Effect of hypoxia on pulmonary gas exchange and hemodynamics

To test the influence of hypoxia upon the pulmonary gaseous exchange and the hemodynamics of the pulmonary circulation 12 healthy test-persons at the age from 33 to 47 years (mean = 36.7 years) were submitted to a pulmonary and cardiocirculatory basis-investigation with determination of VK, VE, VO2, VCO2, Hb, PO2A/a, PCO2A/a, pH, BE, HR, ECG, PVd, PAp, SV, HZV, RL. These investigations were followed by stress examination by means of the bicycle-ergometry in four rectangular steps under conditions of normoxia from 95.5 to 97.3 kPa, x = 96.5 kPa (716 to 730 torr, mean = 723.6 torr) and of hypobarohypoxia in a low-pressure chambre at 66.5 kPa (500 torr) each of 6 min duration. Under the influence of hypoxia a PO2a-decrease in the sense of partial insufficiency could be already observed at rest under conditions of a decreased alveolar oxygen-partial-pressure. At this simultaneously increases the CO2-exhalation. At the same time was found a significant increase of the systolic peripheric and the diastolic pulmonary-arterial pressure. At the increasing step-by-step ergometric employment under conditions of the hypoxia stress were growing significance evidence of different reactions of the pulmonary and cardiocirculatory parameters occurred.     

Superoxide dismutase improves gas exchange and pulmonary hemodynamics in premature lambs

RATIONALE: Oxidant stress may increase the severity of respiratory distress syndrome (RDS) after premature birth by altering vasoreactivity and increasing lung edema, but the acute effects of superoxide dismutase (SOD) treatment on gas exchange, lung compliance (CL), and pulmonary vascular resistance in premature animals with RDS are unknown. OBJECTIVE: We studied the effects of intratracheal recombinant human SOD treatment (rhSOD) on gas exchange, CL, and pulmonary hemodynamics in 46 premature lambs with RDS. Methods: After C-section delivery, lambs were randomly assigned to treatment with SOD (2.5-10 mg/kg) with or without inhaled nitric oxide (iNO, 5 ppm), and mechanically ventilated for 4 hours. At the end of the study, pressure-volume curves and wet-dry lung weights were measured to assess CL and edema, respectively. MAIN RESULTS: Despite an initial rise in Pa(O(2)), Pa(O(2)) in control animals progressively declined over the 4-hour treatment period (Pa(O(2)) = 25.0 +/- 7.5 mm Hg at 4 hours). In comparison with control animals, early treatment with SOD at 5 and 10 mg/kg improved Pa(O(2)) at 4 hours (167 +/- 44 and 269 +/- 33 mm Hg, respectively; p < 0.05 vs. control), but did not decrease lung edema or improve CL. In contrast, late treatment with SOD did not improve Pa(O(2)). Treatment with iNO increased Pa(O(2)) (196 +/- 22 vs. 25 +/- 8 mm Hg, control animals; p < 0.01), but the response to iNO was not augmented by combined therapy (SOD + iNO). After 4 hours of ventilation with FI(O(2)) = 1.00, rhSOD treatment lowered pulmonary vascular resistance compared with control animals. CONCLUSIONS: Early intratracheal rhSOD treatment improves oxygenation in premature lambs with RDS and prevents the development of pulmonary hypertension.     

Inhalative strategies for improvement of pulmonary hemodynamics and gas exchange in sepsis and severe pulmonary hypertension

Chronic pulmonary hypertension and septic lung failure display different clinical features resulting in severe disturbances in the pulmonary circulation. In these diseases, the pulmonary bloodflow is impaired by a pathologic constriction of blood vessels that may lead to right ventricular overloading as well as serious worsening of gas exchange mainly caused by ventilation/perfusion mismatch. Various mechanisms deteriorating the vascular function may induce both an irreversible and a reversible contraction of pulmonary vessels, respectively. Two pharmacological approaches exist to reduce the vascular resistance: Reduction of the increased vascular tone by relaxation of vascular smooth muscle cells (effect of vasodilators). Inhibition of thrombus-mediated obliteration of the lung perfusion by use of anticoagulant and fibrinolytic drugs. Prevention of the structural reorganization of pulmonary vessels (vascular remodeling) by use of vasodilators with anti-inflammatory and anti-proliferative potency such as prostanoids. The systemic (intravenous or oral) application of vasodilative agents in sepsis and chronic pulmonary hypertension has, however, important side effects: Antagonism of the hypoxic pulmonary vasoconstriction aggravates the ventilation/perfusion mismatch (decrease in arterial oxygenation). Side effects of these vasodilators (systemic hypotension). The inhalative route of application is superior because of the pulmonary enrichment of the applied agent (pulmonary selectivity). Furthermore, a preferential deposition in the well-ventilated areas of the lung is achieved (intrapulmonary selectivity). Thus, the decrease in pulmonary-vascular resistance is paralleled by both optimized ventilation-perfusion matching and subsequently improved gas exchange. First clinical studies with inhaled nitric oxide and aerosolized prostacyclin have been performed in intubated and mechanically ventilated patients with septic lung failure. At present, the use of the long-acting prostacyclin analogue ilomedin for ambulant treatment of patients with chronic pulmonary hypertension is under investigation.     

