Cardiovascular Diseases & Diagnosis

Background: Oxidative stress is associated with endothelial dysfunction, the initial step in the pathogenesis of various cardiovascular disorders.

Methods: HUVECs were divided into 3 groups including control group, model group (cells treated with 10^-6 M Ang II for 24 hr) and treatment groups (cells treated with 0.1 mM, 0.25 mM, 0.5 mM and 1 mM ALA for 30 minutes and further incubated with 10^-6 M Ang II for 24 hrs). The cytoprotective effect of ALA against Ang II was tested by MTT assay, ROS generation was evaluated using Di-chloroflourescein (DCFH) and Mitosox Red, NO, ET-1 and antioxidant enzymes (SOD, GPx, CAT) and IDH) activity were analyzed by their respective kits. Furthermore, Western blot was used to detect the protein expression of Akt, p-Akt, eNOS, p-eNOS, Nrf₂, PGC1-α, Sirt₃ and Nox₄. RT-PCR was used to detect the gene expression of Nox₄ and eNOS.

Results: The results indicated that ALA in a dose-dependent manner lowered Ang II-induced loss in endothelial cell viability, reactive oxygen species and ET-1 production. Furthermore, ALA pre-treatment increased NO Level and antioxidant enzyme activity which is crucial for ROS elimination. The western blot results showed that Ang II markedly decreased Akt, eNOS, Nrf₂, PGC1-α, Sirt₃ protein expression which was enhanced with the pre-treatment of ALA that was further inhibited by a Wortmannin and L-NAME.

Conclusion: Our findings demonstrated that ALA possesses antioxidant activity against Ang II-induced oxidative stress partly by antagonizing AT₁ receptor, suppressing Ang II-induced NADPH oxidase, increasing antioxidant enzyme activity and up-regulating PI3K/Akt/eNOS/NO dependent signaling pathway.

Background: In this study, we aimed to investigate the effects of midazolam sedation on intravascular volume in intubated patients diagnosed with sepsis and treated with invasive mechanical ventilation in continuous positive airway pressure mode using echocardiography (ECHO) parameters.

Methods and Results: One hundred fifty-two intensive care unit patients aged 30-50 years with spontaneous breathing who were intubated, ventilated in continuous positive airway pressure mode via invasive mechanical ventilation, were determined to have fluid deficit. Cardiac index, cardiac out-put and velocity time integral measurements were performed by passive leg rising test before and after midazolam sedation in hypovolemic patients that were determined to respond to fluid treatment and changes in passive leg rising test before and after midazolam were compared. >15% cardiac out-put, >10% cardiac index, and >15% velocity time integral increase in passive leg rising test before midazolam administration showed that patients were hypovolemic and responded to fluid therapy. <15% cardiac out-put, <10% cardiac index, and <15% velocity time integral increase in passive leg rising test after midazolam administration showed that patients were not hypovolemic.

Conclusion: We recommend that passive leg raising test, which is performed to determine the intravascular volume status of critically ill intensive care unit patients determined to be hypovolemic and responding to fluid therapy, should be performed before midazolam sedation.