Publications (77) View all
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Article: Combined intraoperative use of Diltiazem and N-acetylcystein increases myocardial damage and oxidative stress during off-pump cardiac surgery.
International journal of cardiology 04/2013; · 7.08 Impact Factor -
Article: Enhanced-Reality Video Fluorescence: A Real-Time Assessment of Intestinal Viability.
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ABSTRACT: OBJECTIVE:: Our aim was to evaluate a fluorescence-based enhanced-reality system to assess intestinal viability in a laparoscopic mesenteric ischemia model. MATERIALS AND METHODS:: A small bowel loop was exposed, and 3 to 4 mesenteric vessels were clipped in 6 pigs. Indocyanine green (ICG) was administered intravenously 15 minutes later. The bowel was illuminated with an incoherent light source laparoscope (D-light-P, KarlStorz). The ICG fluorescence signal was analyzed with Ad Hoc imaging software (VR-RENDER), which provides a digital perfusion cartography that was superimposed to the intraoperative laparoscopic image [augmented reality (AR) synthesis]. Five regions of interest (ROIs) were marked under AR guidance (1, 2a-2b, 3a-3b corresponding to the ischemic, marginal, and vascularized zones, respectively). One hour later, capillary blood samples were obtained by puncturing the bowel serosa at the identified ROIs and lactates were measured using the EDGE analyzer. A surgical biopsy of each intestinal ROI was sent for mitochondrial respiratory rate assessment and for metabolites quantification. RESULTS:: Mean capillary lactate levels were 3.98 (SD = 1.91) versus 1.05 (SD = 0.46) versus 0.74 (SD = 0.34) mmol/L at ROI 1 versus 2a-2b (P = 0.0001) versus 3a-3b (P = 0.0001), respectively. Mean maximal mitochondrial respiratory rate was 104.4 (±21.58) pmolO2/second/mg at the ROI 1 versus 191.1 ± 14.48 (2b, P = 0.03) versus 180.4 ± 16.71 (3a, P = 0.02) versus 199.2 ± 25.21 (3b, P = 0.02). Alanine, choline, ethanolamine, glucose, lactate, myoinositol, phosphocholine, sylloinositol, and valine showed statistically significant different concentrations between ischemic and nonischemic segments. CONCLUSIONS:: Fluorescence-based AR may effectively detect the boundary between the ischemic and the vascularized zones in this experimental model.Annals of surgery 03/2013; · 7.90 Impact Factor -
Article: Platelet Antiaggregation Therapy and Subinguinal Endovascular Revascularization.
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ABSTRACT: BACKGROUND: Platelet antiaggregation therapy (PAT) is widely acknowledged to be a positive prognostic factor after revascularization, either at the coronary or the peripheral level. This study evaluated the results of infrainguinal endovascular procedures performed for critical ischemia, in accordance with patient compliance to clopidogrel treatment. MATERIALS AND METHODS: This retrospective study included patients who underwent infrainguinal endovascular therapy for critical ischemia between January 2003 and December 2009. For 1 month, patients received the same postoperative PAT protocol: aspirin associated with clopidogrel, and then clopidogrel in the long term. Patient follow-up was set at 3 months, 6 months, 1 year, and then yearly thereafter. Survival rates, primary patency (PP), and limb salvage (LS) were studied in accordance with therapy compliance. Patients were classified into 2 groups: group 1 for compliant patients and group 2 for noncompliant patients in the long term. From January 2003 to December 2009, 153 infrainguinal endovascular procedures were performed on 150 patients experiencing critical ischemia who had benefited from the authors' postoperative PAT protocol. RESULTS: Both groups were comparable in terms of comorbidity. Of the procedures performed in groups 1 (N = 105) and 2 (N = 45), 62.8% (n = 66) and 44.4% (n = 20), respectively, were femoral, 14.3% (n = 15) and 22.2% (n = 10), respectively, were infrapopliteal, and 22.9% (n = 24) and 33.4% (n = 15), respectively, were mixed. Mean follow-up time was 30.3 ± 20.2 months (range, 1-70 months). The survival rate was comparable between the groups (P = 0.46). PP and LS rates were significantly higher in group 1 than in group 2 (PP: 84% vs. 80%, respectively, at 1 year, 79% vs. 50%, respectively, at 2 years, 65% vs. 30%, respectively, at 3 years, and 60% vs. 18%, respectively, at 4 years; P = 0.02; LS: 92% vs. 78%, respectively, at 1 year, 86% vs. 62%, respectively, at 2 years, 80% vs. 55%, respectively, at 3 years, and 77% vs. 36%, respectively, at 4 years; P = 0.04). CONCLUSIONS: This study shows that in common practice, 31% of patients stop their clopidogrel therapy, with a negative impact on PP and LS. These results indicate that medical follow-up after endovascular surgery must be reinforced.Annals of Vascular Surgery 02/2013; · 1.03 Impact Factor -
Article: Cyclosporine A normalizes mitochondrial coupling, reactive oxygen species production, and inflammation and partially restores skeletal muscle maximal oxidative capacity in experimental aortic cross-clamping.
