A retrievable, dual-chamber stent protects against warm ischemia of donor organs in a model of donation after circulatory death.

BACKGROUND: Ischemic injury during the agonal period of donation after circulatory death donors remains a significant barrier to increasing abdominal transplants. A major obstacle has been the inability to improve visceral perfusion, while at the same time respecting the ethics of the organ donor. A retrievable dual-chamber stentgraft could potentially isolate the organ perfusion from systemic hypotension and hypoxia, without increasing cardiac work or committing the donor. METHODS: Retrievable dumbbell-shaped stents were laser welded from nitinol wire and covered with polytetrafluoroethylene. Yorkshire pigs were assigned to either agonal control or dumbbell-shaped dual-chamber stentgraft. A central lumen maintained aortic flow, while an outer visceral chamber was perfused with oxygenated blood. A 1-hour agonal phase of hypoxia and hypotension was simulated. Stents were removed by simple sheath advancement. Cardiac monitoring, labs, and visceral flow were recorded followed by recovery of the animal to a goal of 48 hours. RESULTS: Cardiac stress did not increase during stent deployment. Visceral pO2 and flow were dramatically improved in stented animal relative to control animals. Five of 7 control animals were killed after renal failure complications, whereas all stent animals survived. Histology confirmed increased ischemic changes among control kidneys compared to stented animals. CONCLUSION: A dual-chamber stent improved outcomes after a simulated agonal phase. The stent did not increase cardiac work, thus respecting a key ethical consideration. The ability of a dual-chamber stent to prevent ischemia during organ recovery may become a powerful tool to address the critical donor organ shortage.

Damage control of caval injuries in a porcine model using a retrievable Rescue stent.

OBJECTIVE: Early hemorrhage control before the operating room is essential to reduce the significant mortality associated with traumatic injuries of the vena cava. Conventional approaches present logistical challenges on the battlefield or in the trauma bay. A retrievable stent graft would allow rapid hemorrhage control in the preoperative setting when endovascular expertise is not immediately available and without committing a patient to the limitations of current permanent stents. This study details a refined retrievable Rescue stent for percutaneous delivery that was examined in a porcine survival model of penetrating caval hemorrhage. METHODS: A retrievable caval stent was reduced in delivery profile to a 9F sheath using finite element analysis. The final stent was constructed with a "petal and stem" design using nitinol wire followed by covering with polytetrafluoroethylene. Seven Yorkshire pigs (79-86 kg) underwent 22F injury of the infrarenal vena cava with intentional class II hemorrhage (1200 mL). Percutaneous deployment of the Rescue stent was used to temporize hemorrhage for 60 minutes, followed by resuscitation with cell saver blood and permanent caval repair. Hemorrhage control was documented with photography and angiography. Vital signs were recorded and laboratory values were measured out to 48 hours postoperatively. Data were examined with a repeated-measures analysis of variance. RESULTS: The profile of the caval Rescue stent was successfully reduced from 16F to 9F while remaining within fracture and shape memory limits for nitinol. In addition, both rapid deployment and recapture were preserved. Following intentional hemorrhage after caval injury, animals revealed a significant drop in mean arterial pressure (average, 30 mm Hg), acidosis, and elevated lactate level compared with before injury. Compared with uncontrolled hemorrhage, which resulted in death in <9 minutes, the Rescue stent achieved hemorrhage control in <1 minute after venous access in all seven animals. All animals were successfully recovered after permanent repair. There was no significant change in levels of transaminases, bilirubin, creatinine, or hemoglobin at 48 hours compared with preinjury baseline. CONCLUSIONS: A retrievable Rescue stent achieved rapid percutaneous hemorrhage control after a significant traumatic injury of the vena cava and allowed successful recovery of all injured animals. Further development of this approach may have utility in preoperative damage control of caval injuries.

CD34 affinity pheresis attenuates a surge among circulating progenitor cells following vascular injury.

BACKGROUND: Intimal hyperplasia (restenosis) is an exaggerated healing response leading to failure of half of vascular interventions. Increasing evidence suggests that circulating progenitor cells contribute to intimal pathology, and clinical studies have demonstrated a correlation between progenitor cells and the incidence of restenosis after cardiovascular interventions. The aims of this study were to characterize the temporal response of CD34+ progenitors following vascular injury in an ovine model and to evaluate an affinity pheresis approach to attenuate this response. METHODS: An ovine model underwent either operative vascular injury or a nonvascular surgery (n = 3 per group). Blood was examined perioperatively over 2 weeks by flow cytometry. Next, an affinity pheresis approach to mediate systemic depletion of CD34 progenitors was designed. Custom agarose pheresis matrix with antibody affinity toward CD34 or an isotype control was evaluated in vitro. Next, following vascular injury, sheep underwent perioperative whole blood volume pheresis toward either the progenitor cell marker CD34 (n = 3) or an isotype control (n = 4) for 14 days. Animals were monitored by physical exam as well as complete blood counts. Cells recovered by pheresis were eluted and examined by flow cytometry. RESULTS: Flow cytometry revealed a focal surge of circulating CD34 cells after vascular injury but not among surgical controls (P = .05). Toward the goal of an approach to attenuate the surge of CD34 progenitors, an evaluation of high-flow affinity matrix revealed efficacy in removal of progenitors from ovine blood in vitro. Next, a separate group of animals undergoing affinity pheresis after vascular injury was evaluated to mediate systemic depletion of CD34+ cells. Again, a surge of CD34+ cells was observed among isotype pheresis animals following vascular intervention but was attenuated over 20-fold by a CD34 pheresis approach (P = .029). Furthermore, an average of 77 million CD34-positive cells were eluted from the CD34 pheresis matrix. Despite multiple sessions of pheresis, complete blood counts remained essentially unchanged over 2 weeks. CONCLUSIONS: Despite evidence suggesting a role for CD34+ circulating progenitor cells in restenotic pathology, the temporal pattern of CD34 progenitors after vascular injury has not been previously defined. We have demonstrated a surge among circulating CD34+ cells that appears confined to procedures involving vascular injury and that this event seems to occur early after vascular injury. We further conclude that CD34 affinity pheresis attenuates the surge. This approach for direct depletion of progenitors may have important implications for the study of progenitors in vascular restenosis.