Hypothermia and postconditioning after cardiopulmonary resuscitation reduce cardiac dysfunction by modulating inflammation, apoptosis and remodeling

Background: Mild therapeutic hypothermia following cardiac arrest is neuroprotective, but its effect on myocardial dysfunction that is a critical issue following resuscitation is not clear. This study sought to examine whether hypothermia and the combination of hypothermia and pharmacological postconditioning are cardioprotective in a model of cardiopulmonary resuscitation following acute myocardial ischemia. Methodology/Principal Findings: Thirty pigs (28–34 kg) were subjected to cardiac arrest following left anterior descending coronary artery ischemia. After 7 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started according to the current AHA guidelines. After successful return of spontaneous circulation (n = 21), coronary perfusion was reestablished after 60 minutes of occlusion, and animals were randomized to either normothermia at 38°C, hypothermia at 33°C or hypothermia at 33°C combined with sevoflurane (each group n = 7) for 24 hours. The effects on cardiac damage especially on inflammation, apoptosis, and remodeling were studied using cellular and molecular approaches. Five animals were sham operated. Animals treated with hypothermia had lower troponin T levels (p<0.01), reduced infarct size (34±7 versus 57±12%; p<0.05) and improved left ventricular function compared to normothermia (p<0.05). Hypothermia was associated with a reduction in: (i) immune cell infiltration, (ii) apoptosis, (iii) IL-1beta and IL-6 mRNA up-regulation, and (iv) IL-1beta protein expression (p<0.05). Moreover, decreased matrix metalloproteinase-9 activity was detected in the ischemic myocardium after treatment with mild hypothermia. Sevoflurane conferred additional protective effects although statistic significance was not reached. Conclusions/Significance: Hypothermia reduced myocardial damage and dysfunction after cardiopulmonary resuscitation possible via a reduced rate of apoptosis and pro-inflammatory cytokine expression

Winter Homeless Services: Bringing Our Neighbors in from the Cold 2009

Seven hundred people experiencing or at risk of homelessness are killed from hypothermia annually in the United States. Forty-four percent of the nation's homeless are unsheltered. From the urban streets of our populated cities to the remote back-country of rural America, hypothermia - or subnormal temperature in the body - remains a leading, critical and preventable cause of injury and death among those experiencing homelessness. The National Coalition for the Homeless (NCH) has published Winter Homeless Services: Bringing Our Neighbors in from the Cold to raise awareness of the dangers and consequences of hypothermia on people experiencing homelessness. NCH maintains that knowledge, networking and temporary seasonal shelter and outreach are three of the most important elements to an effective regional or local approach to the reduction and prevention of exposure and hypothermia. This report is a snapshot of winter homeless services nationwide. NCH staff has gathered information for this report from ninety-four respondents representing forty states and the District of Columbia, from urban, suburban and rural communities. NCH interviewed state and local coalitions, healthcare providers, and shelter operators in order to gain the best and broadest possible understanding of cold weather services available through these direct service providers and first responders. There is general consensus among public health officials, medical professionals and service providers that to reduce the incidence of hypothermia nationwide, local communities should implement effective and timely strategies to address the needs of vulnerable populations, including creating temporary homeless shelters and extending the hours of operation for existing shelters

The circadian system alters thermoregulation depending on the time of day and feeding condition

The circadian rhythm of body temperature (Tb) is a well-known phenomenon. However, it is unknown how the circadian system affects thermoregulation. Food deprivation in mice induces a greater reduction of Tb particularly in the light phase. We examined the role of the clock gene and the suprachiasmatic nucleus (SCN) during induced hypothermia. At 20C with fasting, mice increased their metabolic heat production in the dark phase and maintained T~b~, whereas in the light phase, heat production was less, resulting in hypothermia. Under these conditions, neuronal activity in the SCN, assessed by cFos expression, increased only in the light phase. The differences between the phases in Clock mutant mice were less marked. The neural network between the SCN and paraventricular nucleus appeared to be important in hypothermia. These findings suggest that the circadian system per se is influenced by both the feeding condition and environmental temperature and that it modulates thermoregulation

Combined Cyclosporin A and Hypothermia Treatment Inhibits Activation of BV-2 Microglia but Induces an Inflammatory Response in an Ischemia/Reperfusion Hippocampal Slice Culture Model

