Irina Enache

Effect of postconditioning on mitochondrial dysfunction in experimental aortic cross-clamping

Cross‐clamping of the aorta during abdominal aortic aneurysm surgery induces muscle ischaemia with resultant morbidity. This study tested whether ischaemic postconditioning would decrease mitochondrial dysfunction in skeletal muscle by reducing oxidative stress.

Pulmonary Arterial Hypertension-Specific Drug Therapy in COPD Patients with Severe Pulmonary Hypertension and Mild-to-Moderate Airflow Limitation.

Background: Patients with severe pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD) present a poor outcome. Specific PH treatment could improve the clinical and hemodynamic status of these patients but may worsen arterial blood gases. Objectives: Our study retrospectively included 28 patients with severe precapillary PH (mean pulmonary arterial pressure >35 mm Hg) associated with mild-to-moderate COPD [forced expiratory volume in 1 s (FEV1) >50% predicted]. All patients underwent specific pulmonary arterial hypertension (PAH) treatment as mono-, bi- or triple therapy. Methods: Our single-center study was conducted based on retrospective data of 537 right heart catheterizations (RHCs) performed on patients with COPD from January 2004 to June 2014. An echocardiography, comprehensive blood tests, pulmonary function tests, and a high-resolution computed tomography were performed before the RHCs. All patients underwent RHC with a Swan-Ganz catheter. Results: Compared to baseline, patients treated with specific PAH drugs showed a significant increase in cardiac index at long term (2.5 ± 0.7 liters/min/m2 at baseline vs. 3.2 ± 0.6 liters/min/m2 at 6/12 months; p = 0.003) as well as a decrease in pulmonary vascular resistance in the long term (8.4 ± 4.2 Wood units at baseline vs. 5 ± 1.7 Wood units at 6/12 months; p = 0.008). There was a slight decrease in arterial oxygen tension (PaO2) after 3 months of treatment (-2.4 ± 7.21 mm Hg; p = 0.066). During a median follow-up of 3 years, 12 patients (42.8%) died (including all causes of death). Conclusions: This preliminary report suggests that the use of specific PH therapy in severe PH associated with mild-to-moderate COPD can improve pulmonary hemodynamic parameters, with worsening of PaO2, which had no clinical significance and did not lead to specific PAH therapy withdrawal in any patient.

Right Heart Hemodynamics in Pulmonary Hypertension – An Echocardiography and Catheterization Study –

BACKGROUND Echocardiography (ECHO) plays a key role in both the diagnosis and prognosis of pulmonary hypertension (PH). Many equations have been published to assess right heart hemodynamics using ECHO. The objective of this study was to test the accuracy and precision of different echocardiographic equations in comparison with the right heart catheterization. METHODSANDRESULTS Complete right heart hemodynamic assessments were prospectively obtained from 115 individuals (mean age 66±1 years; 57 males) who had known or suspected PH. Several equations were tested for the estimation of right atrial pressure, mean and systolic pulmonary artery pressure (MPAP), cardiac output, pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). The accuracy of ECHO was good, with a mean difference <2 mmHg for all of the pressure calculations and ±0.6 L/min for cardiac output. However, the PVR estimation was weak using any one of the formulae. For all the parameters, the precision of ECHO was moderate. The MPAP calculation detected PH with a sensibility of 97% and specificity of 83%. However, ECHO underdiagnosed post-capillary PH. CONCLUSIONS ECHO is a good method for the diagnosis of PH, with an adequate calculation of right pressures, but cannot accurately calculate PCWP and PVR. (Circ J 2016; 80: 2019-2025).

The opening interrupter technique for respiratory resistance measurements in children

Background and objective:  The interrupter resistance (Rint) can be calculated from various estimates of alveolar pressure based on mouth pressure during occlusion. We compared Rint, as measured by the opening interrupter technique (Rint1), and the linear back‐extrapolation method (Rint2), with the ‘gold standard’ airway resistance measured by plethysmography (Raw).

