Unilateral Pulmonary Artery Occlusion Research Articles

Oxygen Transport during Incremental Exercise Load as a Predictor of Operative Risk in Lung Cancer Patients

To evaluate functional parameters related to the morbidity and mortality after thoracotomy, exercise loading was applied in 31 lung cancer patients under right heart catheterization. The routine pulmonary function and predicted postoperative pulmonary function (ppo) parameters were also evaluated. Patients were grouped according to postoperative complications: no complications (group 1, n = 17), nonfatal complications (group 2, n = 10), and fatal complications (group 3, n = 4). In all the patients %VCppo was above 40 percent and in patients undergoing pneumonectomy, pulmonary artery mean pressure during the unilateral pulmonary artery occlusion test was below 25 mm Hg. FEV1 percent and MVV/BSA were statistically significant between groups 1 and 2 but were not between groups 1 and 3 or groups 2 and 3. The %FEV1 ppo was statistically significant between groups 1 and 2 and groups 1 and 3 but was not between groups 2 and 3. Thus, the routine pulmonary function and predicted postoperative lung function tests, although they are mandatory for screening patients who are at risk, did not definitely discriminate between patients experiencing nonfatal and fatal complications after thoracotomy. VO2/BSALa20, CILa20, O2D/BSALa20, and TPVRILa20 were statistically significant between groups 1 and 3 and groups 2 and 3: in all the group 3 patients, as well as three patients of group 1 and one of group 2, VO2/BSALa20 was below 350 ml/min/m2. On the other hand, O2D/BSALa20 was below 500 ml/min/m2 in all the group 3 patients, while it was above 560 ml/min/m2 in all patients in groups 1 and 2. O2D/BSALa20 was the only parameter that definitely discriminated between experiencing nonfatal and fatal complications. We conclude that in addition to the generally accepted functional guidelines, VO2/BSALa20 should be above 400 ml/min/m2 and O2D/BSALa20 should be above 500 ml/min/m2 in patients who will undergo thoracotomy.

Experimental study in a rabbit model of ischemia-reperfusion lung injury during cardiopulmonary bypass

Adult white rabbits were subjected to 2 hours of partial cardiopulmonary bypass (flow rate 90 ml/min/kg) at 32 degrees C, and unilateral pulmonary artery occlusion was used to simulate total cardiopulmonary bypass in the lung subjected to arterial occlusion, with the other side used as the control lung. The lung subjected to arterial occlusion was reperfused by one of the following methods: (1) by whole blood (WB group), (2) by leukocyte-depleted blood (LD group), and (3) by whole blood with protease inhibitor (nafamostat mesilate, FUT group), expecting its anticomplement action. In the fourth group, the lung was inflated with oxygen during pulmonary artery occlusion followed by whole blood reperfusion (OXY group). As a result, lungs subjected to pulmonary artery occlusion showed significant decreases in tissue concentrations of adenosine triphosphate and regional tissue blood flow during cardiopulmonary bypass. Furthermore, recovery of adenosine triphosphate was depressed in the WB group and recovery of regional tissue blood flow in the WB and OXY groups. Ultrastructural findings in alveolar epithelial cells and capillary endothelial cells showed worsening at reperfusion in only the WB group. Transpulmonary gradients of C5a and leukocyte showed significant increases at reperfusion in the WB and OXY groups. Alveolar-arterial oxygen difference was significantly higher in the WB group than in the others. Results indicate that complete cessation of pulmonary artery flow in normothermic cardiopulmonary bypass may cause ischemia of the lung followed by reperfusion injuries with the no-reflow phenomenon, with possible involvement of activation of leukocytes and complement.

