Pulmonary Arterial PO2 Research Articles

Efficacy of spirometry in COPD patients with pulmonary hypertension: A study in a tertiary care unit

Therapy for COPD patients, in particular those with advanced stage, is generally disappointing and frustrating for both the doctors and patient. Of the symptoms, dyspnea is an important and debilitating symptom for which most patient with COPD seek medical attention. For the evaluation of lung function test for pulmonary hypertension, arterial PO2 and FEV1 seem to be most reliable.COPD was diagnosed as per GOLD criteria. Baseline FEV was measured by spirometer. The patient then received two puffs of salbutamol. 15 minutes later 3-5 forced expiratory maneuver was repeated and the best FEV was recorded. Symptoms Score, and dyspnea grade were correlated with FEV both pre and post bronchodilator. The mean age of the 52 patients was 60±10.6 Years. The mean symptom score was 4.07 with SD : ± 0.81. 7.69% patients were in MRC dyspnea scale grade 1, 21.15% patients had grade 2 dyspnea, 25% patients had grade 3 dyspnea, 40.38% patients had grade 4 dyspnea and 5.76% patients had dyspnea of grade 5. There was a strong significance in the correlation of Symptom scale with Pre bronchodilator % predicted FEVand with post bronchodilator % predicted FEVThere was a high correlation between dyspnea and pulmonary hypertension measured by percentage predictive value. Spirometry was found to be very useful for the diagnosis and staging of COPD. This could be used in primary diagnosis of patients with COPD.

How Do We Monitor Oxygenation during the Management of PPHN? Alveolar, Arterial, Mixed Venous Oxygen Tension or Peripheral Saturation?

Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal to postnatal period. Oxygen tension (PO2) in the alveolus (PAO2) and pulmonary artery (PaO2) are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen therapy is the mainstay of PPHN management. However, optimal monitoring and targeting of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimizing oxygen delivery to vital organs remains unknown. Noninvasive pulse oximetry measures peripheral saturations (SpO2) and a target range of 91–95% are recommended during acute PPHN management. However, for a given SpO2, there is wide variability in arterial PaO2, especially with variations in hemoglobin type (HbF or HbA due to transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, mixed venous PO2, and SpO2 in the management of PPHN. Translational and clinical studies suggest maintaining a PaO2 of 50–80 mmHg decreases PVR and augments pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN targeting SpO2 or PO2. Also, most critically ill patients have umbilical arterial catheters and postductal PaO2 may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO2 and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO2/SpO2 target ranges for the management of PPHN and compare outcomes.

Inflammatory Response after Immediate versus Delayed Ex-Vivo Lung Perfusion in a Porcine Cardiac Arrest Donation Model

Ex Vivo Lung Perfusion (EVLP) is a promising tool for evaluation and reconditioning in marginal donor lungs. However, the optimal protocol is discussed controversially. It is our hypothesis that different EVLP protocols and different perfusion solutions result in different cytokine patterns during EVLP. Following cardiac arrest and 30 min of no-touch warm ischemia, pig lungs were harvested, flushed and stored in cold preservation solutions. Different groups were processed as immediate long EVLP (I-EVLP, 12 h), delayed short EVLP (4 h) after 9 hours of cold storage (D-EVLP). Lungs were perfused with different acellular solutions: Steen solution or modified HTK solution containing either dextran(CD) or dextran and albumin (CDA). Pulmonary gas exchange, biochemical and structural parameters were recorded hourly. Cytokine / chemokine levels were analyzed in perfusates at baseline and after 1 and 4 h of EVLP. ∆ pO2 (pulmonary venous - pulmonary arterialpO2) was higher in D-EVLP group, especially at h 1: I-EVLP: 259 ± 132, D-EVLP: 291 ± 96 and h 2: I-EVLP: 228 ± 125, D-EVLP: 252 ± 116 (n.s.). Compared to D-EVLP, lungs that underwent EVLP with CD and CDA showed significantly higher oxygen capacity (∆ pO2 CD: 402.79 +30.33 mmHg, CDA: 414.86 + 9.77 mmHg). Within 4 h ELVP, concentrations of IFN-γ, TNF-a, IL-1α/β, IL-10, CXCL8 (IL-8) and IL-18 increased significantly (all p<0.05) in the four groups. Of note, no significant differences could be detected between I- vs. D-EVLP lungs and CD vs. CDA solutions. In a non-heart beating porcine lung donor model with relevant ischemic tissue damage, lungs were perfused with normothermic EVLP. Even after 9 hours cold static preservation (CSP) and 4 hours EVLP lung, function is comparable to direct EVLP. The modified HTK solution with dextran and dextran/ albumin had significantly better oxygenation. Cytokines and chemokines including the cell death marker IL-18 increase during 4 h of EVLP but a delay before EVLP may not dramatically worsen the inflammatory response.

Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

Comparison of mechanical and manual ventilation during transport of patients to the intensive care unit after cardiac surgery

Objectives: We compared effects of mechanical and manual ventilation during transport to the intensive care unit(ICU) in cardiac surgeries. Materials and methods: After ethical approval, 66 patients (ASAgrade II and III, 20-80years) were assigned randomly. Ventilation during transport to ICU was performed manual (Group EV; n=36) or mechanical ventilation (Group MV; n=30). Measurements were recorded: operation room (A), during transport (T) and in ICU (YB). Systolic, diastolic pressures (SAP, DAP), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), heart rate (HR), cardiac output (CO), blood gases (pH, PCO2, PO2, BE) and peripheral oxygen saturation (SpO2) were recorded. Stroke volume index (SVI), systemic and pulmonary vascular resistance indices (SVRI, PVRI) and mean arterial pressures(MAP) were calculated. Results: Patients were similar. Duration of transport was shorter in Group MV (p< 0.01). The alterations in HR, MAP, DAP, CVP, PAP, PCWP, PVRI, SVRI, SVI, CO, SpO2 were similar, the increase in SAP during T period was higher in Group MV (p<0.05). Pulmonary arterial pH in Group MV was lower (p< 0.05). Arterial and pulmonary arterial pO2, pCO2 decreased in Group MV, there was increase in Group EV during ICU (p< 0.001, p< 0.01, p< 0.01, p< 0.05). During T period hypotension and tachycardia in Group EV, and hypertension in Group MV were observed. Conclusions: Mechanical ventilation had short transport time, less alterations in hemodynamic and respiration values and less complication rates. We concluded that the use of mechanical ventilation is a safer method for the intrahospital transport of critical patients.

Positive effects of oxygenation on simulated post-transplantation lung edema and pulmonal arterial resistance

