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Induction of therapeutic hypothermia via the esophagus: a proof of concept study.

ABSTRACT: Induction of hypothermia (a 4 °C decrease from baseline) improves outcomes in adult cardiac arrest and neonatal hypoxic ischemic encephalopathy, and may benefit other conditions as well. Methods used to implement or prevent hypothermia typically require skin contact with blankets or pads or intravascular access with catheter devices. The study was to evaluate the potential to induce mild therapeutic hypothermia via an esophageal route in a porcine model.Single-animal proof-of-concept study of a prototype esophageal device in a 70 kg Yorkshire swine. We measured the rate of temperature change after placement of a prototype device to induce hypothermia via the esophagus, and compared this rate to known temperature changes that occur under similar laboratory conditions without a hypothermic device.Swine temperature decreased from a starting temperature of 37.8 °C to 33.8 °C (achieving the goal of a 4 °C decrease) in 175 minutes, resulting in a cooling rate of 1.37 °C/h. Histopathology of the esophagus showed normal tissue without evidence of injury.A prototype of an esophageal cooling device induced hypothermia effectively in a large single-swine model.

SUBMITTER: Kulstad EB

PROVIDER: S-EPMC4129793 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Induction of therapeutic hypothermia via the esophagus: a proof of concept study.

Kulstad Erik B EB Courtney D Mark DM Waller Donald D

World journal of emergency medicine 20120101 2

<h4>Background</h4>Induction of hypothermia (a 4 °C decrease from baseline) improves outcomes in adult cardiac arrest and neonatal hypoxic ischemic encephalopathy, and may benefit other conditions as well. Methods used to implement or prevent hypothermia typically require skin contact with blankets or pads or intravascular access with catheter devices. The study was to evaluate the potential to induce mild therapeutic hypothermia via an esophageal route in a porcine model.<h4>Methods</h4>Single- ...[more]

PMID: 25215049

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Project description:Myxobolus cerebralis is a cnidarian-myxozoan parasite that causes salmonid whirling disease. M. cerebralis alternates between two hosts: (1) a vertebrate salmonid and (2) an invertebrate oligochaete, Tubifex tubifex. There is no successful treatment for salmonid whirling disease. MyxSP-1 is a M. cerebralis serine protease implicated in whirling disease pathogenesis. We hypothesized that short-interfering RNA (siRNA)-induced RNA interference (RNAi) can silence MyxSP-1 in the invertebrate host and abrogate the M. cerebralis life cycle. This would preclude whirling disease infection in the salmonid host. To test this hypothesis, we first developed a siRNA delivery protocol in T. tubifex. Second, we determined the effective dose for siRNA treatment of M. cerebralis-infected T. tubifex. M. cerebralis-infected T. tubifex were treated with different concentrations of MyxSP-1 or negative control siRNAs (1μM, 2μM, 5μM or 7μM) at 15°C for 24h, 48h, 72h and 96h, respectively. We monitored MyxSP-1 knockdown using real-time quantitative PCR (qPCR). siRNA treatment with MyxSP-1 siRNA at 2μM concentration for 24h at 15°C showed maximum significant MyxSP-1 knockdown in T. tubifex. Third, we determined the time points in the M. cerebralis life cycle in T. tubifex at which siRNA treatment was most effective. M. cerebralis-infected T. tubifex were treated with MyxSP-1 or negative control siRNAs (2μM concentration for 24h at 15°C) at 24 hours post-infection (24hpi), 48hpi, 72hpi, 96hpi, 1 month post-infection (1mpi), 2mpi and 3mpi, respectively. We observed that siRNA treatment of T. tubifex was most effective at 1mpi, 2mpi and 3mpi. Fourth, we immersed specific-pathogen-free rainbow trout fry in water inhabited by MyxSP-1 siRNA-treated T. tubifex (at 1mpi, 2mpi and 3mpi). The salmonids did not develop whirling disease and showed significant MyxSP-1 knockdown. We also observed long-term RNAi in T. tubifex. Together these results demonstrate a novel RNAi-based therapeutic proof of concept in vivo against salmonid whirling disease.

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Induction of therapeutic hypothermia via the esophagus: a proof of concept study.

Publications

Induction of therapeutic hypothermia via the esophagus: a proof of concept study.

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