J Korean Med Sci.  2010 Mar;25(3):380-386. 10.3346/jkms.2010.25.3.380.

Polyphenol (-)-Epigallocatechin Gallate during Ischemia Limits Infarct Size Via Mitochondrial K(ATP) Channel Activation in Isolated Rat Hearts

• Song DK
• Jang Y
• Kim JH
• Chun KJ
• Lee D
• Xu Z

• KMID: 1778032
• DOI: http://doi.org/10.3346/jkms.2010.25.3.380

Abstract

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K(ATP)) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective K(ATP) channel blocker glibenclamide (GLI) and a selective mitochondrial K(ATP) (mK(ATP)) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dt(max), and -dP/dt(min) throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5+/-2.5% in EGCG 1 micrometer and 4.0+/-1.7% in EGCG 10 micrometer, P<0.001 vs. control 27.2+/-1.4%). This anti-infarct effect was totally abrogated by 10 micrometer GLI (24.6+/-1.5%, P<0.001 vs. EGCG). Similarly, 100 micrometer HD also aborted the anti-infarct effect of EGCG (24.1+/-1.2%, P<0.001 vs. EGCG ). These data support a role for the K(ATP) channels in EGCG-induced cardioprotection. The mK(ATP) channels play a crucial role in the cardioprotection by EGCG.

Keyword

Epigallocatechin Gallate; KATP Channels; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury

MeSH Terms

Animals
Anti-Arrhythmia Agents/pharmacology
Antioxidants/*pharmacology
Catechin/*analogs & derivatives/pharmacology
Decanoic Acids/pharmacology
Glyburide/pharmacology
Heart/*drug effects/physiology/physiopathology
Hemodynamics
Humans
Hydroxy Acids/pharmacology
KATP Channels/*metabolism
Male
Mitochondria, Heart/*drug effects/metabolism
Myocardial Infarction/*pathology
Myocardial Ischemia/*pathology
Potassium Channel Blockers/pharmacology
Rats
Rats, Wistar
Anti-Arrhythmia Agents
Antioxidants
Decanoic Acids
Hydroxy Acids
KATP Channels
Potassium Channel Blockers
Glyburide
Catechin

Figure

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  Fig. 1 Experimental protocols. For measurement of contractile function and infarct size, isolated rat hearts were exposed to 30 min ischemia followed by 2 hr reperfusion. Drugs were perfused from 10 min before and to the end of index ischemia. EGCG, polyphenol (-)-epigallocatechin gallate.

• 

  Fig. 2 Area at necrosis (AN) expressed as a percentage of the AAR (area at risk) in control hearts and hearts treated with the polyphenol (-)-epigallocatechin gallate (EGCG). Open circles indicate the infarct sizes from individual hearts. Filled circles in each group indicate the group mean infarct size; mean±SEM. Both concentrations (1 and 10 µM) of EGCG treatment during ischemic period significantly attenuate AN/AAR in isolated rat hearts. EGCG1, 1 µM EGCG; EGCG10, 10 µM EGCG. *P<0.001 vs. control; †P<0.05 vs. EGCG1.

• 

  Fig. 3 Area at necrosis (AN) expressed as a percentage of the AAR (area at risk) by treatment of 10 µM glibenclamide (GLI) and 100 µM 5-hydroxydecanoate (HD) combined with 1 µM polyphenol (-)-epigallocatechin gallate (EGCG) during ischemic period in isolated rat hearts. Open circles indicate the infarct sizes from individual hearts. Filled circles in each group indicate the group mean infarct size; mean±SEM. Both a nonselective KATP channel blocker GLI and a mitochondrial KATP channel blocker HD totally blocked the anti-infarct effect by EGCG. Treatment of control hearts with GLI or HD alone had no effect on infarct size. *P<0.001 vs. control.

• 

  Fig. 4 Functional recovery after 30 min of index ischemia followed by 2 hr of reperfusion in isolated rat hearts. EGCG treatment during ischemia did not change the functional recovery concerning LVDP, RPP, +dP/dtmax, and -dP/dtmin after 2 hr of reperfusion. LVDP, left ventricular developed pressure; RPP, rate-pressure product; +dP/dtmax and -dP/dtmin, maximum and minimum of first derivative of left ventricular pressure derivative.

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