Antibody against neutrophil adhesion improves reperfusion and limits alveolar infiltrate following unilateral pulmonary artery occlusion

Relief of unilateral pulmonary arterial occlusion results in bilateral lung injury and results in only partial restoration of pulmonary blood flow distal to the site of occlusion. We hypothesized that the “no reflow” phenomenon was in part due to neutrophil adherence and aggregation in the pulmonary vasculature. The study was carried out in two phases. First, we studied the effect of neutrophil depletion on left lung blood flow following 24 hr of left pulmonary artery occlusion. Hydroxyurea was used to deplete circulating neutrophils to 77 ± 18/mm 3 (means ± sem) ( n = 6) as compared to 708 ± 165/mm 3 in control rabbits ( n = 8). In both groups left lung blood flow immediately following reperfusion was markedly reduced at 6.4 ± 2.2% of cardiac output in control rabbits and 7.3 ± 2.3 in treated rabbits. However, at 4 hr, neutrophil-depleted animals had significantly greater flow (18.7 ± 3.6 vs 8.4 ± 2.3% for control rabbits, P < 0.05). In both groups, flow remained substantially below the normal rabbit left lung blood flow of 39.8 ± 2.2%. To test whether the improved reflow was due to decreased numbers of neutrophils limiting aggregation, or whether active neutrophil adherence played a role, we tested the effect of a monoclonal antibody that interferes with neutrophil adhesiveness (MoAb 60.3) on reflow and on neutrophil emigration into the alveoli. We found that MoAb 60.3 did not affect initial reflow. However, at 24 hr, flow in treated rabbits was virtually normal (38.8 ± 1.5+%) but remained markedly diminished in untreated animals at 25.5 ± 3.9%. MoAb 60.3 also markedly diminished neutrophil emigration into the alveoli following reperfusion. We conclude that neutrophils play a significant role in preventing reflow following lung ischemia and that inhibition of neutrophil adhesiveness reverses this phenomenon and decreases the inflammatory response in the alveolus.

Role of ICAM-1 in neutrophil-mediated lung vascular injury after occlusion and reperfusion

We examined the role of intracellular adhesion molecule 1 (ICAM-1 or CD54) in the development of pulmonary edema in rabbits after pulmonary artery occlusion and reperfusion using a monoclonal antibody (MAb) RR1/1 directed against ICAM-1, a ligand for the CD18 leukocyte adhesion glycoprotein complex. A vascular clamp was placed around the left pulmonary artery for 24 h and then released to allow reperfusion for 2 h. Lungs subjected to 24 h of unilateral pulmonary artery occlusion showed increased binding of 125I-labeled RR1/1 and immunocytochemical evidence of ICAM-1 expression in pulmonary vascular endothelial cells compared with the contralateral lung. MAbs RR1/1 (0.5 mg/kg) or IB4 (1.0 mg/kg) (MAb directed against an epitope on the CD18 adhesion glycoprotein) was infused 45-60 min before the start of reperfusion to assess the roles of ICAM-1 and CD18 in the response. After reperfusion, the lungs were removed, suspended from one end of a weighing balance, and perfused with Ringer-albumin (0.5 g/100 ml), and the changes in lung weight were monitored for 60 min. Lung tissue myeloperoxidase (MPO) content (a marker of neutrophil sequestration) was determined after reperfusion. The increases in lung weight gain in the RR1/1- and IB4-treated groups of 960 +/- 100 and 865 +/- 110 mg, respectively, were less (P less than 0.05) than in untreated controls (3,550 +/- 725 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Complement Activation Is a Secondary Rather than a Causative Factor in Rabbit Pulmonary Artery Ischemia/Reperfusion Injury

