Chakradhar Anjali, Mroueh Jessica, Talbot Simon G
Harvard Medical School, Boston, MA, USA.
Brigham and Women's Hospital, Boston, MA, USA.
Hand (N Y). 2024 Nov 19:15589447241287806. doi: 10.1177/15589447241287806.
In response to the widespread occurrence of limb loss and the transformative potential of extremity vascularized composite allotransplantation (VCA), we examine the impact of warm and cold ischemia duration on limb survival and functional recovery. Our insights into warm ischemia are largely derived from relevant literature on replantation and revascularization. Studies indicate that achieving reperfusion within 5 to 6 hours of warm ischemia is critical for limb survival, and within 3 hours for curbing significant functional deficits. For limbs preserved in static cold conditions, as is standard practice in VCA, reperfusion should be attained within 10 to 12 hours of cold ischemia. However, our analysis exposes a lack of data on extremity functional recovery following cold ischemia, particularly in humans or large animal models. This underscores a gap in the literature that could guide clinical ischemia management in VCA if addressed. We anticipate optimal functional recovery between 3 and 6 hours of cold ischemia, as supported by outcomes in rats. Prolonged ischemia times are also associated with graft rejection, posing unique challenges to VCA. Tissues exhibit diverse responses, with muscle and nerve being highly susceptible to ischemic damage, and skin acquiring heightened immunogenicity. Ischemia management emerges as a focus for future policy and research initiatives. On the horizon, exploring updated transplantation protocols, vascular shunts, stabilizing perfusion solutions, and subnormothermic machine perfusion could mitigate ischemic damage and enhance clinical outcomes in extremity VCA.
鉴于肢体缺失的广泛发生以及肢体血管化复合组织异体移植（VCA）的变革潜力，我们研究了热缺血和冷缺血持续时间对肢体存活及功能恢复的影响。我们对热缺血的认识很大程度上源于有关再植和血管重建的相关文献。研究表明，在热缺血5至6小时内实现再灌注对肢体存活至关重要，而在3小时内实现再灌注对于抑制显著的功能缺陷至关重要。对于在静态冷条件下保存的肢体（这是VCA的标准做法），应在冷缺血10至12小时内实现再灌注。然而，我们的分析发现缺乏关于冷缺血后肢体功能恢复的数据，尤其是在人类或大型动物模型中。这凸显了文献中的一个空白，如果得到解决，可能会指导VCA中的临床缺血管理。我们预计冷缺血3至6小时之间可实现最佳功能恢复，大鼠的研究结果支持这一点。长时间的缺血时间也与移植物排斥反应相关，给VCA带来了独特的挑战。不同组织表现出不同的反应，肌肉和神经对缺血损伤高度敏感，而皮肤的免疫原性增强。缺血管理成为未来政策和研究倡议的重点。展望未来，探索更新的移植方案、血管分流术、稳定灌注溶液和亚低温机器灌注可以减轻缺血损伤并改善肢体VCA的临床结果。
