Variability in pulmonary function following rapid altitude ascent to the Amundsen-Scott South Pole station.

The impact of acute altitude exposure on pulmonary function is variable. A large inter-individual variability in the changes in forced expiratory flows (FEFs) is reported with acute exposure to altitude, which is suggested to represent an interaction between several factors influencing bronchial tone such as changes in gas density, catecholamine stimulation, and mild interstitial edema. This study examined the association between FEF variability, acute mountain sickness (AMS) and various blood markers affecting bronchial tone (endothelin-1, vascular endothelial growth factor (VEGF), catecholamines, angiotensin II) in 102 individuals rapidly transported to the South Pole (2835 m). The mean FEF between 25 and 75% (FEF(25-75)) and blood markers were recorded at sea level and after the second night at altitude. AMS was assessed using Lake Louise questionnaires. FEF(25-75) increased by an average of 12% with changes ranging from -26 to +59% from sea level to altitude. On the second day, AMS incidence was 36% and was higher in individuals with increases in FEF(25-75) (41 vs. 22%, P = 0.05). Ascent to altitude induced an increase in endothelin-1 levels, with greater levels observed in individuals with decreased FEF(25-75). Epinephrine levels increased with ascent to altitude and the response was six times larger in individuals with decreased FEF(25-75). Greater levels of endothelin-1 in individuals with decreased FEF(25-75) suggest a response consistent with pulmonary hypertension and/or mild interstitial edema, while epinephrine may be upregulated in these individuals to clear lung fluid through stimulation of ß(2)-adrenergic receptors.

Pulmonary function in patients with reduced left ventricular function: influence of smoking and cardiac surgery.

STUDY OBJECTIVE: The impact of stable, chronic heart failure on baseline pulmonary function remains controversial. Confounding influences include previous coronary artery bypass or valve surgery (CABG), history of obesity, stability of disease, and smoking history. DESIGN: To control for some of the variables affecting pulmonary function in patients with chronic heart failure, we analyzed data in four patient groups, all with left ventricular (LV) dysfunction (LV ejection fraction [LVEF] < or =35%): (1) chronic heart failure, nonsmokers, no CABG (n = 78); (2) chronic heart failure, nonsmokers, CABG (n = 46); (3) chronic heart failure, smokers, no CABG (n = 40); and (4) chronic heart failure, smokers, CABG (n = 48). Comparisons were made with age- and gender-matched patients with a history of coronary disease but no LV dysfunction or smoking history (control subjects, n = 112) and to age-predicted norms. RESULTS: Relative to control subjects and percent-predicted values, all groups with chronic heart failure had reduced lung volumes (total lung capacity [TLC] and vital capacity [VC]) and expiratory flows (p < 0.05). CABG had no influence on lung volumes and expiratory flows in smokers, but resulted in a tendency toward a reduced TLC and VC in nonsmokers. Smokers with chronic heart failure had reduced expiratory flows compared to nonsmokers (p < 0.05), indicating an additive effect of smoking. Diffusion capacity of the lung for carbon monoxide (DLCO) was reduced in smokers and in subjects who underwent CABG, but not in patients with chronic heart failure alone. There was no relationship between LV size and pulmonary function in this population, although LV function (cardiac index and stroke volume) was weakly associated with lung volumes and DLCO. CONCLUSIONS: We conclude that patients with chronic heart failure have primarily restrictive lung changes with smoking causing a further reduction in expiratory flows.

Airway function after cyclooxygenase inhibition during hyperpnea-induced bronchoconstriction in guinea pigs.

