Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans.

We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.

Hypoxic ventilatory response and arterial desaturation during heavy work.

Arterial desaturation in athletes during intense exercise has been reported by several authors, yet the etiology of this phenomenon remains obscure. Inadequate pulmonary ventilation, due to a blunted respiratory drive, has been implicated as a factor. To investigate the relationship between the ventilatory response to hypoxia, exercise ventilation, and arterial desaturation, 12 healthy male subjects [age, 23.8 +/- 3.6 yr; height, 181.6 +/- 5.6 cm; weight, 73.7 +/- 6.2 kg; and maximal O2 uptake (VO2max), 63.0 +/- 2.2 ml.kg-1 min-1] performed a 5-min treadmill test at 100% of VO2max, during which arterial blood samples and ventilatory data were collected every 15 s. Alveolar PO2 (PAO2) was determined using the ideal gas equation. On a separate occasion the ventilatory response to isocapnic hypoxia was measured. Arterial PO2 decreased by an average of 29 Torr during the test, associated with arterial desaturation [arterial O2 saturation (SaO2) 92.0%]. PAO2 was maintained; however, alveolar-arterial gas pressure difference increased progressively to greater than 40 Torr. Minimal hypocapnia was observed, despite marked metabolic acidosis. There was no significant correlation observed between hypoxic drives and ventilation-to-O2 uptake ratio or SaO2 (r = 0.1 and 0.06, respectively, P = NS). These data support the conclusions that hypoxic drives are not related to maximal exercise ventilation or to the development of arterial desaturation during maximal exercise.

Ventilation-perfusion inequality during normoxic and hypoxic exercise in the emu.

Many avian species exhibit an extraordinary ability to exercise under hypoxic condition compared with mammals, and more efficient pulmonary O(2) transport has been hypothesized to contribute to this avian advantage. We studied six emus (Dromaius novaehollandaie, 4-6 mo old, 25-40 kg) at rest and during treadmill exercise in normoxia and hypoxia (inspired O(2) fraction approximately 0.13). The multiple inert gas elimination technique was used to measure ventilation-perfusion (V/Q) distribution of the lung and calculate cardiac output and parabronchial ventilation. In both normoxia and hypoxia, exercise increased arterial Po(2) and decreased arterial Pco(2), reflecting hyperventilation, whereas pH remained unchanged. The V/Q distribution was unimodal, with a log standard deviation of perfusion distribution = 0.60 +/- 0.06 at rest; this did not change significantly with either exercise or hypoxia. Intrapulmonary shunt was <1% of the cardiac output in all conditions. CO(2) elimination was enhanced by hypoxia and exercise, but O(2) exchange was not affected by exercise in normoxia or hypoxia. The stability of V/Q matching under conditions of hypoxia and exercise may be advantageous for birds flying at altitude.

Pulmonary gas exchange during exercise in athletes. I. Ventilation-perfusion mismatch and diffusion limitation.

To investigate pulmonary gas exchange during exercise in athletes, 10 high aerobic capacity athletes (maximal aerobic capacity = 5.15 +/- 0.52 l/min) underwent testing on a cycle ergometer at rest, 150 W, 300 W, and maximal exercise (372 +/- 22 W) while trace amounts of six inert gases were infused intravenously. Arterial blood samples, mixed expired gas samples, and metabolic data were obtained. Indexes of ventilation-perfusion (VA/Q) mismatch were calculated by the multiple inert gas elimination technique. The alveolar-arterial difference for O2 (AaDO2) was predicted from the inert gas model on the basis of the calculated VA/Q mismatch. VA/Q heterogeneity increased significantly with exercise and was predicted to increase the AaDO2 by > 17 Torr during heavy and maximal exercise. The observed AaDO2 increased significantly more than that predicted by the inert gas technique during maximal exercise (10 +/- 10 Torr). These data suggest that this population develops diffusion limitation during maximal exercise, but VA/Q mismatch is the most important contributor (> 60%) to the wide AaDO2 observed.

