QSOX1, a novel actor of cardiac protection upon acute stress in mice.

QSOX1, a sulfhydryl oxidase, was shown to be upregulated in the heart upon acute heart failure (AHF). The aim of the study was to unravel QSOX1 roles during AHF. We generated and characterized mice with QSOX1 gene deletion. The QSOX1-/- mice were viable but adult male exhibited a silent dilated cardiomyopathy. The QSOX1-/- hearts were characterized by low protein SERCA2a levels associated with a calcium homeostasis alteration, high levels of the endoplasmic reticulum (ER) chaperone proteins Grp78/Bip, and of the ER apoptosis sensor CHOP, indicating a chronic unfolded protein response (UPR). Importantly the QSOX1invalidation led to overexpression of two ER oxidases, ERO1-α and PRDX4. Acute stress was induced by isoproterenol injection (ISO, 300 mg/kg/12 h) for 2 days. In both groups, the PERK UPR pathway was transiently activated 6 h after the first ISO injection as indicated by eIF2 phosphorylation. By day-3 after the onset of stress, both WT and QSOX1-/- mice exhibited AHF profile but while high cardiac QSOX1 level was induced in WT hearts, ERO1-α and PRDX4 levels drop down in QSOX1-/-. At that time, QSOX1-/- hearts exhibited an enhanced inflammation (CD68+ cells and Galectin-3 expression) and oxidative stress (DHE staining and oxyblot) when compared to WT ones. In conclusion, the lack of QSOX1 promotes the upregulation of two ER oxidases ERO1α and PRDX4 that likely rescues oxidative protein folding in the hearts. However, signs of chronic ER stress remained present and were associated with a dilated cardiomyopathy. The superimposition of acute stress allowed us to propose that QSOX1 participate to the early response to cardiac stress but not to immediate UPR response. Taken altogether, the data indicated that QSOX1 is required 1) for a proper protein folding in the endo/sarcoplasmic reticulum (ER/SR) and 2) for resolution and protective response during acute stress.

Acute hyperventilation increases the central venous-to-arterial PCO2 difference in stable septic shock patients.

BACKGROUND: To evaluate the effects of acute hyperventilation on the central venous-to-arterial carbon dioxide tension difference (∆PCO2) in hemodynamically stable septic shock patients. METHODS: Eighteen mechanically ventilated septic shock patients were prospectively included in the study. We measured cardiac index (CI), ∆PCO2, oxygen consumption (VO2), central venous oxygen saturation (ScvO2), and blood gas parameters, before and 30 min after an increase in alveolar ventilation (increased respiratory rate by 10 breaths/min). RESULTS: Arterial pH increased significantly (from 7.35 ± 0.07 to 7.42 ± 0.09, p < 0.001) and arterial carbon dioxide tension decreased significantly (from 44.5 [41-48] to 34 [30-38] mmHg, p < 0.001) when respiratory rate was increased. A statistically significant increase in VO2 (from 93 [76-105] to 112 [95-134] mL/min/m2, p = 0.002) was observed in parallel with the increase in alveolar ventilation. While CI remained unchanged, acute hyperventilation led to a significant increase in ∆PCO2 (from 4.7 ± 1.0 to 7.0 ± 2.6 mmHg, p < 0.001) and a significant decrease in ScvO2 (from 73 ± 6 to 67 ± 8%, p < 0.001). A good correlation was found between changes in arterial pH and changes in VO2 (r = 0.67, p = 0.002). Interestingly, we found a strong association between the increase in VO2 and the increase in ∆PCO2 (r = 0.70, p = 0.001). CONCLUSIONS: Acute hyperventilation provoked a significant increase in ∆PCO2, which was the result of a significant increase in VO2 induced by hyperventilation. The clinician should be aware of the effects of acute elevation of alveolar ventilation on ∆PCO2.

Impact of fiber-optic laryngoscopy on the weaning process from mechanical ventilation in high-risk patients for postextubation stridor.