A comparison of four algorithms for the measurement of interrupter respiratory resistance in adults

The aim of our study was to compare four algorithms for the measurement of respiratory resistance in adults using the interrupter technique. Four methods to estimate alveolar pressure from the mouth pressure during occlusion were assessed in 122 normal adults (57 males, 65 females, aged 18-79 yr, mean 41.2 +/- 15.6): taking the mean oscillation pressure (Rint), performing a linear back extrapolation (RintL) or a linear regression for the whole curve (RintRL), taking the end-occlusion pressure (RintE). Mean values for Rint, RintL and RintRL in males were respectively 0.23 +/- 0.04, 0.22 +/- 0.04 and 0.22 +/- 0.04 kPa s L(-1), not statistically different. In females values were respectively 0.27 +/- 0.05, 0.26 +/- 0.05 and 0.26 +/- 0.05 kPa s L(-1), not statistically different. RintE was higher than the remainder and was the only measure correlating weakly with morphometric variables: RintE = 1.152 - (0.00152 x age (yr)) - (0.00382 x height (cm)), r = 0.31 (p < 0.05) in females; RintE = 0.227 - (0.00122 x age (yr)) + (0.00830 x body mass index (kg m(-2))) with r = 0.34 (p < 0.05) in males. We conclude that it is equivalent to estimate alveolar pressure from or extrapolating it to the beginning of occlusion in healthy adults but when taking the end-occlusion pressure, resistance is higher and depends in part on morphometric parameters.

Impact of 3D Conformal Radiotherapy on Lung Function of Patients with Lung Cancer: A Prospective Study

Background: The development of three-dimensional conformal radiotherapy (3D-RT) has enabled the restriction of the dose to normal lung, limiting radiation-induced lung injury. Objectives: This study was designed to describe the time course of lung function until 7.5 months after 3D-RT in patients with lung cancer, and assess the relationship between lung function changes and dose-volume histogram (DVH) analysis or computed tomography scan changes. Radiation doses were optimized according to recent guidelines. Methods: Sixty-five lung cancer patients treated with 3D-RT agreed to participate in this prospective, hospital-based study. Lung volumes, forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) were measured before radiotherapy (RT), 10 weeks, 4 and 7.5 months after the beginning of 3D-RT. Results: Eleven lung cancer patients (17%) developed grade 2-3 respiratory symptoms after RT. At 7.5 months, vital capacity (VC) was 96 ± 2%, total lung capacity (TLC) 95 ± 2%, FEV1 93 ± 2% and DLCO 90 ± 2% of the initial value. Only 15% of patients showed pulmonary function reduction >20%. Patients with FEV1 or DLCO <60% before RT did not show significant changes after RT. There were weak correlations between reduction of VC, TLC, FEV1 or DLCO and radiation dosimetric parameters and between reduction of VC or FEV1 and radiation-induced pneumonitis images. Conclusions: In lung cancer, the reduction of lung function within 7.5 months after 3D-RT was small and correlated, albeit weakly, with DVH parameters. Patients with initially impaired lung function showed tiny changes in spirometry and DLCO values.

Can exhaled NO fraction predict radiotherapy-induced lung toxicity in lung cancer patients?

BackgroundA large increase in nitric oxide fraction (FeNO) after radiotherapy (RT) for lung cancer may predict RT-induced lung toxicity.MethodsIn this study, we assessed the relationships between FeNO variations and respiratory symptoms, CT scan changes or dose volume histogram (DVH) parameters after RT. We measured FeNO before RT, 4, 5, 6, 10 weeks, 4 and 7.5 months after RT in 65 lung cancer patients.ResultsEleven lung cancer patients (17%) complained of significant respiratory symptoms and 21 (31%) had radiation pneumonitis images in >1/3 of the irradiated lung after RT. Thirteen patients (20%) showed increases in FeNO >10 ppb. The sensitivity and specificity of a >10 ppb FeNO increase for the diagnosis of RT-associated respiratory symptoms were 18% and 83%, respectively. There was no correlation between DVH parameters or CT scan changes after RT and FeNO variations. Three patients (5%) showed intriguingly strong (2 or 3-fold, up to 55 ppb) and sustained increases in FeNO at 4 and 5 weeks, followed by significant respiratory symptoms and/or radiation-pneumonitis images.ConclusionSerial FeNO measurements during RT had a low ability to identify lung cancer patients who developed symptoms or images of radiation pneumonitis. However, three patients presented with a particular pattern which deserves to be investigated.