We have previously demonstrated that reperfusion of a rabbit lung in vivo after 24 h of unilateral pulmonary artery occlusion results in edema, transient leukopenia, and intravascular leukocyte aggregation. We hypothesized that complement was activated by reperfusion and that this in turn contributed to lung injury. In the preliminary phase of the study, we found that ischemia followed by reperfusion resulted in a drop in C3 to 15 +/- 10% (mean +/- SEM) of the prereperfusion value as compared with no change in a group of control animals that had undergone an identical thoracotomy but without pulmonary artery occlusion and reperfusion (p less than 0.05). We then studied three groups of animals to determine if complement depletion with cobra venom factor (CVF) prior to ischemia and reperfusion would prevent the injury. Rabbits treated with CVF but without occlusion and reperfusion did not develop significant lung edema, with left and right lung wet/dry ratios of 5.32 +/- 0.11 and 5.26 +/- 0.12, respectively. For rabbits that were not treated with CVF but underwent ischemia and reperfusion, the comparable numbers were 6.15 +/- 0.36 and 5.19 +/- 0.32 (p less than 0.05 for right versus left). For CVF-treated rabbits that underwent ischemia and reperfusion, the right/left difference persisted (6.77 +/- 0.48 versus 5.35 +/- 0.14, p less than 0.01). Immunocytochemistry documented C3 deposition in non-CVF rabbits that underwent ischemia and reperfusion but not in CVF-treated rabbits. We conclude that ischemia/reperfusion of the lung results in complement activation, but it is not a complement-dependent injury.

Cardio-pulmonary function evaluated by selective pulmonary arterial occlusion test

We succesfully performed 3 repeat pulmonary resections for recurrent cancer in the contralateral lung, after evaluating cardio-pulmonary function by a unilateral pulmonary arterial occlusion test (UPAO) and a selective pulmonary arterial occlusion test (SPAO). UPAO revealed a marked decreases of cardio-pulmonary reserve capacity in the operated lung. However, SPAO revealed that the cardio-pulmonary reserve capacity in the residual lung tissue would be enough to compensate for the loss of pulmonary vasculature by the second pulmonary resction. Thus we conclude that SPAO is useful in the preoperative evaluation of patients with impaired cardio-pulmonary reserve capacity.

Pulmonary vascular resistance in neonatal swine: Response to right pulmonary artery occlusion, isoproterenol, and prostaglandin E 1

The pulmonary physiological response of adults to unilateral pulmonary artery (PA) occlusion has been well-characterized as resulting in a decrease in the pulmonary vascular resistance (PVR), in order to maintain the same PA pressure and accommodate the entire cardiac output (CO). We evaluated the response of the neonate to unilateral PA occlusion and how this response is altered by infusions of isoproterenol (isuprel) and prostaglandin E 1 (PGE 1) in the neonatal swine model. Twenty farm piglets (five at 1 day, three at 5 days, seven at 14 days, and five at 60 days as controls) underwent left lateral thoracotomy and measurement of PA and left atrial (LA) pressures, CO, and PVR with the right PA open and occluded. To determine if neonatal PVR could be influenced by a vasodilator (indicating the vascular capacity is not fixed) or by an inotrope (indicating the lung is not maximally recruited) this experiment was then repeated with infusions of PGE 1 (a vasodilator) at doses of 0.1, 0.5, and 1.0 μg/kg/min and subsequently with Isuprel (an inotrope and vasodilator) at doses of 0.1, 0.5, 1.0 μg/kg/min. Control measurements taken without unilateral PA occlusion showed that PVR is high at 1 day of age but progressively decreases to a level 89% lower by 60 days of age. The vascular capacity of the neonatal lung is fixed and responds to unilateral PA occlusion with a dramatic increases in PVR. This response cannot be altered by either a vasodilator (PGE 1) or an inotrope (Isuprel) thereby limiting the utility of these drugs in treating neonatal pulmonary hypertension. The adult response pattern to unilateral PA occlusion first appears at 60 days in the pig. These results may have implications for the management of newborns with pulmonary hypertension or neonates undergoing pulmonary resection.

Recurrent High-Altitude Illness Associated with Right Pulmonary Artery Occlusion from Granulomatous Mediastinitis

While travelling across the intermountain West at an altitude of approximately 2,300 m, a 35-year-old man developed symptoms of HAPE. Delay in diagnosis and treatment was nearly lethal. Subsequent evaluation demonstrated unilateral pulmonary artery occlusion, presumably resulting from antecedent granulomatous mediastinitis. This case report supports the concept of evaluating anyone developing HAPE at relatively low altitude for an underlying predisposition.

