Dexmedetomidine preconditioning attenuates ischemia/reperfusion injury in isolated rat hearts with endothelial dysfunction

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Abstract

Background and purposes

Dexmedetomidine preconditioning (DP) can mimic pharmacological preconditioning and induce cardiac protection. There are controversies on the roles of coronary endothelia in cardioprotection of dexmedetomidine. Herein, we tested the hypothesis that protection of dexmedetomidine is not endothelial dependent in heart against myocardial ischemia/reperfusion (I/R) injury.

Methods

Langendorff-perfused rat hearts were pretreated by 60 mM of potassium to produce endothelial dysfunction (ED), then medicated with dexmedetomidine, and subsequently subjected to 30 min of global ischemia followed by 60 min of reperfusion. To investigate the cardioprotective effect of dexmedetomidine in heart with ED, isolated rat hearts were randomly divided into the following six groups: sham, I/R, DP, ED, ED + I/R, and ED + DP + I/R. Heart rates, left ventricular function, and coronary perfusion pressure were assessed for each heart. Infarct size was evaluated by triphenyltetrazolium chloride staining. High-sensitivity cardiac troponin T (hs-cTNT) of coronary flow perfusion was determined.

Results

After the isolated hearts with pretreatment of 60 mM of potassium chloride, diastolic function of coronary endothelia in performance of response to histamine was significantly decreased (P < 0.05). DP attenuated I/R-induced infarct size of the left ventricle (P < 0.05) and decreased hs-cTNT (P < 0.05). Additionally, left ventricular developed pressure, +dp/dtmax, and -dp/dtmax were elevated in rat hearts pretreated with dexmedetomidine. Furthermore, dexmedetomidine-mediated cardiac protection against I/R injury was still remained in isolated hearts with coronary ED.

Conclusion

Continuous perfusion of 60 mM of potassium for 10 min can produce coronary ED in isolated rat hearts. Dexmedetomidine maintains its protective function against I/R injury in heart with coronary ED. Myocardial protection of dexmedetomidine is non-endothelial function dependent in alleviating I/R injury.

Abbreviations

-dp/dtmax
left ventricular maximal rate of pressure decline
+dp/dtmax
left ventricular maximal rate of pressure rise
CPP
coronary perfusion pressure
ED
endothelial dysfunction
ELISA
enzyme linked immunosorbent assay
eNOS
endothelial nitric oxide synthase
HR
heart rate
Hs-cTNT
high-sensitivity cardiac troponin T
I/R
ischemia/reperfusion
LV
left ventricular
LVEDP
left ventricular end diastolic pressure
LVDP
left ventricular developed pressure
LVSP
left ventricular systolic pressure
MI
myocardial infarction
TTC
triphenyltetrazolium chloride

Keywords

Dexmedetomidine
Preconditioning
Ischemia/reperfusion
hs-cTNT

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1

These authors contribute equally to this work.