Effects of cigarette smoke and chronic hypoxia on airways remodeling and resistance. Clinical significance

Abstract

Previously we have reported that association of cigarette smoke (CS) and chronic hypoxia (CH) interact positively to physiopathologically remodel pulmonary circulation. In present study we have exposed guinea pigs to CS smoke (four cigarettes/day; 3 months; CS) and to chronic hypoxia (12% O(2), 15 days; CH) alone or in combination (CSCH animals) and evaluated airways remodeling and resistance assessed as Penh (enhance pause). We measured Penh while animals breathe air, 10% O(2) and 5% CO(2) and found that CS and CH animals have higher Penh than controls; Penh was even larger in CSCH animals. A rough parallelism between Penh and thickness of bronchiolar wall and muscular layer and Goblet cell number was noticed. We conclude that CS and CH association accelerates CS-induced respiratory system damage, evidenced by augmented airway resistance, bronchial wall thickness and muscularization and Goblet cell number. Our findings would suggest that appearance of hypoxia would aggravate any preexisting pulmonary pathology by increasing airways resistance and reactivity.

A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD

“…However, with the increasing awareness of the clinically important extrapulmonary manifestations linked to COPD, a number of studies have now begun to try to elucidate the mechanisms governing skeletal muscle dysfunction, whether or not accompanied by loss of muscle mass. Consistent with COPD, previous studies have shown marked reduction in body weight gain [15,16] as well as increased oxidative stress [6] in guinea pig hindlimb muscles following only 3 months of daily CS exposure. In contrast, macroscopic data suggest that mouse models poorly reproduce the systemic effects of human COPD.…”

“…Moreover, no changes in the proportion of Type I and Type II fibres can be detected between CS-exposed and shams [6]. Detailed information on exposure protocols, pulmonary function data and histological assessments from this study, which demonstrate that observations in lung function and pulmonary structural changes of COPD patients are indeed replicated in the CS-exposed guinea pigs, have been reported in two separate publications [15,19]. …”

“…To access whether the current guinea pig model show a transcriptional response, we used our newly developed microarray platform (Additional file 1) with mRNA extracted from whole lung and two metabolically distinct hindlimb muscles ( gastro and soleus) sampled from shams and nose-only CS exposed animals approximately 1 month after a significant ( P <0.01) decrease in body mass gain could first be detected [15]. Indeed, we were able to identify a relatively large number of genes differentially expressed in all three tissues from all experimental groups (Figure 1; see Additional file 6 for individual gene changes).…”

“…The guinea pig ( Cavia porcellus ), one of the most popular animal models to study infectious diseases [14], has been shown to tolerate CS exposure without the rapid weight loss observed in other pre-clinical models [15]. However, promisingly long-term CS-exposed guinea pigs fail to appropriately gain body weight compared to age-matched sham controls [6,16].…”

Intermittent hypoxia and diet-induced obesity: effects on oxidative status, sympathetic tone, plasma glucose and insulin levels, and arterial pressure

“…Further comparison of MV in O vs. OIH groups showed that MV was smaller in every condition in OIH ( ϩ P Ͻ 0.05, ϩϩ P Ͻ 0.01 OIH vs. O); that is, IH treatment also diminished total ventilation in animals fed high fat. Penh (a unitless index) is the unique indicator of airway reactivity and airway resistance that can be obtained in conscious, unrestrained animals and therefore is freed from the bias imposed by anesthesia or restraining stress [see (53)]. We found that only in the O group did Penh show a tendency to increase in every condition, reaching statistical significance (P Ͻ 0.05) while breathing 7% O 2 and 5% CO 2 (i.e., at highest air flow; data not shown).…”