Pulmonary gas exchange during exercise in pigs.

Increased ventilation-perfusion (VA/Q) inequality is observed in approximately 50% of humans during heavy exercise and contributes to the widening of the alveolar-arterial O2 difference (A-aDO2). Despite extensive investigation, the cause remains unknown. As a first step to more direct examination of this problem, we developed an animal model. Eight Yucatan miniswine were studied at rest and during treadmill exercise at approximately 30, 50, and 85% of maximal O2 consumption (VO2 max). Multiple inert-gas, blood-gas, and metabolic data were obtained. The A-aDO2 increased from 0 +/- 3 (SE) Torr at rest to 14 +/- 2 Torr during the heaviest exercise level, but arterial PO2 (PaO2) remained at resting levels during exercise. There was normal VA/Q inequality [log SD of the perfusion distribution (log) = 0.42 +/- 0.04] at rest, and moderate increases (log = 0.68 +/- 0.04, P < 0.0001) were observed with exercise. This result was reproducible on a separate day. The VA/Q inequality changes are similar to those reported in highly trained humans. However, in swine, unlike in humans, there was no inert gas evidence for pulmonary end-capillary diffusion limitation during heavy exercise; there was no systematic difference in the measured PaO2 and the PaO2 as predicted from the inert gases. These data suggest that the pig animal model is well suited for studying the mechanism of exercise-induced VA/Q inequality.

Effect of prolonged heavy exercise on pulmonary gas exchange in horses.

During short-term maximal exercise, horses have impaired pulmonary gas exchange, manifested by diffusion limitation and arterial hypoxemia, without marked ventilation-perfusion (VA/Q) inequality. Whether gas exchange deteriorates progressively during prolonged submaximal exercise has not been investigated. Six thoroughbred horses performed treadmill exercise at approximately 60% of maximal oxygen uptake until exhaustion (28-39 min). Multiple inert gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained at rest and 5-min intervals during exercise. Oxygen uptake, cardiac output, and alveolar-arterial PO2 gradient were unchanged after the first 5 min of exercise. Alveolar ventilation increased progressively during exercise, from increased tidal volume and respiratory frequency, resulting in an increase in arterial PO2 and decrease in arterial PCO2. At rest there was minimal VA/Q inequality, log SD of the perfusion distribution (log SDQ) = 0.20. This doubled by 5 min of exercise (log SDQ = 0.40) but did not increase further. There was no evidence of alveolar-end-capillary diffusion limitation during exercise. However, there was evidence for gas-phase diffusion limitation at all time points, and enflurane was preferentially overretained. Horses maintain excellent pulmonary gas exchange during exhaustive, submaximal exercise. Although VA/Q inequality is greater than at rest, it is less than observed in most mammals and the effect on gas exchange is minimal.

Sustained submaximal exercise does not alter the integrity of the lung blood-gas barrier in elite athletes.

The extreme thinness of the pulmonary blood-gas barrier results in high mechanical stresses in the capillary wall when the capillary pressure rises during exercise. We have previously shown that, in elite cyclists, 6-8 min of maximal exercise increase blood-gas barrier permeability and result in higher concentrations of red blood cells, total protein, and leukotriene B4 in bronchoalveolar lavage (BAL) fluid compared with results in sedentary controls. To test the hypothesis that stress failure of the barrier only occurs at the highest level of exercise, we performed BAL in six healthy athletes after 1 h of exercise at 77% of maximal O2 consumption. Controls were eight normal nonathletes who did not exercise before BAL. In contrast with our previous study, we did not find higher concentrations of red blood cells, total protein, and leukotriene B4 in the exercising athletes compared with control subjects. However, higher concentrations of surfactant apoprotein A and a higher surfactant apoprotein A-to-phospholipid ratio were observed in the athletes performing prolonged exercise, compared with both the controls and the athletes from our previous study. These results suggest that, in elite athletes, the integrity of the blood-gas barrier is altered only at extreme levels of exercise.

