Tom S. Hurst

Predictors of longitudinal changes in pulmonary function among swine confinement workers.

OBJECTIVEnTo determine predictors of longitudinal changes in pulmonary function in swine confinement workers.nnnDESIGNnLongitudinal study conducted from November 1989 to June 1991 and January 1994 to May 1995.nnnSETTINGnSwine confinement workers in Saskatchewan.nnnPARTICIPANTSnForty-two swine confinement workers who were studied in 1989/90 and studied again in 1994/95.nnnRESULTSnOf 98 male swine confinement workers (mean age SD 36.3 11.1 years) studied at baseline, 42 were studied again five years following. Complete information on baseline across-shift pulmonary function (preshift forced expiratory volume in 1 s [FEV1], forced vital capacity [FVC], and every 2 h FEV1 and FVC during the shift), and five-year follow-up pulmonary function (with FEV1 and FVC) were available on all 42 subjects. Mean across-shift changes (preshift measurement to last measurement of the day) at baseline were -159. 8 61.7 mL in FEV1 and -35.3 65.6 mL in FVC. Mean annual rate change between baseline and follow-up for FEV1 was -53.9 61.7 mL/year and for FVC -48.9 71.6 mL/year. After adjusting for age, height, smoking and hours spent in the barn, the baseline across-shift change in FEV1 and FVC was a significant predictor of annual rate change in FEV1 (P=0.01) and FVC (P=0.02), respectively. To determine the effects of indoor air quality on longitudinal lung function decline, indoor air environmental measurements were analysed. Complete information on respiratory health and indoor air quality was available on 34 of the 42 subjects. Assessment of indoor environment of swine barns included a summer and winter measurement for airborne dust, gases and endotoxin levels. After adjusting for age, height, smoking, ammonia and hours spent in the barn, the endotoxin level (Eu/mg)was a significant predictor of annual rate change for FEV1 but not FVC.nnnCONCLUSIONSnThese results suggest that shift change is an important predictor of longitudinal changes in lung function in swine confinement workers and that endotoxin exposures may mediate annual decline in FEV1 in these workers.

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.

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.