Melatonin Attenuates Ischemia/Reperfusion-Induced Oxidative Stress by Activating Mitochondrial Fusion in Cardiomyocytes.

Myocardial ischemia/reperfusion (I/R) injury can stimulate mitochondrial reactive oxygen species production. Optic atrophy 1- (OPA1-) induced mitochondrial fusion is an endogenous antioxidative mechanism that preserves the mitochondrial function. In our study, we investigated whether melatonin augments OPA1-dependent mitochondrial fusion and thus maintains redox balance during myocardial I/R injury. In hypoxia/reoxygenation- (H/R-) treated H9C2 cardiomyocytes, melatonin treatment upregulated OPA1 mRNA and protein expression, thereby enhancing mitochondrial fusion. Melatonin also suppressed apoptosis in H/R-treated cardiomyocytes, as evidenced by increased cell viability, diminished caspase-3 activity, and reduced Troponin T secretion; however, silencing OPA1 abolished these effects. H/R treatment augmented mitochondrial ROS production and repressed antioxidative molecule levels, while melatonin reversed these changes in an OPA1-dependent manner. Melatonin also inhibited mitochondrial permeability transition pore opening and maintained the mitochondrial membrane potential, but OPA1 silencing prevented these outcomes. These results illustrate that melatonin administration alleviates cardiomyocyte I/R injury by activating OPA1-induced mitochondrial fusion and inhibiting mitochondrial oxidative stress.

Evaluation and prognostic value of Cv-aCO2/Da-vO2 in patients with septic shock receiving fluid resuscitation Cv-aCO2/Ca-vO2.

The present study aimed to evaluate the prognostic value of venous-arterial CO2 to arterial-venous O2 (Cv-aCO2/Da-vO2) for patients with septic shock treated by fluid resuscitation. A total of 108 cases who received fluid resuscitation for septic shock at the Intensive Care Unit were retrospectively screened according to the 2012 surviving sepsis campaign guidelines. Patients were divided into 2 groups according to the Cv-aCO2/Da-vO2 ratio at 6 h after fluid resuscitation: Group A, Cv-aCO2/Da-vO2 >1; group B, Cv-aCO2/Da-vO2 ≤1. The resuscitation target rate and transfused resuscitation volume at 6 h exhibited no significant difference between the 2 groups. The cardiac output at 6 and 24 h, as well as the ratio of patients who reached the target of resuscitation within 24 h, the 24-h lactic acid clearance rate and the number of cases with central venous oxygen saturation >70% were significantly decreased in group A compared with those in group B (all P<0.05). The Sequential Organ Failure Assessment score at day 3 in group A was higher compared with that in group B (7.94±1.6 vs. 6.82±1.9; P=0.0013). The mortality rate at day 7 and 35 was higher in group A compared with that in group B (29/52 vs. 6/56, P<0.001; 48/52 vs. 36/56; P<0.001). In conclusion, the Cv-aCO2/Da-vO2 was able to effectively evaluate the success rate of resuscitation and, regarding prognosis, it was able to identify patients at high risk of adverse outcomes.

Prognostic utility of combination of NT-proBNP with high sensitive cTn I in patients with heart failure: Results from retrospective study in an emergency department.

BACKGROUND: N-terminal proBNP (NT-proBNP) and cardiac troponin I (cTn I) are widely used for the diagnosis of myocardial injury, but have not been used for routine evaluation in heart failure (HF) population. AIMS: To evaluate the prognostic utility of combination of NT-proBNP and cTn I in patients with HF, including serial NT-proBNP/cTn I measurements and discharge NT-proBNP/cTn I levels. PATIENTS AND METHODS: A total of 610 patients presenting in our emergency department for acute HF were studied. The mortality and HF-related readmission were endpoints in the study. NT-proBNP and cTn I were tested on admission including first 5 consecutive days, and on discharge. RESULTS: A discharge cTn I cut-off value at 24 ng/L and discharge NT-proBNP cut-off value at 350 ng/L were determined. The cTn I level more than 24 ng/L and NT-proBNP level more than 350 ng/L are associated with increased risk for mortality and readmission (p < 0.01). The mortality and HF-related readmission was significantly increased in patients with high cTn I + high NT-proBNP (p < 0.05), high cTn I + low NT-proBNP (p < 0.05), and low cTn I + high NT-proBNP (p < 0.0%). The increased cTn I or increased NT-proBNP measured in the first 5 consecutive days were significantly associated with 60-day HF-related events (p < 0.05), but the serial measurements did not have a predictive value of 1-year HF outcome. CONCLUSION: This study demonstrates that elevations of discharge cTn I and NT-proBNP are associated with increased 1-year mortality and HF-related readmission. Patients with increasing serial cTnI and NT-proBNP had increased risk for 60-day HF-related events. The two markers can act as independent predicators, and complete each other in prognostic utility of HF patients.

N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study.

BACKGROUNDS: Using biomarkers to predict mortality in patient with severe sepsis or septic shock is of importance, as these patients frequently have high mortality and unsatisfied outcome. N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) play extremely important roles in prognostic value in the mortality of severe sepsis and septic shock. AIMS: The present study was retrospectively designed to evaluate the predicting mortality of NT-proBNP and cTnI in elderly patients with severe sepsis or septic shock administered in the intensive care unit (ICU) and also to evaluate whether the predicting ability of Acute Physiology and Chronic Health Evaluation II (APACHE-II) score or C-reactive protein (CRP) was increased in combination with the biomarkers. PATIENTS AND METHODS: A cohort of 430 patients (aged ≥65 years) with severe sepsis or septic shock admitted to our ICU between October 2011 and December 2013 was included in the study. Patient data including clinical, laboratory, and survival and mortality were collected. All patients were examined with NT-proBNP, cTnI, CRP, and APACHE-II score and were categorized as the survived and deceased groups according to the outcome 30 days after ICU treatment. RESULTS: The levels of NT-proBNP and cTnI (P < .01) or CRP (P < .05) were significantly higher in the deceased group than those in the survived group. The predicting mortality of APACHE-II score alone was low but largely improved, when it was combined with both NT-proBNP and cTnI (P < .05). CONCLUSION: The alteration of NT-proBNP and cTnI levels strongly predicated the ICU prognosis in elderly patients with severe sepsis or septic shock. N-terminal pro-brain natriuretic peptide and cTnI were superior to CRP in predicting mortality. The predicting ability of APACHE-II score was improved only when combined with NT-proBNP and cTnI.