Pulmonary gas exchange during exercise in highly trained cyclists with arterial hypoxemia.

The causes of exercise-induced hypoxemia (EIH) remain unclear. We studied the mechanisms of EIH in highly trained cyclists. Five subjects had no significant change from resting arterial PO(2) (Pa(O(2)); 92.1 +/- 2.6 Torr) during maximal exercise (C), and seven subjects (E) had a >10-Torr reduction in Pa(O(2)) (81.7 +/- 4.5 Torr). Later, they were studied at rest and during various exercise intensities by using the multiple inert gas elimination technique in normoxia and hypoxia (13.2% O(2)). During normoxia at 90% peak O(2) consumption, Pa(O(2)) was lower in E compared with C (87 +/- 4 vs. 97 +/- 6 Torr, P < 0.001) and alveolar-to-arterial O(2) tension difference (A-aDO(2)) was greater (33 +/- 4 vs. 23 +/- 1 Torr, P < 0. 001). Diffusion limitation accounted for 23 (E) and 13 Torr (C) of the A-aDO(2) (P < 0.01). There were no significant differences between groups in arterial PCO(2) (Pa(CO(2))) or ventilation-perfusion (VA/Q) inequality as measured by the log SD of the perfusion distribution (logSD(Q)). Stepwise multiple linear regression revealed that lung O(2) diffusing capacity (DL(O(2))), logSD(Q), and Pa(CO(2)) each accounted for approximately 30% of the variance in Pa(O(2)) (r = 0.95, P < 0.001). These data suggest that EIH has a multifactorial etiology related to DL(O(2)), VA/Q inequality, and ventilation.

Effect of prolonged, heavy exercise on pulmonary gas exchange in athletes.

During maximal exercise, ventilation-perfusion inequality increases, especially in athletes. The mechanism remains speculative. We hypothesized that, if interstitial pulmonary edema is involved, prolonged exercise would result in increasing ventilation-perfusion inequality over time by exposing the pulmonary vascular bed to high pressures for a long duration. The response to short-term exercise was first characterized in six male athletes [maximal O2 uptake (V(O2)max) = 63 ml x kg-1 x min-1] by using 5 min of cycling exercise at 30, 65, and 90% V(O2) max. Multiple inert-gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained. Resting log SD of the perfusion distribution (log SDQ) was normal [0.50 +/- 0.03 (SE)] and increased with exercise (log SDQ = 0.65 +/- 0.04, P < 0.005), alveolar-arterial O2 difference increased (to 24 +/- 3 Torr), and end-capillary pulmonary diffusion limitation occurred at 90% V(O2)max. The subjects recovered for 30 min, then, after resting measurements were taken, exercised for 60 min at approximately 65% V(O2)max. O2 uptake, ventilation, cardiac output, and alveolar-arterial O2 difference were unchanged after the first 5 min of this test, but log SDQ increased from 0.59 +/- 0.03 at 5 min to 0. 66 +/- 0.05 at 60 min (P < 0.05), without pulmonary diffusion limitation. Log SDQ was negatively related to total lung capacity normalized for body surface area (r = -0.97, P < 0.005 at 60 min). These data are compatible with interstitial edema as a mechanism and suggest that lung size is an important determinant of the efficiency of gas exchange during exercise.

Pulmonary gas exchange during exercise in women: effects of exercise type and work increment.