Neutrophil depletion with hydroxyurea ameliorates lung reperfusion injury

Forty-eight hours of pulmonary artery occlusion followed by four hours of reperfusion results in a syndrome of permeability edema with alveolar infiltration of neutrophils and intravascular neutrophil aggregation. We hypothesized that lung reperfusion injury was mediated in part by neutrophils and attempted to decrease the injury by neutrophil depletion. We placed inflatable balloon occluders around the left pulmonary artery of 13 dogs. Eight treated dogs received 200 mg/kg hydroxyurea daily until the leukocyte count had decreased to 20% of baseline. Dogs then underwent 48 hours of left pulmonary artery occlusion followed by four hours of reperfusion. Five control (untreated) dogs underwent an identical protocol but did not receive hydroxyurea. Both groups of dogs became febrile immediately following reperfusion and had a mild initial decrease in pulmonary artery pressure. Morphologic ranking of the lungs demonstrated hemorrhage in both lungs in untreated dogs, which was significantly greater than in the lungs of the treated dogs ( P < .05 for each lung). The continuously perfused right lung had areas of alveolar flooding in untreated but not in treated dogs. Hemorrhage, edema, and lung dry weight/kilogram body weight all correlated with initial peripheral leukocyte count. We conclude that leukocytes play a role in the injury produced by unilateral pulmonary artery occlusion and reperfusion.

Severe Reduction in End-Tidal PCO2 following Unilateral Pulmonary Artery Occlusion in a Child with Pulmonary Hypertension

Department of Anesthesiology, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands and Department of Anest Kesiology, University Hospital Leiden, Leiden, The Netherlands. Address correspondence to Dr. Schuller, Department of Anesthesiology, University of Amsterdam, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Accepted for publication January 17, 1989.

Combined surgery for lung cancer and giant emphysematous bulla : a case report

A 77-year-old male was admitted because of dyspnea and an abnormal chest X-ray. He had been followed for giant bulla in the left lung for 3 years. On admission, his chest roentgenogram revealed a giant bulla occupying one half of the left lung and a tumor shadow in the right upper lung field. Pulmonary function tests, including %VC, FEV 10 and unilateral pulmonary artery occlusion test, demonstrated the impaired left pulmonary function.Bronchial biopsy of the orifice of S1 a confirmed the diagnosis of well-differentiated squamous cell carcinoma. Simultaneous operation for bilateral lung disease was successfully performed a combination of Naclerio-Langer bullectomy with a stapling device, fibrin glue for the giant emphysematous bulla in the left lower lobe and right upper lobectomy for the lung cancer (t1n1m0 p-stage II) through a median sternotomy.Surgical indications and operative techniques for giant bulla and lung cancer are discussed.

The effects of unilateral pulmonary artery occlusion on pulmonary extravascular water volume and broncho-alveolar lavage under unilateral pulmonary artery occlusion

The effects of unilateral pulmonary artery occlusion on pulmonary extravascular water volume and broncho-alveolar lavage under unilateral pulmonary artery occlusion

Determination of the upper safety limit for lung resection

In lobectomy using animals, a stepwise gradual increase in the volume of lung resection is encountered by elevation of the pulmonary arterial pressure followed by reduction of the cardiac output, when lung resection exceeds a certain limit in volume.In a unilateral pulmonary arterial occlusion test, we compared the exercise-loaded cardiopulmonary function with the postoperative cardiopulmonary function.In consideration of the cardiopulmonary reserve capacity, the physiological safety limit of the lung resection was found to correspond to the total pulmonary vascular resistance of 700 dyne.sec.cm-5/m2 in the contralateral lung.We usually perform lung resection on lung cancer patients regardless of age, provided that they preserve cardiopulmonary function within the above limit.However, patients with this safety limit easily develop postoperative lung complication. The upliftment of the safety limit in lung resection is considered to depend on prevention of postoperative lung complication. This paper pointed out that a large number of resectable cases are included in lung cancer patients in whom lung resection is contraindicated for preservation of ventilatory function.

