Decline In PaO2 Research Articles

Colonic oxygen microbubbles augment systemic oxygenation and CO2 removal in a porcine smoke inhalation model of severe hypoxia

Inhalation injury can lead to pulmonary complications resulting in the development of respiratory distress and severe hypoxia. Respiratory distress is one of the major causes of death in critically ill patients with a reported mortality rate of up to 45%. The present study focuses on the effect of oxygen microbubble (OMB) infusion via the colon in a porcine model of smoke inhalation-induced lung injury. Juvenile female Duroc pigs (n = 6 colonic OMB, n = 6 no treatment) ranging from 39 to 51 kg in weight were exposed to smoke under general anesthesia for 2 h. Animals developed severe hypoxia 48 h after smoke inhalation as reflected by reduction in SpO2 to 66.3 ± 13.1% and PaO2 to 45.3 ± 7.6 mmHg, as well as bilateral diffuse infiltrates demonstrated on chest X-ray. Colonic OMB infusion (75–100 mL/kg dose) resulted in significant improvements in systemic oxygenation as demonstrated by an increase in PaO2 of 13.2 ± 4.7 mmHg and SpO2 of 15.2 ± 10.0% out to 2.5 h, compared to no-treatment control animals that experienced a decline in PaO2 of 8.2 ± 7.9 mmHg and SpO2 of 12.9 ± 18.7% over the same timeframe. Likewise, colonic OMB decreased PaCO2 and PmvCO2 by 19.7 ± 7.6 mmHg and 7.6 ± 6.7 mmHg, respectively, compared to controls that experienced increases in PaCO2 and PmvCO2 of 17.9 ± 11.7 mmHg and 18.3 ± 11.2 mmHg. We conclude that colonic delivery of OMB therapy has potential to treat patients experiencing severe hypoxemic respiratory failure.

Fractal dimension in CT low attenuation areas is predictive of long-term oxygen therapy initiation in COPD patients: Results from two observational cohort studies.

Some chronic obstructive pulmonary disease (COPD) patients develop hypoxemia with disease progression, with some even requiring long-term oxygen therapy (LTOT). Lung function, especially diffusing capacity, and the annual decline in PaO2, are reported to be predictive factors of chronic respiratory failure. However, the association between lung morphometry evaluated using computed tomography (CT) images and LTOT initiation is unknown. We retrospectively evaluated the relationship between clinical indices, including pulmonary function, body mass index (BMI), and CT parameters, at baseline and LTOT initiation in two prospective COPD cohorts. In the Nara Medical University cohort (n=76), the low attenuation area (LAA) and its fractal dimension (fractal D) were adapted as the indices for parenchymal destruction in CT images. The association between these CT measurements and LTOT initiation was replicated in the Kyoto University cohort (n=130). In the Nara Medical University cohort, lower BMI (hazard ratio [HR]:0.70, p=0.006), lower % diffusing capacity (%DLCO) (HR: 0.92, p=0.006), lower %DLCO/VA (HR, 0.90, p=0.008), higher RV/TLC (HR, 1.26, p=0.012), higher LAA% (HR: 1.18, p=0.001), and lower fractal D (HR: 3.27×10-8, p<0.001) were associated with LTOT initiation. Multivariate analysis in the Kyoto University cohort confirmed that lower %DLCO and lower fractal D were independently associated with LTOT initiation, whereas LAA% was not. Fractal D, which is the index for morphometric complexity of LAA in CT analysis, is predictive of LTOT initiation in COPD patients.

Annual decline in arterial blood oxygen predicts development of chronic respiratory failure in COPD with mild hypoxaemia: A 6-year follow-up study.

