Universität zu Köln

Fosgerau, Keld, Weber, Uno J., Gotfredsen, Jacob W., Jayatissa, Magdalena, Buus, Carsten, Kristensen, Niels B., Vestergaard, Mogens, Teschendorf, Peter, Schneider, Andreas, Hansen, Philip, Raunso, Jakob, Kober, Lars ORCID: 0000-0002-6635-1466, Torp-Pedersen, Christian and Videbaek, Charlotte (2010). Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. BMC Cardiovasc. Disord., 10. LONDON: BMC. ISSN 1471-2261

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Abstract

Background: The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. Methods: First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion. Results: Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal Delta T (degrees C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with Delta T > -3 degrees C for more than 12 hours. Conclusions: Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fosgerau, Keld UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Uno J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gotfredsen, Jacob W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jayatissa, Magdalena UNSPECIFIED UNSPECIFIED UNSPECIFIED Buus, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Kristensen, Niels B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vestergaard, Mogens UNSPECIFIED UNSPECIFIED UNSPECIFIED Teschendorf, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Raunso, Jakob UNSPECIFIED UNSPECIFIED UNSPECIFIED Kober, Lars UNSPECIFIED orcid.org/0000-0002-6635-1466 UNSPECIFIED Torp-Pedersen, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Videbaek, Charlotte UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-494364
DOI:	10.1186/1471-2261-10-51
Journal or Publication Title:	BMC Cardiovasc. Disord.
Volume:	10
Date:	2010
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1471-2261
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CARDIAC-ARREST; MODERATE HYPOTHERMIA; TRPV1 RECEPTORS; CAPSAICIN; THERMOREGULATION; NEUROPROTECTION; PHARMACOLOGY; FEASIBILITY; COMPONENT; CHANNELS Multiple languages Cardiac & Cardiovascular Systems Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49436