TY - JOUR
T1 - Characteristics of Dexmedetomidine Postconditioning in the Field of Myocardial Ischemia-Reperfusion Injury
AU - Bunte, Sebastian
AU - Behmenburg, Friederike
AU - Majewski, Nicole
AU - Stroethoff, Martin
AU - Raupach, Annika
AU - Mathes, Alexander
AU - Heinen, André
AU - Hollmann, Markus W.
AU - Huhn, Ragnar
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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 α2-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.
AB - 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 α2-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.
UR - http://www.scopus.com/inward/record.url?scp=85076874644&partnerID=8YFLogxK
U2 - https://doi.org/10.1213/ANE.0000000000004417
DO - https://doi.org/10.1213/ANE.0000000000004417
M3 - Article
C2 - 31633505
SN - 0003-2999
VL - 130
SP - 90
EP - 98
JO - Anesthesia and analgesia
JF - Anesthesia and analgesia
IS - 1
ER -