Effects of vasodilators on pulmonary hemodynamics and gas exchange in left ventricular failure

Nitroprusside (NP) has been shown to improve left ventricular function in patients with congestive heart failure, but despite an increased cardiac output and decreased pulmonary capillary pressure, arterial oxygen tension (P_aO₂) may fall. In order to determine the mechanism of this hypoxemia, and to determine if similar effects occur with non-parenteral vasodilators, hemodynamic, respiratory, and blood gas responses to NP, hydralazine (H), and hydralazine combined with isiosorbide dinitrate (H+N) were studied in 10 patients with left ventricular failure. At the dosages used, all three drug regimens increased cardiac output equivalently, but pulmonary vascular responses differed. NP and H+N decreased mean pulmonary artery pressure, pulmonary wedge pressure, and pulmonary arteriolar resistance, while H did not. NP decreased P_aO₂ by 10.4 mm. Hg (p < .01) and H+N decreased it by 5.3 mm. Hg (p < .06) while H did not alter P_aO₂. Arteriolar-alveolar oxygen gradient increased with NP (150 ± 39 per cent, p < .01) and with H+N (73 ± 23 per cent, p < .01) but not H alone (51 ± 16 per cent). Similarly, per cent change in venous admixture increased on NP (28.7 ± 3.3 to 38.5 ± 3.1 per cent, p < .01) and H+N (28.1 ± 3.3 to 36.8 ± 3.5 per cent, p < .01) but not H alone (28.1 ± 3.3 to 31.5 ± 4.1 per cent). There was no increase in arterial carbon dioxide tension or change in pulmonary function studies with any of the drugs. Due to the increase in cardiac output, oxygen delivery index (cardiac output times arterial oxygen content) increased with each regimen despite the changes in P_aO₂. Changes in arteriolar-alveolar oxygen gradient correlate with the changes in pulmonary arteriolar resistance. Thus vasodilators which have prominent pulmonary vascular effects can decrease P_aO₂ in patients with congestive heart failure, and this effect is most likely due to increasing ventilation-perfusion inequities.     

Disorders of hemodynamics and pulmonary gas exchange in the acute period of myocardial infarct

In 40 patients with massive myocardial infarction, the central hemodynamics was examined by probing the right-sided chambers of the heart and the pulmonary artery. The cardiac output was measured by thermodilution. The gas exchange (respiratory minute volume, capnography, gas analysis of arterial and mixed venous blood) was explored. Arterial hypoxemia was found to be associated with increased intrapulmonary blood shunting in patients with acute myocardial infarction complicated by congestive heart failure. Deterioration of arterial hypoxemia was promoted by a combination of increased overall pulmonary shunting and decreased residual venous oxygenation. Abnormalities in the ventilation-perfusion relations are of great importance.     

Effects of sublingual nitroglycerin on resting pulmonary gas exchange and hemodynamics in man.

Simultaneous hemodynamic, ventilation and blood gas measurements were performed in 19 males during cardiac catheterization for evaluation of chest pain syndrome before and 3 to 5 min after 0.4 mg sublingual nitroglycerin. Pulmonary arterial pressures and total pulmonary vascular resistance fell (P less than 0.001 for both), and mean systemic arterial pressure decreased (P less than 0.05). However, peripheral vascular resistance, cardiac output, and mixed venous PO2 did not change. Total and tidal ventilation, PCO2, pH, and base excess remained unchanged. However, the arterial PO2 decreased from a mean of 80 +/- 3 (SEM) to 72 +/- 2 mm Hg (P less than 0.001) and mean venous admixture increased from 8.8 +/- 1% to 12.6 +/- 1.5% (P less than 0.001). The alveolar arterial PO2 difference increased (P less than 0.001) and the dead space tidal volume ratio rose (P less than 0.05). We conclude that the decrease in arterial PO2 following sublingual nitroglycerin is caused by redistribution of pulmonary blood flow with imbalance in ventilation-perfusion relationships or shunting.     

