Comparison of a Continuous Noninvasive Temperature to Monitor Core Temperature Measures During Targeted Temperature Management
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AbstractBackground: Temperature modulating devices (TMD) currently utilize core temperature measurements during targeted temperature management (TTM) that are currently limited to esophageal (Et), bladder (Bt), or rectal (Rt) temperatures. We assessed the ability of a continuous noninvasive temperature monitor to accurately approximate core temperature during TTM. Methods: All patients undergoing TTM using a gel pad surface TMD and an existing core temperature monitoring device were eligible for this study. Core and continuous noninvasive temperature monitoring values were simultaneously recorded for up to 72 h of TTM. The two sets of temperature data were downloaded from a clinical data acquisition storage system at 1-min intervals. The Bland–Altman method assessed agreement between the core and continuous noninvasive temperature monitor values, by measuring the mean difference (± 2 SD) between these values. Results: There were 20 subjects that underwent study between January 2018 and March 2018 (55% women, age: 57 ± 14 years old, BMI: 28.9 + 9.8 kg/m2, 100% mechanically ventilated). The comparison patient temperature source was predominantly esophageal (n = 10) followed by bladder (n = 5) or rectal (n = 5). There were a total of 999 h of paired patient temperature data from esophageal (50%), bladder (25%), and rectal (25%) temperatures. Bland–Altman analysis demonstrated good agreement with the superficial temperature monitor and core temperature measures in all patients overall, with a difference mean of 0.06 ± 0.39 C (P = 0.99) and no proportional bias noted (β =0.002, P = 0.917). Conclusions: Continuous noninvasive temperature monitoring is a suitable alternative method for assessing core temperature during TTM. Future studies should focus on developing connectivity with a continuous noninvasive temperature monitor to approximate core temperature during TTM.
KeywordContinuous noninvasive temperature monitoring
Targeted temperature management
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85087611884&doi=10.1007%2fs12028-020-01036-9&partnerID=40&md5=783cd4a4bf028d5390b8e5cdd7594ce8; http://hdl.handle.net/10713/13379
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Repression of TNFalpha gene activation at febrile range temperature through modification of recruitment of transcriptional regulatorsCooper, Zachary A.; Hasday, Jeffrey D. (2009)We have previously shown that exposure to febrile-range temperatures (FRT, 39.5-40°C) reduces lipopolysaccaride (LPS)-induced tumor necrosis factor-α (TNFα) expression, in part through the direct interaction of heat shock factor-1 (HSF-1) with the TNFα gene promoter. However, it is not known whether exposure to FRT also modifies other proximal LPS-induced signaling events or recruitment of transcriptional regulators to the TNFα promoter. Using HSF-1-null mice, we confirmed that HSF-1 is required for FRT-induced repression of TNFα in vitro by LPS-stimulated bone marrow derived macrophages and in vivo in mice challenged intratracheally with LPS. Exposing LPS-stimulated RAW 264.7 mouse macrophages to FRT reduced TNFα expression, while increasing interleukin (IL)-1β expression despite the two genes being regulated by the same MyD88-dependent pathway. Global activation of the three LPS induced signaling intermediates that lead to cytokine gene expression, ERK and p38 MAPKs and NFκB, was not affected by exposing RAW 264.7 cells to FRT as assessed by western blot analysis of ERK and p38 phosphorylation and analysis of NFκB activation by EMSA and reporter plasmid expression assays. However, chromatin immunoprecipitation (ChIP) analysis demonstrated that exposure to FRT reduced LPS-induced recruitment of NFκB-p65 to the TNFα promoter, while increasing its recruitment to the IL-1β promoter. An additional ChIP analysis shows that LPS stimulated a 90% increase in recruitment of Sp1 to the proximal TNFα promoter at 37�C, which was completely abrogated by exposure to FRT even though FRT exposure increased intranuclear Sp1 DNA-binding as measured by EMSA. LPS also stimulated recruitment of both Elk-1 and ATF-2 to the proximal promoter, but FRT exposure had no significant effect on this process. ChIP analysis of the 1452 bp TNFα 5'flanking sequence (-1300/+152) revealed no additional heat shock response elements (HSEs) and no effect of FRT on chromatin acetylation on this sequence. These data suggest that FRT exerts its effects on cytokine gene expression in a gene specific manner through downstream effects on promoter activation, rather than through proximal receptor activation/signaling events. In conclusion, we describe new mechanisms through which TNFα expression is reduced at FRT through gene-specific reduction of NFκB and Sp1 recruitment to the TNFα promoter.