Introduction: Hypothermia attenuates cerebral ischemia-induced neuronal cell death associated with neuroinflammation. The calcineurin inhibitor cyclosporin A (CsA) has been shown to be neuroprotective by minimizing activation of inflammatory pathways. Therefore, we investigated whether the combination of hypothermia and treatment with CsA has neuroprotective effects in an oxygen-glucose deprivation/reperfusion (OGD/R) injury model in neuronal and BV-2 microglia monocultures, as well as in an organotypic hippocampal slice culture (OHSC). Methods: Murine primary neurons, BV-2 microglia, and OHSC were pretreated with CsA and exposed to 1 h OGD (0.2% O2) followed by reperfusion at normothermia (37°C) or hypothermia (33.5°C). Cytotoxicity was measured by lactate dehydrogenase and glutamate releases. Damage-associated molecular patterns (DAMPs) high mobility group box 1 (HMGB1), heat shock protein 70 (Hsp70), and cold-inducible RNA-binding protein (CIRBP) were detected in cultured supernatant by western blot analysis. Interleukin-6 (IL-6), Interleukin-1α and -1β (IL-1α/IL1-β), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP1), inducible nitric oxide synthase (iNOS), glia activation factors ionized calcium-binding adapter molecule 1 (Iba1), and transforming growth factor β1 (TGF-β1) gene expressions were analyzed by RT-qPCR. Results: Exposure to OGD plus 10 μM CsA was sufficient to induce necrotic cell death and subsequent release of DAMPs in neurons but not BV-2 microglia. Moreover, OGD/R-induced secondary injury was also observed only in the neurons, which was not attenuated by cooling and no increased toxicity by CsA was observed. BV-2 microglia were not sensitive to OGD/R-induced injury but were susceptible to CsA-induced toxicity in a dose dependent manner, which was minimized by hypothermia. CsA attenuated IL-1β and Iba1 expressions in BV-2 microglia exposed to OGD/R. Hypothermia reduced IL-1β and iNOS expressions but induced TNF-α and Iba1 expressions in the microglia. However, these observations did not translate to the ex vivo OHCS model, as general high expressions of most cytokines investigated were observed. Conclusion: Treatment with CsA has neurotoxic effects on primary neurons exposed to OGD but could inhibit BV-2 microglia activation. However, CsA and hypothermia treatment after ischemia/reperfusion injury results in cytotoxic neuroinflammation in the complex ex vivo OHSC

Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI

Hypothermia in the early neonatal period

Background: Hypothermia in neonates is a common problem and is associated with increased morbidity and mortality. Prevention of hypothermia is therefore an essential aspect of neonatal care especially in the immediate neonatal period. Aim: To evaluate the efficacy of thermal care of the neonate in the labour ward at St Luke's Hospital, Malta. Method: Retrospective study analysing the temperature on admission to the nursery from the labour ward. A consecutive sample of 754 neonates admitted during 2002 was studied. Results: The proportion of babies admitted with normal body temperature (36.5-37.5°C) was 25.5%. The rest were mildly (36.0-36.5°C) (42.2%) or moderately (<36.0°C) (32.2%) hypothermic. Significantly less normothermia was evident in winter births (19.6%) than in summer births (38.1%) (Chi squared=26.5, p<0.0001). Implications: The results indicate the need for an improvement in thermal support in the labour ward.peer-reviewe

Hypothermia in the early neonatal period : follow-up study

Background: Thermal care is an essential aspect of the routine care of the newborn because hypothermia is an important and preventable contributor to morbidity. Aim: To evaluate whether the new practice of postponing bathing of the newborn at St Luke's Hospital has resulted in an improvement in neonatal thermal care. Methods: Analysis of the temperature on admission to the nursery from labour ward during 2005 of a consecutive sample of 877 infants, compared to the results obtained from a similar study in 2002. Results: The proportion of babies admitted with normal body temperature (36.5-37.5°C) was 43.4% in 2005, compared to 25.5% in 2002. The proportion of babies admitted with moderate hypothermia was reduced from 32.3% in 2002 to 14.4% in 2005. Implications: Delayed bathing has resulted in a significant improvement in thermal care of the newborn.peer-reviewe