Chronic respiratory failure (CRF) with hypoxaemia is an important pathophysiology in patients with chronic obstructive pulmonary disease (COPD), and existing mild hypoxaemia may be a sign of future CRF development. However, little is known about the trajectory of partial arterial pressure of oxygen (PaO2 ) decline in patients with COPD. We assessed decline in PaO2 and the impact of short-term reductions in PaO2 to predict future decline in PaO2 . A total of 172 outpatients with COPD from a prospective cohort study were enrolled. Pulmonary function tests and arterial blood gas (ABG) analyses were conducted at baseline and 1 year after enrolment and changes in PaO2 (ΔPaO2 ) and other parameters were calculated. Survival and incidence of CRF (as assessed by prescription of long-term home oxygen therapy) were monitored for 6 years. A total of 164 patients completed the observation period and 101 patients had mild hypoxaemia (PaO2 < 80 Torr) at baseline. No patients with normal PaO2 (≥80 Torr) developed CRF, and 10 patients with mild hypoxaemia developed CRF in 6 years. Baseline airflow limitation and diffusion capacity were significantly associated with development of CRF. Receiver-operating characteristic curve analysis showed that ΔPaO2 of -3.05 Torr/year is a useful cut-off value to predict development of CRF in 6 years (hazard ratio (HR): 12.6, 95% CI: 3.48-58.73, P < 0.0001). Patients with COPD and mild hypoxaemia may benefit from repeat ABG after 1 year. Although PaO2 trajectories widely varied, significant annual changes in PaO2 of at least -3.0 Torr/year were predictive of CRF development.

Pulmonary function in aging

Aging generates four important changes in the structure and function of the respiratory system. There is a reduction in the elastic recoil of the lung causing "senile emphysema", a condition characterized by reduction in the alveolar surface area without alveolar destruction, which is associated with hyperinflation, increased lung compliance and reduction in alveolar-capillary diffusing capacity. There is a decrease in the compliance of the chest watt, due to calcification of its articulations, dorsal kyphosis and "barrel chest". There is a decrease in the strength of respiratory muscles which correlates with cardiac Index, nutritional status and hyperinflation, and there is a reduction in the ventilatory response to hypoxia and hypercapnia as well as in the perception of increased airway resistance. The increased static lung compliance combined with the decreased chest watt compliance leads to an increase in the functional residual capacity with aging. On the other hand, the loss of alveolar and airways elastic recoil combined with the reduction in the strength of the expiratory muscles, leads to an increase in residual volume and decreased maximal expiratory airflow rates and vital capacity. Despite these changes, the respiratory system maintains an adequate gas exchange at rest and during exercise during the whole life span, showing a normal PaCO2 and a slight decline in PaO2 (-0,3 mmHg per year) which is attenuated to become almost undetectable over the age of 70.

Función respiratoria en la senectud

Aging generates four important changes in the structure and function of the respiratory system. There is a reduction in the elastic recoil of the lung causing "senile emphysema", a condition characterized by reduction in the alveolar surface area without alveolar destruction, which is associated with hyperinflation, increased lung compliance and reduction in alveolar-capillary diffusing capacity. There is a decrease in the compliance of the chest watt, due to calcification of its articulations, dorsal kyphosis and "barrel chest". There is a decrease in the strength of respiratory muscles which correlates with cardiac Index, nutritional status and hyperinflation, and there is a reduction in the ventilatory response to hypoxia and hypercapnia as well as in the perception of increased airway resistance. The increased static lung compliance combined with the decreased chest watt compliance leads to an increase in the functional residual capacity with aging. On the other hand, the loss of alveolar and airways elastic recoil combined with the reduction in the strength of the expiratory muscles, leads to an increase in residual volume and decreased maximal expiratory airflow rates and vital capacity. Despite these changes, the respiratory system maintains an adequate gas exchange at rest and during exercise during the whole life span, showing a normal PaCO2 and a slight decline in PaO2 (-0,3 mmHg per year) which is attenuated to become almost undetectable over the age of 70.