The effects of ventilation with positive end-expiratory pressure on the bronchial circulation

We studied the effects of ventilation with 10 cm H2O PEEP for 2 h in dogs with temporary unilateral pulmonary arterial occlusion (TUPAO) on bronchial blood flow to the occluded lung using the microsphere dispersion technique. We found that blood flow to the occluded left lung in dogs was 9.9 ml/min (0.122 ml·min−·g−). Within 30 min following the addition of 10 cm H2O PEEP blood flow fell by 70–80% (to 2.3 ml/min) caused both by a 3-fold decrease in vascular conductance and a 25% fall in systemic blood pressure. The reduction in left bronchial blood flow persisted for at least 2 h. We conclude from these data that ventilation with PEEP in the presence of pulmonary artery occlusion has a severe, persistent adverse effect on bronchial blood flow. This reduction in bronchial blood flow is beyond what can be explained by the changes in airway pressure. The additional increase in bronchial vascular resistance may be caused by the increase in lung volume, by reflex bronchial vasoconstriction, or by release of mediators locally.

Influence of pulmonary blood flow and O 2 flux on D O 2 in avian lungs

O 2 diffusing capacity (D O 2 ) was measured in anesthetized, unidirectionally ventilated ducks during hypercapnic hypoxia. D O 2 averaged 78.2 μmol·(min·Torr) −1. This value increased to 97.3 μmol·(min·Torr) −1 after correction for ventilation-perfusion inequality. D O 2 increased when pulmonary O 2 exchange (M O 2 ) and pulmonary blood flow (Ṁ) were increased by either 2,4 dinitrophenol (DNP, ca. 5 mg/kg i.v.) or temporary unilateral pulmonary artery occlusion (TUPAO). D O 2 increased with M O 2 42.4 μmol·(mmol·Torr) −1 (R=0.664), and with Q̇ 80.3 μmol·(L·Torr) −1 (R=0.895). Since there is evidence against expansion of membrane diffusing capacity through recruitment and distention of pulmonary capillaries in avian lungs, we suggest that the close coupling of D O 2 to Q̇ reflects a reduction of functional lung heterogeneity at higher blood flows, perhaps due to better matching of V̇ to D, or D to Q̇.

Physiological dead space and effective parabronchial ventilation in ducks.

Gas exchange in avian lungs is described by a cross-current model that has several differences from the alevolar model of mammalian gas exchange [e.g., end-expired PCO2 greater than arterial PCO2 (PaCO2)]. Consequently the methods available for estimating effective ventilation and physiological dead space (VDphys) in alveolar lungs are not suitable for an analysis of gas exchange in birds. We tested a method for measuring VDphys in birds that is functionally equivalent to the conventional alveolar VDphys. A cross-current O2-CO2 diagram was used to define the ideal expired point (PEi) and VDphys was calculated as from the equation, VDphys = [(PEiCO2--PECO2)/PEiCO2]. VT, where VT is tidal volume. In seven Pekin ducks VDphys was 13.8 ml greater than anatomic dead space and measured changes in the instrument dead space volume. VDphys also reflected changes in ventilation-perfusion inequality induced by temporary unilateral pulmonary arterial occlusion. Bohr dead space, calculated by substituting end-expired PCO2 for PEiCO2, was insensitive to such inhomogeneity. Enghoff dead space, calculated by substituting PaCO2 for PEiCO2, is theoretically incorrect for cross-current gas exchange and was often less than anatomic dead space. We conclude that VDphys is a useful index of avian gas exchange and propose a standard definition for effective parabronchial ventilation (VP) analogous to alveolar ventilation (i.e., VP = VE--VDphys, where VE is total ventilation).

Pulmonary vascular resistance during unilateral pulmonary arterial occlusion in ducks.