Prostaglandin F2 alpha and indomethacin in hepatogenic pulmonary angiodysplasia. Effects on pulmonary hemodynamics and gas exchange

We treated a 68-year-old man with cirrhosis of the liver associated with moderate hypoxemia. Contrast-enhanced echocardiography revealed late opacification of the left ventricle, and pulmonary perfusion imaging with 99mTc macroaggregated albumin showed evidence of a significant uptake in both lungs and in the liver, spleen, and kidneys. Right cardiac catheterization revealed pulmonary hypotension, low pulmonary vascular resistance, and high cardiac output. We administered prostaglandin F2 alpha intravenously (0.2 microgram/kg/min for 30 minutes) and indomethacin orally (75 mg/day for three days). There was some degree of resolution of the hypoxemia and increases in both pulmonary arterial pressure and pulmonary vascular resistance. These findings suggest that the pathophysiology of hepatogenic pulmonary angiodysplasia is a reversible intrapulmonary vascular dilatation. These conditions can to some extent be modulated by vasoactive substances such as prostaglandins or other eicosanoids.     

Forced convection modulates gas exchange in cnidarians

Boundary layer thickness is a potentially important component of the diffusive pathway for gas exchange in aquatic organisms. The soft coral Alcyonium siderium (Octocorallia) and sea anemone Metridium senile (Actiniaria) exhibit significant increases in respiration with water flow over a range of Reynolds numbers encountered subtidally. A nondimensional mass transfer analysis of the effect of forced convection demonstrates the importance of the state of the organism's boundary layer in regulating metabolism in these invertebrates. Flow-modulated gas exchange may limit secondary productivity in subtidal environments.     

Effects of indomethacin on pulmonary hemodynamics and gas exchange in patients with pulmonary artery hypertension, interference with hydralazine

To assess the ability of indomethacin (Indo) to influence pulmonary vascular tone in patients with chronic lung disease, we studied the hemodynamic and gas exchange alterations induced by a 50-mg indomethacin infusion in 10 patients suffering from varying degrees of pulmonary artery hypertension and hypoxemia. The most pronounced effects were observed 3 h after Indo administration. Mean systemic arterial pressure (Psa) increased from 76 +/- 4 to 86 +/- 4 mm Hg (p less than 0.01), whereas mean pulmonary arterial pressure (Ppa) was unchanged. The cardiac index (CI) decreased from 3.1 +/- 0.2 to 2.8 +/- 0.2 L/min/m2 (p less than 0.02) because of the reduced heart rate, which decreased from 86 +/- 5 to 80 +/- 4 beats/min (p less than 0.05). Systemic and pulmonary vascular resistance indexes increased, respectively, from 22 +/- 2 to 27.5 +/- 2 U/m2 (p less than 0.001) and from 11.9 +/- 2 to 13.4 +/- 2 U/m2 (p less than 0.05). We measured an increase in PaO2, from 49.5 +/- 4 to 57.5 +/- 4 mm Hg (p less than 0.001) simultaneously with a reduced venous admixture, from 39.5 +/- 4 to 30.5 +/- 3% (p less than 0.001). The calculated PO2 uptake was unchanged, but mixed venous O2 tension increased from 30.5 to 33.5 mm Hg (p less than 0.01). Because Indo may interfere with the hypotensive effect of hydralazine and because hydralazine has been proposed in the treatment of patients with pulmonary hypertension, 7 of these patients also received 0.35 mg/kg hydralazine and Indo plus hydralazine (Indo + H) injected simultaneously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Repetitive hemodilution in chronic obstructive pulmonary disease and pulmonary hypertension: effects on pulmonary hemodynamics, gas exchange, and exercise capacity.

