Transition of Resuscitative Endovascular Balloon Occlusion of the Aorta from Zone 3 to Zone 1 to Treat Hemodynamic Collapse during Continued Hemorrhage.

INTRODUCTION: Noncompressible torso hemorrhage (NCTH) accounts for most potentially survivable deaths on the battlefield. Treatment of NCTH is challenging, especially in far-forward environments with limited capabilities. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has shown promise in the care of patients with NCTH. REBOA involves introducing a balloon catheter into the descending aorta in a specific occlusion region (zones 1, 2, or 3) and acts as a hemorrhage control adjunct with resuscitative support. The balloon is placed in zone 3 in the infrarenal aorta for high junctional or pelvic injuries and in zone 1 proximal to the diaphragm for torso hemorrhage. Zone 1 REBOA provides more resuscitative support than zone 3; however, the potential for ischemia and reperfusion injuries is greater with zone 1 than with zone 3 REBOA placement. This study aims to determine the possible benefit of transitioning the REBOA balloon from zone 3 to zone 1 to rescue a patient with ongoing venous bleeding and impending cardiovascular collapse. MATERIALS AND METHODS: Yorkshire male swine (70-90 kg, n = 6 per group) underwent injury to the femoral artery, which was allowed to bleed freely for 60 s, along with a simultaneous controlled venous hemorrhage. After 60 s, the arterial bleed was controlled with hemostatic gauze and zone 3 REBOA was inflated. Five hundred milliliters of Hextend was used for initial fluid resuscitation. The controlled venous bleed continued until a mean arterial pressure (MAP) of 30 mmHg was reached to create an impending cardiovascular collapse. The animals were then randomized into either continued zone 3 REBOA or transition from zone 3 to zone 1 REBOA. Following 30 min, a "hospital phase" was initiated, consisting of cessation of the venous hemorrhage, deflation of the REBOA balloon, and transfusion of one unit of whole blood administered along with saline and norepinephrine to maintain a MAP of 60 mmHg or higher. The animals then underwent a 2-h observation period. Survival, hemodynamics, and blood chemistries were compared between groups. RESULTS: No significant differences between groups were observed in hemodynamic or laboratory values at baseline, postinitial injury, or when MAP reached 30 mmHg. Survival was significantly longer in animals that transitioned into zone 1 REBOA (log-rank analysis, P = .012). The average time of survival was 14 ± 10 min for zone 3 animals vs. 65 ± 59 min for zone 1 animals (P = .064). No animals in the zone 3 group survived to the hospital phase. Zone 1-treated animals showed immediate hemodynamic improvement after transition, with maximum blood pressure reaching near baseline values compared to those in the zone 3 group. CONCLUSIONS: In this swine model of NCTH, hemodynamics and survival were improved when the REBOA balloon was transitioned from zone 3 to zone 1 during an impending cardiovascular collapse. Furthermore, these improved outcome data support the pursuit of additional research into mitigating ischemia-reperfusion insult to the abdominal viscera while still providing excellent resuscitative support, such as intermittent or partial REBOA.

Synthesis of immune modulators by smooth muscles.

The primary function of smooth muscle cells is to contract and alter the stiffness or diameter of hollow organs such as blood vessels, the airways and the gastrointestinal and urogenital tracts. In addition to purely structural functions, smooth muscle cells may play important metabolic roles, particularly in various inflammatory responses. In cell culture, these cells have been shown to be metabolically dynamic, synthesizing and secreting extracellular matrix proteins, glycosaminoglycans and a wide variety of cell-cell signaling proteins, such as interleukins, chemokines and peptide growth factors. Secreted cell signaling proteins participate in the inflammatory response of smooth muscle-containing organs, and some can also stimulate smooth muscle migration, proliferation and contraction. The cellular signaling pathways controlling synthesis of these signaling proteins are similar to those used by cells mediating innate immunity and may contribute to pathogenesis of diverse diseases including atherosclerosis, asthma, inflammatory bowel diseases and preterm labor. Appreciating the role of smooth muscle cells in these diseases may lead to better understanding of the beneficial effects of anti-inflammatory drugs as well as identification of new targets for anti-inflammatory therapy.

p38 MAPK and NF-kappaB mediate COX-2 expression in human airway myocytes.

We have previously demonstrated that p38 and extracellular signal-regulated protein kinase (ERK) mitogen-activated protein kinases (MAPK) are components of proinflammatory induced cytokine expression in human airway myocytes. The experiments described here further these studies by examining p38 MAPK and NF-kappaB regulation of cyclooxygenase-2 (COX-2) expression in response to a complex inflammatory stimulus consisting of 10 ng/ml interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), and interferon (IFN)-gamma. COX-2 expression was induced with this stimulus in a time-dependent manner, with maximal expression seen 12-20 h after treatment. Semiquantitative RT-PCR and immunoblotting experiments demonstrate decreased COX-2 expression following treatment with the p38 MAPK inhibitor SB-203580 (25 microM) or the proteosome inhibitor MG-132 (1 microM). SB-203580 did not affect cytokine-stimulated IkappaBalpha degradation, NF-kappaB nuclear binding activity, or NF-kappaB-dependent signaling from the COX-2 promoter, indicating that p38 MAPK and NF-kappaB may affect COX-2 expression via separate signaling pathways. SB-203580, but not MG-132, also increased the initial rate of COX-2 mRNA decay, indicating p38 MAPK, but not NF-kappaB, participates in the regulation of COX-2 mRNA stability. These findings suggest that although p38 MAPK and NF-kappaB signaling regulate steady-state levels of COX-2 expression, p38 MAPK additionally affects stability of COX-2 mRNA in cytokine-stimulated human airway myocytes.