Artificial organs
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Medical treatment of burns and chronic wounds remains a challenge. We discussed a therapy concept that combines skin cell spray transplantation with a novel wound dressing based on artificial hollow fiber membrane capillaries. In skin cell-based therapy development, autologous skin progenitor cells are isolated from a healthy skin area and sprayed onto the wound. ⋯ The functions of the dressing are comparable with those of dialysis; the capillaries, however, are applied externally onto the wound. Perfusion with a clinical peripheral nutrition and buffer solution can provide wound irrigation, wound debris removal, cell nutrition, pH regulation, and electrolyte balance while potentially serving to address delivery of regenerative factors and antibiosis. An innovative active skin wound dressing that provides cell support and stimulates regeneration by wound irrigation is discussed.
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We have previously shown that deferoxamine (DFO) infusion protected myocardium against reperfusion injury in patients undergoing open heart surgery, and reduced brain edema, intracranial pressure, and lung injury in pigs with acute hepatic ischemia (AHI). The purpose of this research was to study if DFO could attenuate sepsis inflammatory response syndrome (SIRS) and confer renoprotection in the same model of AHI in anesthetized pigs. Fourteen animals were randomly allocated to two groups. ⋯ Profound proteinuria, strips of extensive necrosis of tubular epithelial cells, and occasional apoptotic tubular epithelial cells were already present in Group C, but not in Group DFO animals at the time of euthanasia. DFO infusion attenuated lipid peroxidation, blocked IL-6 production, and substantially diminished SIRS and MOD, including tubulointerstitial damage in pigs after acute ischemic hepatic failure. This finding shows that iron, IL-6, and lipid peroxidation are important participants in the pathophysiology of renal injury in the course of generalized inflammation and provides novel pathways of therapeutic interventions for renal protection.
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The novel Permanent Life Support (PLS; Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) as peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support system has been investigated as treatment for patients with refractory cardiogenic shock (CS). Between January 2007 and July 2011, 73 consecutive adult patients were supported on peripheral PLS ECMO system at our institution (55 men; age 60.3 ± 11.6 years, range: 23-84 years). Indications for support were failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n = 50) and primary donor graft failure (n = 8), post-acute myocardial infarction CS (n = 12), and CS on chronic heart failure (n = 3). ⋯ Stepwise logistic regression identified blood lactate level and CK-MB relative index at 72 h after ECMO initiation, and number of PRBCs transfused on ECMO as significant predictors of mortality on ECMO (P = 0.011, odds ratio [OR] = 2.48; 95% confidence interval [CI] = 1.11-3.12; P = 0.012, OR = 2.81, 95% CI = 1.026-2.531; and P = 0.012, OR = 1.94, 95% CI = 1.02-5.21; respectively). Patients with an initial poor hemodynamic status could benefit by rapid peripheral installation of PLS ECMO. The blood lactate level, CK-MB relative index, and PRBCs transfused should be strictly monitored during ECMO support.
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Polynitroxylated pegylated hemoglobin (PNPH) as a multifunctional therapeutic takes advantage of the ability of hemoglobin (Hb) to transport oxygen, the antioxidative stress activities from the redox coupling of nitroxide and heme iron, and the hypercolloid properties of pegylation. The published preclinical data demonstrating that PNPH acts as a neurovascular protective multifunctional therapeutic in an animal model simulating prehospital resuscitation of traumatic brain injury (TBI) with hemorrhagic shock (HS) are reviewed. Preliminary results on the potential utility of PNPH for neurovascular protection in thrombolytic stroke therapy and for correction of vascular dysfunction through transfusion in sickle-cell disease (SCD) are also discussed. We hypothesize that with PNPH, Hb has more than been tamed--it has become a therapeutic and not just a nontoxic extracellular oxygen carrier--and that successful PNPH development as a multifunctional therapeutic that protects the neurovasculature and reduces oxidative stress may represent a paradigm shift in transfusion and critical care medicine, which may meet a number of unmet medical needs resulting from oxidative stress and inadequate blood flow, such as HS, TBI, SCD, and stroke.