BACKGROUND: In cor pulmonale associated with severe chronic obstructive pulmonary disease (COPD), disturbances of pulmonary microcirculation may contribute significantly to hypoxemia, pulmonary hypertension, and exercise intolerance. OBJECTIVE: It was tested whether reduction of blood viscosity induced by repetitive hemodilution might improve pulmonary hemodynamics and oxygen uptake. METHODS: Seven patients with stable COPD (forced expiratory volume in 1 s 33 +/- 3 % of predicted, means +/- SE) and pulmonary hypertension were phlebotomized 5-6 times over a period of 3 months with substitution of 6% hydroxyethyl starch (molecular weight 40, 000). This resulted in a stepwise reduction of the hematocrit from 53.3 +/- 2.6 to 45.8 +/- 3.1% and a reduction of whole blood viscosity from 9.8 +/- 0.6 to 8.8 +/- 0.7 mPa x s at a shear rate of 2.0 s-1. Before and after the treatment period, patients underwent cardiopulmonary exercise testing and right heart catheterization. RESULTS: Mean pulmonary artery pressure (PAm) decreased from 30 +/- 3 to 22 +/- 2 mm Hg and arterial oxygen partial pressure (PaO2) increased from 63.2 +/- 2.2 to 71.8 +/- 3.7 mm Hg at rest. During peak exercise, PAm decreased from 59 +/- 7 to 53 +/- 7 mm Hg and PaO2 increased from 54.0 +/- 5.7 to 63.2 +/- 2.4 mm Hg after hemodilution. Peak oxygen consumption rose from 573 +/- 84 to 750 +/- 59 ml x min-1, corresponding to an increase in cardiac index from 4.25 +/- 0.5 to 5.88 +/- 0.76 liters x min-1 x m-2. Pulmonary vascular resistance fell from 345 +/- 53 to 194 +/- 32 dyn x s x cm-5. The patients' peak exercise capacity increased from 9.2 +/- 2. 0 before to 13.5 +/- 3.2 kJ at the end of the study (p < 0.05 for all differences, paired t test). CONCLUSION: The findings suggest that a prolonged improvement of pulmonary microcirculation by reducing blood viscosity may improve pulmonary gas exchange, central hemodynamics, and exercise tolerance in patients with severe COPD and pulmonary hypertension.     

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.     

Effects of hydralazine on hemodynamics, ventilation, and gas exchange in patients with chronic obstructive pulmonary disease and pulmonary hypertension

Reports on hemodynamic effects of hydralazine on pulmonary hypertension (primary or secondary) usually include cases with severe disease or with mixed varieties of pulmonary vascular disease. Serious side effects and death have been reported. Effects of this drug on ventilation and gas exchange are unknown. We investigated the short-term effects of hydralazine treatment on hemodynamics, ventilation, and gas exchange in a relatively homogeneous group of patients with severe chronic obstructive pulmonary disease and moderate exertional pulmonary hypertension (mean pulmonary artery pressure, 43 +/- 3 mmHg). Hydralazine produced significant improvement in cardiac index, total pulmonary resistance, and oxygen transport. We also observed significant improvement in alveolar ventilation (mean PaCO2, decreased from 47 +/- 2 to 40 +/- 3 mmHg at rest and from 51 +/- 3 to 43 +/- 3 mmHg during exercise). The severe exertional hypoxemia of the group (mean PaO2, 48 +/- 2 mmHg) improved significantly (mean PaO2, 57 +/- 3 mmHg). Four of 11 patients showed increased exercise tolerance after hydralazine. This change is probably related to a combined improvement in hemodynamics plus a newly observed improvement in gas exchange and ventilation. Three of 14 patients could not tolerate hydralazine because of marked tachycardia. Serious side effects were not observed in the remaining group.     

The effects of urapidil therapy on hemodynamics and gas exchange in exercising patients with chronic obstructive pulmonary disease and pulmonary hypertension

To examine the hemodynamic changes induced by vasodilator therapy with urapidil during exercise in patients with chronic obstructive pulmonary disease (COPD) and their potential impact on symptom-limited maximal oxygen consumption, we studied 12 clinically stable patients using a randomized, crossover design. Placebo or urapidil (60 mg orally thrice a day) was given during 48 h preceding each incremental maximal exercise testing. Urapidil compared to placebo consistently lowered the pulmonary artery pressure either at rest from 29 +/- 2.5 to 24 +/- 1.5 mm Hg (p less than 0.001) or during exercise from 55 +/- 3 to 46 +/- 2 mm Hg (p less than 0.01). At rest, the systemic arterial pressure was reduced from 97.5 +/- 4 to 88.5 +/- 3 mm Hg (p less than 0.001) with no significant difference in heart rate or cardiac index. During exercise, systemic arterial pressure decreased from 135 +/- 4 to 119 +/- 3 mm Hg (p less than 0.001). As compared to placebo, urapidil tended to increase the cardiac index from 6.1 +/- 0.4 to 6.6 +/- 0.4 L/min.m2 (NS) and to decrease heart rate, from 122 to 116 beats/min (NS); the resulting stroke volume index increased with urapidil from 49 +/- 3 to 57 +/- 4 ml/m2 (p less than 0.01); at rest, urapidil did not induce alteration in gas exchange, while during exercise, C(a-v)O2 decreased from 8.6 +/- 0.5 to 7.7 +/- 0.4 vol% (p less than 0.01), SVO2 increased from 39.5 +/- 2 to 44.5 +/- 1.5% (p less than 0.01), and SaO2 from 82 +/- 2 to 85 +/- 2% (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of inspired oxygen tension on hemodynamics and pulmonary gas exchange in patients undergoing coronary artery surgery

