Alessandro Rubini

Context: Calcium channel blockers may theoretically exhibit relaxing effects not only on vascular smooth muscle but also on airway smooth muscle. Objective: To investigate possible effects of nifedipine on respiratory mechanics in the rat. Methods: Respiratory system mechanical parameters were measured by the end-inflation occlusion method in the rat in vivo before and after the intraperitoneal administration of nifedipine. Results: We found that nifedipine affects respiratory mechanics, inducing a reduction of airway resistance and of respiratory system elastance, probably because of a relaxing action on airway and parenchimal smooth muscle cells. Conclusion: Should these results be further confirmed by human investigations, a possible role of nifedipine in pharmacological respiratory system’s diseases treatment may be suggested.

The working hypothesis is that the prone position with respect to supine may change the geometric configuration of the lungs inside the chest wall, thus their reciprocal mechanical interactions, leading to possible effects on stress relaxation phenomena and respiratory mechanics. The effects of changing body posture from supine to prone on respiratory system mechanics, particularly on stress relaxation, were investigated in the rat by the end-inflation occlusion method. In the prone with respect to supine position, an increment of the frictional resistance of the airway (from 0.13 ± 0.01 to 0.19 ± 0.02 cm H₂O/l sec⁻¹, p < 0.05) and a decrement of the stress relaxation-linked pressure dissipation (from 0.51 ± 0.05 to 0.45 ± 0.05 cm H₂O/l sec⁻¹, p < 0.01) were found. Respiratory system elastance and total resistive pressure dissipation did not change significantly. Accordingly, a significant increase of the frictional “ohmic” mechanical inspiratory work of breathing and a decrease of the visco-elastic work of inspiration were demonstrated, while no significant changes occurred for the total mechanical work of breathing and its total resistive and elastic components. It is concluded that postural changes affect the visco-elastic characteristics of the respiratory system and the related stress relaxation phenomena by influencing the disposition and relation of the lungs inside the chest wall and their relative geometrical configuration, and the interaction phenomena of the constitutive parenchymal structures, i.e., elastin and collagen fibers. Since the prone position resulted in no serious or disadvantageous respiratory system mechanical derangement, it is suggested it may be usefully applied in nursing or for therapeutic goals.

In a prospective randomized double-blind study, we evaluated the post-operative biological and clinical effects of a single preoperative hyperbaric-treatment the day before surgery for pancreatic ductal adenocarcinoma. Twenty one patients were randomized and divided into two groups: group-A (10 patients, 48%) were exposed to a HyperBaric Oxygen (HBO) session the day before intervention [Pre-Intervention Day (PID)], group-B (11 patients, 52%) breathed air for 40 min in a hyperbaric chamber pressurized to 1.15 ATA (placebo group). For all patients blood samples were obtained before HBO treatment or the placebo procedure (T0); at the end of HBO session or placebo procedure (T1); on the first post-operative day (POD)(T2) and on seventh POD(T3) day, measuring interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12 and TNF-α, recording postoperative pancreatic fistula (POPF), biliary-fistula, fever, intra-abdominal abscess, bleeding, pulmonary complications, delayed gastric emptying and requirement for post-operative antibiotics. The results of the present pilot study suggest that a single preoperative hyperbaric oxygen treatment on the day before surgery may reduce the complication rate in pancreatic resection.

We measured respiratory ratio (RR), pulmonary ventilation (VE) and end-tidal carbon dioxide partial pressure (ETPCO2) at rest and during cycling aerobic workloads (20%, 40%, 60% of estimated maximal oxygen uptake). Measurements were taken after overnight fasting and after an oral glucose load. RR, VE and ETPCO2 increased with workload. Glucose load caused RR and VE increments at rest (0.75 ± 0.01 vs. 0.86 ± 0.02, p < 0.01, and 10.8 ± 0.43 vs. 12.1 ± 0.49 l/min, p < 0.01, respectively) and for each workload (20% estimated maximal oxygen uptake: 0.77 ± 0.01 vs. 0.855 ± 0.02, p < 0.01, and 16.2 ± 0.73 vs. 17.7 ± 0.8 l/min, p < 0.01; 40% estimated maximal oxygen uptake: 0.76 ± 0.02 vs. 0.82 ± 0.01, p < 0.01, and 25.9 ± 1.1 vs. 28.3 ± 1.3 l/min, p < 0.05; 60% estimated maximal oxygen uptake: 0.85 ± 0.02 vs. 0.91 ± 0.02, p < 0.01, and 37.4 ± 1.7 vs. 40.9 ± 1.9 l/min, p < 0.05) but ETPCO2 did not change. The differences in RR before and after glucose load became smaller as the workload increased. Linear regression analysis of VE and carbon dioxide output yielded virtually identical results for both fasting and glucose load conditions. We have concluded that: a) for the metabolic carbon dioxide load increment due to glucose-induced RR increment, the physiological response is an increase of VE at all workloads. This response modulates constant ETPCO2 values; b) on workload increment, skeletal muscle increasingly utilises more and more glycogen stores, regardless of the blood glucose availability. This reduces the usefulness of dietary manipulations decreasing carbon dioxide metabolic load during muscular work in respiratory failure; c) the absolute value of metabolic carbon dioxide load exerts a role in ventilation regulation at rest and during aerobic exercise.

We previously demonstrated that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the “ohmic” and viscoelastic components of inspiratory resistances, probably because of increased oxygen tension toxic effects. We presently investigated the possible consequences of a single exposure to 2.5-atmospheres absolute air (hyperbarism) lasting 90 min. We used the end-inflation occlusion method on anesthetized rats after about 15 min from previous exposure to hyperbarism. The method allows the measurements of respiratory system elastance and of the ohmic and viscoelastic components of airway resistance, which respectively depend on the Newtonian pressure dissipation due to the ohmic airway resistance to airflow and on the viscoelastic pressure dissipation caused by respiratory system tissue stress relaxation. The expressions of inducible NO synthase (iNOS) and endothelial NO synthase (eNOS) in the lung’s tissues were also investigated, together with the histological characteristics of lung tissue. Data were compared with those obtained in control animals and in previously studied animals exposed to hyperoxic hyperbarism. Unlike with hyperoxic hyperbarism, hyperbarism per se did not change significantly the parameters of respiratory mechanics in the control animals (respiratory system elastance and ohmic and viscoelastic resistances were 2.01 ± 0.17 vs. 1.74 ± 0.08 cm H₂O/ml, and 0.13 ± 0.02 vs. 0.13 ± 0.03 and 0.425 ± 0.04 vs. 0.33 ± 0.03 cm H₂O/ml s⁻¹ in control vs. experimental animals, respectively, none significantly different), nor did it induce evident effects on lung histology. An increment of both iNOS and eNOS expressions was documented instead (0.50 ± 0.05 vs. 0.75 ± 0.07 and 1.04 ± 0.1 and 1.4 ± 0.15, respectively). Our results indicate that, at variance with hyperoxic hyperbarism, the acute exposure to only hyperbarism does not affect either the elastic or the resistive respiratory system properties, or lung histology.