Reducing Aortic Barotrauma and Vascular Extracellular Matrix Degradation by Pacemaker-Mediated QRS Widening.

Background The extent of pressure-related damage might be related to acceleration rate of the applied pressure (peak dP/dt) in the vascular system. In this study, we sought to determine whether dP/dt applied to the aortic wall (aortic dP/dt) and in turn vascular extracellular matrix degradation can be mitigated via modulation of left ventricular (LV) contractility (LV dP/dt) by pacemaker-mediated desynchronization. Methods and Results First, in 34 patients, changes in aortic dP/dt values in 3 aortic segments in response to pacemaker-mediated stepwise QRS widening leading to gradual desynchronization of the LV contraction by means of steadily changed atrioventricular delay (AVD) with temporary dual-chamber pacing was examined before and after beta-blocker (15 mg IV metoprolol) administration. Second, serum matrix metalloproteinase-9 levels were measured in the 20 patients with permanent pacemaker while they were on sinus rhythm with normal QRS width and 3 weeks after wide QRS rhythm ensured by dual pacing, dual sensing, and dual response to sensing with short AVD. LV dP/dt substantially correlated with dP/dt measured in ascending (r=0.83), descending (r=0.89), and abdominal aorta (r=0.96). QRS width strongly correlated with dP/dt measured in ascending (r=-0.95), descending (r=-0.92), and abdominal (r=-0.96) aortic segments as well. In patients with permanent pacemaker, wide QRS rhythm led to a significant reduction in serum matrix metalloproteinase-9 levels (from 142.5±32.9 pg/mL to 87.5±32.4 pg/mL [P<0.001]) at the end of 3 weeks follow-up. Conclusions QRS prolongation by short AVD dual pacing, dual sensing, and dual response to sensing results in concomitant decreases in peak dP/dt values in the LV and in all aortic segments with or without background beta-blocker administration, which in turn led to a significant reduction in circulating matrix metalloproteinase-9 levels. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03665558.

Molecular Mechanisms of Ventilator-Induced Lung Injury.

OBJECTIVE: Mechanical ventilation (MV) has long been used as a life-sustaining approach for several decades. However, researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly, which is termed as ventilator-induced lung injury (VILI). This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms. DATA SOURCES: This review was based on articles in the PubMed database up to December 2017 using the following keywords: "ventilator-induced lung injury", "pathogenesis", "mechanism", and "biotrauma". STUDY SELECTION: Original articles and reviews pertaining to mechanisms of VILI were included and reviewed. RESULTS: The pathogenesis of VILI was defined gradually, from traditional pathological mechanisms (barotrauma, volutrauma, and atelectrauma) to biotrauma. High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas, volutrauma, and atelectrauma. In the past two decades, accumulating evidence have addressed the importance of biotrauma during VILI, the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release, reactive oxygen species production, complement activation as well as mechanotransduction. CONCLUSIONS: Barotrauma, volutrauma, atelectrauma, and biotrauma contribute to VILI, and the molecular mechanisms are being clarified gradually. More studies are warranted to figure out how to minimize lung injury induced by MV.

[L-carnitine decreases oxidative stress induced by experimental hypobaric hypoxia].

INTRODUCTION: It is known that exposure to severe hypobaric hypoxia induces changes of reactive oxygen species (ROS) and antioxidant systems. L-carnitine, a natural compound, has an antioxidant effect and decreases lipid peroxidation. The aim of this study was to investigate the protective effects of L-carnitine treatment on oxidative stress induced by exposure to hypobaric hypoxia. MATERIAL AND METHODS: 30 male Wistar rats were divided into 3 equal-size groups: 1st group - a control group, kept in normoxic conditions; 2nd group - rats exposed to hypobaric hypoxia in the barochamber (simulated high altitude equivalent to 5500 meters) for a 14-day placebo; 3rd group - rats exposed to hypobaric hypoxia for 14 days and treated with L-carnitine (L-carnitine, 100 mg/kg) every day. After 14 days, the serum levels of lipid peroxides expressed by the value of malondialdehyde (MDA), and the serum levels of carbonylated proteins (CP), glutathione (GSH) and donor hydrogen ability (DHA) were determined for all rats. RESULTS: The results indicated an increase in MDA and CP levels, after the exposure to hypobaric hypoxia. L-carnitine significantly decreased (p <0.05) the levels of the MDA and CP and significantly increased (p <0.05) the serum antioxidant capacity: glutathione and DHA. CONCLUSION: This study suggests that the administration of L-carnitine can be beneficial in attenuating the oxidative stress associated with exposure to high altitude.

Hypercapnia: is there a cause for concern?

Concern that barotrauma may lead to further deterioration in pulmonary function in patients with ARDS has stimulated interest in developing methods of reducing it. These new modalities have had limited acceptance. The reasons for this include technical difficulties, associated complications, and the hypercapnia produced by the reduction in minute ventilation associated with diminished peak inspiratory pressure (PIP). Recent reports have shown that hypercapnia does not produce many of the adverse effects previously attributed to it. We studied the effects of moderate levels of hypercapnia produced by inverse ratio ventilation with low tidal volumes in patients with severe pulmonary dysfunction (Lung Injury Score > or = 2.5). The mean peak PaCO2 and PIP of the group were 63.3 +/- 15.7 mm Hg and 44.0 +/- 12.4 cm H2O, respectively. We found no adverse effects on cardiac function, oxygen utilization, or long-term neurologic function in patients after hypercapnia. We conclude that moderate levels of hypercapnia are safe, and may be permitted in the care of patients with severe pulmonary dysfunction.

PO2 levels in middle ear effusions and middle ear mucosa.

We measured PO2 values in mucoid and serous middle ear effusions (M-MEE, S-MEE) and in the middle ear mucosa of patients with otitis media with effusion (OME) and compared these values with those obtained from patients with middle ear barotrauma (MEBT). The mean and S.D. values of PO2 in M-MEE, S-MEE and MEBT effusions were 28.9 +/- 11.3, 31.5 +/- 9.5 and 37.0 +/- 15.4 mmHg, respectively; the mean and S.D. values in mucosa were 27.1 +/- 11.9, 27.0 +/- 13.2 and 32.5 +/- 1.0 mmHg, respectively. In health, PO2 values in middle ear mucosa are regulated by its blood supply, oxygen solubility in blood and the blood-to-cavity partial pressure gradient of the gas. When the Eustachian tube (ET) function is severely impaired, PO2 values in the middle ear air cavity depend on the mucosal condition, though some studies have shown a lack of relationship between ET function and PO2 values. Our results show that PO2 values in MEBT are consistently higher than in OME, suggesting that the attributable factor could be a better ET function in MEBT.