Pathophysiological profile of non-ventilated lung injury in healthy female pigs undergoing mechanical ventilation.

BACKGROUND: Lung regions excluded from mechanical insufflation are traditionally assumed to be spared from ventilation-associated lung injury. However, preliminary data showed activation of potential mechanisms of injury within these non-ventilated regions (e.g., hypoperfusion, inflammation). METHODS: In the present study, we hypothesized that non-ventilated lung injury (NVLI) may develop within 24 h of unilateral mechanical ventilation in previously healthy pigs, and we performed extended pathophysiological measures to profile NVLI. We included two experimental groups undergoing exclusion of the left lung from the ventilation with two different tidal volumes (15 vs 7.5 ml/kg) and a control group on bilateral ventilation. Pathophysiological alteration including lung collapse, changes in lung perfusion, lung stress and inflammation were measured. Lung injury was quantified by histological score. RESULTS: Histological injury score of the non-ventilated lung is significantly higher than normally expanded lung from control animals. The histological score showed lower intermediate values (but still higher than controls) when the tidal volume distending the ventilated lung was reduced by 50%. Main pathophysiological alterations associated with NVLI were: extensive lung collapse; very low pulmonary perfusion; high inspiratory airways pressure; and higher concentrations of acute-phase inflammatory cytokines IL-6, IL-1ß and TNF-α and of Angiopoietin-2 (a marker of endothelial activation) in the broncho-alveolar lavage. Only the last two alterations were mitigated by reducing tidal volume, potentially explaining partial protection. CONCLUSIONS: Non-ventilated lung injury develops within 24 h of controlled mechanical ventilation due to multiple pathophysiological alterations, which are only partially prevented by low tidal volume.

Respiratory failure that occurs in cases of atelectasis, pneumonia and acute hypoxemic respiratory failure a machine called a mechanical ventilator is used to move air in and out of the patient's lungs. We know that the use of a mechanical ventilator can induce lung injury, but complete exclusion from ventilation might not be safe. Using pig lungs to mimic the patient's lungs, we evaluated the use of a ventilator against non-use. We find that the lungs sustained injury regardless of ventilator use. The non-ventilated lung injury consisted of collapse (lack of expansion), low amount of blood flow, high ventilation pressure and inflammatory response. Physicians should be aware that also the regions of the lung not receiving ventilation are at risk of injury.

Cardiac magnetic resonance findings and prognosis in type 1 myotonic dystrophy.

BACKGROUND: Cardiac involvement is a major determinant of prognosis in type 1 myotonic dystrophy (DM1), but limited information is available about myocardial remodeling and tissue changes. The aim of the study was to investigate cardiac magnetic resonance (CMR) findings and their prognostic significance in DM1. METHODS: We retrospectively identified all DM1 patients referred from a neurology unit to our CMR laboratory from 2009 to 2020. RESULTS: Thirty-four patients were included (aged 45 ±â€Š12, 62% male individuals) and compared with 68 age-matched and gender-matched healthy volunteers (43 male individuals, age 48 ±â€Š15 years). At CMR, biventricular and biatrial volumes were significantly smaller (all P < 0.05), as was left ventricular mass (P < 0.001); left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) were significantly lower (all P < 0.01). Five (15%) patients had a LVEF less than 50% and four (12%) a RVEF less than 50%. Nine patients (26%) showed mid-wall late gadolinium enhancement (LGE; 5 ±â€Š2% of LVM), and 14 (41%) fatty infiltration. Native T1 in the interventricular septum (1041 ±â€Š53 ms) was higher than for healthy controls (1017 ±â€Š28 ms) and approached the upper reference limit (1089 ms); the extracellular volume was slightly increased (33 ±â€Š2%, reference <30%). Over 3.7 years (2.0-5.0), 6 (18%) patients died of extracardiac causes, 5 (15%) underwent device implantation; 5 of 21 (24%) developed repetitive ventricular ectopic beats (VEBs) on Holter monitoring. LGE mass was associated with the occurrence of repetitive VEBs (P = 0.002). Lower LV stroke volume (P = 0.017), lower RVEF (P = 0.016), a higher LVMi/LVEDVI ratio (P = 0.016), fatty infiltration (P = 0.04), and LGE extent (P < 0.001) were associated with death. CONCLUSION: DM1 patients display structural and functional cardiac abnormalities, with variable degrees of cardiac muscle hypotrophy, fibrosis, and fatty infiltration. Such changes, as evaluated by CMR, seem to be associated with the development of ventricular arrhythmias and a worse outcome.

Integrating electrical impedance tomography and transpulmonary pressure monitoring to personalize PEEP in hypoxemic patients undergoing pressure support ventilation.

Monitoring with electrical impedance tomography (EIT) during a decremental PEEP trial has been used to identify the PEEP that yields the optimal balance of pulmonary overdistension and collapse. This method is based on pixel-level changes in respiratory system compliance and depends on fixed or measured airway driving pressure. We developed a novel approach to quantify overdistension and collapse during pressure support ventilation (PSV) by integrating transpulmonary pressure and EIT monitoring and performed pilot tests in three hypoxemic patients. We report that our experimental approach is feasible and capable of identifying a PEEP that balances overdistension and collapse in intubated hypoxemic patients undergoing PSV.

Pathophysiology and Clinical Meaning of Ventilation-Perfusion Mismatch in the Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) remains an important clinical challenge with a mortality rate of 35-45%. It is being increasingly demonstrated that the improvement of outcomes requires a tailored, individualized approach to therapy, guided by a detailed understanding of each patient's pathophysiology. In patients with ARDS, disturbances in the physiological matching of alveolar ventilation (V) and pulmonary perfusion (Q) (V/Q mismatch) are a hallmark derangement. The perfusion of collapsed or consolidated lung units gives rise to intrapulmonary shunting and arterial hypoxemia, whereas the ventilation of non-perfused lung zones increases physiological dead-space, which potentially necessitates increased ventilation to avoid hypercapnia. Beyond its impact on gas exchange, V/Q mismatch is a predictor of adverse outcomes in patients with ARDS; more recently, its role in ventilation-induced lung injury and worsening lung edema has been described. Innovations in bedside imaging technologies such as electrical impedance tomography readily allow clinicians to determine the regional distributions of V and Q, as well as the adequacy of their matching, providing new insights into the phenotyping, prognostication, and clinical management of patients with ARDS. The purpose of this review is to discuss the pathophysiology, identification, consequences, and treatment of V/Q mismatch in the setting of ARDS, employing experimental data from clinical and preclinical studies as support.