Objective: Ischemia-reperfusion injury still causes severe problems after lung transplantation. It is supposed that systemic oxygen supply to the transplanted lungs could improve transplantation outcome. By using an ex vivo model of isolated perfused and ventilated rabbit lungs we investigated the influence of systemic oxygenation on pulmonary function during simulated transplantation. Methods: The heart-lung blocks of 12 New Zealand White rabbits (2.22±0.4kg) were excised and transferred to a 37°C water-heated artificial thorax chamber. Negative pleural pressure ventilation was initiated and perfusion with recirculating, albumin-containing Tyrode-Solution was slowly increased to a constant end flow of 100ml/min. The lungs were arranged in a stable perfusion and ventilation mode for 30min. Afterwards lungs underwent a flush-perfusion with Perfadex® Solution, followed by an ischemic storage for 4h on ice, thereafter ventilation and reperfusion for 2h were continued to simulate a transplantation situation (oxygenated group, pulmonary artery pO2=120mmHg). In another series the perfusate inflow was additionally gassed with nitrogen (connecting a fiber oxygenator) to simulate deoxygenation (deoxygenated group, pulmonary artery pO2=50mmHg). Hemodynamic and ventilatory parameters (pulmonary artery pressure (PAP), pulmonary compliance, pulmonary resistance, lung weight) were continuously detected. Results: After 2h reperfusion time in the oxygenated group we found a significant lower PAP and lung weight compared to the deoxygenated group (p<0.05). PAP and lung weight steadily increased after reestablishment of lung perfusion (PAP: initial 8.78±0.89 cmH2O, 30min reperfusion 7.2±1.48 cmH2O, 2h reperfusion 11.5±1.06 cmH2O; lung weight: initial 22.1±1.32g, 30min reperfusion 26.1±1.87g, 2h reperfusion 35.4±4.23g). This development was significantly influenced by the intravascular pO2 (PAP: initial 9.65±0.43 cmH2O, 30min reperfusion 7.92±0.52 cmH2O, 2h reperfusion 8.02±0.63 cmH2O; lung weight: initial 17.9±1.54g, 30min reperfusion 19.0±1.68g, 2h reperfusion 21.5±2.29g, p<0.05). Conclusions: Oxygenation of the lung perfusate during simulated transplantation attenuates post transplant edema formation and decreases pulmonal arterial hypertension. Transfering this to the surgical situation, revascularisation of bronchial arteries after lung transplantation might initiate positive effects in the early phase after lung transplantation.

90 Clinical Lung Transplantation after Ex Vivo Evaluation of Uncontrolled Non Heart-Beating Donors Lungs: Initial Experience

<h3>Purpose</h3> To describe the first series of Ex Vivo evaluations of human lungs from Maastricht type I non heart-beating donors and clinical transplantations with these organs. <h3>Methods and Materials</h3> Eight potential male donors entered the non heart-beating protocol after sudden cardiac arrest in the street and unsuccessful resuscitation. Bipulmonary blocks were topically cooled and flushed with antegrade and retrograde cold Perfadex. A normothermic Ex Vivo evaluation was initiated, perfusing the lungs with a flow 40% of the estimated cardiac output and protectively ventilating after reaching 32°C. Oxygenation tests were performed hourly. Three criteria were to be met for acceptance: ΔpO2(difference between atrium and pulmonary artery pO2) over 400mmHg, stable or improving evaluation data and surgeon approval of lung appearance and procedure. <h3>Results</h3> Ex Vivo evaluation was correctly perfomed in all cases. Average perfusion time was 273min. Four blocks did not pass the evaluation because of low oxygenation and declining compliance. Bronchiolitis, diffuse emphysema and bone marrow emboli were found in the pre-Ex Vivo pathology analyses of rejected lungs. Four blocks passed the evaluation after an average time of perfusion of 270min. The mean ΔpO2 was 461mmHg and the mean compliance was 87.2mlL/cmH2O with a tendency to increase in each evaluation. Acceptable blocks were cold preserved until implantation. Four bilateral lung transplantations were performed (3 emphysema, 1 bronchiectasis) with a total "out of the body" time of 15h19m and 17h35m for first and second lung. There were no cases of grade 3 PGD (31.6% PGD=0; 10.5% PGD=1) Two patients died of non-Ex Vivo related causes after 92 and 122 days. Two patients are alive and well after 204 and 333 days, with no signs of BOS. <h3>Conclusions</h3> Ex vivo evaluation of uncontrolled non-heart beating donor-lungs enables us to ensure an optimal function under physiological conditions before clinical implantation and promises a more widespread use of this kind of donors in the future.