Exercise-induced arterial hypoxemia (EIAH) has been reported in male athletes, particularly during fast-increment treadmill exercise protocols. Recent reports suggest a higher incidence in women. We hypothesized that 1-min incremental (fast) running (R) protocols would result in a lower arterial PO(2) (Pa(O(2))) than 5-min increment protocols (slow) or cycling exercise (C) and that women would experience greater EIAH than previously reported for men. Arterial blood gases, cardiac output, and metabolic data were obtained in 17 active women [mean maximal O(2) uptake (VO(2 max)) = 51 ml. kg(-1). min(-1)]. They were studied in random order (C or R), with a fast VO(2 max) protocol. After recovery, the women performed 5 min of exercise at 30, 60, and 90% of VO(2 max) (slow). One week later, the other exercise mode (R or C) was similarly studied. There were no significant differences in VO(2 max) between R and C. Pulmonary gas exchange was similar at rest, 30%, and 60% of VO(2 max). At 90% of VO(2 max), Pa(O(2)) was lower during R (mean +/- SE = 94 +/- 2 Torr) than during C (105 +/- 2 Torr, P < 0.0001), as was ventilation (85.2 +/- 3.8 vs. 98.2 +/- 4.4 l/min BTPS, P < 0.0001) and cardiac output (19.1 +/- 0.6 vs. 21.1 +/- 1.0 l/min, P < 0.001). Arterial PCO(2) (32.0 +/- 0.5 vs. 30.0 +/- 0.6 Torr, P < 0.001) and alveolar-arterial O(2) difference (A-aDO(2); 22 +/- 2 vs. 16 +/- 2 Torr, P < 0.0001) were greater during R. Pa(O(2)) and A-aDO(2) were similar between slow and fast. Nadir Pa(O(2)) was

Measurement of cardiac output during exercise by open-circuit acetylene uptake.

Noninvasive measurement of cardiac output (QT) is problematic during heavy exercise. We report a new approach that avoids unpleasant rebreathing and resultant changes in alveolar PO(2) or PCO(2) by measuring short-term acetylene (C(2)H(2)) uptake by an open-circuit technique, with application of mass balance for the calculation of QT. The method assumes that alveolar and arterial C(2)H(2) pressures are the same, and we account for C(2)H(2) recirculation by extrapolating end-tidal C(2)H(2) back to breath 1 of the maneuver. We correct for incomplete gas mixing by using He in the inspired mixture. The maneuver involves switching the subject to air containing trace amounts of C(2)H(2) and He; ventilation and pressures of He, C(2)H(2), and CO(2) are measured continuously (the latter by mass spectrometer) for 20-25 breaths. Data from three subjects for whom multiple Fick O(2) measurements of QT were available showed that measurement of QT by the Fick method and by the C(2)H(2) technique was statistically similar from rest to 90% of maximal O(2) consumption (VO(2 max)). Data from 12 active women and 12 elite male athletes at rest and 90% of VO(2 max) fell on a single linear relationship, with O(2) consumption (VO(2)) predicting QT values of 9.13, 15.9, 22.6, and 29.4 l/min at VO(2) of 1, 2, 3, and 4 l/min. Mixed venous PO(2) predicted from C(2)H(2)-determined QT, measured VO(2), and arterial O(2) concentration was approximately 20-25 Torr at 90% of VO(2 max) during air breathing and 10-15 Torr during 13% O(2) breathing. This modification of previous gas uptake methods, to avoid rebreathing, produces reasonable data from rest to heavy exercise in normal subjects.

Pulmonary hemodynamic response to exercise in subjects with prior high-altitude pulmonary edema.

Individuals with a prior history of (susceptible to high altitude pulmonary edema (HAPE-S) have high resting pulmonary arterial pressures, but little data are available on their vascular response to exercise. We studied the pulmonary vascular response to exercise in seven HAPE-S and nine control subjects at sea level and at 3,810 m altitude. At each location, both normoxic (inspired PO2 = 148 Torr) and hypoxic (inspired PO2 = 91 Torr) studies were conducted. Pulmonary hemodynamic measurements included pulmonary arterial and pulmonary arterial occlusion pressures. A multiple regression analysis demonstrated that the pulmonary arterial pressure reactivity to exercise was significantly greater in the HAPE-S group. This reactivity was not influenced by altitude or oxygenation, implying that the response was intrinsic to the pulmonary circulation. Pulmonary arterial occlusion pressure reactivity to exercise was also greater in the HAPE-S group, increasing with altitude but independent of oxygenation. These findings suggest an augmented flow-dependent pulmonary vasoconstriction and/or a reduced vascular cross-sectional area in HAPE-S subjects.

