Irvin Mayers

Neutrophil-mediated acute lung injury after extracorporeal perfusion

A pulmonary injury of varying severity occurs routinely after cardiopulmonary bypass. We studied the pulmonary complications of partial cardiopulmonary bypass in four groups of dogs to better define the injury and to evaluate the efficacy of two interventions (addition of a leukocyte filter or cyclooxygenase inhibition) on preservation of systemic oxygenation. All animals received a standard anesthetic (pentobarbital, morphine, and vecuronium) and, after sternotomy, three groups of animals received 3 hours of partial cardiopulmonary bypass. The animals were randomized to receive partial bypass alone (n = 6), indomethacin and bypass (n = 5), or a leukocyte filter and bypass (n = 5). A fourth group (n = 5) did not receive bypass and served as a time control. We measured blood gases and also obtained histologic samples to assess the degree of lung injury. We found that bypass alone caused a significant reduction (p < 0.05) in arterial oxygen tension 1 hour after the conclusion of bypass (175 +/- 53 mm Hg) compared with prebypass values (357 +/- 41 mm Hg). Pretreatment with indomethacin ameliorated the decrease in arterial oxygen tension from prebypass to postbypass values (477 +/- 50 mm Hg versus 339 +/- 57 mm Hg, respectively). Similarly use of a leukocyte filter reduced the decline in arterial oxygen tension from prebypass to postbypass values (440 +/- 71 mm Hg versus 311 +/- 73 mm Hg, respectively). We believe that indomethacin ameliorates the decline in systemic oxygenation associated with bypass by augmentation of hypoxic pulmonary vasoconstriction and that the leukocyte filter acted to reduce pulmonary edema and thereby minimized intrapulmonary shunt.

Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs☆

PURPOSEnThe lazaroids are a new class of potent free-radical scavengers. We tested whether U-74389G, a lazaroid, could attenuate some of the adverse cardiopulmonary effects of sepsis.nnnMETHODSnDogs were randomized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchange, they were then randomized to receive either 0.2 mg/kg endotoxin or a saline infusion. Measurements of hemodynamics and gas exchange were repeated. The study was concluded 70 minutes after endotoxin infusion and the lungs were then removed for histologic evaluation.nnnRESULTSnIn endotoxin-treated control animals, PO2 decreased (278 +/- 123 mm Hg to 67 +/- 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% +/- 1.1% to 28.2% +/- 11.4%, P < .05) after endotoxin. Pretreatment with U-74389G attenuated the decrease in PO2 (476 +/- 61 mm Hg to 226 +/- 143) and the increase in intrapulmonary shunt (12.6% +/- 6.1% to 14.3% +/- 6.8%) observed after endotoxin. The extent of lung injury and systemic hemodynamics were similar between control or U-74389G-treated dogs.nnnCONCLUSIONSnA free-radical-scavenger can attenuate the gas exchange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics.

High-frequency oscillatory ventilation of a canine bronchopleural fistula

We hypothesized that during high-frequency oscillatory ventilation (HFOV) of a central bronchopleural fistula (BPF), gas flow through the fistula (Vleak) should vary with ventilatory frequency. In six pentobarbital-anesthetized, open-chested dogs, we inserted a cannula into the left lower lobe bronchus. After 30 min of HFOV at 5 Hz (fistula closed), they received four periods of HFOV (fistula open) at frequencies of 5, 10, 15, and 20 Hz. With the fistula open, we could adequately ventilate at all four frequencies. Vleak ranged between 5.1 +/- 0.7 and 4.1 +/- 0.7 L/min and it was not significantly different at any frequency by analysis of variance. Airway opening pressure (Pao) was 3.9 +/- 0.6 cm H2O with the fistula closed. Pao decreased significantly to 1.9 +/- 0.2 cm H2O during 5 Hz ventilation (fistula open). Pao at the other frequencies was similar to fistula-closed ventilation. We believe that expiratory flow limitation at frequencies greater than 5 Hz may explain our findings.