The Effects of Airway Pressure and Inspiratory Time on Bacterial Translocation

Mechanical ventilation with high peak inspiratory pressure (PIP) induces lung injury and bacterial translocation from the lung into the systemic circulation. We investigated the effects of increased inspiratory time on translocation of intratracheally inoculated bacteria during mechanical ventilation with and without extrinsic positive end-expiratory pressure (PEEP). Rats were ventilated in pressure-controlled mode with 14 cm H2O PIP, 0 cm H2O PEEP, I:E ratio 1/2, and Fio2 1.0. Subsequently, 0.5 mL of 10(5) cfu/mL Pseudomonas aeruginosa was inoculated through tracheostomy and rats were randomly assigned to six groups; two low-pressure groups (LP)1/2, 14 cm H2O PIP, 0 cm H2O PEEP, I:E = 1/2, and LP2/1 14 cm H2O PIP, 0 cm H2O PEEP, I:E = 2/1; two high-pressure groups (HP)1/2, 30 cm H2O PIP, 0 cm H2O PEEP, I:E = 1/2, and HP2/1, 30 cm H2O PIP, 0 cm H2O PEEP, I:E = 2/1; two HP PEEP groups (HPP)1/2, 30 cm H2O PIP, 10 cm H2O PEEP, I:E = 1/2, and HPP2/1, 30 cm H2O PIP, 10 cm H2O PEEP, I:E = 2/1. Blood cultures were obtained every 30 min. The rats were killed and their lungs were processed. When compared with baseline values, Pao2 decreased in the LP1/2, LP2/1, HP1/2, and HP2/1 groups at the last time point, but the decline in Pao2 reached statistical significance in only the HP1/2 group. The bacterial translocation rate was greater in group HPP2/1 than group HPP1/2 (P = 0.01). We found that high PIP, with or without prolonged inspiratory time, increased the rate of bacterial dissemination. PEEP prevented bacterial translocation in the high PIP group. However, the protective effect of PEEP was lost when inspiratory time was prolonged.

Fibreoptic bronchoscopy in sedated infants facilitated by an airway endoscopy mask

Fibreoptic bronchoscopy (FB) is frequently associated with a decline in PaO2, whose degree and duration can be substantial especially in infants. The effect of a face mask, which allows the administration of 100% oxygen and continuous positive airway pressure during FB, on the incidence and severity of hypoxaemia was studied in thirty-one consecutive infants. Sedation was provided by intravenous propofol titrated to allow patient comfort. A transient fall in SpO2 <95% was recorded in 6/31 patients during endoscopy of the upper airway (lasting 1.6+/-1.1 min) and in 11/31 patients during endoscopy of the lower airways (lasting 1.4+/-1.1 min). Capillary blood gas analysis before and after endoscopy of the lower airways demonstrated an increase in the PCO2 6.4+/-1.3 to 7.3+/-1.4 kPa (49+/-10 to 56+/-11 mmHg). The risk of hypoxaemia in sedated infants breathing spontaneously is low when 100% oxygen and continuous positive airway pressure are administered during FB

Delayed administration of inhaled nitric oxide preserves alveolar-capillary membrane integrity in porcine gram-negative sepsis.