Exercise-induced VA/Q inequality in subjects with prior high-altitude pulmonary edema.

Ventilation-perfusion (VA/Q) mismatch has been shown to increase during exercise, especially in hypoxia. A possible explanation is subclinical interstitial edema due to high pulmonary capillary pressures. We hypothesized that this may be pathogenetically similar to high-altitude pulmonary edema (HAPE) so that HAPE-susceptible people with higher vascular pressures would develop more exercise-induced VA/Q mismatch. To examine this, seven healthy people with a history of HAPE and nine with similar altitude exposure but no HAPE history (control) were studied at rest and during exercise at 35, 65, and 85% of maximum 1) at sea level and then 2) after 2 days at altitude (3,810 m) breathing both normoxic (inspired Po2 = 148 Torr) and hypoxic (inspired Po2 = 91 Torr) gas at both locations. We measured cardiac output and respiratory and inert gas exchange. In both groups, VA/Q mismatch (assessed by log standard deviation of the perfusion distribution) increased with exercise. At sea level, log standard deviation of the perfusion distribution was slightly higher in the HAPE-susceptible group than in the control group during heavy exercise. At altitude, these differences disappeared. Because a history of HAPE was associated with greater exercise-induced VA/Q mismatch and higher pulmonary capillary pressures, our findings are consistent with the hypothesis that exercise-induced mismatch is due to a temporary extravascular fluid accumulation.

Liver viability after ischemia-reperfusion.

Lack of a reproducible model to quantitatively assess hepatocellular injury following ischemia has made it difficult to assess new strategies for minimizing hepatic injury. We studied the progression of hepatocellular injury after ischemia and ischemia with reperfusion in rats. Irreversible injury was quantitated using a triphenyltetrazolium chloride assay that was shown to correlate with ultrastructural changes. Adenosine triphosphate decreased to 36% of basal values after 30 minutes, but returned to normal with reperfusion with no decrease in viability. In contrast, viability fell by 30% after 60 minutes of ischemia, and by 64% when 60 minutes of ischemia was followed by reperfusion. We conclude that reperfusion of ischemic liver increases the degree of irreversible damage. The model employed here seems to be useful for studying ischemic and reperfusion injury in the liver.

The effect of salbutamol on performance in elite nonasthmatic athletes.

The effect of salbutamol on performance was studied in seven male nonasthmatic highly trained (VO2max > or = 60 ml.kg-1 x min-1) cyclists. Salbutamol (S = 2 puffs = 200 micrograms) or placebo (P) was administered by metered-dose inhaler, through a spacer device, 20 min prior to testing in a double-blind, randomized cross-over design. Testing sessions on a cycle ergometer included the measurement of maximal oxygen uptake (VO2max), peak power, maximal heart rate, and pulmonary function. A timed sprint to exhaustion was performed after 45 min of exercise at 70% of VO2max, and a Wingate anaerobic test was used to measure total work and peak power. There was a nonsignificant decrease in VO2max (P = 63.5 +/- 3.2; S = 62.6 +/- 3.3 ml.kg-1 x min-1). No difference was found in peak power, maximum heart rate, endurance sprint time, Wingate peak power, or total work. After an anticipated baseline increase was taken into account, the pattern of change in FEV1 over time did not differ between salbutamol and placebo. It was concluded that a therapeutic dose of aerosol salbutamol does not have an ergogenic effect in elite nonasthmatic athletes, and it is therefore recommended that inhaled salbutamol continue to be permitted in international competition for individuals with exercise induced bronchospasm.

Effects of dietary cholesterol and triglycerides on lipid concentrations in liver, plasma, and bile.

