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Differential effects of hypothermia on neurovascular unit determine protective or toxic results: Toward optimized therapeutic hypothermia.

ABSTRACT: Therapeutic hypothermia (TH) benefits survivors of cardiac arrest and neonatal hypoxic-ischemic injury and may benefit stroke patients. Large TH clinical trials, however, have shown mixed results. Given the substantial pre-clinical literature supporting TH, we explored possible mechanisms for clinical trial variability. Using a standard rodent stroke model (n?=?20 per group), we found smaller infarctions after 2?h pre- or post-reperfusion TH compared to 4?h. To explore the mechanism of this discrepancy, we used primary cell cultures of rodent neurons, astrocytes, or endothelial cells subjected to oxygen-glucose deprivation (OGD). Then, cells were randomly assigned to 33?, 35? or 37? for varying durations after varying delay times. Both 33 and 35? TH effectively preserved all cell types, although 33? was superior. Longer cooling durations overcame moderate delays to cooling initiation. In contrast, TH interfered with astrocyte paracrine protection of neurons in a temperature-dependent manner. These findings suggest that longer TH is needed to overcome delays to TH onset, but shorter TH durations may be superior to longer, perhaps due to suppression of astrocytic paracrine support of neurons during injury. We propose a scheme for optimizing TH after cerebral injury to stimulate further studies of cardiac arrest and stroke.

SUBMITTER: Lyden PD

PROVIDER: S-EPMC6727141 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Differential effects of hypothermia on neurovascular unit determine protective or toxic results: Toward optimized therapeutic hypothermia.

Lyden Patrick D PD Lamb Jessica J Kothari Shweta S Toossi Shahed S Boitano Paul P Rajput Padmesh S PS

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20181121 9

Therapeutic hypothermia (TH) benefits survivors of cardiac arrest and neonatal hypoxic-ischemic injury and may benefit stroke patients. Large TH clinical trials, however, have shown mixed results. Given the substantial pre-clinical literature supporting TH, we explored possible mechanisms for clinical trial variability. Using a standard rodent stroke model (<i>n</i> = 20 per group), we found smaller infarctions after 2 h pre- or post-reperfusion TH compared to 4 h. To explore the mechanism of th ...[more]

PMID: 30461327

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Project description:ObjectivesTo understand factors affecting nurses' attitudes toward the Therapeutic Hypothermia After Pediatric Cardiac Arrest trials and association with approach/consent rates.DesignCross-sectional survey of pediatric/cardiac intensive care nurses' perceptions of the trials.SettingStudy was conducted at 16 of 38 self-selected study sites.SubjectsPediatric and cardiac intensive care nurses.Measurements and main resultsThe primary outcome was the proportion of nurses with positive perceptions, as defined by agree or strongly agree with the statement "I am happy to take care of a Therapeutic Hypothermia after Pediatric Cardiac Arrest patient". Associations between perceptions and study approach/consent rates were also explored. Of 2,241 nurses invited, 1,387 (62%) completed the survey and 77% reported positive perceptions of the trials. Nurses, who felt positively about the scientific question, the study team, and training received, were more likely to have positive perceptions of the trials (p < 0.001). Nurses who had previously cared for a research patient had significantly more positive perceptions of Therapeutic Hypothermia After Pediatric Cardiac Arrest compared with those who had not (79% vs 54%; p < 0.001). Of the 754 nurses who cared for a Therapeutic Hypothermia After Pediatric Cardiac Arrest patient, 82% had positive perceptions, despite 86% reporting it required more work. Sixty-nine percent believed that hypothermia reduces brain injury and mortality; sites had lower consent rates when their nurses believed that hypothermia was beneficial. Institution-specific approach rates were positively correlated with nurses' perceptions of institutional support for the trial (r = 0.54; p = 0.04), ICU support (r = 0.61; p = 0.02), and the importance of conducting the trial in children (r = 0.61; p = 0.01).ConclusionsThe majority of nurses had positive perceptions of the Therapeutic Hypothermia After Pediatric Cardiac Arrest trials. Institutional, colleague, and study team support and training were contributing factors. Despite increased work, nurses remained enthusiastic demonstrating that studies with intensive bedside nursing procedures are feasible. Institutions whose nurses believed hypothermia was beneficial had lower consent rates, suggesting that educating nurses on study rationale and equipoise may enhance study participation.

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Differential effects of hypothermia on neurovascular unit determine protective or toxic results: Toward optimized therapeutic hypothermia.

Publications

Differential effects of hypothermia on neurovascular unit determine protective or toxic results: Toward optimized therapeutic hypothermia.

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