To determine the effect of delayed administration of inhaled nitric oxide (NO) on acute lung injury after the onset of gram-negative sepsis. Nonrandomized controlled study. University medical center laboratory. Yorkshire swine. Five groups of swine were anesthetized, mechanically ventilated, and studied for 5 hours. After surgical preparation, control (n = 10) and NO-treated control (n = 6) animals received a 1-hour infusion of sterile saline solution. Sepsis was induced with a 1-hour intravenous infusion of live Pseudomonas aeruginosa. Untreated animals with sepsis (n = 10) received no treatment. Inhaled NO at 20 ppm was administered to NO30-treated animals with sepsis (n = 7) and NO60-treated animals with sepsis (n = 8) beginning at 30 and 60 minutes after bacterial infusion was begun, respectively. Systemic and pulmonary hemodynamics, arterial blood gas determination, bronchoalveolar lavage protein and neutrophil content, neutrophil oxidant burst, lung myeloperoxidase content, and scanning electron micrographic studies. A progressive, significant (P < .05) decline in PaO2 developed in untreated animals with sepsis, which was prevented in NO30- and NO60-treated animals with sepsis. A significant (P < .05) increase in bronchoalveolar lavage protein and neutrophil counts compared with baseline values was observed in untreated animals with sepsis, indicating acute lung injury. These variables exhibited no notable increase in NO30- and NO60-treated animals with sepsis and were significantly (P < .05) reduced compared with untreated animals with sepsis. The lung myeloperoxidase content was significantly (P < .05) elevated at 5 hours in all groups with sepsis compared with baseline values and the control and NO-treated control groups. The total phorbol myristate acetate-induced polymorphonuclear leukocyte oxidant burst at 5 hours was significantly (P < .05) decreased in the NO30- and NO60-treated animals with sepsis compared with untreated animals with sepsis. Untreated and NO30- and NO60-treated animals with sepsis showed a significant (P < .05) increase in pulmonary artery pressure at 30 minutes, followed by a progressive decline. These changes were significant (P < .05) compared with baseline values and the control groups. No significant (P < .05) difference in pulmonary artery pressure or systemic arterial pressure was found at any time between untreated and NO30- and NO60-treated animals with sepsis. The delayed administration of inhaled NO preserves alveolar-capillary membrane integrity in this porcine model of gram-negative sepsis. The inhibition of neutrophil transendothelial migration, rather than neutrophil rolling or tight adhesion, may be a critical mechanism by which inhaled NO produces this effect. Decreased oxidant production by activated neutrophils may be a secondary mechanism by which inhaled NO reduces acute lung injury.

Arterial Blood Gas Changes During Breath-holding From Functional Residual Capacity

Breath-holding serves as a model for studying gas exchange during clinical situations in which cessation of ventilation occurs. We chose to examine the arterial blood gas changes that occurred during breath-holding, when breath-holding was initiated from functional residual capacity (FRC) while breathing room air. Eight normal subjects who had a radial artery catheter placed for another study were taught to breath-hold on command from FRC. FRC was determined using respiratory inductance plethysmography. Arterial blood gas specimens were obtained at 5-s intervals until the termination of breath-holding. The average breath-holding time (+/-SD) was 35 (+/-10 s). The PaO2, PaCO2, and pH values were plotted against time and individually fit to logistic equations for each subject. The arterial PaO2 fell by a mean of 50 mm Hg during the first 35 s of breath-holding under these conditions, while the arterial PCO2 rose by a mean of 10.2 mm Hg during the first 35 s and the pH fell by a mean of 0.07 in the first 35 s. The rapid decline in PaO2 is greater than that previously reported using different methods and should be considered in clinical situations in which there is an interruption of oxygenation and ventilation at FRC while breathing room air. The changes in PaCO2 and pH are similar to those previously reported in paralyzed apneic patients.

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock: Br J Pharmacol 1995; 114/2: 363–368

1 The present investigation compares the effects of intravenous infusion of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) with that of an inhalation with NO gas in a porcine model of endotoxin (lipopolysaccharide, LPS) shock. In addition, the effects of the combination of these two treatments were also investigated. 2 Male pigs were anaesthetized and instrumented for the measurement of haemodynamic parameters. Blood samples were withdrawn at different time intervals for determination of blood gases, pH, and plasma levels of nitrite/nitrate and tumour necrosis factor. 3 Endotoxin infusion (15 μg kg−1 h−1 for 3 h) caused a progressive fall in mean arterial blood pressure (MABP) and cardiac output (CO) and a biphasic increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistence (PVR). A continuous infusion of l-NMMA (0.1 mg kg−1 min−1) significantly attenuated the fall in MABP, but did not affect MPAP, CO and PVR. NO-inhalation (50 p.p.m.) did not affect MABP, but significantly blunted the biphasic increase in MPAP and PVR and significantly delayed the fall in CO. The combination of l-NMMA infusion (0.1 mg kg−1 min−1) with NO-inhalation (50 p.p.m.) completely prevented the fall in MABP, significantly improved CO, and attenuated the biphasic increase in MPAP and PVR. 4 Endotoxin also caused a decline in Pao2 and a rise of Paco2. Infusion of l-NMMA neither affected the fall in Pao2 nor the increase in Paco2. In contrast, inhalation with NO gas alone as well as the combined administration of l-NMMA infusion and NO-inhalation completely prevented the fall in Pao2 and significantly protected against the increase in Paco2. 5 Infusion of endotoxin for 180 min resulted in a mortality of 58%, which was not affected by l-NMMA (63%). In contrast, treatment of LPS-animals with either NO-inhalation alone or NO-inhalation plus l-NMMA completely prevented mortality. 6 This investigation demonstrates that treatment with NO-inhalation, in order to prevent the dramatic increase in MPAP, PVR and the alterations in peripheral blood gases combined with systemic l-NMMA to improve systemic MABP and thus organ perfusion, may be a new therapeutic regimen in the treatment of septic shock.

