Measurements of Electrophysiological Effects of Components of Acute Ischemia in Langendorff‐Perfused Rat Hearts Using Voltage‐Sensitive Dye Mapping

Nygren, Anders; Baczkó, István; Giles, Wayne R.

doi:10.1111/j.1540-8167.2006.00392.x

Cited by 25 publications

(14 citation statements)

References 55 publications

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“…Several studies using optical mapping have demonstrated that APD is shortened during low flow ischemia. [27][28][29] However, in the current study, we induced global ischemia. Under these experimental conditions, our high resolution imaging device detected only weak change in fluorescence, therefore, we could not record the APD during ischemia.…”

Section: Discussionmentioning

confidence: 99%

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

Kamada

Kanaya

Hirata

et al. 2008

Can J Anesth/J Can Anesth

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reports of original investigations 595 CAN J ANESTH 55: 9 www.cja-jca.org September, 2008 Purpose: Propofol exerts cardioprotective effects, but the involved mechanisms remain obscure. The present study examines the cardioprotective effects of propofol and its role in cardiac function, including its effect on K ATP channel opening and the inhibition of GSK-3β activity in ischemia-reperfused hearts.Methods: Ischemia-reperfusion (I/R) was produced in isolated guinea pig hearts by stopping coronary perfusion for 25 min, followed by reperfusion. The hearts were incubated for ten minutes, with or without propofol (25 or 50 µM), or for five minutes with 500 µM 5-hydroxydecanoate (a mitochondrial K ATP channel blocker) or 30 µM HMR1098 (sarcolemmal K ATP channel blocker), followed by five minutes with 50 µM propofol before ischemia. Action potentials on the anterior epicardial surface of the ventricle were monitored using a high-resolution charge-coupled device camera system, and at five minutes after reperfusion, GSK-3β phosphorylation at the serine residue, Ser9, was examined.Results: After 35 min of reperfusion, propofol (25 and 50 µM) blunted the adverse effects of I/R and reduced infarct size (P < 0.05). In addition, prior incubation with 5-hydroxydecanoate or HMR1098 had no effect on functional recovery improved by 50 µM propofol. At five minutes after reperfusion, propofol (25 and 50 µM) shortened the duration of the action potential and increased the levels of phospho-GSK-3β (P < 0.05). Conclusions:Propofol enhanced mechanical cardiac recovery and reduced infarct size. The data further suggest that GSK-3β play an important role in propofol cardioprotective actions during coronary reperfusion, but mitochondrial K ATP channels do not. Objectif : Le propofol exerce des effets cardioprotecteurs, mais les mécanismes sous-jacents demeurent obscurs. Cette étude examine les effets cardioprotecteurs du propofol et son rôle dans la fonction cardiaque, notamment son effet sur l'ouverture du canal K ATP et l'inhibition de l'activité du GSK-3β dans des coeurs ischémiques puis reperfusés. Méthode : L'ischémie reperfusion (I/R) a été provoquée dans des coeurs isolés de cobayes en interrompant la per fusion

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Section: Discussionmentioning

confidence: 99%

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

Kamada

Kanaya

Hirata

et al. 2008

Can J Anesth/J Can Anesth

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“…Alternatively, it may simply reflect the increased variability in the response in both types of hearts as the effect approaches conduction failure. Finally, we (36) have previously determined that moderate activation of I K,ATP does not significantly affect CV in control hearts. The effects of I K,ATP on conduction were therefore not considered further in this work.…”

Section: Conduction Slowing During Acute Ischemia In Stz-induced Diabmentioning

confidence: 97%

Reduced conduction reserve in the diabetic rat heart: role of iPLA₂activation in the response to ischemia

