Transmitral Pressure Gradients in Patients With Degenerative Mitral Regurgitation After Robotic Mitral Valve Repair With Leaflet Preservation Techniques.

INTRODUCTION: The hemodynamic effects of mitral valve repair (MVr) with respect to transmitral pressure gradients (TMPGs) have not been described well in patients undergoing leaflet preservation techniques. In a population of patients undergoing robotic MVr with leaflet preservation, we investigate the expected change of the postrepair intraoperative TMPG in the postoperative follow-up period. METHODS: We retrospectively studied 144 adult patients who underwent robotic MVr. Demographic, clinical, procedural, and echocardiographic data were collected and analyzed. RESULTS: We found a slight increase in the mean TMPG from the intraoperative postrepair to the immediate postoperative period (intraoperative 3.3 ± 1.4 mmHg vs. first postoperative transthoracic echocardiography [TTE] follow-up 3.6 ± 1.9 mmHg, p = 0.016) with a gradual decline in the long-term follow-up (mean TMPG at last follow-up TTE 2.4+2.1 mmHg). When dichotomizing the patient population using a cutoff of 3 mmHg for the intraoperative mean TMPG, patients with an intraoperative mean TMPG > 3 mmHg had higher mean TMPG gradients at first TTE (4.5 ± 2.4 vs. 3.1 ± 1.3 mmHg, p < 0.001) as well as at last TTE (3.0± 2.2 vs. 2.1 ± 2.0 mmHg, p = 0.01) when compared with patients with an intraoperative mean TMPG ≤ 3 mmHg. There was no difference in clinical outcomes. CONCLUSIONS: Although the hemodynamic effect of MVr seems to be small, patients with an intraoperative TMPG > 3 mmHg have a higher mean TMPG at follow-up. The hemodynamic effect does not seem to have an impact on clinical outcome.

CysLT1 Receptor Is Protective against Oxidative Stress in a Model of Irritant-Induced Asthma.

The bronchoconstrictive and proinflammatory properties of cysteinyl leukotrienes (cysLTs) in allergic asthma mediate their effects predominantly through the cysLT1 receptor (cysLT1R). However, the role of cysLTs and cysLT1R in innate immune-triggered asthma is largely unexplored. We explored the synthesis of cysLTs and cysLT1R as determinants of airway responses in an oxidative stress-induced model of irritant asthma. Wild-type (WT) mice exposed to 100 ppm Cl2 for 5 min had airway neutrophilia, increased cysLT production, and pulmonary expression of cysLT-related biosynthetic genes. CysLT1R-deficient (CysLTr1(-/-)) mice that were exposed to Cl2 demonstrated airway hyperresponsiveness to inhaled methacholine significantly greater than in WT BALB/c mice. Compared to WT mice, airway neutrophilia and keratinocyte chemoattractant production levels were higher in CysLTr1(-/-) mice and airway hyperresponsiveness was ameliorated using a granulocyte depletion Ab. CysLTr1(-/-) mice also demonstrated prolonged bronchial epithelial cell apoptosis following Cl2 WT mice showed increased antioxidant and NF erythroid 2-related factor 2 (Nrf2) gene expression, Nrf2 nuclear translocation in bronchial epithelial cells, and increased reduced glutathione/oxidized glutathione following Cl2 exposure whereas CysLTr1(-/-) mice did not. Furthermore, CysLTr1(-/-) mice demonstrated increased pulmonary E-cadherin expression and soluble E-cadherin shedding compared with WT mice. Loss of a functional cysLT1R results in aberrant antioxidant response and increased susceptibility to oxidative injury, apparently via a cysLT1R-dependent impairment of Nrf2 function.

Neutrophils mediate airway hyperresponsiveness after chlorine-induced airway injury in the mouse.

Chlorine gas (Cl2) inhalation causes oxidative stress, airway epithelial damage, airway hyperresponsiveness (AHR), and neutrophilia. We evaluated the effect of neutrophil depletion on Cl2-induced AHR and its effect on the endogenous antioxidant response, and if eosinophils or macrophages influence Cl2-induced AHR. We exposed male Balb/C mice to 100 ppm Cl2 for 5 minutes. We quantified inflammatory cell populations in bronchoalveolar lavage (BAL), the antioxidant response in lung tissue by quantitative PCR, and nuclear factor (erythroid-derived 2)-like 2 (NRF2) nuclear translocation by immunofluorescence. In vitro, NRF2 nuclear translocation in response to exogenous hypochlorite was assessed using a luciferase assay. Anti-granulocyte receptor-1 antibody or anti-Ly6G was used to deplete neutrophils. The effects of neutrophil depletion on IL-13 and IL-17 were measured by ELISA. Eosinophils and macrophages were depleted using TRFK5 or clodronate-loaded liposomes, respectively. AHR was evaluated with the constant-phase model in response to inhaled aerosolized methacholine. Our results show that Cl2 exposure induced neutrophilia and increased expression of NRF2 mRNA, superoxide dismutase-1, and heme-oxygenase 1. Neutrophil depletion abolished Cl2-induced AHR in large conducting airways and prevented increases in antioxidant gene expression and NRF2 nuclear translocation. Exogenous hypochlorite administration resulted in increased NRF2 nuclear translocation in vitro. After Cl2 exposure, neutrophils occupied 22 ± 7% of the luminal space in large airways. IL-17 in BAL was increased after Cl2, although this effect was not prevented by neutrophil depletion. Neither depletion of eosinophils nor macrophages prevented Cl2-induced AHR. Our data suggest the ability of neutrophils to promote Cl2-induced AHR is dependent on increases in oxidative stress and occupation of luminal space in large airways.