This study was designed to compare the effect of intraoperative administration of 100% oxygen (F₁O₂ = 1.0) with 50% O₂ (air-O₂ mixture, F₁O₂ = 0.5) on cardiovascular and respiratory parameters in adults undergoing coronary artery surgery. Nineteen patients were assigned to receive either F₁O₂ = 1.0 (group A) or F₁O₂ = 0.5 (group B) in a randomized fashion. Anesthesia was induced with fentanyl (15 μg/kg) and diazepam (0.1 to 0.2 mg/kg) and maintained with fentanyl (total dose 501μg/kg) and isoflurane. A bubble oxygenator (F₁O₂ = 1.0) was used during cardiopulmonary bypass (CPB) in both groups. Hemodynamic and respiratory profiles were determined at specific intervals prior to incision, following CPB, and postoperatively. Patients ventilated with F₁O₂ = 0.5 were well oxygenated at measured intraoperative intervals (PaO₂ range 90 to 268 mmHg, saturation 95% to 99%), with adequate mixed venous O₂ levels (PvO₂ range 35 to 65 mmHg, saturation 63% to 89%). Compared with patients receiving F₁O₂ = 1.0, those receiving F₁O₂ = 0.5 had significantly greater increases in cardiac index (CI) (mean ± SEM B: 87% ± 18% v A: 26% ± 12%) and stroke index (B: 10% ± 5% increase v A: 14% ± 7% decrease), and a larger decrease in peripheral resistance (B: 38% ± 7% v A:4% ± 12%) at postoperative day 1 relative to preincision values (P < 0.05). At postoperative day 1, both groups had an elevated alveolar-to-arterial O₂ gradient (A: 55% ± 19% v B: 48% ± 17% increase) and shunt fraction (A: 58% ± 28% v B: 99% ± 35% increase). Although O₂ consumption increased similarly in both groups at postoperative day 1 relative to preincision values (A: 91% ± 23% v B: 113% ± 16%), O₂ delivery was enhanced more in group B than in group A (67% ± 17% v 20% ± 13% increase, respectively, P < 0.05). The data suggest that significant hemodynamic derangements may occur with hyperoxia and that intraoperative administration of 50% O₂ may be more appropriate during coronary artery surgery.     

Effect of fast vs slow intralipid infusion on gas exchange, pulmonary hemodynamics, and prostaglandin metabolism

Intralipid (20 percent, 500 ml) was infused fast (5 h) or slow (10 h) randomly in patients with lung injury to relate changes in plasma prostaglandin (PG) concentrations to gas exchange and pulmonary hemodynamics. Data were collected at baseline, midpoint of infusion, and 2 h following infusion. Vasodilator and vasoconstrictor PG metabolites, 6-keto-PGF1 alpha, and thromboxane B2, respectively, were measured in radial arterial blood samples. Slow Intralipid infusion increased shunt fraction (QS/QT) without changing mean pulmonary artery pressure (MPAP), whereas fast Intralipid infusion increased MPAP without changing QS/QT. Prostaglandin levels did not change significantly during either infusion. However, in both groups when the PG substrate was removed, hemodynamic and metabolite values decreased in parallel. In conclusion, we were unable to demonstrate a cause and effect relationship between plasma levels of 6-keto-PGF1 alpha and thromboxane B2 and the observed pulmonary hemodynamic response to slow or fast Intralipid infusion.     

Pulmonary gas exchange and central hemodynamics at rest and during exercise in patients with chronic obstructive pulmonary disease

Right-heart catheterization and ergometry with arterial and mixed venous blood gas analysis were performed in 27 patients with a wide range of chronic obstructive pulmonary diseases. The purpose of the examination was to evaluate the risk in patients for lung surgery or to detect additional heart diseases. Patients who developed exertional hypoxia (group 1) were compared with others who did not (group 2). In all patients the steady-state maximal workload was determined by ventilatory dysfunction. Both groups had normal values for mixed venous pO2 and normal increase of the circulatory parameters during exercise. The patients with exertional hypoxia differed from the others in that they showed no decrease of venous admixture and alveolar-arterial oxygen gradient. In addition, these patients had increasing pCO2 values at rest compared with exercise, indicating alveolar hypoventilation and ventilation-perfusion mismatching. Because of the good correlation of the absolute values of FEV1 (forced expiratory volume in 1 s) with pulmonary artery pressures, parameters of gas exchange and working capacity, this lung function parameter seems to have a central role in predicting the functional state of patients with chronic obstructive disease. Ergometry and blood gas analysis should be performed in addition because these values cannot be predicted with the calculated postoperative FEV1.