Venovenous extracorporeal membrane oxygenation experience in a community level I trauma center.

BACKGROUND: There is limited literature of venovenous extracorporeal membrane oxygenation use in a community, non-university, setting in the trauma population. METHODS: We reviewed our cases over 2 years from March 2018 to March 2020. This study was conducted in a community hospital with a General Surgery residency with no direct affiliation to a medical school. Primary outcome reviewed was survival to discharge. Secondary outcomes included duration of extracorporeal membranous oxygenation (ECMO) support, blood transfusion requirement, complications, and disposition. RESULTS: Five patients were cannulated during this time period. All patients survived to discharge. Mean time on ECMO was 153.4 h or 6.4 days (range 60-216 h). All patients required a transfusion while cannulated, with a mean of 10 units PRBC transfused (range 3-24). One patient required CPR, one required cessation of heparin drip for bleeding, and one had clinical signs of a stroke. Three patients were discharged to long-term acute care facilities and the other two to acute rehab. CONCLUSIONS: Community level I trauma centers are capable of handling trauma patients requiring ECMO. It does require a multi-disciplinary team of surgical intensivists and cardiothoracic surgeons along with the support of nursing, respiratory therapists, and perfusionists. The outcomes in this limited series show that ECMO can be a tool utilized in the community setting.

Body mass index interaction effects with hyperglycemia and hypocholesterolemia modify blunt traumatic brain injury outcomes: a retrospective study.

INTRODUCTION: There is controversy regarding obesity or body mass index (BMI) effects on postinjury mortality and mechanical ventilation. The aim was to assess outcome associations with BMI and postinjury blood glucose and cholesterol. METHOD: Adult blunt traumatic brain injury patients admitted to a level I trauma center and requiring ≥ 3 days of intensive care were investigated. Admission blood glucose and day-4 total cholesterol were captured from the medical records. Cholesterol ratio was calculated by dividing day-4 values by published national normative levels according to sex, age, and injury date. RESULTS: The parent cohort included 588 patients. The ventilator days ≥ 10 or died group, when compared to the ventilator days < 10 and lived group, had higher Injury Severity Score (ISS) (29.2±9.9 versus [vs.] 23.7±9.7, P < 0.0001), BMI (27.9±6.8 vs. 26.0±5.5, P = 0.0002), and admission glucose (182.6±79 vs. 155.4±59 mg/dl, P < 0.0001, n = 476) and lower emergency department Glasgow Coma Scale score (ED GCS) (6.9±4.7 vs. 10.3±5.0, P < 0.0001) and cholesterol ratio (0.64±0.2 vs. 0.70±0.2, P = 0.0018, n = 364). The ventilator days ≥ 10 or died group had independent associations with increased ISS (P = 0.0709), decreased ED GCS (P = 0.0078), and increased BMI÷cholesterol ratio (P = 0.0003). The ventilator days ≥ 10 or died group had independent associations with increased ISS (P = 0.0013), decreased ED GCS (P < 0.0001), and increased BMI × glucose (P < 0.0001). Ventilator days were increased with higher ISS (P < 0.0001), BMI (P = 0.0014) and glucose (P = 0.0031) and with lower ED GCS (P < 0.0001) and cholesterol ratio (P = 0.0004). Ventilator days had independent associations with increased ISS (P < 0.0001), decreased ED GCS (P = 0.0041), and increased BMI÷cholesterol ratio (P = 0.0010). Ventilator days had independent associations with increased ISS (P < 0.0001), decreased ED GCS (P < 0.0001), and increased BMI × glucose (P = 0.0041). CONCLUSION: For TBI patients, valid risk assessment measurements include ISS (anatomic injury burden), ED GCS (brain function), BMI (preinjury weight status), admission glucose (postinjury metabolism), and day-4 cholesterol ratio (postinjury inflammation).

The contribution of interleukin-2 to effective wound healing.

Ineffective skin wound healing is a significant source of morbidity and mortality. Roughly 6.5 million Americans experience chronically open wounds and the cost of treating these wounds numbers in the billions of dollars annually. In contrast, robust wound healing can lead to the development of either hypertrophic scarring or keloidosis, both of which can cause discomfort and can be cosmetically undesirable. Appropriate wound healing requires the interplay of a variety of factors, including the skin, the local microenvironment, the immune system, and the external environment. When these interactions are perturbed, wounds can be a nidus for infection, which can cause them to remain open an extended period of time, or can scar excessively. Interleukin-2, a cytokine that directs T-cell expansion and phenotypic development, appears to play an important role in wound healing. The best-studied role for Interleukin-2 is in influencing T-cell development. However, other cell types, including fibroblasts, the skin cells responsible for closing wounds, express the Interleukin-2 receptor, and therefore may respond to Interleukin-2. Studies have shown that treatment with Interleukin-2 can improve the strength of healed skin, which implicates Interleukin-2 in the wound healing process. Furthermore, diseases that involve impaired wound healing, such as diabetes and systemic lupus erythematosus, have been linked to deficiencies in Interleukin-2 or defects Interleukin-2-receptor signaling. The focus of this review is to summarize the current understanding of the role of Interleukin-2 in wound healing, to highlight diseases in which Interleukin-2 and its receptor may contribute to impaired wound healing, and to assess Interleukin-2-modulating approaches as potential therapies to improve wound healing.

4-Hydroxynonenal dependent alteration of TRPV1-mediated coronary microvascular signaling.

