The Effect of KATPChannel Activation on Myocardial Cationic and Energetic Status During Ischemia and Reperfusion: Role in Cardioprotection

Fukuda, Hiroyuki; Luo, Cameron S.; Gu, Xin; Guo, Ling; Digerness, Stanley B.; Li, Jiaxian; Pike, Martin M.

doi:10.1006/jmcc.2000.1328

Cited by 28 publications

(13 citation statements)

References 35 publications

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“…Fasudil alone neither improved nor depressed reperfusion functional recovery. Consistent with its documented cardioprotective effects (7,20), pinacidil increased both end-reperfusion LVDP and rate-pressure product to preischemic levels while substantially decreasing end-reperfusion end-diastolic pressure. Notably, however, all end-reperfusion functional parameters in hearts treated with fasudil ϩ pinacidil were similar to those measured in control hearts and were significantly different from those measured in hearts treated with pinacidil alone (Fig.…”

Section: Nmr Spectroscopysupporting

confidence: 59%

“…All animal procedures were approved by and conformed to University of Alabama at Birmingham Institutional Animal Care and Use Committee guidelines. Hearts were isolated from male Sprague-Dawley rats (300 -550 g), Langendorff perfused, and paced as previously described (7). Function was monitored via a left ventricular balloon and a Gould TA240 chart recorder, and was digitally recorded with a Digi-Med Heart Performance Analyzer.…”

Section: Methodsmentioning

confidence: 99%

“…Saturation factors were as previously determined (7). Intracellular pH (pH i) was determined from the Pi frequency position (7). Spectral and functional data were averaged into 4-min time blocks and expressed as means Ϯ SE.…”

Section: Nmr Spectroscopymentioning

confidence: 99%

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Fasudil prevents K_ATP channel-induced improvement in postischemic functional recovery

Nishizawa¹,

Wolkowicz²,

Yamagishi

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Whereas activation of ATP-dependent potassium (KATP) channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced cardioprotection remains elusive. RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATP channel cardioprotection. Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for KATP channel-induced cardioprotection. Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and 31P NMR high-energy phosphate data: 1) untreated, 2) pinacidil (10 μM) to activate KATP channels, 3) fasudil (15 μM) to inhibit ROCK, and 4) both fasudil and pinacidil. Pinacidil significantly improved postischemic mechanical recovery [39 ± 16 vs. 108 ± 4 mmHg left ventricular diastolic pressure (LVDP), untreated and pinacidil, respectively]. Fasudil did not affect reperfusion LVDP (41 ± 13 mmHg) but completely blocked the marked improvement in mechanical recovery that occurred with pinacidil treatment (54 ± 15 mmHg). Substantial attenuation of the postischemic energetic recovery was also observed. These data support the hypothesis that ROCK activity plays a role in KATP channel-induced cardioprotection.

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Section: Nmr Spectroscopysupporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

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Fasudil prevents K_ATP channel-induced improvement in postischemic functional recovery

Nishizawa¹,

Wolkowicz²,

Yamagishi

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…3-5 Pretreatment with K-ATP channel openers maintains mitochondrial respiration without inhibiting the increase in intracellular sodium and decrease in intracellular ATP and phosphocreatine during ischemia, and accelerates recovery of ATP concentration in tissues after ischemia. 16, 17 Moreover, K-ATP channel openers protect endothelial function in the coronary arteries from ischemic reperfusion injury via activation of mitochondrial K-ATP channels. 18, 19 The mitochondrial K-ATP channel may thus be an important mediator of protection of myocardial cells and coronary endothelium, and these mechanisms may thus have significantly reduced cardiovascular deaths associated with fatal MI and other ischemic events in the present nicorandil group compared with the control group.…”

Section: Discussionmentioning

confidence: 99%

Effects of Nicorandil on Cardiovascular Events in Patients With Coronary Artery Disease in The Japanese Coronary Artery Disease (JCAD) Study

Horinaka

Yabe

Yagi

et al. 2010

Circ J

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“…Our data showed that although IPC attenuated ischemic acidification, DZ did not affect the degree of ischemic acidification. It has also been documented that other KATP channel openers, such as cromakalim 33 or pinacidil, 37 did not reduce the fall in pHi at the end of ischemia. It is, therefore, likely that KATP channel openers have no effect on reducing the ischemic acidification as observed with IPC.…”