Increased core temperature during febrile disease modulates cytokine expression, enhances host defense, and improves survival in bacterial infectionJiang, Qingqi; Hasday, Jeffrey D. (1999)Bacterial infections are a common cause of illness. Septic shock is a severe, often life-threatening consequence of Gram-negative bacterial infection which occurs in 500,000 to 750,000 patients per year in the United States. Host defense strategies during infection balance containment and elimination of infection against collateral tissue injury, either of which can be lethal. Fever is a complex, but remarkably consistent response to infection. It constitutes a major feature of the systemic acute phase response, and typically begins very early and persists for several days during infections. Clinical and experimental evidence suggest that the increase in core temperature which occurs during infections is protective, in part by enhancing host defenses. While it is not surprising that a response as consistent and phylogenetically conserved as fever has been integrated into the regulation of host defenses, the mechanisms responsible for these effects are poorly understood. Our work has focused on how febrile range temperatures modify expression of cytokines. Using a mouse model in which core temperature is externally controlled, we showed that changes in core temperature within the normal mouse/human basal to febrile ranges profoundly altered the early cytokine expression pattern in response to the nonreplicating agonist, bacterial endotoxin (LPS). Specifically, the early TNFalpha secretion rate is enhanced, but the duration of maximal TNFalpha production is shortened, generating an enhanced early, self-limited TNFalpha pulse. We identified the Kupffer cell as the predominant source of the excess TNFalpha production in the warmer animals. Plasma IL-6 levels increased 2.7-fold and IL-1beta expression was delayed in the warmer animals. While TNFalpha levels were increased predominantly in livers of the warmer mice, IL-1beta levels were higher in lung, and IL-6 levels were widely increased in multiple organs in the warmer animals. This demonstrates that the thermal component of fever may directly contribute to shaping the host response by regulating the timing, magnitude, and tissue distribution of cytokine generation during the acute phase response. We have extended these studies in LPS-challenged mice by comparing survival, cytokine expression, and bacterial clearance in mice maintained with 36.5° or 39.5°C core temperature during peritonitis with a clinically relevant and lethal pathogen, Klebsiella pneumoniae. The early pulse in plasma TNFalpha expression associated with the increase in core temperature to febrile levels was qualitatively similar to the early, self-limited peak in TNFalpha expression reported in the LPS-challenged mice with 39.5°C core temperature. The 3°C increase in core temperature increased survival of mice infected with K. pneumoniae 5055-Caroli strain reduced mortality from 100% to 50%. This change in survival was associated with a 100,000-fold reduction in peritoneal bacterial load and a 500 to 5000 fold decrease in bacterial load in the blood and distal organs. Interestingly, the febrile mice died with 6-40 fold lower bacterial loads, suggesting different mechanisms of death in the two groups of animals. When K. pneumoniae was cultured in vitro, it grew at nearly identical rates at 37° and 39.5°C, indicating the protective effects of the core temperature increase in vivo was mediated by modulation of host:pathogen interactions rather than through direct effects on the bacteria. The possible mechanisms of these effects are currently being studied in our laboratory.
A temperature-dependent conformational shift in p38α MAPK substrate–binding region associated with changes in substrate phosphorylation profileDeredge, D.; Wintrode, P.L.; Tulapurkar, M.E.; Nagarsekar, A.; Zhang, Y.; Weber, D.J.; Shapiro, P.; Hasday, J.D. (American Society for Biochemistry and Molecular Biology Inc., 2019)Febrile-range hyperthermia worsens and hypothermia mitigates lung injury, and temperature dependence of lung injury is blunted by inhibitors of p38 mitogen-activated protein kinase (MAPK). Of the two predominant p38 isoforms, p38α is proinflammatory and p38β is cytoprotective. Here, we analyzed the temperature dependence of p38 MAPK activation, substrate interaction, and tertiary structure. Incubating HeLa cells at 39.5 °C stimulated modest p38 activation, but did not alter tumor necrosis factor-α (TNFα)-induced p38 activation. In in vitro kinase assays containing activated p38α and MAPK-activated kinase-2 (MK2), MK2 phosphorylation was 14.5-fold greater at 39.5 °C than at 33 °C. By comparison, we observed only 3.1- and 1.9-fold differences for activating transcription factor-2 (ATF2) and signal transducer and activator of transcription- 1α (STAT1α) and a 7.7-fold difference for p38β phosphorylation of MK2. The temperature dependence of p38α:substrate binding affinity, as measured by surface plasmon resonance, paralleled substrate phosphorylation. Hydrogen- deuterium exchangeMS(HDX-MS) of p38α performed at 33, 37, and 39.5 °C indicated temperature-dependent conformational changes in an α helix near the common docking and glutamate: aspartate substrate-binding domains at the known binding site for MK2. In contrast, HDX-MS analysis of p38β did not detect significant temperature-dependent conformational changes in this region. We observed no conformational changes in the catalytic domain of either isoform and no corresponding temperature dependence in the C-terminal p38α-interacting region of MK2. Because MK2 participates in the pathogenesis of lung injury, the observed changes in the structure and function of proinflammatory p38α may contribute to the temperature dependence of acute lung injury.