Rahnema

Shimoni

Nygren³

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Hearts from streptozotocin (STZ)-induced diabetic rats have previously been shown to have impaired intercellular electrical coupling, due to reorganization (lateralization) of connexin43 proteins. Due to the resulting reduction in conduction reserve, conduction velocity in diabetic hearts is more sensitive to conditions that reduce cellular excitability or intercellular electrical coupling. Diabetes is a known risk factor for cardiac ischemia, a condition associated with both reduced cellular excitability and reduced intercellular coupling. Activation of Ca(2+)-independent phospholipase A(2) (iPLA(2)) is known to be part of the response to acute ischemia and may contribute to the intercellular uncoupling by causing increased levels of arachidonic acid and lysophosphatidyl choline. Normally perfused diabetic hearts are known to exhibit increased iPLA(2) activity and may thus be particularly sensitive to further activation of these enzymes. In this study, we used voltage-sensitive dye mapping to assess changes in conduction velocity in response to acute global ischemia in Langendorff-perfused STZ-induced diabetic hearts. Conduction slowing in response to ischemia was significantly larger in STZ-induced diabetic hearts compared with healthy controls. Similarly, slowing of conduction velocity in response to acidosis was also more pronounced in STZ-induced diabetic hearts. Inhibition of iPLA(2) activity using bromoenol lactone (BEL; 10 μM) had no effect on the response to ischemia in healthy control hearts. However, in STZ-induced diabetic hearts, BEL significantly reduced the amount of conduction slowing observed beginning 5 min after the onset of ischemia. BEL treatment also significantly increased the time to onset of sustained arrhythmias in STZ-induced diabetic hearts but had no effect on the time to arrhythmia in healthy control hearts. Thus, our results suggest that iPLA(2) activation in response to acute ischemia in STZ-induced diabetic hearts is more pronounced than in control hearts and that this response is a significant contributor to arrhythmogenic conduction slowing.

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“…Blebbistatin’s toxicity and side effects on ion channels are less pronounced compared to other electromechanical uncouplers, such as cytochalasin D [29] and 2,3-butanedione monoxime [14, 22, 24]. Its main known limitations include photosensitivity and phototoxicity [19, 30].…”

Section: Introductionmentioning

confidence: 99%

Properties of blebbistatin for cardiac optical mapping and other imaging applications

Swift

Asfour

Posnack

et al. 2012

Pflugers Arch - Eur J Physiol

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Blebbistatin is a recently discovered myosin II inhibitor. It is rapidly becoming a compound of choice to reduce motion artifacts during cardiac optical mapping, as well as to study cell motility and cell invasion. Although blebbistatin has a number of advantages over other electromechanical uncouplers, many of its properties have yet to be addressed. Here we describe several methodological issues associated with the use of blebbistatin, including its spectral properties, reversibility, and its effect on tissue metabolic state. We show that if precautions are not taken, perfusion with blebbistatin may result in blebbistatin precipitate that accumulates in the vasculature. Although such precipitate is fluorescent, it is not detectable within wavelength bands that are typically used for transmembrane voltage fluorescence imaging (i.e., emission wavelengths >600 nm). Therefore, blockage of the microcirculation by blebbistatin may cause data misinterpretation in studies that use voltage-sensitive dyes. Blebbistatin may also impact imaging of green fluorophores due to the spectral shift it causes in endogenous tissue fluorescence. 3D excitation–emission matrices of blebbistatin in precipitate form and in various solutions (DMSO, water, and 1 % aqueous albumin) revealed significant changes in the fluorescence of this molecule in different environments. Finally, we examined the reversibility of blebbistatin’s uncoupling effect on cardiac contraction. Our findings provide important new information about the properties of this myosin II inhibitor, which will aid in the proper design and interpretation of studies that use this compound.

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Measurements of Electrophysiological Effects of Components of Acute Ischemia in Langendorff‐Perfused Rat Hearts Using Voltage‐Sensitive Dye Mapping

Abstract: These results provide the necessary background information for interpreting electrophysiological measurements during acute ischemia in the presence of cytochalasin-D.

Cited by 25 publications

References 55 publications

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

Reduced conduction reserve in the diabetic rat heart: role of iPLA₂activation in the response to ischemia

Properties of blebbistatin for cardiac optical mapping and other imaging applications

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Measurements of Electrophysiological Effects of Components of Acute Ischemia in Langendorff‐Perfused Rat Hearts Using Voltage‐Sensitive Dye Mapping

Abstract: These results provide the necessary background information for interpreting electrophysiological measurements during acute ischemia in the presence of cytochalasin-D.

Cited by 25 publications

References 55 publications

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

Reduced conduction reserve in the diabetic rat heart: role of iPLA2activation in the response to ischemia

Properties of blebbistatin for cardiac optical mapping and other imaging applications

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Reduced conduction reserve in the diabetic rat heart: role of iPLA₂activation in the response to ischemia