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock.

1. The present investigation compares the effects of intravenous infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) with that of an inhalation with NO gas in a porcine model of endotoxin (lipopolysaccharide, LPS) shock. In addition, the effects of the combination of these two treatments were also investigated. 2. Male pigs were anaesthetized and instrumented for the measurement of haemodynamic parameters. Blood samples were withdrawn at different time intervals for determination of blood gases, pH, and plasma levels of nitrite/nitrate and tumour necrosis factor. 3. Endotoxin infusion (15 micrograms kg-1 h-1 for 3 h) caused a progressive fall in mean arterial blood pressure (MABP) and cardiac output (CO) and a biphasic increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). A continuous infusion of L-NMMA (0.1 mg kg-1 min-1) significantly attenuated the fall in MABP, but did not affect MPAP, CO and PVR. NO-inhalation (50 p.p.m.) did not affect MABP, but significantly blunted the biphasic increase in MPAP and PVR and significantly delayed the fall in CO. The combination of L-NMMA infusion (0.1 mg kg-1 min-1) with NO-inhalation (50 p.p.m.) completely prevented the fall in MABP, significantly improved CO, and attenuated the biphasic increase in MPAP and PVR. 4. Endotoxin also caused a decline in PaO2 and a rise of PaCO2. Infusion of L-NMMA neither affected the fall in PaO2 nor the increase in PaCO2. In contrast, inhalation with NO gas alone as well as the combined administration of L-NMMA infusion and NO-inhalation completely prevented the fall in Pao2 and significantly protected against the increase in Paco2.5. Infusion of endotoxin for 180 min resulted in a mortality of 58%, which was not affected by L-NMMA (63%). In contrast, treatment of LPS-animals with either NO-inhalation alone or NO inhalation plus L-NMMA completely prevented mortality.6. This investigation demonstrates that treatment with NO-inhalation, in order to prevent the dramatic increase in MPAP, PVR and the alterations in peripheral blood gases combined with systemic L-NMMAto improve systemic MABP and thus organ perfusion, may be a new therapeutic regimen in the treatment of septic shock.

An Analysis of Sequential Physiologic Changes in Hypoxic Cor Pulmonale during Long-term Oxygen Therapy

Physiologic changes were studied retrospectively in 37 patients with hypoxic cor pulmonale who died during long-term oxygen therapy (LTOT). The subjects were assessed during periods of clinical stability for each year on LTOT. At the onset of treatment, their mean age (+/- SEM) was 60.0 +/- 1.3 years, and at the time of death, they were aged 65.0 +/- 1.3 years. The median duration of LTOT was five years. For each year leading up to death, mean values of FEV1, PaO2, and PaCO2 were obtained. A rate of decline of FEV1 of 73 +/- 10 ml/yr was observed, and this was accompanied by a decline in PaO2 of 0.47 +/- 0.01 kPa/yr. Patients died with a mean FEV1 of 0.55 +/- 0.04 L and a PaO2 of 5.1 +/- 0.2 kPa. A small rise in PaCO2 occurred, on average 0.25 +/- 0.09 kPa/yr, throughout the study, but accelerating in many cases during the three years before death. Hypoxic cor pulmonale appears to be associated with a rapid deterioration in airway function, a steady decline in PaO2, and a slow rise in PaCO2 during the years leading up to death. These physiologic changes measured in a stable clinical state while breathing air appear to occur in spite of LTOT. The LTOT may merely prevent death from episodes of severe hypoxemia while the pathophysiologic changes in the lung progress. Hence the benefit to be expected from LTOT is only temporary. Generally, those patients with lower levels of FEV1 will obtain diminishing clinical benefit, inversely related to the severity of airflow obstruction at the time of commencement of LTOT.

