The Effect of Ghrelin upon the Early Immune Response in Lean and Obese Mice during Sepsis

Introduction It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis. Methods In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis. Results In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1 beta and TNF-alpha concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement. Conclusion In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice

Platelet mitochondrial membrane depolarization reflects disease severity in patients with sepsis and correlates with clinical outcome

Introduction: Sepsis is still a leading cause of morbidity and mortality, even in modern times, and thrombocytopenia has been closely associated with unfavorable disease outcome. Decreases in mitochondrial membrane potential (depolarization) were found in different tissues during sepsis. Previous work suggests that mitochondrial dysfunction of platelets correlates with clinical disease activity in sepsis. However, platelet mitochondrial membrane potential (Mmp) has not been investigated in a clinical follow-up design and not with regard to disease outcome. Methods: In this study, platelet mitochondrial membrane depolarization was assessed by means of a fluorescent Mmp-Index with flow cytometry in 26 patients with sepsis compared with control patients. Platelet Mmp-Index on admission was correlated with the clinical disease scores Acute Physiology and Chronic Health Evaluation Score II (APACHE II), Sequential Organ Failure Score (SOFA), and Simplified Acute Physiology Score II (SAPS II). Finally, platelet Mmp-Index on admission and follow-up were compared in the group of sepsis survivors and nonsurvivors. Expression of the prosurvival protein Bcl-xL in platelets was quantified by immunoblotting. Results: Platelet mitochondrial membrane depolarization correlated significantly with the simultaneously assessed clinical disease severity by APACHE II (r = -0.867; P < 0.0001), SOFA (r = -0.857; P < 0.0001), and SAPS II score (r = -0.839; P < 0.0001). Patients with severe sepsis showed a significant reduction in platelet Mmp-Index compared with sepsis without organ failure (0.18 (0.12 to 0.25) versus 0.79 (0.49 to 0.85), P < 0.0006) or with the control group (0.18 (0.12 to 0.25) versus 0.89 (0.68 to 1.00), P < 0.0001). Platelet Mmp-Index remained persistently low in sepsis nonsurvivors (0.269 (0.230 to 0.305)), whereas we observed recovery of platelet Mmp-Index in the survivor group (0.9 (0.713 to 1.017)). Furthermore, the level of prosurvival protein Bcl-xL decreased in platelets during severe sepsis. Conclusion: In this study, we demonstrated that mitochondrial membrane depolarization in platelets correlates with clinical disease severity in patients with sepsis during the disease course and may be a valuable adjunct parameter to aid in the assessment of disease severity, risk stratification, and clinical outcome

Rescue under ongoing CPR from an upper floor: evaluation of three different evacuation routes and mechanical and manual chest compressions: a manikin trial

Background If transport under ongoing cardiopulmonary resuscitation (CPR) from an upper floor is indicated, the ideal CPR-method and evacuation route is unknown hitherto. We aimed to elaborate a strategy for evacuation of patients under ongoing CPR from an upper floor, comparing three different evacuation routes and manual and mechanical chest compressions. Methods A CPR-training manikin recording CPR-quality was placed on the fifth floor and was evacuated to an ambulance via lift, turntable ladder, or staircase. Chest compressions were performed manually or with a mechanical CPR-device. Efficiency endpoints were compression depth and frequency, sufficiency of chest release, compared with European Resuscitation Council (ERC) Guidelines, and duration of the evacuation. Adverse outcomes were disconnection/dislocation of devices and hazards/accidents to the personnel. Results For all evacuation routes, compression depth and frequency were significantly more compliant with ERC-guidelines under mechanical CPR. Manual CPR was associated with considerable deviations from correct compression depth and frequency. Chest release only slightly differed between groups. Evacuation via lift under mechanical CPR was fastest and evacuation via turntable ladder under manual CPR was slowest. No device disconnections or accidents occurred, but hazard to personnel was perceived during evacuation via ladder under manual CPR. Conclusions In this study, a mechanical CPR-device proved to deliver better CPR-quality during evacuation from an upper floor. If a lift accessible with a stretcher is available, this route should be preferred, regardless of manual or mechanical CPR. Turntable ladders can only be meaningfully used with mechanical CPR, otherwise CPR-quality is poor and hazard to the personnel is increased. Not all evacuation routes may be useable in a specific real-life scenario