Airway function deteriorates significantly on cessation of exercise or isocapnic hyperventilation challenges but is largely preserved during the challenge in humans and guinea pigs. PGE(2), an endogenous bronchodilator, might be responsible for the preservation of lung function during hyperventilation (HV). We hypothesized that PGE(2) might have a protective effect during HV, partially explaining the minimal changes in respiratory system resistance (Rrs) usually seen during HV in humans and guinea pigs. Therefore, changes in Rrs were measured during and after HV in anesthetized, mechanically ventilated guinea pigs treated with flurbiprofen (FBN) or placebo. With HV, there was an initial bronchodilation that was unaffected by FBN. Rrs then increased with time during HV, an effect that was blocked by FBN. After HV, Rrs increased further in all groups, but the increase in Rrs was less in the FBN-treated groups. FBN treatment reduced the PGE(2) concentration slightly in lung lavage fluid compared with placebo. We found no enhancement or refractoriness of the Rrs response to repeat bouts of HV and no effect of FBN treatment on the response of Rrs to repeat HV. These results suggest that a constrictor PG is released during and possibly after HV and that the post-HV increase in Rrs is the sum of effects of the PG released during HV and a second constrictor mechanism operating after HV. We found no evidence for bronchodilator PG during or after HV in the guinea pig.

Ventilatory constraints during exercise in patients with chronic heart failure.

We examined the degree of ventilatory constraint in patients with a history of chronic heart failure (CHF; n = 11; mean +/- SE age, 62 +/- 4 years; cardiac index [CI], 2.0 +/- 0.1; and ejection fraction [EF], 24 +/- 2%) and in control subjects (CTLS; n = 8; age, 61 +/- 5 years; CI, 2.6 +/- 0.3) by plotting the tidal flow-volume responses to graded exercise in relationship to the maximal flow-volume envelope (MFVL). Inspiratory capacity (IC) maneuvers were performed to follow changes in end-expiratory lung volume (EELV) during exercise, and the degree of expiratory flow limitation was assessed as the percent of the tidal volume (VT) that met or exceeded the expiratory boundary of the MFVL. CHF patients had significantly (p < 0.05) reduced baseline pulmonary function (FVC, 76 +/- 4%; FEV(1), 78 +/- 4% predicted) relative to CTLS (FVC, 99 +/- 4%; FEV(1), 102 +/- 4% predicted). At peak exercise, oxygen consumption (VO(2)) and minute ventilation (V(E)) were lower in CHF patients than in CTLS (VO(2), 17 +/- 2 vs 32 +/- 2 mL/kg/min; VE, 56 +/- 4 vs 82 +/- 6 L/min, respectively), whereas VE/carbon dioxide output was higher (42 +/- 4 vs 29 +/- 5). In CTLS, EELV initially decreased with light exercise, but increased as VE and expiratory flow limitation increased. In contrast, the EELV in patients with CHF remained near residual volume (RV) throughout exercise, despite increasing flow limitation. At peak exercise, IC averaged 91 +/- 3% and 79 +/- 4% (p < 0.05) of the FVC in CHF patients and CTLS, respectively, and flow limitation was present over > 45% of the VT in CHF patients vs < 25% in CTLS (despite the higher VE in CTLS). The least fit and most symptomatic CHF patients demonstrated the lowest EELV, the greatest degree of flow limitation, and a limited response to increased inspired carbon dioxide during exercise, all consistent with VE constraint. We conclude that patients with CHF commonly breathe near RV during exertion and experience expiratory flow limitation. This results in VE constraint and may contribute to exertional intolerance.

A new dimension in suspension fusion techniques with polyethylene glycol.

Polyethylene glycol (PEG) induces the hybridization of mammalian cells at a much higher frequency when the cells are attached to a substrate during treatment than when the cells are treated in suspension. Since many cell types, e.g., lymphocytes, cannot attach to a substrate, a new technique for the PEG-induced fusion of cells in suspension was developed. This technique, referred to as "pancake fusion," is based on the centrifugation of suspended cells onto a coverslip and the PEG treatment of the cells on the coverslip as if they were attached to a substrate. With this technique, the frequency of hybridization of human white blood cells, which are incapable of attaching to a substrate, can be greatly increased.

Polyethylene glycol-induced mammalian cell hybridization: effect of polyethylene glycol molecular weight and concentration.

The effects of polyethylene glycol (PEG) molecular weight and concentration on mammalian cell hybridization were studied. The peak hybridization-inducing activity with all grades of PEG from 400-6000 was found to occur in the concentration range of 50-55%. However, changes in concentration were seen to have different quantitative effects with different grades of PEG. For monolayer fusions, PEG 1000 at 50% seems to be the optimal combination of PEG molecular weight and concentration, in terms of both efficiency of hybridization and relative insensitivity to dilution effects.