The objective of this study was to assess the impact of fiber-optic laryngoscopy (FOL) on the weaning process from mechanical ventilation in critically ill patients with a positive cuff leak test (CLT) as compared with the current recommended strategy based on corticosteroids.In this prospective observational pilot study conducted over a 1-year period in a 15-bed ICU, CLT was systematically performed before extubation in all intubated patients having passed a spontaneous breathing trial (SBT). After the endotracheal tube cuff was deflated, cuff leak volume (CLVol) was assessed during assisted controlled ventilation. When CLT was positive (CLVol < 110 mL), patients either were evaluated using FOL by our half-time FOL-practitioner when present, or received corticosteroids.Among the 233 patients included, 34 (14.6%) had a positive CLT that hampered extubation. Seventeen were treated by corticosteroids and 17 were evaluated by FOL. In the corticosteroids group, the CLVol was still <110 mL at 24 hours in 9 patients (53%). Corticosteroids strategy merely prolonged the total duration of mechanical ventilation (7 [4-11] vs 4 [2-6] days, P = 0.01) by increasing the time between successful SBT and the moment when extubation was effectively achieved (30 [24-60] vs 1.5 [1-2] hours, P < 0.001). This resulted in 2 self-extubations (12%) and 9 FOL-guided extubations (53%) in the corticosteroids group. Massive swelling of the arytenoids was the most common feature shown by FOL. The patients evaluated by FOL who exhibited the thin anterior V-shaped opening of the vocal cords-the V sign-(n = 26, 100%) were immediately extubated without any stridor or respiratory failure afterward.In this pilot study, a FOL-based extubation strategy was feasible and reliable, and significantly reduced the duration of mechanical ventilation in patients with a positive CLT. We describe the "V sign" of FOL that safely allows a successful prompt extubation in patients considered at high risk for postextubation stridor.

Ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content are better markers of global anaerobic metabolism than lactate in septic shock patients.

BACKGROUND: To evaluate the ability of the central venous-to-arterial CO2 content and tension differences to arteriovenous oxygen content difference ratios (∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2, respectively), blood lactate concentration, and central venous oxygen saturation (ScvO2) to detect the presence of global anaerobic metabolism through the increase in oxygen consumption (VO2) after an acute increase in oxygen supply (DO2) induced by volume expansion (VO2/DO2 dependence). METHODS: We prospectively studied 98 critically ill mechanically ventilated patients in whom a fluid challenge was decided due to acute circulatory failure related to septic shock. Before and after volume expansion (500 mL of colloid solution), we measured cardiac index, VO2, DO2, ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios, lactate, and ScvO2. Fluid-responders were defined as a ≥15 % increase in cardiac index. Areas under the receiver operating characteristic curves (AUC) were determined for these variables. RESULTS: Fifty-one patients were fluid-responders (52 %). DO2 increased significantly (31 ± 12 %) in these patients. An increase in VO2 ≥ 15 % ("VO2-responders") concurrently occurred in 57 % of the 51 fluid-responders (45 ± 16 %). Compared with VO2-non-responders, VO2-responders were characterized by higher lactate levels and higher ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios. At baseline, lactate predicted a fluid-induced increase in VO2 ≥ 15 % with AUC of 0.745. Baseline ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios predicted an increase of VO2 ≥ 15 % with AUCs of 0.965 and 0.962, respectively. Baseline ScvO2 was not able to predict an increase of VO2 ≥ 15 % (AUC = 0.624). CONCLUSIONS: ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios are more reliable markers of global anaerobic metabolism than lactate. ScvO2 failed to predict the presence of global tissue hypoxia.

Repeatability of blood gas parameters, PCO2 gap, and PCO2 gap to arterial-to-venous oxygen content difference in critically ill adult patients.

The objective of this study was to examine the repeatability of blood gas (BG) parameters and their derived variables such as the central venous-to-arterial carbon dioxide tension difference (▵PCO2) and the ratio of ▵PCO2 over the central arteriovenous oxygen content difference (▵PCO2/C(a-cv)O2) and to determine the smallest detectable changes in individual patients.A total of 192 patients with arterial and central venous catheters were included prospectively. Two subsequent arterial and central venous blood samples were collected immediately one after the other and analyzed using the same point-of-care BG analyzer. The samples were analyzed for arterial and venous BG parameters, ▵PCO2, and ▵PCO2/C(a-cv)O2 ratio. Repeatability was expressed as the smallest detectable difference (SDD) and the least significant change (LSC). A change in value of these parameters exceeding the SDD or the LSC should be regarded as real.The SDDs for arterial carbon dioxide tension, arterial oxygen saturation, central venous oxygen saturation (ScvO2), and ▵PCO2 were small: ±2.06 mm Hg, ±1.23%, 2.92%, and ±1.98 mm Hg, respectively, whereas the SDDs for arterial oxygen tension (PaO2) and ▵PCO2/C(a-cv)O2 were high: ±9.09 mm Hg and ±0.57 mm Hg/mL, respectively. The LSCs (%) for these variables were 5.06, 1.27, 4.44, 32.4, 9.51, and 38.5, respectively.The repeatability of all these variables was good except for PaO2 and ▵PCO2/C(a-cv)O2 ratio for which we observed an important inherent variability. Expressed as SDD, a ScvO2 change value of at least ±3% should be considered as true. The clinician must be aware that an apparent change in these variables in an individual patient might represent only an inherent variation.