A closed loop model of pulmonary gas exchange

Objectives: To model acute lung injury (ACI), we previously developed a partial differential equation (PDE) model of gas exchange and inflammation on a respiratory unit (RU). We increase biological fidelity by incorporating metabolism. We explored the computational and theoretical challenges of this more realistic closed loop system of gas exchange under inflammatory stress. Method: First, we added the loss of O2 and gain of CO2 during metabolism to the PDE model creating time-dependent boundary conditions on pulmonary arterial PO2 and PCO2. Then, the PDE model for gas exchange and inflammation on a single RU was simplified mathematically to a system of ordinary differential equations. The model was reduced such that arterial PO2 and PCO2 reflect the combined effects of metabolism and inflammation. Computational gains allow themodel to operate in a closed loop, and with more biological fidelity. Results: The output of the ordinary differential equation full lung model (multiple linked RUs) matches those seen in the PDE full model when heterogeneity of the lung is introduced via a normal distribution of tidal volumes over the total number of RUs. The reduced form of the RU allows heterogeneity in the full lung by changing both alveolar ventilation and perfusion. As with the previous model, we see the shunting is a major contributor to the reduction of PO2 during inflammation. Conclusions: The reduction of our previous model is the final step in developing a useable multiscale model of the lung. The results of this reduced multi-RU model are comparable to time courses of ACI. This model will be linked with an organ model to explore the spread of inflammation.

Sudden death in epilepsy: An experimental animal model

The physiopathogenetic mechanisms possibly involved in sudden unexplained epileptic death (SUDEP), were investigated in the hemispherectomized rat. For this purpose, paroxysmal activity, vagal nerve firing, systemic blood pressure (BP), pulmonary artery pressure, and ECG were simultaneously recorded in an experimental animal model of epilepsy. Recordings were performed in basal conditions and during paroxysmal activity induced by topical application of penicillin-G at hypothalamic and mesencephalic level. During the experiment were also performed hemogas analysis and at end, samples of lung tissue were processed for histology. Activation of hypothalamic (HEF) and mesencephalic (MEF) epileptic foci induced a significant increase of spontaneous vagal nerve firing that was strictly correlated to ECG impairments and hypotension. When paroxysmal activity extinguished, vagal nerve activity and cardiovascular parameters returned to basal conditions. However, in 25% of the animals, co-activation of HEF and MEF always triggered a vagal hypertone which was temporally correlated to cardiac arrhythmias, but also to hyperkalemia, acidosis, pulmonary hypertension and to animal death. Histological control in lungs of deceased animals showed an alveolar and perivessel oedema with an oedematous infiltration in the alveolar and bronchial spaces and mucous secretion. During ictal activity, comparison between survived and deceased animals showed significant differences in the incidence of ECG impairment of pulmonary artery pressures, pO2, and pCO2 pressures, and [K+], [HCO3-], and [pH], concentrations. A possible explanation of the above observations is discussed in relationship to SUDEP physiopathogenesis.

Frusemide and weight carriage alter the acid:base responses of horses to incremental and to brief intense exertion.

We speculated that frusemide would attenuate the acidosis associated with intense exertion, and that weight carriage would mitigate this effect. Therefore, in each of 2 experiments we measured pulmonary artery and systemic arterial blood pH, PCO2, PO2 and pulmonary artery temperature in 9 horses during exertion on a treadmill after each of 3 treatments. The treatments were: 1) injection of saline solution (C), 2) injection of frusemide (1 mg/kg bwt, i.v. 4 h before running) (FU) and 3) injection of frusemide (F) as for FU and the horses carried weight equal to that lost in the 4 h after frusemide administration (FL). In Experiment 1 the horses performed an incremental exercise test of 90 s at each of 4, 7 and 9 m/s (4 degrees incline). In Experiment 2, the horses ran on a treadmill inclined at 4 degrees for 3 min at 3 m/s, at approximately 120% VO2max for 2 min, and 3 m/s for 5 min. Blood samples for measurement of blood pH, PCO2 and PO2 were collected into heparinised glass syringes. Values were adjusted for changes in pulmonary artery blood temperature. Data were analysed using a 2 way repeated measures ANOVA. There was a consistent pattern in both experiments characterised by a mild alkalosis or mitigated acidosis, compared to C, at rest and during exercise and recovery after FU (P < 0.05). Weight carriage blunted or inhibited the effect of frusemide during exercise and recovery. In experiment 2, at the end of the sprint, FU treatment resulted in a less severe acidosis than did C or FI: mixed venous pH for C, FU, and FL at the end of the sprint were 6.93, 6.98 and 6.93, respectively (P interaction = 0.038), mixed venous base excess was -12.4, -9.91, and -11.8 mmol/l, respectively, and arterial base excess of -1.44, -12.7 and -14.1 mmol/l (P interaction = 0.006) respectively. These effects persisted into recovery. A similar pattern of responses occurred during the incremental exercise test, with weight carriage offsetting the alkalinizing effect of frusemide. We conclude that frusemide attenuates the acidosis of intense exertion and that carriage of weight prevents this effect.

