Ventricular fibrillation in preconditioned pig  hearts: role of   K  ATP   +     channels

Rioufol, Gilles; Ovize, Michel; Loufoua, Joseph; Pop, Călin; André‐Fouët, Xavier; Minaire, Y

doi:10.1152/ajpheart.1997.273.6.h2804

Cited by 13 publications

(8 citation statements)

References 20 publications

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“…Ischemic preconditioning did not affect the incidence of ischemic VF and tended to shorten the time of onset of VF in vehicle-treated pigs, consistent with prior studies in swine [42, 43]. Moreover, in preconditioned pigs neither VF incidence nor time of onset was influenced by rosiglitazone, consistent with a prior study showing no effect of glyburide on these measures [44]. …”

Section: Discussionsupporting

confidence: 87%

Thiazolidinedione Drugs Promote Onset, Alter Characteristics, and Increase Mortality of Ischemic Ventricular Fibrillation in Pigs

Sarraf

et al. 2012

Cardiovasc Drugs Ther

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Purpose Despite favorable metabolic and vascular effects, thiazolidinedione (TZD) drugs have not convincingly reduced cardiovascular mortality in clinical trials, raising the possibility of countervailing, off-target effects. We previously showed that TZDs block cardiac ATP-sensitive potassium (KATP) channels in pigs. In this study, we investigated whether TZDs affect onset, spectral characteristics, and mortality of ischemic ventricular fibrillation (VF) and whether such effects are recapitulated by a non-selective KATP blocker (glyburide) or a mitochondrial KATP blocker (5-hydroxydecanoate). Methods A total of 121 anesthetized pigs were pre-treated with TZD (pioglitazone or rosiglitazone, 1 mg/kg IV, resulting in clinically relevant plasma concentrations), glyburide (1 mg/kg IV), 5-hydroxydecanoate (5 mg/kg IV) or inert vehicle. Ischemia was produced by occlusion of the left anterior descending coronary artery. In a subset of pigs treated with rosiglitazone or vehicle, ischemic preconditioning was performed. Results VF developed in all but 6 pigs. In non-preconditioned pigs, onset of VF occurred sooner with pioglitazone (11± 3 min, p<0.05) or rosiglitazone (14±3 min, p=0.06) than with vehicle (20±2 min). Defibrillation of VF was successful in 44% of pigs treated with vehicle, compared with 0% with pioglitazone (p=0.057) and 33% with rosiglitazone (NS). After ischemic preconditioning, defibrillation was successful in 62% of pigs treated with vehicle, compared with 26% treated with rosiglitazone (p=0.03). TZDs attenuated slowing of conduction due to ischemia and shifted ECG power spectra during VF toward higher frequencies. All effects of TZDs were recapitulated by glyburide, but not by 5-hydroxydecanoate, supporting an interaction of TZDs with the sarcolemmal KATP channel. Conclusion In a porcine model, TZDs promote onset and increase mortality of ischemic VF, associated with alterations of conduction and VF spectral characteristics. Similar effects in a clinical setting might adversely impact cardiovascular mortality.

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Section: Discussionsupporting

confidence: 87%

Thiazolidinedione Drugs Promote Onset, Alter Characteristics, and Increase Mortality of Ischemic Ventricular Fibrillation in Pigs

Sarraf

et al. 2012

Cardiovasc Drugs Ther

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“…Many Vaughan Williams class I anti-arrhythmic drugs inhibit K ATP channels in cardiac muscles (32)(33)(34). However, some investigators did not find effects of K ATP channel blockers, such as glibenclamide and 5-hydroxydecanoate, on the incidence of arrhythmia after ischemic insult (35)(36)(37). These controversial observations might be due to different experimental conditions or protocols, but it cannot be excluded that the effects of glibenclamide on mitochondrial channels differ in different animal models or conditions.…”

Section: Discussionmentioning

confidence: 99%

Thrombin Receptor and Ventricular Arrhythmias after Acute Myocardial Infarction

Tang

Deng

Long

et al. 2008

Mol Med

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The mechanism mediating the development of ventricular arrhythmia (VA) after acute myocardial infarction (AMI) is still uncertain. Thrombin receptor (TR) activation has been proven to be arrhythmogenic in many other situations, and we hypothesize that it may participate in the genesis of post-AMI VA. Using a left coronary artery ligation rat model of AMI, we found that a local injection of hirudin into the left ventricle (LV) significantly reduced the ratio of VA durations to infarction sizing, whereas injection of thrombin receptor-activating peptide (TRAP) increased the ratios of VA duration to infarction sizing. The effects of TR activation on whole-cell currents were investigated in isolated myocytes. TRAP increased a glibenclamide-sensitive outward current. Pretreatment of rats with glibenclamide (4 mg/kg intraperitoneally) eliminated the effects of a local injection of TRAP on the ratios of VA durations to infarction sizing. TR mRNA and protein expression in the ischemic left ventricle had reached its peak by 20 min postligation in the rat AMI model (P < 0.05). TR-immunoreactive myocytes were observed in infarcted LV but were seldom seen in the right ventricle or in the normal heart. By 60 min, TR transcript levels had returned to control levels. We conclude that increased TR activation and expression in the infarcted LV after AMI may contribute to VA through a mechanism involving glibenclamide-sensitive potassium channels.