Endotracheal Suctioning-Induced Heart Rate Alterations

The purpose of the experimental study was to identify mechanical and/or neural factors contributing to the heart rate alterations associated with endotracheal suctioning (ETS). Effects of catheter insertion alone and catheter insertion with the application of negative pressure on the partial pressure of arterial oxygen (PaO2) and heart rate prior to and following vagal blockade with atropine were examined. Eleven newborn swine less than 24 h of age were randomly exposed to (a) suction catheter insertion alone and (b) suction catheter insertion and the application of suction. Preoperatively, the subjects were anesthetized with ketamine and xylazine (.05 mL/kg). The ECG in lead II was recorded on a Gould 2600S recorder. Arterial blood (aB) O2 levels were withdrawn 1 min before and at 20 s, 1 min, 2 min, and 3 min following ETS and analyzed on a calibrated Corning 158 semi-automated aB gas machine. There was a significant decline in PaO2 from baseline at 20 s post ETS in both the no suction and suction protocols, p less than .05. The application of suction caused a greater decline in mean PaO2 (41 torr) compared to no suction (13 torr) at 20 s post ETS which was similar in pattern following vagal blockade (suction: 37 torr; no suction: 2 torr). Following the first pass of the catheter, mean heart rate (HR) declined 14 beats per min with suction and 9 beats per min with no suction. The difference was obliterated following the second pass of the catheter. There was no difference in the HR following vagal blockade.

Dimethylthiourea Reverses Sepsis-Induced Pulmonary Hypertension in Piglets

Dimethylthiourea (DMTU), a putative hydroxyl radical scavenger, attenuates thromboxane generation and pulmonary hypertension in the piglet model of group B streptococcal (GBS) sepsis. This study tested the hypothesis that DMTU reverses ongoing GBS-induced pulmonary hypertension coincident with decreased thromboxane production. Piglets (n = 15) received a 60 min infusion of GBS (10(-8) cfu/kg/min). Mean pulmonary artery pressure (Ppa), arterial blood gases (ABGs), and thromboxane B2 (TXB) levels were measured at 10 min intervals throughout the study. GBS infusion resulted in a marked increase in pulmonary artery pressure (mean delta Ppa = 31 mm Hg) and a significant decline in PaO2 (mean = -80 torr) within 10 min of beginning the infusion. pH decreased from a mean of 7.47 to 7.37. DMTU, 750 mg/kg, or normal saline vehicle was infused over 10-15 min beginning 10 min after initiating GBS. Ppa decreased significantly within 10 min of DMTU infusion. Piglets receiving vehicle had a slow decline in Ppa. Piglets receiving DMTU also had an improvement in PaO2 and showed no further drop in pH. Piglets receiving vehicle had no improvement in PaO2 and demonstrated a continued decline in pH. TXB levels did not differ between the groups at any time interval. We conclude that DMTU can partially reverse GBS-induced pulmonary hypertension, but may function through mechanisms independent of thromboxane generation.

Fiberoptic Bronchoscopy in Ventilated Patients: Evaluation of Cardiopulmonary Risk under Midazolam Sedation