Histamine receptor antagonists, cyclooxygenase blockade, and tumor necrosis factor during acute septic insult.

Tumor necrosis factor (TNF) may be a major endogenous mediator of sepsis-induced acute organ injury. We proposed that treatment of septic pigs with the combined agents ibuprofen, a cyclooxygenase inhibitor, and histamine receptor antagonists, cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) would result in lower circulating levels of TNF and decreased parameters of sepsis-induced injury in these animals. To test this, plasma TNF activity, cardiac index, systemic and pulmonary arterial pressures, arterial PO2 and bronchoalveolar lavage protein content were monitored for 300 min in four groups of anesthetized pigs: saline-infused control pigs (n = 4); pigs infused for 60 min with Pseudomonas aeruginosa (5 x 10(8) organisms/mL, .3 mL/20 kg/min) (n = 5) and pigs infused for 60 min with P. aeruginosa plus ibuprofen (12.5 mg/kg) alone (n = 4) or ibuprofen plus cimetidine (150 mg) and diphenhydramine (30 mg/kg) at 0 and 120 min (CID, n = 4). Within 60 min, pigs infused with P. aeruginosa exhibited increased plasma TNF activity (>8-fold increase in ng/mL TNF; L929 cytolysis assay) and showed alterations in all hemodynamic and pulmonary parameters. Ibuprofen or CID administration in the septic pigs decreased peak TNF activity by 4.6 and 10.2 ng/mL, respectively, and CID treatment was correlated with better attenuation of certain sepsis-induced alterations. These results show that CID treatment attenuates sepsis-induced injury and that this is correlated with reduced plasma TNF activity in a porcine model of sepsis-induced acute organ injury.

Effect of Synchronized, Systolic, Lower Body, Positive Pressure on Hemodynamics in Human Septic Shock: A Pilot Study

The pathophysiologic disturbance observed in volume-resuscitated patients with septic shock is primarily that of hyperdynamic circulation with a markedly reduced systemic vascular resistance. We hypothesized that external, mechanically applied, phasic lower body positive pressure could increase systemic vascular resistance and, thus, blood pressure in patients with refractory septic shock. A total of nine studies were performed on seven patients with septic shock refractory to volume resuscitation and vasopressors. All pre-existing therapies were continued unaltered during the study period. Phasic lower body positive pressure was produced by rapid synchronized inflation of pneumatic fabric cuffs fitted around each lower extremity. The cuffs were inflated for 200 ms to a pressure of 150 mm Hg, and the timing of inflation was adjusted to coincide with the peak systolic arterial pressure. Hemodynamic measurements were obtained at baseline and after 15 min of phasic lower body positive pressure. This off-on cycle was repeated twice for each study. Phasic lower body positive pressure increased mean arterial pressure by 12% and cardiac index by 14% (p = 0.01) over baseline (p < or = 0.001). Heart rate, central venous pressure, pulmonary capillary wedge pressure, arterial pH, arterial pO2, and mixed venous pO2 were unchanged. Synchronized external systolic compression of the lower extremities increased mean arterial pressure and cardiac output in seven patients with refractory septic shock. This hemodynamic improvement was independent of changes in calculated systemic vascular resistance.