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“…Although the antiarrhythmic effects of sar-K ATP channel antagonists has been documented during ischemia, there were controversial in vivo data of the literature supporting either proarrhythmic or antiarrhythmic effects (Baczko et al, 1997;Rioufol et al, 1997;Kita et al, 1998;Wirth et al, 1999; Table 4). Different agonists and antagonists including specific and nonspecific agents were used to assess anti-and pro-arrhythmic effects of ATP-sensitive K ϩ channels.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Sarcolemmal and Mitochondrial K_ATP Channels Activated by 17β-Estradiol on Reperfusion Arrhythmias and Infarct Sizes in Canine Hearts

Tsai

Su²,

Chou³

et al. 2002

J Pharmacol Exp Ther

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We have demonstrated the effects of estrogen on modulation of ATP-sensitive K ϩ channels; however, the subcellular location of these channels is unknown. The purpose of the present study was to investigate the role of the sarcolemmal and mitochondrial ATP-sensitive K ϩ channels in a canine model of myocardial infarction after stimulation with 17␤-estradiol. Anesthetized dogs were subjected to 60 min of the left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Infarct size was markedly reduced in estradiol-treated dogs compared with controls (14 Ϯ 6 versus 42 Ϯ 6%, P Ͻ 0.0001), indicating the effective dose of estradiol administrated. Pretreatment with the mitochondrial ATP-sensitive K ϩ channel antagonist 5-hydroxydecanoate completely abolished estradiol-induced cardioprotection. The sarcolemmal ATP-sensitive K ϩ channel antagonist 1-15-12-(5-chloro-o-anisamido)ethylmethoxyphenyl)sulfonyl-3-methylthiourea (HMR 1098) did not significantly attenuate estradiol-induced infarct size limitation.In addition, estradiol administration significantly reduced the incidence and duration of reperfusion-induced ventricular tachycardia and ventricular fibrillation. Although 5-hydroxydecanoate alone caused no significant effect on the incidence of reperfusion arrhythmias in the presence or absence of estradiol, the administration of HMR 1098 abolished estrogen-induced improvement of reperfusion arrhythmias. Pretreatment with the estrogen-receptor antagonist faslodex (ICI 182,780) did not alter estrogen-induced infarct-limiting and antiarrhythmic effects. These results demonstrate that estrogen is cardioprotective against infarct sizes and fatal reperfusion arrhythmias by different ATP-sensitive K ϩ channels for an estrogen receptor-independent mechanism. The infarct size-limiting and antiarrhythmic effects of estrogen were abolished by 5-hydroxydecanoate and HMR 1098, suggesting that the effects may result from activation of the mitochondrial and sarcolemmal ATP-sensitive K ϩ channels, respectively.

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Ventricular fibrillation in preconditioned pig hearts: role of K ATP + channels

Cited by 13 publications

References 20 publications

Thiazolidinedione Drugs Promote Onset, Alter Characteristics, and Increase Mortality of Ischemic Ventricular Fibrillation in Pigs

Thiazolidinedione Drugs Promote Onset, Alter Characteristics, and Increase Mortality of Ischemic Ventricular Fibrillation in Pigs

Thrombin Receptor and Ventricular Arrhythmias after Acute Myocardial Infarction

Differential Effects of Sarcolemmal and Mitochondrial K_ATP Channels Activated by 17β-Estradiol on Reperfusion Arrhythmias and Infarct Sizes in Canine Hearts

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Ventricular fibrillation in preconditioned pig hearts: role of K ATP + channels

Cited by 13 publications

References 20 publications

Thiazolidinedione Drugs Promote Onset, Alter Characteristics, and Increase Mortality of Ischemic Ventricular Fibrillation in Pigs

Thiazolidinedione Drugs Promote Onset, Alter Characteristics, and Increase Mortality of Ischemic Ventricular Fibrillation in Pigs

Thrombin Receptor and Ventricular Arrhythmias after Acute Myocardial Infarction

Differential Effects of Sarcolemmal and Mitochondrial KATP Channels Activated by 17β-Estradiol on Reperfusion Arrhythmias and Infarct Sizes in Canine Hearts

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Product

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Differential Effects of Sarcolemmal and Mitochondrial K_ATP Channels Activated by 17β-Estradiol on Reperfusion Arrhythmias and Infarct Sizes in Canine Hearts