One hundred seven acutely ill ventilated patients were prospectively studied to ascertain the severity and frequency of alterations in gas exchange and hemodynamic parameters during brief bronchoscopy. Sedation was performed using midazolam (0.1 mg/kg IV) without topical anesthesia. An average decline in PaO2 of 26 percent was observed at the end of the procedure, compared to the baseline value, and this was associated with a mild increase in PaCO2 in spite of the use of a special adapter. Alterations in mean systolic blood pressure appeared to be modest, consisting of a 10 percent decrease from the control level, related to sedation, and a 10 percent rise from baseline during the procedure, associated with a concomitant mild tachycardia. At that time, central hemodynamic measurements performed in a subset of 31 patients showed a significant increase in cardiac output associated with higher pulmonary wedge pressure. Fourteen patients developed hypoxemia of less than 60 mm Hg on FIO2 adjusted to 0.8. Of the ten risk factors univariately associated with hypoxemia, only the presence of ARDS (p less than 0.001) and "fighting" the ventilator during the procedure (p less than 0.05) remained significant after stepwise logistic regression. Attempts to prevent hypoxemia in critically ill patients should focus on inducing complete sedation, with careful attention to hemodynamic status, or providing maximal levels of oxygen to the ventilator (or both).

Effects of a leukotriene antagonist on the early hemodynamic manifestations of group B streptococcal sepsis in piglets.

In order to evaluate the influence of leukotrienes on group B streptococcal (GBS) sepsis we studied the effect of a leukotriene antagonist, FPL 57231, on the early hemodynamic changes occurring secondary to an infusion of live GBS. Paralyzed, mechanically ventilated piglets received a continuous intravenous infusion of bacteria (5 X 10(8) org/kg/min) while systemic arterial pressure and pulmonary artery pressure were measured continuously. Cardiac output was measured by thermodilution; and plasma samples for determination of thromboxane B2 and 6-keto-PGF1 alpha were taken at preset intervals. In addition to GBS, treatment animals received a continuous infusion of FPL 57231 starting 15 min after the bacterial infusion was begun. Study animals as a whole responded to bacteria within 15 min with a marked elevation in pulmonary artery pressure from 13.6 +/- 4 to 44.6 +/- 6 mm Hg (p less than 0.001), and a decline in PaO2 (79 +/- 9 to 44 +/- 5 mm Hg) (p less than 0.001) and a cardiac output (0.27 +/- 0.07 to 0.15 +/- 0.06 liter/min/kg) (p less than 0.0001). In animals treated with FPL 57231 these changes were reversed or significantly attenuated by 60 min. In the control group pH deteriorated significantly to 7.17 +/- 0.1 compared to baseline values (p less than 0.01) by 60 min, while treatment group animals maintained a pH of 7.3 +/- 0.23. Thromboxane B2 and 6-keto PGF1 alpha were similar in both groups and did not change during the study period. In addition, survival was significantly longer in treatment (191 +/- 44 min) compared to control animals (100 +/- 32 min) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of Profound Reductions of PaO2 on O2 Transport and Utilization in Congenital Heart Disease

A group of eight adult patients with congenital cyanotic heart disease (CCHD) with PaO2 values of less than 32 mm Hg at rest and/or exercise were studied. Four of the patients were re-studied after heart-lung transplantation and restoration of PaO2 to normal values. All eight patients showed increased red cell counts (polycythemia), whereas frankly elevated hemoglobin concentrations were found in only one patient. There was no impressive change in the affinity of hemoglobin for O2 as compared to normal subjects. Blood lactate concentrations were normal at rest before transplantation, rose very modestly during moderate exercise, and were normal following transplantation indicating that the concept of anaerobic threshold is not valid in the present group of patients. Cardiac index was not elevated in the pretransplantation period, indicating that an elevated cardiac output is not an essential adaptive mechanism for dealing with hypoxia. In the pre-transplant period, O2 consumption was elevated as compared to normal values and almost doubled during exercise despite a further decline in PaO2 and SaO2; this establishes that the rate of mitochondrial O2 utilization is maintained despite profound reduction in PaO2. These patients are capable of moderate exercise and normal brain function despite severe hypoxia and the absence or attenuation of various adaptive mechanisms for dealing with hypoxia. Further study of the specifics of O2 transport and utilization in similar patients should prove rewarding.

Cardiovascular changes in group B streptococcal sepsis in the piglet: response to indomethacin and relationship to prostacyclin and thromboxane A2.