Effect of synchronized, systolic, lower body, positive pressure on hemodynamics in human septic shock. A pilot study.

The pathophysiologic disturbance observed in volume-resuscitated patients with septic shock is primarily that of hyperdynamic circulation with a markedly reduced systemic vascular resistance. We hypothesized that external, mechanically applied, phasic lower body positive pressure could increase systemic vascular resistance and, thus, blood pressure in patients with refractory septic shock. A total of nine studies were performed on seven patients with septic shock refractory to volume resuscitation and vasopressors. All pre-existing therapies were continued unaltered during the study period. Phasic lower body positive pressure was produced by rapid synchronized inflation of pneumatic fabric cuffs fitted around each lower extremity. The cuffs were inflated for 200 ms to a pressure of 150 mm Hg, and the timing of inflation was adjusted to coincide with the peak systolic arterial pressure. Hemodynamic measurements were obtained at baseline and after 15 min of phasic lower body positive pressure. This off-on cycle was repeated twice for each study. Phasic lower body positive pressure increased mean arterial pressure by 12% and cardiac index by 14% (p = 0.01) over baseline (p < or = 0.001). Heart rate, central venous pressure, pulmonary capillary wedge pressure, arterial pH, arterial pO2, and mixed venous pO2 were unchanged. Synchronized external systolic compression of the lower extremities increased mean arterial pressure and cardiac output in seven patients with refractory septic shock. This hemodynamic improvement was independent of changes in calculated systemic vascular resistance.

Properties of a superoxide anion-generating microsomal NADH oxidoreductase, a potential pulmonary artery PO2 sensor.

In this study, we describe properties of a microsomal NADH oxidoreductase that is a potential PO2-dependent source of vasoactive reactive O2 species in the calf pulmonary artery. Microsomes show an NADH-dependent production of superoxide anion (O2-.), as detected by lucigenin-elicited chemiluminescence, a superoxide dismutase inhibited reduction of nitro blue tetrazolium (NBT) and 2,6-dichlorophenol-indophenol, and O2 consumption. The microsomal production of O2-. was modulated by physiologically relevant levels of NADH and PO2, and O2-. production was reduced by inhibitors of NADH-dependent microsomal electron transport. Microsomes catalyzed an NADH-mediated reduction of several electron acceptor dyes, cytochrome c (rotenone insensitive) and methemoglobin. On reduction with dithionite, a cytochrome with an absorbance at approximately 558 nm was observed. Arterial O2-. levels (chemiluminescence) were also reduced by NBT and microsomal electron transport inhibitors. In pulmonary arteries, NBT selectively inhibited PO2 and lactate elicited changes in force generation, presumably by trapping O2-. and preventing H2O2 formation. Thus these studies are consistent with an involvement of O2-.-derived H2O2 generation via a microsomal NADH-cytochrome b558 electron transport system in calf pulmonary artery smooth muscle PO2 and lactate-elicited tone responses.

Assessment of postpreservation rat lung function using a new model for extended venous reperfusion.

Understanding the physiological significance of biochemical events after lung preservation in rats has been hampered by the lack of a suitable model for physiological assessment. We have developed an ex vivo paracorporeal rat lung perfusion model that permits hemodynamic and gas exchange evaluation of lung function. After anesthesia and heparinization, the heart-lung block was removed and the left lung was reperfused for 1 h at a constant flow of 4 ml/min with homologous venous blood drained from the inferior vena cava of the paracorporeal (host) rat. The lung effluent was returned at the same flow rate to the host distal aorta. The model was validated by the assessment of lung function after room temperature ischemia. Animals were allocated into three groups (n = 6) according to the ischemic interval (group 1, 20 min; group 2, 3 h; group 3, 4 h). In groups 1 and 2, PO2, PCO2, mean airway pressure, and pulmonary arterial pressure were within the normal ranges and stable throughout the experiment. In contrast, lungs in group 3 demonstrated higher pulmonary arterial pressure and lower blood effluent PO2 than were found in either group 1 or 2. A significant weight gain during reperfusion was observed only in group 3 (4.23 +/- 0.9 g; P < 0.002). For each lung, the final blood effluent PO2 correlated with the weight gain (R2 = 0.81; P < 0.0001). Our results indicate that this model can be used reliably to detect lung dysfunction after ischemic injury.

