Natalia Jimenez

Therapeutic delivery of hydrogen sulfide for salvage of ischemic skeletal muscle after the onset of critical ischemia

BACKGROUND Recent evidence suggests that hydrogen sulfide is capable of mitigating the degree of cellular damage associated with ischemia-reperfusion injury (IRI). METHODS This study evaluated the potential utility of hydrogen sulfide in preventing IRI in skeletal muscle by using in vitro (cultured myotubes subjected to sequential hypoxia and normoxia) and in vivo (mouse hind limb ischemia, followed by reperfusion) models to determine whether intravenous hydrogen sulfide delivered after the ischemic event had occurred (pharmacologic postconditioning) conferred protection against IRI. Injury score and apoptotic index were determined by analysis of specimens stained with hematoxylin and eosin and terminal deoxynucleotide transferase-mediated deoxy-uridine triphosphate nick-end labeling, respectively. RESULTS In vitro, hydrogen sulfide reduced the apoptotic index after 1, 3, or 5 hours of hypoxia by as much as 75% (P = .002), 80% (P = .006), and 83% (P < .001), respectively. In vivo, hydrogen sulfide delivered after the onset of hind limb ischemia and before reperfusion resulted in protection against IRI-induced cellular changes, which was validated by significant decreases in the injury score and apoptotic index. The timing of hydrogen sulfide delivery was crucial: when delivered 20 minutes before reperfusion, hydrogen sulfide conferred significant cytoprotection (P < .001), but treatment 1 minute before reperfusion did not provide protection (P = NS). CONCLUSIONS These findings confirm that hydrogen sulfide limits IRI-induced cellular damage in myotubes and skeletal muscle, even when delivered after the onset of ischemia in this murine model. These data suggest that when given in the appropriate dose and within the proper time frame, hydrogen sulfide may have significant therapeutic applications in multiple clinical scenarios.

Hydrogen sulfide attenuates intestinal ischemia-reperfusion injury when delivered in the post-ischemic period

Background and Aim:  To investigate whether pharmacologic post‐conditioning of intestinal tissue with hydrogen sulfide (HS) protects against ischemia reperfusion injury (IRI).

Development of an acellular bioengineered matrix with a dominant vascular pedicle.

BACKGROUND This study assessed the feasibility of creating a tissue engineering platform by decellularization of fasciocutaneous tissue. MATERIALS AND METHODS A fasciocutaneous flap based upon the superficial inferior epigastric artery was harvested from the abdominal wall of 8-wk-old male Sprague-Dawley rats. All cellular components were removed by sequential treatment with sodium azide, DNAse, and sodium deoxycholate. The degree of decellularization was qualitatively assessed by histology and quantitatively assessed by spectrophotometry. Persistence of relevant extracellular matrix proteins was shown following staining with orcein and hematoxylin. The duration of circuit patency was determined by continuous perfusion with a peristaltic perfusion pump. RESULTS Gross and histologic examination demonstrated removal of cellular constituents with preservation of tissue matrix architecture, including macrochannels and microchannels. This was confirmed by the application of spectrophotometry to DNA isolates, which showed that the decellularized flap retained 4.04 ng/μL DNA, compared with the non-processed control, which retained 37.03 ng/μL DNA, and the acellular control, which was read as having 0.65 ng/μL DNA. The extracellular matrix of vessel walls was shown to remain intact. Peristaltic perfusion of the cannulated pedicle inflow channel with phosphate buffered saline at a rate of 200 μL/min confirmed circuit patency for 6 h. CONCLUSION Fasciocutaneous flaps harvested with an intact vascular pedicle and associated tissue vascular network can be successfully decellularized and perfused ex vivo. This methodology, which is scalable to human size tissues, provides promise as a technique for the production of customizable engineered tissues.

Body contouring after bariatric surgery: how much is really being done?

Abstract The proportion of postbariatric surgery patients who undergo body contouring (BC) procedures is unknown. We designed a study to explore demographic features and patient education regarding BC in the bariatric surgery (BS) population. A survey was mailed to 1158 patients who underwent BS by 2 surgeons between 2003 and 2011. A total of 284 (24.5%) patients responded. Seventy-two patients (25.4%) reported discussing BC surgery with their bariatric surgeon perioperatively. Forty patients (14.1%) were referred for plastic surgery consultation. Thirty-three patients (11.6%) underwent BC procedures. The most frequent reasons cited for not undergoing BC were expense (29.2%) and lack of awareness regarding options (23.6%). Thirty-nine percent of respondents reported that they might have chosen differently, had they received more information. As a result of insufficient perioperative counseling, the majority of BS patients are unaware of the multitude of BC procedures available. Additional efforts toward improving patient (and surgeon) education regarding postbariatric BC options are warranted.

164A: OPTIMIZING NEOVASCULARIZATION OF TISSUE REGENERATION TEMPLATES BY RATIONAL DESIGN AND MICROFABRICATION

Objective: Tissue engineering has long sought to design constructs that rapidly achieve functionality upon implantation. Current techniques, however, cannot produce pre-fabricated tissues with an intact microvascular network that is connected to macrovascular inflow and outflow vessels. Therefore, we assessed the feasibility of decellularizing tissue with an intact vascular pedicle that contains a dominant artery and vein.

7: SOLVING THE QUESTION OF PROTECTION: HYDROGEN SULFIDE CONFERS PROTECTION FROM IRI VIA ACTIVATION OF THE JAK-STAT PATHWAY

Introduction: Although there is an increasing body of evidence that demonstrates that hydrogen sulfide (HS) provides significant protection against Ischemia Reperfusion Injury (IRI), the mechanism by which this protection is conferred remains poorly understood. The JAK-STAT signaling pathway is known to regulate multiple cell processes including proliferation, differentiation and apoptosis via modulation of nuclear gene expression. Previous work has shown that this pathway is activated by mechanical preconditioning, which provides protection against IRI. We hypothesize this critical cell survival pathway would be similarly activated by treatment with HS in the setting of IR.

Therapeutic Delivery of Hydrogen Sulfide to Profoundly Ischemic Muscle: Timing Is Everything

INTRODUCTION: Hydrogen sulfide (HS) is protective effect against the detrimental effects of ischemia-reperfusion injury (IRI) when delivered either before or after an ischemic event has occurred. The optimal timing of treatment, however, remains undefined. In order to better understand the potential clinical application of HS, we sought to define the therapeutic window during which delivery of HS is protective.