We measured mean pulmonary arterial pressure (Ppa) during temporary unilateral pulmonary arterial occlusion (TUPAO) in 10 ducks. Ppa increased from 11.4 +/- 0.8 mmHg during control conditions to 18.8 +/- 1.8 during TUPAO. In 5 of the 10 ducks we also measured mean left atrial pressure (Pla) and cardiac output (Q). In these ducks Ppa significantly increased with TUPAO from 13.9 +/- 0.4 to 22.0 +/- 1.2 mmHg, whereas Pla and Q did not change significantly. Pulmonary vascular resistance (PVR) increased from 10.6 +/- 1.3 to 24.1 +/- 5.3 mmHg X min X 1(-1) on TUPAO. By assuming equal vascular resistance in either lung it can be calculated that the vascular resistance in only one lung was 22.5 +/- 3.5 mmHg X min X 1(-1) during control conditions. Thus doubling flow resulted in no significant change in one lung's vascular resistance. A morphometric study of both lungs of a domestic goose that were rapidly frozen during TUPAO indicated very little compliance in pulmonary blood capillaries. The relative volume of exchange tissue occupied by blood capillaries was 0.28 in the occluded lung and 0.36 in the perfused lung. Surface-to-volume ratios of blood capillaries were 12,524 cm-1 in the occluded lung and 11,056 cm-1 in the perfused lung. We conclude that PVR in birds is relatively insensitive to changes in Q, in contrast to mammals.

Temporary Unilateral Pulmonary Artery Occlusion: A Method for Controlling Swan-Ganz Catheter–Induced Hemoptysis

A patient undergoing mitral and aortic valve replacement suffered catheter-induced pulmonary artery trauma and massive hemoptysis during weaning from cardiopulmonary bypass. Hemorrhage ceased when the ipsi-lateral pulmonary artery was occluded. Forty-eight hours later the temporary band was removed, and the patient did well without further bleeding.

Site of deposition and factors affecting clearance of aerosolized solute from canine lungs.

We determined the influence of several factors on lung solute clearance using aerosolized 99mTc-diethylenetriaminepentaacetate. We used a jet nebulizer-plate separator-balloon system to generate particles with an activity median aerodynamic diameter of 1.1 micron, administered the aerosol in a standard fashion, and determined clearance half times (t1/2) with a gamma-scintillation camera. The following serial studies were performed in five anesthetized, paralyzed, intubated, mechanically ventilated dogs: 1) control, with ventilatory frequency (f) = 15 breaths/min and tidal volume (VT) = 15 ml/kg during solute clearance; 2) repeat control, for reproducibility; 3) increased frequency, with f = 25 breaths/min and VT = 10 ml/kg; 4) positive end-expiratory pressure (PEEP) of 10 cmH2O; 5) unilateral pulmonary arterial occlusion (PAO); and 6) bronchial arterial occlusion (BAO). Control t1/2 was 25 +/- 5 min and did not change in the repeat control, increased frequency, or BAO experiments. PEEP markedly decreased t1/2 to 13 +/- 3 min (P less than 0.01), and PAO increased it to 37 +/- 6 min (P less than 0.05). We conclude that clearance from the lungs by our method is uninfluenced by increased frequency, increases markedly with PEEP, and depends on pulmonary, not bronchial, blood flow.

Microvascular injury distal to unilateral pulmonary artery occlusion.

We explored three questions: 1) does edema fluid accumulate distal to temporary unilateral pulmonary artery occlusion (TUPAO); 2) if so how rapidly does it accumulate; and 3) how is it affected by positive end-expiratory pressure (PEEP)? Using a tracheal divider we measured pulmonary capillary blood flow (Qc), tissue volume (Vt), and diffusing capacity (DLCO) in each lung with a rebreathing method. After control measurements in 12 dogs, the left pulmonary artery was occluded and measurements were repeated at intervals during 4 h of occlusion and 30 min after release of the occlusion. Six of the dogs were ventilated with 10 cmH2O PEEP. Finally the lungs were removed, weighed, and fixed for histology. TUPAO caused a 29% increase in Vt of the left lung without PEEP and a 59% increase with PEEP. After release of the occlusion, Qc and DLCO in the left lung returned to control levels within 30 min in dogs not on PEEP but remained depressed in dogs ventilated with PEEP even though PEEP was removed. At postmortem the left lung weighed more than expected in both groups of dogs but was significantly heavier in those on PEEP. Histology confirmed bronchovascular cuffing with edema and hemorrhage.