Dietary cholesterol (CHL) and triglycerides (TG) can influence plasma, hepatic, and biliary lipid composition, but effects on lipids in these three compartments during the early stages of CHL gallstone formation have not been studied in parallel. We fed prairie dogs diets containing one of four test oils (safflower, coconut, olive, or menhaden) at either 5 or 40% of calories, in the presence of 0 or 0.34% CHL, for 3 wk. In the absence of dietary CHL, increases in dietary TG produced 50-200% increases in the concentrations of biliary CHL and hepatic cholesteryl ester (CE), while the concentrations of hepatic free CHL (FC) as well as plasma FC and CE remained relatively unchanged. Increasing dietary CHL to 0.34% resulted in increases in hepatic FC of approximately 50% for all four fats regardless of whether they were supplied at 5 or 40% of calories. CHL supplementation caused more pronounced increases in biliary CHL (200-400%), hepatic CE (50-200%), plasma FC (up to 100%), and plasma CE (up to 150%), and these increases were exacerbated by concurrent supplementation of dietary fat and CHL (biliary CHL: 300-700%; hepatic CE: 100-250%; plasma FC: up to 165%; plasma CE: 100-350%). These results indicate that enhanced secretion of biliary CHL and, to a lesser extent, increased synthesis of hepatic CE, may be primary mechanisms for maintaining the hepatic FC pool. Furthermore, dietary CHL and high levels of fat intake are independent risk factors for increasing biliary CHL concentrations, and adverse effects on lipid concentrations in plasma and bile tend to be exacerbated by ingestion of diets rich in both fat and CHL.

Typing field isolates of infectious bronchitis by the plaque-reduction test.

A technique is described for typing field isolates of infectious bronchitis virus by plaque-reduction assay of the serum antibody response of chickens experimentally infected with such isolates. Also reported are use of the technique with field isolates and a comparison of results obtained in plaque-reduction assay and in tracheal-ring organ-culture assay.

Evaluation of the hemagglutination-inhibition test for measuring the response of chickens to avian infectious bronchitis virus vaccination.

An infectious bronchitis virus (IBV) hemagglutination-inhibition (HI) test was used to assay serum-antibody titers after IBV vaccination of IBV-susceptible specific-pathogen-free broilers and commercial layers. Three-week-old broilers were vaccinated via eye-drop with IBV strains that represent the antigenic spectrum of commercial vaccines--Holland, Massachusetts 41 (41 Ms), Connecticut 46, Florida 18288, or JMK strain--and revaccinated 3 weeks later with either the same or a heterologous strain. Weekly serum samples were tested by IBV HI with homologous and heterologous antigens. Vaccinates, except for those vaccinated with the Holland strain, were HI-positive with homologous but not heterologous antigens by 1 to 2 weeks postvaccination. Sixteen-week-old IBV-vaccinated commercial layers were revaccinated with IBV Holland 52 (H 52) strain and subsequently infected with Arkansas 99 (Ark 99) and SE 17 strains. In contrast to the limited HI cross-reactivity of serum from IBV-vaccinated broilers, there were extensive cross-reactions in HI tests with 41 Ms, H 52, Ark 99, and SE 17 antigens of revaccinated layers. These results demonstrate that the IBV HI test is more strain-specific than previous reports indicate, especially when the test samples are from early postvaccination.

Reversion to virulence of chicken-passaged infectious bronchitis vaccine virus.

Serial passage of two infectious bronchitis virus (IBV) vaccine strains in chickens enhanced their capacity to increase the incidence and severity of Mycoplasma synoviae (MS) airsacculitis. Included in this report were the mild Massachusetts-type Connaught strain and the Arkansas 99 vaccine strain of IBV. The Connaught strain and one of two Ark 99 vaccine strains passaged in chickens increased the incidence of airsacculitis markedly compared with nonpassaged virus. The other Ark 99 vaccine virus already exacerbated MS airsacculitis, before passage in chickens, and its influence did not increase on passage. All IBV strains studied to date have either possessed this trait or reacquired it on passage in the natural host.