Cardioprotective Effect of Pretreatment with A Single High-Dose Atorvastatin via Regulating Myocardial Uncoupling Protein 3 in a Rat Ischemia/Reperfusion Model

Objective: Since ischemia/reperfusion (I/R) can cause malignant arrhythmia, we explored the cardioprotective effect of pretreatment with a single and large dose of atorvastatin in the SD rat model. Methods: Rats were distributed into atorvastatin (Ator), I/R model and sham groups (n = 8/group) by random number table method. In Ator group, atorvastatin was gavaged with a single dose (80 mg/kg) 12 h before I/R. The heart was treated with ischemia for 30 min and then reperfusion for 2 h. Results: Myocardial infarct area was induced by I/R when compared with Sham group. Compared with I/R group, the pretreatment of atorvastatin significantly reduced area at risk/left ventricle (40.78 ± 1.39% vs. 46.76 ± 1.42%, p < 0.01), infarct area/area at risk (21.47 ± 1.65% vs. 29.16 ± 1.21%, p < 0.01), and lactate dehydrogenase activity (3056.17 ± 136.22 RFU vs. 3864.15 ± 162.92 RFU, p < 0.05). I/R induced uncoupling protein 3 (UCP3) in transcriptional and translational levels, but atorvastatin significantly increased the UCP3 expression when compared with I/R group, 1.91 ± 0.42 vs. 1.42 ± 0.21 fold (p < 0.05) in mRNA levels measured by RT-PCR and 2.07 ± 0.18 versus 1.45 ± 0.23 fold in protein levels by Western blots. Conclusion: A single high-dose atorvastatin pretreatment 12 h before I/R reduces the infarct area in I/R model in rats. The cardioprotection may be via regulating myocardial UCP3.

Stereotactic Body Radiotherapy for Idiopathic Subtricuspid Ventricular Arrythmia

Introduction: In cases of recurrent ventricular arrythmias (RVA) after radiofrequency ablation (RFA), stereotactic body radiotherapy (SBRT) using a single high dose of has emerged as an effective treatment. Methods And Results: SBRT was performed as treatment of an Idiopathic Subtricuspid Ventricular Arrythmia recurrent to RFA with progressive cardiac function deterioration despite the staggered use of antiarrhythmic drugs. No sedation was required, and the patient tolerated the procedure with no related complications. During post-procedural follow-up the arrhythmic density dropped from 33% to 1% in 90 days. Conclusions: SBRT can be an effective treatment for RVA that should be further investigated.

The Optimal Condition of Poly(I: C)-Induced Knockout of Cre Recombinase for Mx1-Cre/ Cre-loxP Mice

BackgroundThe Cre-loxP system is widely applied for conditional knockout mice, commonly used to study the function of specific genes. Although some different promoters drive Cre expression, the poly(I: C)-inducible Mx1-Cre is the most commonly used to delete the target gene in experimental hematology. However, the optimal induction knockout condition for Mx1-Cre/ Cre-loxP mice using the Poly(I:C)-inducible Cre-loxP conditional system remains unclear. Here, we present two different components and three injection protocols of poly(I: C) to find the optimized condition. ResultsThe results showed that the better knockout efficiency of Cre-loxP in mice injected with pure poly(I: C) has than those injected with poly(I: C) with some components. From the perspective of lethal genes (Brg1), data showed that mice injected with a single high dose (500 µg) of pure Poly (I:C) had a lower knockout rate. For mice injected media-dose (10µg/g) poly(I: C) triple, which induced a high knockout rate, but the mortality rate was still high. Importantly, the mice injected low-dose (6µg/g) poly(I: C) triple, both the knockout rate and survival rate of mice was high. Similarly, the knockout rate of non-lethal mice injected with media-dose (10µg/g) or low-dose (6μg/g) poly(I: C) triple was very high, but injected with a single high dose (500 µg) of pure poly(I: C) had a low knockout rate. ConclusionOur studies provided the optimized condition for using poly(I: C)-inducible effective knockout and maintaining the survival rate for the Cre-loxP mice, which might be applied in other knockout mice for this system to ensure both the gene knockout and the mice survival.

