Universität zu Köln

Bunte, Sebastian, Behmenburg, Friederike, Majewski, Nicole, Stroethoff, Martin, Raupach, Annika, Mathes, Alexander, Heinen, Andre, Hollmann, Markus W. and Huhn, Ragnar ORCID: 0000-0002-3114-7190 (2020). Characteristics of Dexmedetomidine Postconditioning in the Field of Myocardial Ischemia-Reperfusion Injury. Anesth. Analg., 130 (1). S. 90 - 99. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 0003-2999

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Abstract

BACKGROUND: Timing and onset of myocardial ischemia are mostly unpredictable. Therefore, postconditioning could be an effective cardioprotective intervention. Because ischemic postconditioning is an invasive and not practicable treatment, pharmacological postconditioning would be a more suitable alternative cardioprotective measure. For the alpha 2-adrenoreceptor agonist, dexmedetomidine postconditioning has been shown. However, data on a concentration-dependent effect of dexmedetomidine are lacking. Furthermore, it is unclear whether the time point and/or duration of dexmedetomidine administration in the reperfusion period is of relevance. We set out to determine whether infarct size reduction by dexmedetomidine is concentration dependent and whether time point and/or duration of dexmedetomidine application has an impact on the effect size of cardio protection. METHODS: Hearts of male Wistar rats were randomized and placed on a Langendorff system perfused with Krebs-Henseleit buffer at a constant pressure of 80 mm Hg. All hearts were subjected to 33 minutes of global ischemia and 60 minutes of reperfusion. In part I of the study, a concentration-response effect was determined by perfusing hearts with various concentrations of dexmedetomidine (0.3-100 nM) at the onset of reperfusion. Based on these results, part II of the study was conducted with 3 nM dexmedetomidine. Application of dexmedetomidine started directly at the onset of reperfusion (Dex60) and 15 minutes (Dex15), 30 minutes (Dex30), or 45 minutes (Dex45) after the start of reperfusion and lasted always until the end of the reperfusion period. Infarct size was determined by triphenyltetrazolium chloride staining. RESULTS: In part I, infarct size in control (Con) hearts was 62% +/- 4%. Three-nanometer dexmedetomidine was the lowest most effective cardioprotective concentration and reduced infarct size to 24% +/- 7% (P < .0001 versus Con). Higher concentrations did not confer stronger protection. Infarct size in control hearts from part II was 66% +/- 6%. Different starting times and/or durations of application resulted in similar infarct size reduction (all P < .0001 versus Con). CONCLUSIONS: Postconditioning by dexmedetomidine is concentration dependent in ranges between 0.3 and 3 nM. Increased concentrations above 3 nM do not further enhance this cardioprotective effect. This cardioprotective effect is independent of time point and length of application in the reperfusion period.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bunte, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Behmenburg, Friederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Majewski, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Stroethoff, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Raupach, Annika UNSPECIFIED UNSPECIFIED UNSPECIFIED Mathes, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinen, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Hollmann, Markus W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huhn, Ragnar UNSPECIFIED orcid.org/0000-0002-3114-7190 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-352583
DOI:	10.1213/ANE.0000000000004417
Journal or Publication Title:	Anesth. Analg.
Volume:	130
Number:	1
Page Range:	S. 90 - 99
Date:	2020
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	0003-2999
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ISCHEMIA/REPERFUSION INJURY; PROTECTS; CARDIOPROTECTION; ACTIVATION; HEART; RATS Multiple languages Anesthesiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/35258