Changes inPetCO2 and pulmonary blood flow after bronchial occlusion in dogs

The use ofPetCO2 in detecting accidental bronchial intubation was investigated. ThePetCO2 was measured in six mongrel dogs after occluding the left mainstem bronchus in three conditions; pentobarbital anaesthesia, 0.8% halothane insufflation together withpentobarbital anaesthesia, and simultaneous left pulmonary artery and bronchial airway occlusion with intravenous pentobarbital anaesthesia. An external flow probe measured left pulmonary artery blood flow. ThePetCO2 decreased after bronchial occlusion during pentobarbital (35 ± 3 vs 30 ± 5 mmHg) and halothane-pentobarbital (30 ± 6 vs 25 ± 6 mmHg) conditions (P < 0.05). However, within three minutes of bronchial occlusion, the values ofPetCO2 had returned to their pre-occlusion values. After five minutes of bronchial occlusion pulmonary artery blood flow in the non-ventilated lung decreased (P < 0.05) during pentobarbital (770 ± 533 ml · min−1 vs 575 ± 306 ml · min−1) and halothane-pentobarbital (495 ± 127 ml · min−1 vs 387 ± 178ml · min−1) conditions. Simultaneous bronchial and pulmonary artery occlusion prevented any changes inPetCO2. It was concluded that accidental one- lung ventilation results in small and transient decreases inPetCO2. A redistribution of blood flow from the nonventilated to ventilated lung occurs which restoresPetCO2 to the original values observed with twolung ventilation.RésuméL’utilisation de laPetCO2 pour détecter l’intubation bronchique accidentelle a été évaluée. LaPetCO2 a été mesurée chez six chiens bâtards après avoir obstrué la bronche souche gauche sous trois conditions: une anesthésie avec pentobarbital, une anesthésie avec pentobarbital et insufflation d’halothane à 0,8%, et une anesthésie avec pentobarbital et obstruction simultanée de l’artère pulmonaire gauche et de la voie aérienne bronchique gauche. Une sonde à débit externe a été utilisée pour mesurer le débit sanguin de l’artère pulmonaire gauche. LaPetCO2 diminuait après l’obstruction bronchique lors de l’anesthésie avec pentobarbital (35 ± 3 vs 35 ± 5 mmHg) et l’anesthésie avec halothanepentobarbital (30 ± 6 vs 25 ± 6 mmHg) (P < 0,05). Cependant, moins de trois minutes après l’obstruction bronchique, les valeurs de laPetCO2 étaient revenues à leurs valeurs préocclusion. Cinq minutes après l’occlusion bronchique, les débits sanguins de l’artère pulmonaire du poumon non ventilé diminuaient (P < 0,05) durant l’anesthésie au pentobarbital (770 ± 533 ml · min−1 vs 575 ± 306 ml · min−1) et à l’halothane-pentobarbital (495 ± 127 ml · min−1 vs 387 ± 178 ml · min−1). L’occlusion simultanée de l’artère pulmonaire et de la bronche prévenait tous les changements de laPetCO2. En conclusion, la ventilation accidentelle d’un seul poumon conduit à une légère diminution transitoire de laPetCO2. Une redistribution du débit sanguin du poumon non ventilé vers le poumon ventilé se produit, ce qui rétablit laPetCO2 à sa valeur originate observée lors de la ventilation à deux poumons.

Halothane inhibits hypoxic pulmonary vasoconstriction in the presence of cyclooxygenase blockade

Using an isolated lung the effects of halothane on hypoxic pulmonary vasoconstriction (HPV) were studied in the presence of cyclooxygenase blockade. The pulmonary vasculature can be divided into arterial, middle and venous segment resistances. Analysis of the vascular pressure-flow relationship further separates resistance into a flow dependant resistance (1/slope) and a zero-flow pressure intercept (Pcrit). We ventilated six lobes with control (35 per cent O2) and hypoxic (three per cent O2) gas mixtures with the addition of either 0, 0.5, 1.0, or 2.0 per cent halothane. We found that after addition of indomethacin (5 mg · kg− 1), ventilation with three per cent O2 increased total resistance by 87 per cent over baseline with the increase primarily in the middle vascular segment. During normoxic ventilationPcrit was 7.9 cm H2O and this increased significantly with hypoxia to 11.5 cm H2O). Only 2.0 per cent halothane blocked the increases in middle segment resistance and inPcrit. We conclude that following cyclooxygenase blockade, halothane inhibits HPV by acting on middle segment vessels.RésuméNous avons étudié, sur poumon isolé, les effets de l’halothane sur la vasoconstriction pulmonaire hypoxique (HPV) en présence d’inhibiteur de la cyclooxygénase. Les secteurs artériel, médian et veineux contribuent successivement à la résistance vasculaire pulmonaire. En analysant les courbes pressiondébit, on peut calculer la résistance (1/pente) et la pression d’ouverture (PCRIT). NOUS ventilions six lobes pulmonaires avec de I’oxygène à 35 pour cent (contrôle) ou à trois pour cent (hypoxie) en y ajoutant 0, 0,5, 1,0 ou 2,0 pour cent d’halothane. Après l’injection de 5 mg · kg− 1 d’indométhacine et avec trois pour cent d’O2, la résistance totale augmentait de 87 pour cent par rapport au contrôle, surtout en secteur médian. LaPcrit était significativement moins élévee en condition normoxique, passant de 7,9 à 11,5 cmH2O en condition hypoxique. Il fallait deux pour cent d’halothane pour bloquer cette augmentation de resistance et de pression d’ouverture. Done, malgré une inhibition de la cyclooxygénase, l’halothane renverse l’HPV du secteur vasculaire médian.

