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IKs protects from ventricular arrhythmia during cardiac ischemia and reperfusion in rabbits by preserving the repolarization reserve.

Guo X, Gao X, Wang Y, Peng L, Zhu Y, Wang S - PLoS ONE (2012)

Bottom Line: Both findings were consistent with an increased incidence of PVBs.Blockade of I(Ks) caused MAP triangulation, which precipitated ventricular arrhythmias.Downregulation of KCNQ1 protein may be the underlying cause of these changes.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

ABSTRACT

Introduction: The function of the repolarization reserve in the prevention of ventricular arrhythmias during cardiac ischemia/reperfusion and the impact of ischemia on slowly activated delayed rectifier potassium current (I(Ks)) channel subunit expression are not well understood.

Methods and results: The responses of monophasic action potential duration (MAPD) prolongation and triangulation were investigated following an L-768,673-induced blockade of I(Ks) with or without ischemia/reperfusion in a rabbit model of left circumflex coronary artery occlusion/reperfusion. Ischemia/reperfusion and I(Ks) blockade were found to significantly induce MAPD90 prolongation and increase triangulation at the epicardial zone at 45 min, 60 min, and 75 min after reperfusion, accompanied with an increase in premature ventricular beats (PVBs) during the same period. Additionally, I(Ks) channel subunit expression was examined following transient ischemia or permanent infarction and changes in monophasic action potential (MAP) waveforms challenged by β-adrenergic stimulation were evaluated using a rabbit model of transient or chronic cardiac ischemia. The epicardial MAP in the peri-infarct zone of hearts subjected to infarction for 2 days exhibited increased triangulation under adrenergic stimulation. KCNQ1 protein, the α subunit of the I(Ks) channel, was downregulated in the same group. Both findings were consistent with an increased incidence of PVBs.

Conclusion: Blockade of I(Ks) caused MAP triangulation, which precipitated ventricular arrhythmias. Chronic ischemia increased the incidence of ventricular arrhythmias under adrenergic stimulation and was associated with increased MAP triangulation of the peri-infarct zone. Downregulation of KCNQ1 protein may be the underlying cause of these changes.

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MAPDs, triangulations and MAP waveforms comparison between the IR+L-768,673 and IR+vehicle groups.(A) Epicardial MAPDs and triangulation recorded from the ischemia/reperfusion zone (apical) in the IR+L-768,673 group and the IR+vehicle group. Triangulations of the IR+L-768,673 group were increased compared with those of the IR+vehicle group by 31.1%, 26.5%, and 19.3% at R45, R60, and R75 respectively. Results are mean ± standard deviation (STD). * P<0.05 vs. IR+vehicle. (B) Comparison of monophasic action potential (MAP) waveforms between the IR+L-768,673 and IR+vehicle groups at R45, R60, and R75.
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pone-0031545-g002: MAPDs, triangulations and MAP waveforms comparison between the IR+L-768,673 and IR+vehicle groups.(A) Epicardial MAPDs and triangulation recorded from the ischemia/reperfusion zone (apical) in the IR+L-768,673 group and the IR+vehicle group. Triangulations of the IR+L-768,673 group were increased compared with those of the IR+vehicle group by 31.1%, 26.5%, and 19.3% at R45, R60, and R75 respectively. Results are mean ± standard deviation (STD). * P<0.05 vs. IR+vehicle. (B) Comparison of monophasic action potential (MAP) waveforms between the IR+L-768,673 and IR+vehicle groups at R45, R60, and R75.

Mentions: In the interval between reperfusion for 25 min (R25) and R90, the MAPD90 and MAPD60, but not the MAPD30, of the ischemia/reperfusion zone were significantly prolonged in the IR+L-768,673 group, when compared with the IR+vehicle group (Figure 2A). This denoted that in the presence of L-768,673, the reperfusion-induced prolongation of both the MAPD90 and MAPD60 was more evident and the return of the MAPD90 and MAPD60 to baseline was delayed; however, the MAPD30 did not show the same trend. This deviation led to an increase of triangulation (MAPD90–MAPD30) in the interval between R45 and R75, compared with the IR+vehicle group (Figure 2A). The MAP waveform of the IR+L-768,673 group was characteristic of a slowing of the fast repolarization (Figure 2B). Whereas, remote zone MAPDs recorded in all of the four groups exhibited mild, insignificant fluctuations (Figure 3).