Seventeen piglets were infected with a continuous intravenous infusion of live group B beta-hemolytic streptococci (GBS). Hemodynamic changes were recorded, and blood samples were drawn for measurement of thromboxane B2 (TxB2) (stable metabolite of thromboxane A2) and 6-keto-PGF1 alpha (stable metabolite of prostacyclin). Control animals (n = 9) received only bacteria, while treatment animals (n = 8) received indomethacin, 3 mg/kg IV, 15 min after the start of the bacterial infusion. Control animals responded to the bacteria within 15 min with marked elevation in mean pulmonary artery pressure (Ppa) from 15 +/- 8 to 39 +/- 6 mm Hg and decline in PaO2 from 80 +/- 11 to 51 +/- 6 mm Hg and cardiac output (CO) from 0.24 +/- 0.07 to 0.13 +/- 0.07 liters/min/kg. Mean arterial blood pressure (AoP) significantly decreased from baseline value of 95 +/- 13 to 51 +/- 32 mm Hg by 180 min. In animals treated with indomethacin, these changes were reversed or significantly attenuated. The hemodynamic changes were associated temporally with elevations in plasma concentrations of TxB2 or 6-keto-PGF1 alpha. In the first 60 min, TxB2 levels in both groups correlated with Ppa (r = 0.72, p less than 0.001) and PaO2 (r = -0.60, p less than 0.001). A strong negative correlation between TxB2 and CO was observed over the first 180 min (r = -0.73, p less than 0.001). There was a statistically significant correlation between AoP and 6-keto-PGF1 alpha concentration between 60 and 180 min (r = -0.54, p less than 0.002). Indomethacin improved the hemodynamic function in this model of GBS sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of nitroglycerin-induced hypoxemia.

We and others have previously demonstrated a consistent significant decline in arterial oxygen tension (PaO2) after sublingual nitroglycerin in premedicated and unpremedicated patients both with and without coronary artery disease and/or obstructive ventilatory disease. Thus, in our 19 patients, PaO2 fell by an average of 17% (12 mm Hg), mean systemic arterial pressure by 19% (17 mm Hg), pulmonary arterial pressure by 38% (6 mm Hg), pulmonary arterial occlusive pressure by 62% (5.3 mm Hg), and cardiac index by 16% (0.37 liter/min/m2) [P less than 0.001 for each] after nitroglycerin. Previous experimental studies suggest that the mechanism for the reduction of PaO2 may be relief of hypoxic pulmonary vasoconstriction with an increase in perfusion to poorly ventilated or nonventilated regions of the lungs. To examine this possibility, pulmonary vasodilatation was precluded by administration of a pulmonary vasoconstrictor (phenylephrine) simultaneously with nitroglycerin in nine patients with coronary artery disease. No significant change was observed in systemic or pulmonary arterial pressure, pulmonary arterial occlusive pressure, or systemic and pulmonary vascular resistance, and PaO2 did not decline. In ten other patients with coronary artery disease, the intrapulmonary right-to-left shunt fraction was determined before and after sublingual nitroglycerin; only a minimal increase in shunt fraction of 1.4% was observed, quantitatively insufficient to account for the observed decline in PaO2, thus excluding a predominant effect of nitroglycerin on nonventilated alveoli as a cause of the hypoxemia. We conclude that the reduction of PaO2 after nitroglycerin administration is attributable to pulmonary vasodilatation with a relative increase in perfusion of poorly ventilated lung units.

Arterial oxygenation during hemodialysis.

A FALL in partial pressure of arterial oxygen, or oxygen tension (Pao2), occurring during hemodialysis is a well described phenomenon.1 , 2 The published data, however, are disparate over its cause and clinical implications. Bischel, Scoles and Mohler3 described a small but statistically significant fall in Pao2 at the end of dialysis and concluded that pulmonary arterial microembolization from the dialysis membrane was its cause. Other authors1 , 2 , 4 have described a decline in Pao2 of greater magnitude during the course of dialysis. Craddock and his associates4 believed that the underlying mechanism was related to complement-mediated leukostasis in pulmonary capillaries. . . .