Cardiac output effects of high-frequency oscillatory ventilation in normal dogs

We compared the hemodynamic effects of high-frequency oscillatory ventilation (HFOV) with conventional continuous positive pressure ventilation (CPPV). Six mongrel dogs were anesthetized with chloralose and evaluated over a range of mean airway pressures (Pao) during CPPV and HFOV. Pao during HFOV was measured by allowing alveolar pressure to come into equilibrium with airway opening pressure and was set to equal mean Pao during CPPV. Pao during CPPV was set by adding positive end-expiratory pressure (PEEP) of 0, 5, 10, and 15 cm H2O. Transmural pulmonary capillary wedge pressures (Pwp) were maintained at near 11 mm Hg in both groups during all four ventilatory periods. Cardiac output as measured in triplicate by thermal dilution was similar between HFOV and CPPV at each level of mean airway pressure. After matching mean airway pressure and transmural Pwp we were unable to find any sparing effect of HFOV on cardiac output over a wide range of airway pressures. We conclude that there is not an independent effect of HFOV on cardiac output.

Vasodilators do not abolish pulmonary vascular critical closing pressure

To examine whether the critical closing pressure (Pcrit) of the pulmonary vasculature is dependent upon vasomotor tone, we measured Pcrit in six dog lobes before and after the administration of vasodilators. We evaluated the pressure-flow (P-Q) relationship in zone 2 flow conditions in situ perfused dog lobe (control period). We calculated Pcrit as the mean extrapolated zero-flow pressure intercepts for the P-Q relationship. We also used arterial and venous occlusions under zone 3 conditions to partition pulmonary vascular resistance into arterial, middle and venous segment resistances. We then repeated all measurements following administration of papaverine (150 micrograms/ml) and sodium nitroprusside (200 micrograms/min) into the venous reservoir (vasodilator period). Resistance in all three vascular segments was significantly reduced during vasodilator conditions. Pcrit decreased from 3.68 +/- 0.76 cm H2O to 2.53 +/- 0.92 cm H2O during control and vasodilator periods respectively (P less than 0.05). The slopes of the P-Q relationships were similar during both conditions. Our data support a model in which vasomotor tone normally sets Pcrit but in which the pulmonary vasculature can exhibit the phenomenon of critical closure even with vasomotor tone pharmacologically ablated.

Doxapram preserves the pulmonary vascular response to hypoxia in endotoxin-treated canine lung lobes☆

Abstract We studied the direct effects of doxapram on pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in normal canine lung lobes (N = 6) before and after endotoxin administration. We used the technique of arterial and venous occlusions to subdivide pulmonary vascular resistance into total (Rtot), arterial, venous, and middle (Rm) segment resistances. We sequentially ventilated the lobes with control (35% O 2 ) and hypoxic (3% 0 2 ) gas mixtures prior to and following both low-dose (20 μg/kg/min) and high-dose (200 μg/kg/min) infusions of doxapram. We then administered endotoxin (1 mg/kg) and repeated control and hypoxic ventilatory periods during low-dose doxapram infusion. An additional six lobes were identically treated except that saline was infused instead of doxapram, and all measurements were repeated. Rtot and Rm increased ( P P P 2 O/mL/min and 0.027 ± 0.015 cm H 2 O/mL/min, respectively) but not during saline infusion (0.007 ± 0.004 cm H 2 O/mL/min and 0.006 ± 0.003 cm H 2 O/mL/min, respectively). We conclude that doxapram can directly augment hypoxic pulmonary vasoconstriction even in the absence of systemic neuronal or humeral input. Of more clinical importance, doxapram infusion may allow expression of hypoxic pulmonary vasoconstriction following endotoxin. This in turn could act to improve ventilation/ perfusion matching and also to decrease pulmonary edema.

Vasodilators or vasoconstrictors prevent hypoxic pulmonary vasoconstriction

Abstract Prostaglandins modulate pulmonary vascular resistance (PVR) and hypoxic pulmonary vasoconstriction (HPV). We studied the effects of a prostaglandin vasodilator (PGI 2 ) and vasoconstrictor (PGE 2 ) in the pulmonary circulation and compared these effects to the nonprostaglandin vasodilator sodium nitroprusside (SNP) and vasoconstrictor norepinephrine (NE) during 35% and 3% O 2 ventilation. Pulmonary vascular resistance was divided into arterial, middle (Rm), and venous segmental resistances in 20 isolated left lower canine lobes using a stop-flow technique. Pulmonary vascular resistance was also analyzed as the slope and intercept (P CRIT ) of the pressure-flow relationship. We found that only PGI 2 specifically prevented the increase in Rm and P CRIT due to hypoxia. Sodium nitro prusside predominantly decreased venous segment resistance and, even in the presence of SNP, hypoxia significantly ( P 2 O/mL/min) compared with control ventilation (0.0078 ± 0.0043 cm H 2 O/mL/min). Both PGE 2 and NE increased PVR primarily by increasing the venous segmental resistance. After the addition of PGE 2 or NE, hypoxic ventilation did not result in further increases of Rm or P CRIT . We conclude that PGI 2 but not SNP selectively inhibits HPV and that neither PGE 2 nor NE further augment HPV. The direct effect of these drugs on the pulmonary circulation and their resultant changes in systemic oxygen delivery must be considered prior to their use in the clinical setting.