MO562ACUTE IMPACT OF A SINGLE HIGH DOSE OF FERRIC CARBOXYMALTOSE ON ENDOTHELIAL FUNCTION IN CKD NON-DIALYSIS PATIENTS

Background and Aims Anemia is highly prevalent in CKD, and most frequently is caused by iron deficiency. Intravenous iron therapy is often and efficiently used, even in non-dialysis CKD patients. Still, experimental data suggested that intravenous iron could alter endothelial function, rising concerns related to the possible cardiovascular long-term effects. In this regard, we clinically assessed the acute impact of a high dose of iron ferric carboxymaltose (FCM), a commonly used iron formulation, on endothelial function in CKD iron-naive non-dialysis patients. Method In this prospective crossover single center study, forty CKD iron-deficient non-dialysis patients [median age 66.5 (56;73) years, 62% female, median estimated glomerular filtration rate 24 (11;36) mL/min, 78% in the very high-risk category according to KDIGO, 90% with hypertension and 40% with diabetes mellitus] were included. The study was approved by Ethics Committee of the UMF “Carol Davila” Bucharest. Pregnancy and breast feeding, anemia of other cause, history of erythropoietin therapy, high-degree inflammation, active malignancies, glomerulonephritis or liver diseases, immunosuppressive therapy, hemoglobin &lt;7g/dl, ferritin &gt; 500 ng/ml and/or transferrin saturation &gt; 50%, baseline flow mediated dilatation (FMD) &lt; 7%, antioxidant supplements and active smoking were exclusion criteria. The effect on endothelial function was clinically assessed by comparing FMD at 15 minutes before and 15 minutes after 2 infusions: first, the comparator (250 mL 0.9% saline), and 24 hours apart, FCM (1000 mg in 250 mL 0.9% saline). FMD was measured using a Doppler ultrasound system according to guidelines recommendations. Wilcoxon paired test was used to test the post- and pre-infusion differences. Results Flow mediated vasodilatation and blood pressure at baseline was similar before each intervention. Neither comparator nor FCM infusion had any effect on acute changes in systolic and diastolic blood pressure. Arterial reactivity was not acutely affected after FCM [ΔFCM 0.01 (-0.35;0.15) versus saline solution 0.001 (-0.4;0.5), p=0.9]. Conclusion A single high dose of ferric carboxymaltose did not acutely impaired endothelial function evaluated by flow mediated vasodilatation, in a CKD non-dialysis cohort.

Single High-Dose Vitamin D Supplementation as an Approach for Reducing Ultramarathon-Induced Inflammation: A Double-Blind Randomized Controlled Trial

Purpose: A growing number of studies indicate the importance of vitamin D supplementation for sports performance. However, the effects of a single high-dose vitamin D supplementation on ultramarathon-induced inflammation have not been investigated. We here analyzed the effect of a single high-dose vitamin D supplementation on the inflammatory marker levels in ultramarathon runners after an ultramarathon run (maximal run 240 km). Methods: In the study, 35 runners (amateurs) were assigned into two groups: single high-dose vitamin D supplementation group, administered vitamin D (150,000 IU) in vegetable oil 24 h before the start of the run (n = 16); and placebo group (n = 19). Blood was collected for analysis 24 h before, immediately after, and 24 h after the run. Results: Serum 25(OH)D levels were significantly increased after the ultramarathon in both groups. The increase was greater in the vitamin D group than in the control group. Based on post-hoc and other analyses, the increase in interleukin 6 and 10, and resistin levels immediately after the run was significantly higher in runners in the control group than that in those in the supplementation group. Leptin, oncostatin M, and metalloproteinase tissue inhibitor levels were significantly decreased in both groups after the run, regardless of the supplementation. Conclusions: Ultramarathon significantly increases the serum 25(OH)D levels. Attenuation of changes in interleukin levels upon vitamin D supplementation confirmed that vitamin D has anti-inflammatory effect on exercise-induced inflammation.