Activated Protein C: An Emerging Therapeutic Agent in the Prevention of Ischemia-Reperfusion Injury

Bezuhly, Michael; Liwski, Robert; West, Kenneth A.; Morris, Steven F.

doi:10.1055/s-2008-1080540

Cited by 5 publications

(1 citation statement)

References 80 publications

(96 reference statements)

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“…In the field of plastic surgery, long procedures such as free flap procedures tend to have a higher incidence of reperfusion injuries, which lead to intravascular wall damage due to the formation of reactive oxygen species. As a result of the endothelial damage, compromised areas become subsequently exposed to hypoxic conditions, which set the stage for microvascular thrombosis by inducing pro-coagulation and disruption of vascular integrity due to microsurgical errors [ 9 ].…”

Section: Reviewmentioning

confidence: 99%

From Risk Assessment to Intervention: A Systematic Review of Thrombosis in Plastic Surgery

Patel,

Camacho,

Shifchik

et al. 2023

Cureus

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Thromboembolism is a feared complication in plastic surgery and is linked to higher rates of morbidity and mortality. Despite extensive research, there is a lack of consistency between recommendations and clinical protocols to be implemented pre and post-surgery to reduce the incidence of thromboembolism. A systematic literature review was conducted using Pubmed and Scopus databases to determine the risk factors, screening methods, and existing treatment models for thromboembolism prevention. Articles in non-English languages were excluded. Analysis indicated that predominant risk factors include age (>35), elevated body mass index, coagulation disorders, smoking, estrogen therapies, genetic predisposition, vascular endothelium damage, stasis, and use of general anesthesia in patients with a history of cancer. Implementation of a proper prophylactic protocol is dependent on understanding the interplay between the aforementioned risk factors and the utilization of well-defined, evidence-based guidelines, such as the 2005 Caprini Risk Assessment Model and ultrasound surveillance. The literature review revealed that mechanical prophylaxis is the primary prevention method, followed by thromboprophylaxis for patients with higher Caprini scores. Plastic surgeons often underestimate the present risk stratification tools available for the prophylactic intervention of thromboembolism due to the fear of bleeding or hematoma complications postoperatively. In summary, this literature review emphasizes the importance of plastic surgeons selecting protocols that is inclusive of the patient's risk profile to yield a reduced risk of thromboembolism.

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Section: Reviewmentioning

confidence: 99%

From Risk Assessment to Intervention: A Systematic Review of Thrombosis in Plastic Surgery

Patel,

Camacho,

Shifchik

et al. 2023

Cureus

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Activated Protein C Improves Ischemic Flap Survival and Modulates Proangiogenic and Antiinflammatory Gene Expression

Bezuhly

Morris

Juskevicius

et al. 2009

Plastic and Reconstructive Surgery

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The Effect of Activated Protein C on Attenuation of Ischemia-Reperfusion Injury in a Rat Muscle Flap Model

Zhang

Fang

Arnold

et al. 2015

Annals of Plastic Surgery

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Ischemia-reperfusion injury is often the final and irreversible factor causing flap failure in microsurgery. The salvage of a microsurgical flap with an ischemia-reperfusion injury contributes to the success of microsurgical flap transfers. Activated protein C (APC), a serine protease with anticoagulant and anti-inflammatory activities, has been shown to improve ischemic flap survival. To date, APC has yet to be applied to models of free flap with ischemia-reperfusion injury. In this study, we aimed to investigate the effect of APC on gracilis flap ischemia-reperfusion injury induced by gracilis vessels clamping and reopening. Sixty male Sprague-Dawley rats were randomly divided into 2 groups. After 4 hours of clamping for ischemia, flaps were reperfused and recombinant human APC (25 μg/kg) or saline was injected in the flaps through pedicles. At 0, 1, 4, 18, and 24 hours after injection (n = 6 for each time point), the tissue samples were harvested. The muscle viability at 24 hours in saline group was 54.8% (15.1%), whereas the APC-treated group was 90.0% (4.3%) (P < 0.05). The induced nitric oxide synthase (iNOS) mRNA expression increased with the time after reperfusion, which were 0.93 (0.25) to 2.09 (0.22) in saline group, and 0.197 (0.15) to 0.711 (0.15) in the APC-treated group. iNOS mRNA expression in the APC-treated group was significantly higher than the saline group at 1, 18, and 24 hours (P < 0.05). Numerous inflammatory cells were observed infiltrating and invading the muscle fibers in the saline group more than the APC-treated group. Increased number of polymorphonuclear cells was also noted in the saline group compared with the APC-treated group (P < 0.05). In conclusion, APC treatment can significantly attenuate ischemia-reperfusion injury and increase the survival of the free flap through down-regulating iNOS mRNA expression and reducing the inflammatory cells. Further research is still needed to be done on various mechanisms in which APC is protective to prevent tissue damage.

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Activated Protein C: An Emerging Therapeutic Agent in the Prevention of Ischemia-Reperfusion Injury

Cited by 5 publications

References 80 publications

From Risk Assessment to Intervention: A Systematic Review of Thrombosis in Plastic Surgery

From Risk Assessment to Intervention: A Systematic Review of Thrombosis in Plastic Surgery

Activated Protein C Improves Ischemic Flap Survival and Modulates Proangiogenic and Antiinflammatory Gene Expression

The Effect of Activated Protein C on Attenuation of Ischemia-Reperfusion Injury in a Rat Muscle Flap Model

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