Section: Ipc and Intracellular Ph During Ischemiamentioning

confidence: 98%

Difference in the Cardioprotective Mechanisms Between Ischemic Preconditioning and Pharmacological Preconditioning by Diazoxide in Rat Hearts

Wakahara¹,

Katoh²,

Yaguchi³

et al. 2004

Circ J

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schemic preconditioning (IPC) is a phenomenon whereby brief intermittent periods of ischemia protect the myocardium against subsequent lethal ischemia. 1 Although the mechanisms responsible for IPC still remain elusive, several factors, such as adenosine, acetylcholine and opioids, which activate protein kinase C, have been implicated in the cardioprotective effect of IPC. 2 Recently, ATP-sensitive potassium (KATP) channels and reactive oxygen species (ROS), among the signaling pathways mediating IPC, have attracted considerable attention. Though the involvement of sarcolemmal KATP channels in IPC was first suggested, 3 subsequent studies have reported that mitochondrial KATP (mitoKATP) channels play a potential role for the cardioprotective effects of KATP channel openers. 4 More recent studies have indicated that the opening of mitoKATP channels induces cardioprotection by generating ROS, which may act as intracellular messengers. 5,6 It has been reported that pretreatment with mitoKATP channel openers 4 or exogenous H2O2 7,8 induces IPC-like protective effects, and that IPC-induced cardioprotection is antagonized by mitoKATP channel inhibitors 9,10 or ROS scavengers. 11,12 These findings support the hypothesis that IPC is mediated through the opening of mitoKATP channels and ROS production. Nevertheless, several investigators have argued against the contribution of mitoKATP channels [13][14][15]17 to IPC. The protective effects of IPC and the mitoKATP channel opener diazoxide (DZ) in whole heart models have been generally evaluated as reduced infarct size and improved contractile function during reperfusion. IPC also has beneficial effects on energy metabolism, such as reduced intracellular acidification during ischemia and postischemic preservation of high-energy phosphates. [18][19][20] Measurement of these parameters may reveal the difference in the cardioprotective mechanisms between IPC and DZ. Moreover, a comparison of IPC and DZ under the same experimental condition would minimize the discrepancy in the results caused by the experimental conditions and models used. However, few studies have compared the effects of IPC and DZ on energy metabolism under the same experimental conditions. Therefore, in the present study we investigated the involvement of the opening of mitoKATP channels and ROS production in IPC-and DZ-induced cardioprotection, using the mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) and the antioxidant N-acetylcysteine (NAC), in perfused Background Recent studies have implicated the opening of mitochondrial KATP (mitoKATP) channels and the production of reactive oxygen species (ROS) in the cardioprotective mechanism of ischemic preconditioning (IPC). Methods and ResultsThe involvement of mitoKATP channels and ROS in the cardioprotective effects of both IPC and the mitoKATP channel opener diazoxide (DZ) was investigated in ischemic/reperfused rat hearts. The effects of IPC and DZ on myocardial high-energy phosphate concentrations and intracellular pH (pHi) were also examined using 31...

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The Effect of KATPChannel Activation on Myocardial Cationic and Energetic Status During Ischemia and Reperfusion: Role in Cardioprotection

Cited by 28 publications

References 35 publications

Fasudil prevents K_ATP channel-induced improvement in postischemic functional recovery

Fasudil prevents K_ATP channel-induced improvement in postischemic functional recovery

Effects of Nicorandil on Cardiovascular Events in Patients With Coronary Artery Disease in The Japanese Coronary Artery Disease (JCAD) Study

Difference in the Cardioprotective Mechanisms Between Ischemic Preconditioning and Pharmacological Preconditioning by Diazoxide in Rat Hearts

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The Effect of KATPChannel Activation on Myocardial Cationic and Energetic Status During Ischemia and Reperfusion: Role in Cardioprotection

Cited by 28 publications

References 35 publications

Fasudil prevents KATP channel-induced improvement in postischemic functional recovery

Fasudil prevents KATP channel-induced improvement in postischemic functional recovery

Effects of Nicorandil on Cardiovascular Events in Patients With Coronary Artery Disease in The Japanese Coronary Artery Disease (JCAD) Study

Difference in the Cardioprotective Mechanisms Between Ischemic Preconditioning and Pharmacological Preconditioning by Diazoxide in Rat Hearts

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Fasudil prevents K_ATP channel-induced improvement in postischemic functional recovery

Fasudil prevents K_ATP channel-induced improvement in postischemic functional recovery