We demonstrated previously that TRPV1-dependent regulation of coronary blood flow (CBF) is disrupted in diabetes. Further, we have shown that endothelial TRPV1 is differentially regulated, ultimately leading to the inactivation of TRPV1, when exposed to a prolonged pathophysiological oxidative environment. This environment has been shown to increase lipid peroxidation byproducts including 4-Hydroxynonenal (4-HNE). 4-HNE is notorious for producing protein post-translation modification (PTM) via reactions with the amino acids: cysteine, histidine and lysine. Thus, we sought to determine if 4-HNE mediated post-translational modification of TRPV1 could account for dysfunctional TRPV1-mediated signaling observed in diabetes. Our initial studies demonstrate 4-HNE infusion decreases TRPV1-dependent coronary blood flow in C57BKS/J (WT) mice. Further, we found that TRPV1-dependent vasorelaxation was suppressed after 4-HNE treatment in isolated mouse coronary arterioles. Moreover, we demonstrate 4-HNE significantly inhibited TRPV1 currents and Ca2+ entry utilizing patch-clamp electrophysiology and calcium imaging respectively. Using molecular modeling, we identified potential pore cysteines residues that, when mutated, could restore TRPV1 function in the presence of 4-HNE. Specifically, complete rescue of capsaicin-mediated activation of TRPV1 was obtained following mutation of pore Cysteine 621. Finally, His tag pull-down of TRPV1 in HEK cells treated with 4-HNE demonstrated a significant increase in 4-HNE binding to TRPV1, which was reduced in the TRPV1 C621G mutant. Taken together these data suggest that 4-HNE decreases TRPV1-mediated responses, at both the in vivo and in vitro levels and this dysfunction can be rescued via mutation of the pore Cysteine 621. Our results show the first evidence of an amino acid specific modification of TRPV1 by 4-HNE suggesting this 4-HNE-dependent modification of TRPV1 may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes.

Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction.

We demonstrated previously that TRPV1-dependent coupling of coronary blood flow (CBF) to metabolism is disrupted in diabetes. A critical amount of H2O2 contributes to CBF regulation; however, excessive H2O2 impairs responses. We sought to determine the extent to which differential regulation of TRPV1 by H2O2 modulates CBF and vascular reactivity in diabetes. We used contrast echocardiography to study TRPV1 knockout (V1KO), db/db diabetic, and wild type C57BKS/J (WT) mice. H2O2 dose-dependently increased CBF in WT mice, a response blocked by the TRPV1 antagonist SB366791. H2O2-induced vasodilation was significantly inhibited in db/db and V1KO mice. H2O2 caused robust SB366791-sensitive dilation in WT coronary microvessels; however, this response was attenuated in vessels from db/db and V1KO mice, suggesting H2O2-induced vasodilation occurs, in part, via TRPV1. Acute H2O2 exposure potentiated capsaicin-induced CBF responses and capsaicin-mediated vasodilation in WT mice, whereas prolonged luminal H2O2 exposure blunted capsaicin-induced vasodilation. Electrophysiology studies re-confirms acute H2O2 exposure activated TRPV1 in HEK293A and bovine aortic endothelial cells while establishing that H2O2 potentiate capsaicin-activated TRPV1 currents, whereas prolonged H2O2 exposure attenuated TRPV1 currents. Verification of H2O2-mediated activation of intrinsic TRPV1 specific currents were found in isolated mouse coronary endothelial cells from WT mice and decreased in endothelial cells from V1KO mice. These data suggest prolonged H2O2 exposure impairs TRPV1-dependent coronary vascular signaling. This may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes.

Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac metabolism in diabetic mice: role of nitric oxide and BK channels.

We have previously shown transient receptor potential vanilloid subtype 1 (TRPV1) channel-dependent coronary function is compromised in pigs with metabolic syndrome (MetS). However, the mechanisms through which TRPV1 channels couple coronary blood flow to metabolism are not fully understood. We employed mice lacking TRPV1 [TRPV1((-/-))], db/db diabetic, and control C57BKS/J mice to determine the extent to which TRPV1 channels modulate coronary function and contribute to vascular dysfunction in diabetic cardiomyopathy. Animals were subjected to in vivo infusion of the TRPV1 agonist capsaicin to examine the hemodynamic actions of TRPV1 activation. Capsaicin (1-100 µg·kg(-1)·min(-1)) dose dependently increased coronary blood flow in control mice, which was inhibited by the TRPV1 antagonist capsazepine or the nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (L-NAME). In addition, the capsaicin-mediated increase in blood flow was attenuated in db/db mice. TRPV1((-/-)) mice exhibited no changes in coronary blood flow in response to capsaicin. Vasoreactivity studies in isolated pressurized mouse coronary microvessels revealed a capsaicin-dependent relaxation that was inhibited by the TRPV1 inhibitor SB366791 l-NAME and to the large conductance calcium-sensitive potassium channel (BK) inhibitors iberiotoxin and Penetrim A. Similar to in vivo responses, capsaicin-mediated relaxation was impaired in db/db mice compared with controls. Changes in pH (pH 7.4-6.0) relaxed coronary vessels contracted to the thromboxane mimetic U46619 in all three groups of mice; however, pH-mediated relaxation was blunted in vessels obtained from TRPV1((-/-)) and db/db mice compared with controls. Western blot analysis revealed decreased myocardial TRPV1 protein expression in db/db mice compared with controls. Our data reveal TRPV1 channels mediate coupling of myocardial blood flow to cardiac metabolism via a nitric oxide-dependent, BK channel-dependent pathway that is corrupted in diabetes.