IKs protects from ventricular arrhythmia during cardiac ischemia and reperfusion in rabbits by preserving the repolarization reserve.

Guo X, Gao X, Wang Y, Peng L, Zhu Y, Wang S - PLoS ONE (2012)

MAPDs, triangulations and MAP waveforms comparison between the IR+L-768,673 and IR+vehicle groups.(A) Epicardial MAPDs and triangulation recorded from the ischemia/reperfusion zone (apical) in the IR+L-768,673 group and the IR+vehicle group. Triangulations of the IR+L-768,673 group were increased compared with those of the IR+vehicle group by 31.1%, 26.5%, and 19.3% at R45, R60, and R75 respectively. Results are mean ± standard deviation (STD). * P<0.05 vs. IR+vehicle. (B) Comparison of monophasic action potential (MAP) waveforms between the IR+L-768,673 and IR+vehicle groups at R45, R60, and R75.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3285162&req=5

pone-0031545-g002: MAPDs, triangulations and MAP waveforms comparison between the IR+L-768,673 and IR+vehicle groups.(A) Epicardial MAPDs and triangulation recorded from the ischemia/reperfusion zone (apical) in the IR+L-768,673 group and the IR+vehicle group. Triangulations of the IR+L-768,673 group were increased compared with those of the IR+vehicle group by 31.1%, 26.5%, and 19.3% at R45, R60, and R75 respectively. Results are mean ± standard deviation (STD). * P<0.05 vs. IR+vehicle. (B) Comparison of monophasic action potential (MAP) waveforms between the IR+L-768,673 and IR+vehicle groups at R45, R60, and R75.
Mentions: In the interval between reperfusion for 25 min (R25) and R90, the MAPD90 and MAPD60, but not the MAPD30, of the ischemia/reperfusion zone were significantly prolonged in the IR+L-768,673 group, when compared with the IR+vehicle group (Figure 2A). This denoted that in the presence of L-768,673, the reperfusion-induced prolongation of both the MAPD90 and MAPD60 was more evident and the return of the MAPD90 and MAPD60 to baseline was delayed; however, the MAPD30 did not show the same trend. This deviation led to an increase of triangulation (MAPD90–MAPD30) in the interval between R45 and R75, compared with the IR+vehicle group (Figure 2A). The MAP waveform of the IR+L-768,673 group was characteristic of a slowing of the fast repolarization (Figure 2B). Whereas, remote zone MAPDs recorded in all of the four groups exhibited mild, insignificant fluctuations (Figure 3).

Bottom Line: Both findings were consistent with an increased incidence of PVBs.Blockade of I(Ks) caused MAP triangulation, which precipitated ventricular arrhythmias.Downregulation of KCNQ1 protein may be the underlying cause of these changes.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

ABSTRACT

Introduction: The function of the repolarization reserve in the prevention of ventricular arrhythmias during cardiac ischemia/reperfusion and the impact of ischemia on slowly activated delayed rectifier potassium current (I(Ks)) channel subunit expression are not well understood.

Methods and results: The responses of monophasic action potential duration (MAPD) prolongation and triangulation were investigated following an L-768,673-induced blockade of I(Ks) with or without ischemia/reperfusion in a rabbit model of left circumflex coronary artery occlusion/reperfusion. Ischemia/reperfusion and I(Ks) blockade were found to significantly induce MAPD90 prolongation and increase triangulation at the epicardial zone at 45 min, 60 min, and 75 min after reperfusion, accompanied with an increase in premature ventricular beats (PVBs) during the same period. Additionally, I(Ks) channel subunit expression was examined following transient ischemia or permanent infarction and changes in monophasic action potential (MAP) waveforms challenged by β-adrenergic stimulation were evaluated using a rabbit model of transient or chronic cardiac ischemia. The epicardial MAP in the peri-infarct zone of hearts subjected to infarction for 2 days exhibited increased triangulation under adrenergic stimulation. KCNQ1 protein, the α subunit of the I(Ks) channel, was downregulated in the same group. Both findings were consistent with an increased incidence of PVBs.

Conclusion: Blockade of I(Ks) caused MAP triangulation, which precipitated ventricular arrhythmias. Chronic ischemia increased the incidence of ventricular arrhythmias under adrenergic stimulation and was associated with increased MAP triangulation of the peri-infarct zone. Downregulation of KCNQ1 protein may be the underlying cause of these changes.

Show MeSH
Related in: MedlinePlus