Peculiarities of the influence of mitochondrial ATP-dependent K+ channels activation on the function of external respiration under experimental pneumonia

The studies were performed on male Wistar rats weighing 250-270 with experimental pneumonia (EP) induced by the method of A.M. Kulik. The animals were divided into the following groups: 1 – control; 2 - experimental pneumonia; 3 (first experimental group) - animals, which in parallel with the simulation of pneumonia were intraperitoneally administered uridine at a dose of 0.3 mg/100 g of body weight (daily within 1 week); 4 (second experimental group) - animals in which uridine was administered daily starting from day 4 (at the peak of pneumonia). Animals with EP were examined at 5th (n = 10), 9th (n = 8) and 12th (n = 6) days of the disease development, as well as 1 (n = 5) and 2 (n = 5) months after EP modeling. It was shown that in the first experimental group on the 5th day of EP development, an isoventilator restructuring of respiration was observed. In this group, from day 12 to the end of the study, there was a stenoventilator restructuring of breathing, which was characterized by an increase in tidal volume, alveolar ventilation, oxygen consumption and, accordingly, an increase in oxygen extraction from the alveoli and in the oxygen effect of the respiratory cycle. It can be assumed that in this group, an increase in the intensity of metabolism is provided by the effective activity of the respiratory system. In the second experimental group, isoventilator changes in respiration were observed with a gradual decrease in oxygen consumption and other indicators of the respiratory system efficiency. After 2 months, these changes became significant. Thus, we can talk about significant differences in the effect of uridine on the function of external respiration (i.e., apparently, on the activity of the mitochondrial ATP-dependent K+ channel) during EP, which depended on the period of onset of uridine administration. Application of uridine immediately (1st experimental group) looks more effective and even has a stimulating effect on the respiratory function over a long period of experiment. The administration of uridine starting from the 4 partially normalizes the respiration parameters. However, after 1 month there is a depression of the functions of the respiratory system, which, probably, may further worsen. The reasons for the differences in the identified dynamics require further investigation.

Searching for synergy: combining systemic daptomycin treatment with localised phage therapy for the treatment of experimental pneumonia due to MRSA

Objective Bacteriophages (or phages) are viruses which infect and lyse bacteria. The therapeutic use of phages (phage therapy) has regained attention in the last decades as an alternative strategy to treat infections caused by antimicrobial-resistant bacteria. In clinical settings it is most likely that phages are administered adjunct to antibiotics. For successful phage therapy it is therefore crucial to investigate different phage-antibiotic combinations in vivo. This study aimed to elucidate the combinatorial effects of systemic daptomycin and nebulised bacteriophages for the treatment of experimental pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Results Using a rat model of ventilator-associated pneumonia caused by MRSA, the simultaneous application of intravenous daptomycin and nebulised phages was not superior to aerophage therapy alone at improving animal survival (55% vs. 50%), or reducing bacterial burdens in the lungs, or spleen. Thus, this combination does not seem to be of benefit for use in patients with MRSA pneumonia.

Impact of positive biphasic pressure during low and high inspiratory efforts in Pseudomonas aeruginosa-induced pneumonia

Background During pneumonia, normal alveolar areas coexist adjacently with consolidated areas, and high inspiratory efforts may predispose to lung damage. To date, no study has evaluated different degrees of effort during Biphasic positive airway pressure (BIVENT) on lung and diaphragm damage in experimental pneumonia, though largely used in clinical setting. We aimed to evaluate lung damage, genes associated with ventilator-induced lung injury (VILI) and diaphragmatic injury, and blood bacteria in pressure-support ventilation (PSV), BIVENT with low and high inspiratory efforts in experimental pneumonia. Material and methods Twenty-eight male Wistar rats (mean ± SD weight, 333±78g) were submitted Pseudomonas aeruginosa-induced pneumonia. After 24-h, animals were ventilated for 1h in: 1) PSV; 2) BIVENT with low (BIVENTLow-Effort); and 3) BIVENT with high inspiratory effort (BIVENTHigh-Effort). BIVENT was set at Phigh to achieve VT = 6 ml/kg and Plow at 5 cmH2O (n = 7/group). High- and low-effort conditions were obtained through anaesthetic infusion modulation based on neuromuscular drive (P0.1). Lung mechanics, histological damage score, blood bacteria, and expression of genes related to VILI in lung tissue, and inflammation in diaphragm tissue. Results Transpulmonary peak pressure and histological damage score were higher in BIVENTHigh-Effort compared to BIVENTLow-Effort and PSV [16.1 ± 1.9cmH2O vs 12.8 ± 1.5cmH2O and 12.5 ± 1.6cmH2O, p = 0.015, and p = 0.010; median (interquartile range) 11 (9–13) vs 7 (6–9) and 7 (6–9), p = 0.021, and p = 0.029, respectively]. BIVENTHigh-Effort increased interleukin-6 expression compared to BIVENTLow-Effort (p = 0.035) as well as expressions of cytokine-induced neutrophil chemoattractant-1, amphiregulin, and type III procollagen compared to PSV (p = 0.001, p = 0.001, p = 0.004, respectively). Tumour necrosis factor-α expression in diaphragm tissue and blood bacteria were higher in BIVENTHigh-Effort than BIVENTLow-Effort (p = 0.002, p = 0.009, respectively). Conclusion BIVENT requires careful control of inspiratory effort to avoid lung and diaphragm damage, as well as blood bacteria. P0.1 might be considered a helpful parameter to optimize inspiratory effort.