Cardio-respiratory responses to hypoxia combined with CO2 inhalation during maximal exercise

We measured the effects of adding CO2 to an inhaled hypoxic gas mixture on cardio-respiratory parameters during maximal exercise. Eight young males performed four incremental maximal exercise tests on cycle under ambient air, hypoxia (FIO2 0.125), inhaled CO2 (FICO2 0.045), and combination of hypoxia and inhaled CO2. The highest ventilation (VE) and VE/CO2 output were recorded in CO2 inhalation and combined treatments. Arterial O2 partial pressure was higher in combined than in hypoxia treatment, but the difference between the treatments narrowed from rest to end-exercise, at least partly because the magnitude of the increase in VE (%) at exercise was smaller in combined treatment than in hypoxia. Arterial O2 content was higher in combined treatment than in hypoxia at rest, but no more at maximal exercise. Cardiac output was higher and O2 extraction lower when breathing O2-poor gas mixtures than under the two other treatments. For a given oxygen consumption, hypoxia and combined treatment showed similar cardiac output and O2 extraction.

Mitochondrial function following downhill and/or uphill exercise training in rats.

Introduction: The goal of this study was to compare the effects of downhill (DH), uphill (UH), and UH‐DH exercise training, at the same metabolic rate, on exercise capacity and skeletal muscle mitochondrial function. Methods: Thirty‐two Wistar rats were separated into a control and 3 trained groups. The trained groups exercised for 4 weeks, 5 times per week at the same metabolic rate, either in UH, DH, or combined UH‐DH. Twenty‐four hours after the last training session, the soleus, gastrocnemius, and vastus intermedius muscles were removed for assessment of mitochondrial respiration. Results: Exercise training, at the same metabolic rate, improved maximal running speed without specificity for exercise modalities. Maximal fiber respiration was enhanced in soleus and vastus intermedius in the UH group only. Conclusions: Exercise training, performed at the same metabolic rate, improved exercise capacity, but only UH‐trained rats enhanced mitochondrial function in both soleus and vastus intermedius skeletal muscle. Muscle Nerve 54: 925–935, 2016

Impact of altered alveolar volume on the diffusing capacity of the lung for carbon monoxide in obesity.

Background: Studies on the diffusing capacity of the lung for carbon monoxide (DL_CO) in obese patients are conflicting, some studies showing increased DL_CO and others unaltered or reduced values in these subjects. Objectives: To compare obese patients to controls, examine the contribution of alveolar volume (VA) and CO transfer coefficient (K_CO) to DL_CO, and calculate DL_CO values adjusted for VA. Methods: We measured body mass index (BMI), waist circumference (WC), spirometry and DL_CO in 98 adult obese patients without cardiopulmonary or smoking history and 48 healthy subjects. All tests were performed in the same laboratory. Results: Using conventional reference values, mean DL_CO and VA were lower (–6%, p < 0.05, and –13%, p < 0.001, respectively), and K_CO was higher (+9%, p < 0.05) in obese patients than in controls. VA decreased whereas K_CO increased with increasing BMI and WC in the obese group. Patients with lower DL_CO had low K_CO in addition to decreased VA. In contrast, some obese patients maintained normal VA, which, coupled with high K_CO, resulted in higher DL_CO. The main result is that diffusion capacity differences between obese patients and controls disappeared using reference equations adjusting DL_CO for VA. Conclusions: Using conventional reference equations, our obese patients show slightly lower mean DL_CO, lower mean VA and higher mean K_CO than controls, but with a large range of DL_CO values and patterns. Adjusting DL_CO for VA suggests that low lung volumes are the main cause of low DL_CO and high K_CO values in obese patients.