Omics of endothelial cell dysfunction in sepsis.

During sepsis, defined as life-threatening organ dysfunction due to dysregulated host response to infection, systemic inflammation activates endothelial cells and initiates a multifaceted cascade of pro-inflammatory signaling events, resulting in increased permeability and excessive recruitment of leukocytes. Vascular endothelial cells share many common properties but have organ-specific phenotypes with unique structure and function. Thus, therapies directed against endothelial cell phenotypes are needed to address organ-specific endothelial cell dysfunction. Omics allow for the study of expressed genes, proteins and/or metabolites in biological systems and provide insight on temporal and spatial evolution of signals during normal and diseased conditions. Proteomics quantifies protein expression, identifies protein-protein interactions and can reveal mechanistic changes in endothelial cells that would not be possible to study via reductionist methods alone. In this review, we provide an overview of how sepsis pathophysiology impacts omics with a focus on proteomic analysis of mouse endothelial cells during sepsis/inflammation and its relationship with the more clinically relevant omics of human endothelial cells. We discuss how omics has been used to define septic endotype signatures in different populations with a focus on proteomic analysis in organ-specific microvascular endothelial cells during sepsis or septic-like inflammation. We believe that studies defining septic endotypes based on proteomic expression in endothelial cell phenotypes are urgently needed to complement omic profiling of whole blood and better define sepsis subphenotypes. Lastly, we provide a discussion of how in silico modeling can be used to leverage the large volume of omics data to map response pathways in sepsis.

External cardiac defibrillation during wet-surface cooling in pigs.

OBJECTIVE: During surface cooling with ice-cold water, safety and effectiveness of transthoracic defibrillation was assessed. METHODS: In a pig ventricular fibrillation cardiac arrest model, once (n = 6), defibrillation was done first in a dry and then in a wet condition using the ThermoSuit System (Life Recovery Systems, HD, LLC, Kinnelon, NJ), which circulates a thin layer of ice-cold water (approximately 4 degrees C) over the skin surface. Another time (n = 6), defibrillation was done first in a wet and then in a dry condition. Success of defibrillation was defined as restoration of spontaneous circulation, and the current and voltage of the defibrillation signal was measured. RESULTS: There was a tendency toward less number of shocks needed for achieving restoration of spontaneous circulation in the wet condition as compared with the number of shocks needed in the dry condition. The energy delivered in both dry and wet conditions was 144 +/- 3 J. DISCUSSION: Transthoracic defibrillation is safe and effective in a wet condition after cooling with ice-cold water.

Rapid induction of therapeutic hypothermia using convective-immersion surface cooling: safety, efficacy and outcomes.

Therapeutic hypothermia has become an accepted part of post-resuscitation care. Efforts to shorten the time from return of spontaneous circulation to target temperature have led to the exploration of different cooling techniques. Convective-immersion uses a continuous shower of 2 degrees C water to rapidly induce hypothermia. The primary purpose of this multi-center trial was to evaluate the feasibility and speed of convective-immersion cooling in the clinical environment. The secondary goal was to examine the impact of rapid hypothermia induction on patient outcome. 24 post-cardiac arrest patients from 3 centers were enrolled in the study; 22 agreed to participate until the 6-month evaluations were completed. The median rate of cooling was 3.0 degrees C/h. Cooling times were shorter than reported in previous studies. The median time to cool the patients to target temperature (<34 degrees C) was 37 min (range 14-81 min); and only 27 min in a subset of patients sedated with propofol. Survival was excellent, with 68% surviving to 6 months; 87% of survivors were living independently at 6 months. Conductive-immersion surface cooling using the ThermoSuit System is a rapid, effective method of inducing therapeutic hypothermia. Although the study was not designed to demonstrate impact on outcomes, survival and neurologic function were superior to those previously reported, suggesting comparative studies should be undertaken. Shortening the delay from return of spontaneous circulation to hypothermic target temperature may significantly improve survival and neurologic outcome and warrants further study.