less than 0.001) due to both increased stroke volume and heart rate. Despite a marked deterioration of ventilation-perfusion (VA/Q) matching with increased true intrapulmonary shunt flow from 28.6% to 38.6% (P less than 0.01) of the cardiac output, the PaO2 was unchanged due to increased mixed venous oxygen content indicated by an augmented mixed venous PO2 (from 37.0 to 41.9 mmHg, P less than 0.01). This caused a 35% (P less than 0.001) increase of the systemic oxygen delivery rate. Thus, short-term infusions of PGI2 reduced PAP and PCP without deleterious effects on arterial oxygenation in patients with ARDS. Hence, PGI2 may be useful to lower pulmonary vascular pressures in patients with ARDS.

Positive correlation between ‘the arterial oxygen extraction tension’ and mixed venouspO2but lack of correlation between ‘the oxygen compensation factor’ and cardiac output in 38 patients

pH and blood gases were measured in simultaneous samples of arterial blood from the radial artery and mixed venous blood from the pulmonary artery using an ABL300 and OSM3 (Radiometer A/S, Denmark). Cardiac output was measured by thermodilution. The patients were suffering from chronic obstructive pulmonary disease or adult respiratory distress syndrome. The data indicate that patients respond to a decreased arterial oxygen availability by allowing the mixed venous pO2 to fall rather than by increasing the cardiac output to maintain a normal mixed venous pO2. In other words, the arterial oxygen extraction tension and the oxygen compensation factor were both highly correlated to the mixed venous pO2 but unrelated to the cardiac index. For this reason the arterial oxygen extraction tension appears to be a more relevant parameter of the overall arterial oxygen availability than the oxygen compensation factor. Comparison of the arterial and mixed venous data confirms the accuracy of the Oxygen Status Algorithm for calculating the various oxygen parameters, including the p50, the estimated 2,3-diphosphoglycerate concentration, and the estimated physiological shunt, on the basis of a single arterial blood sample.

The oxygen status of the arterial blood revised: Relevant oxygen parameters for monitoring the arterial oxygen availability

The new generation of very accurate multi-wavelength oximeters, e.g. OSM3, for in vitro measurement of the hemoglobin oxygen saturation, total hemoglobin concentration, and carboxy- and methemoglobin fractions opens new aspects of oxygen monitoring. Combined with the data from the blood gas analyzer (e.g. ABL300) these very accurate measurements allow the calculation of several derived oxygen parameters on the basis of a set of newly developed calculation algorithms. The traditional parameters obtained from an arterial sample are the oxygen tension (pO2) and the hemoglobin oxygen saturation (sO2). Clinical examples illustrate that the pO2 and the sO2 even in combination may give misleading information. The new algorithm calculates three extra oxygen parameters. 1) The oxygen extraction tension, px, defined as the tension required to extract 2.3 mmol of oxygen per liter blood. It signals the mixed venous pO2 level on the assumption that the arterio-venous oxygen difference is normal (2.3 mmol/L). 2) The concentration of extractable oxygen, cx, defined as the concentration of oxygen extracted at a tension of 5.0 kPa. 3) The oxygen compensation factor, Qx, derived as (2.3 mmol/L)/cx. It may be interpreted as the increase in cardiac output necessary to maintain a normal mixed venous pO2 of 5 kPa. These three parameters indicate the oxygen availability of the blood and summarize important properties of the arterial blood in relation to oxygen supply of the tissues, including the arterial pO2, the 'active' hemoglobin concentration (equivalent to the oxygen capacity), and the hemoglobin oxygen affinity (p50). The set of data measured with the blood gas analyzer, e.g. the ABL300 combined with the data measured with the OSM3 contains much more information than is routinely utilized. This information is extracted and summarized by our calculation algorithm. Omitting the calculation of the extra oxygen parameters involves a risk of losing valuable information.