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ABSTRACT: OBJECTIVE: By binding to cyclophilin D, cyclosporine A (CsA) inhibits mitochondrial permeability transition pore (mPTP) opening and prevents mitochondrial dysfunction and ultimately cell death after ischemia-reperfusion (IR) injury in cardiac muscle. This study tested whether CsA would decrease skeletal muscle oxidative stress and mitochondrial dysfunctions after aortic cross-clamping related IR. METHODS: Forty-five Wistar rats were investigated. The sham group (n = 8) had aortic exposure but no ischemia, the IR group (n = 10) had aortic cross-clamping for 3 hours followed by 2 hours of reperfusion, and the IR+CsA group (n = 9) had two intraperitoneal injections of 10 mg of CsA at 90 and 150 minutes of ischemia before reperfusion. Mitochondrial coupling (acceptor control ratio) and mitochondrial respiratory chain complexes' activities were measured. Reactive oxygen species (ROS) production, cyclophilin D expression, and muscle inflammation were determined using dihydroethidium staining, Western blot, and immunohistochemistry, respectively. An additional 18 sham rats were investigated to determine CsA blood levels and the effects of CsA on mitochondrial respiration and calcium retention capacity, a marker of mPTP opening, both in myocardium and gastrocnemius with and without CsA. RESULTS: Compared with sham, IR decreased mitochondrial coupling (1.38 ± 0.06 vs 1.98 ± 0.20; P = .0092), increased ROS production (3992 ± 706 arbitrary units [AU] vs 1812 ± 322 AU; P = .033), was associated with macrophage infiltration, and decreased maximal oxidative capacity (V(max): 4.08 ± 0.38 μmol O(2)/min/g vs 5.98 ± 0.56 μmol O(2)/min/g; P = .015). Despite IR, CsA treatment totally restored mitochondrial coupling (1.93 ± 0.12; P = .023 vs IR), normalized ROS (1569 ± 348 AU; P = .0098 vs IR), and decreased inflammation. The V(max) was slightly enhanced (5.02 ± 0.39 μmol O(2)/min/g; P = .33 vs IR; P = .35 vs sham). Compared with myocardium, gastrocnemius muscle was characterized by a decreased cyclophilin D content (-50%) associated with an earlier opening of mPTP (calcium retention capacity increased from 10.85 ± 1.35 μM/mg dry weight [DW] to 12.11 ± 2.77 μM/mg DW; P = .65; and from 11.07 ± 1.67 to 37.65 ± 11.41 μM/mg DW; P = .0098 in gastrocnemius and heart, respectively). CONCLUSIONS: Cyclosporine A normalized ROS production, decreased inflammation, and restored mitochondrial coupling during aortic cross-clamping. Incomplete V(max) protection might be due to low cyclophilin D expression in gastrocnemius, preventing CsA from blocking mPTP opening.Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 01/2013; · 3.52 Impact Factor -
Article: Skeletal muscle mitochondrial dysfunction precedes right ventricular impairment in experimental pulmonary hypertension.
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ABSTRACT: We assessed the time courses of mitochondrial biogenesis factors and respiration in the right ventricle (RV), gastrocnemius (GAS), and left ventricle (LV) in a model of pulmonary-hypertensive rats. Monocrotaline (MT) rats and controls were studied 2 and 4 weeks after injection. Compensated and decompensated heart failure stages were defined according to obvious congestion signs. mRNA expression and protein level of peroxisome proliferator activated receptor gamma co-activator 1α (PGC-1α), citrate synthase (CS) mRNA and activity, and mitochondrial respiration were investigated. In addition, mRNA expression of sirtuin1, nuclear respiratory factor 1, and mitochondrial transcription factor A were studied. As early as 2 weeks, the expression of the studied genes was decreased in the MT GAS. At 4 weeks, the MT GAS and MT RV showed decreased mRNA levels whatever the stage of disease, but PGC-1α protein and CS activity were significantly reduced only at the decompensated stage. The functional result was a significant fall in mitochondrial respiration at the decompensated stage in the RV and GAS. The mRNA expression and mitochondrial respiration were not significantly modified in the MT LV. MT rats demonstrated an early decrease in expression of genes involved in mitochondrial biogenesis in a skeletal muscle, whereas reduced protein expression, and the resulting mitochondrial respiratory dysfunction appeared only in rats with overt heart failure, in the GAS and RV. Dissociations between mRNA and protein levels at the compensated stage deserve to be further studied.Molecular and Cellular Biochemistry 10/2012; · 2.06 Impact Factor