Pulmonary artery catheter monitoring during single-lung ventilation in dogs.

The effect of pulmonary artery (PA) catheter insertion on cardiac output measurements and the effect of single-lung ventilation on data derived from catheters placed in both the right and left pulmonary arteries were examined in 17 anesthetized mongrel dogs. Serial tricarboncyanine dye measurements of cardiac output were taken at baseline and after insertion of each of two PA catheters, one catheter in each lung, to detect possible changes in cardiac output due to instrumentation. In the second part of the study, single-lung ventilation was achieved through a Kottmeier double-lumen tube. Right and left paired values of thermodilution cardiac output, PA systolic pressure, and PA PO2 were compared during ventilation of both lungs, during right lung ventilation, during return to ventilation of both lungs, and during left lung ventilation. Mean dye-dilution cardiac outputs were not significantly different after one or two catheters were inserted. Paired right and left values were similar for thermodilution cardiac output, PA PO2, and pulmonary systolic pressure, regardless of ventilation conditions. Even during single-lung ventilation, data obtained from PA catheters in the ipsilateral and contralateral lung were equivalent in supine dogs.

Eprazinone alters lung lavage lipid levels and transtracheal ion transport.

Eprazinone therapy improves pulmonary function and arterial pO2 in patients with chronic bronchitis; however, the mechanism of action is unknown. The purpose of this study was to determine if eprazinone alters either lung surfactant levels in bronchoalveolar lavage fluid (BAL) of normal rats, or ion transport across canine tracheal epithelium mounted in Ussing chambers. In the surfactant studies, normal rats were force fed three doses (50, 100, and 200 mg/kg) of eprazinone for 4 days. Eprazinone at a dose of 200 mg/kg significantly increased total and individual (with the exception of phosphatidylinositol) phospholipid levels and decreased total neutral lipids. Lower doses of eprazinone significantly decreased neutral lipid levels without affecting the phospholipids. There was no change in BAL levels of protein or cells and no abnormal histology. In airway epithelial studies, mucosal addition of eprazinone produced a dose-dependent partially reversible decrease in short-circuit current (Isc). The decrease in Isc at lower eprazinone concentrations was accounted for entirely by a decrease in net chloride secretion while at higher concentrations both sodium and chloride transport were affected. Submucosal eprazinone had no affect on ion transport. These studies suggest that eprazinone influences both BAL lipid levels and ion transport, either of which could lead to a beneficial therapeutic effect.

Improvement in oxygen tensions and pulmonary blood flow with intermittent distal aortic compression during normoxia, hypoxic hypoxia, and hyperoxia in neonatal piglets

We investigated the hypothesis that, in a newborn piglet during normoxia, hypoxia, and hyperoxia, increasing aortic pressure transiently by intermittent short-duration aortic compression would affect left-to-right shunting of blood and thus increase pulmonary artery blood flow, pulmonary arterial PO2, and aortic PO2 proximal to the point of compression. We also investigated whether a balloon atrial septostomy, by providing an open channel for communication between the right- and left-sided circulations, would further improve pulmonary blood flow and aortic PO2. Studies were performed in eight 7- to 10-day-old newborn piglets in three phases (FIO2 of 0.21, 0.12, and 1.0) before and after balloon arterial septostomy in each piglet. Blood gas measurements and hemodynamic variables were recorded before and at the end of a 30-sec period of aortic compression. During aortic compression, all the animals demonstrated a 50 to 70 mm Hg increase in aortic pressure proximal to the compression. Before balloon septostomy, there were 21%, 41%, and 8% increases in aortic PO2 in the room air, hypoxic, and hyperoxic phases of the experiment, respectively. There were also statistically significant increments in pulmonary blood flow and arterial pressures. After balloon septostomy, there were 35%, 25%, and 21% increments in aortic PO2 during the room air, hypoxic, and hyperoxic phases of the experiment, respectively. However, there was no statistically significant further improvement in the effects of aortic compression on PO2 with septostomy compared with those effects before septostomy. Our results suggest that increasing systemic arterial pressures in order to forcibly affect left-to-right shunting of blood may be potentially beneficial in the management of hypoxia in situations where low pulmonary artery blood flow may be contributing to hypoxia, e.g., in persistent pulmonary hypertension of the newborn.

