Recombinant human C1 inhibitor improves acute cardiac function and attenuates acute myocarditis after traumatic brain injury and hemorrhagic shock in swine

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B578
Abstract ID: 7628

Presenting Author:
Yansong Li , PI , UT Hlth. San Antonio Long Sch. of Med.

Abstract:

Accumulating evidence reveals that the existence of traumatic hemorrhage (TH)-induced secondary cardiac injury (THISCI) is associated with poor patient outcomes. The lack of effective therapies to mitigate THISCI is a serious unmet need in TH patients. The complement cascade is activated immediately after TH, which is associated with hypovolemic shock, systemic/cardiac inflammation, poor response to fluid resuscitation, and mortality. The aim of this study was to investigate the efficacy of recombinant human C1 inhibitor (rhC1-INH) on THISCI in pigs. Anesthetized female swine received a combination of moderate traumatic brain injury and 48% hemorrhage. The injured animals were randomized to two groups: (1) Injury + Placebo and (2) Injury + rhC1-INH. After 24h, systemic levels of complement hemolytic activity (CH50), functional rhC1-INH and cardiac troponin I (cTnI), and cardiac injury in left ventricular tissues were assessed. rhC1-INH reached its peak (~9 U/ml) by 15 min after rhC1-INH dosing and remained ≥ 2 U/ml up to ~20h. Early administration of rhC1-INH inhibited CH50 (30~60%), decreased circulating levels of cTnI (85~92%), attenuated cardiac inflammation and microscopic damages, maintained systolic blood pressure, and reduced shock index and blood lactate compared to the Injury + Placebo. Thus, rhC1-INH could emerge as a promising adjunct to damage control resuscitation that may significantly protect against THISCI in severe TH patients in prehospital settings.