Pulmonary pressure-flow relationships in the fetal lamb during in utero ventilation

Pressure-flow relationships in the ventilated lung have not been previously determined in undelivered fetal sheep. Therefore we studied 11 late-gestation chronically prepared fetal sheep during positive-pressure ventilation with different gas mixtures to determine the roles of mechanical distension and blood gas tensions on pressure-flow relationships in the lung. Ventilation with 3% O2-7% CO2 produced a substantial fall in pulmonary vascular resistance even though arterial blood gases were not changed. Increases in pulmonary arterial PO2 during ventilation were associated with falls in pulmonary vascular resistance beyond that measured during mechanical distension. Decreases in pulmonary arterial PCO2 and associated increases in pH were also associated with falls in pulmonary vascular resistance. Pulmonary blood flow ceased at a pulmonary arterial pressure that exceeded left atrial pressure, indicating that left atrial pressure does not represent the true downstream component of driving pressure through the pulmonary vascular bed. The slope of the driving pressure-flow relationship in the normal mature fetal lamb was therefore different from the ratio of pulmonary arterial pressure to pulmonary arterial flow. We conclude that mechanical ventilation, increased PO2 and decreased PCO2, and/or increased pH has an important influence on the fall in pulmonary vascular resistance elicited by positive pressure in utero ventilation of the fetal lamb and that the downstream driving pressure for pulmonary blood flow exceeds left atrial pressure.

The effect of adenosine triphosphate on the functional status of the ductus arteriosus

We investigated whether a low-dose infusion of ATP-MgCl2 could affect the functional status of the ductus arteriosus during hypoxia-induced pulmonary vasoconstriction. Three-day-old piglets were made hypoxic by ventilation with a mixture containing 10% oxygen, 4% CO2, and balance nitrogen. Serial infusions of ATP-MgCl2 at 0.1, 0.5, and 1.0 mg/kg/min were compared with preinfusion hypoxia baselines. The functional status of the ductus arteriosus was determined by change in transit time of a bolus of iced saline between thermistor probes in the pulmonary artery and aorta. The method was validated using a Blalock-Taussing shunt (subclavian to pulmonary artery) in 3-week-old piglets instrumented in a similar manner. In these three-day-old piglets, hypoxia alone produced a significant elevation in pulmonary artery pressure and reduction in PO2. All dose rates of ATP-MgCl2 produced a significant decrease in mean pulmonary artery pressure. Systemic pressure was significantly decreased only during the 1.0-mg/kg/min infusion. Transit times of a bolus of iced saline during the validation were definitive for characterizing a situation of "shunt open" or "shunt closed." Infusion of ATP-MgCl2 produced no change in the status of the ductus arteriosus in 45 (94%) of the determinations. In only three cases was the effect of ATP-MgCl2 sufficient to result in a functional change in the status of the ductus arteriosus. Pre- and postductal pulmonary artery PO2 were not altered during ATP-MgCl2 infusion, thus corroborating the transit time determinations. From these results, we conclude that an infusion of ATP-MgCl2 does not alter the functional status of the ductus arteriosus.