Altered Calcium Handling and Ventricular Arrhythmias in Acute Ischemia

Baumeister, Peter; Quinn, T. Alexander

doi:10.4137/cmc.s39706

Cited by 22 publications

(24 citation statements)

References 129 publications

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“…Severe metabolic changes begin a few seconds after coronary occlusion: high-energy phosphates are hydrolyzed, intracellular pH lowers as a consequence of the activation of anaerobic glycolysis, and extracellular potassium levels increase [90,91] . The latter lasts for roughly 10 min, during which the resting membrane potential decreases, approaching the firing threshold potential, thus accelerating electrical conduction [92] . The intracellular acidosis also drives an increase in cytosolic calcium, facilitating early and late depolarization, as well as spatial and temporal fluctuations in the duration of action potentials [93] .…”

Section: Arrhythmogenic Metabolic Changes During Myocardial Ischemiamentioning

confidence: 99%

Energetic metabolism in cardiomyocytes: molecular basis of heart ischemia and arrhythmogenesis

Martínez¹,

Machado²,

Luzardo³

et al. 2017

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Cardiac muscle contraction is a strictly regulated process which conjugates a series of electrophysiological, biochemical and mechanic events, resulting in the pumping of blood to all bodily tissues. These phenomena require a very high energetic demand both for generating the necessary mechanical force, and for maintaining cellular homeostasis during the process. In the myocardium, fatty acids (FA) represent the main energy substrate, although other secondary substrates, such as glucose and ketone bodies, may also be used. Nevertheless, under certain conditions such as heart failure or myocardial ischemia, FA metabolism may become deleterious via mechanisms such as oxidative stress and arrhythmogenesis. In an ischemic milieu, various metabolic changes occur as a consequence of hypoxia, favoring cell necrosis, ventricular arrhythmias, and death. Major events in this context include an increase in extracellular K + , a decrease in pH, and accumulation of intracellular calcium. This review includes a detailed description of the molecular basis underlying myocardial contraction and energetic metabolism in cardiomyocytes, aiming to promote an integral understanding of the pathophysiology of heart ischemia. This in turn may aid in the development of future, more satisfactory alternative treatments in the management of acute coronary ischemia episodes.

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Section: Arrhythmogenic Metabolic Changes During Myocardial Ischemiamentioning

confidence: 99%

Energetic metabolism in cardiomyocytes: molecular basis of heart ischemia and arrhythmogenesis

Martínez¹,

Machado²,

Luzardo³

et al. 2017

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“…In a recent study, Damasceno et al provided evidence to show that audiogenic epileptic seizure increased the peak amplitude of myocyte intracellular Ca ++ due to enhanced sympathetic activity (10). Myocardial Ca ++ overload contributes to myocardial tissue injury in various cellular mechanisms and may cause the generation of ventricular arrhythmias through the mechanism of delayed afterdepolarization (36)(37)(38). In the present study, the increased beta-adrenergic activation due to the possible excess adrenergic discharge may have caused myocardial cell Ca ++ overload.…”

Section: Discussionmentioning

confidence: 99%

The effect of generalized seizure activity on ischemia-induced cardiac arrhythmias and myocardial injury with histopathological evaluation in anesthetized rats

2018

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Background/aim: Epileptic seizure leads to sudden unexpected death in epilepsy (SUDEP) among affected patients. The causes of SUDEP are still unclear. The aim of this study was to research the effect of epilepsy on myocardial injury and arrhythmias during experimentally induced acute myocardial ischemia. Materials and methods: Wistar albino rats were divided into four groups: sham, pentylentetrazole (PTZ) + sham, ischemia, and PTZ + ischemia groups. PTZ (65 mg/kg, ip) was given 2 h before ischemia. Seizure scoring was conducted by evaluating the PTZ-induced behavioral changes in the rats. The left main coronary artery was ligated in anesthetized rats for 30 min. The incidence and the number of ventricular arrhythmias were determined. Histopathological scoring was performed for tissue injury by using a microscope. Results: Seizure scores were not different among the groups (P > 0.05). The incidence and number of ventricular tachycardia (VT) episodes were significantly higher in the PTZ + ischemia group than in the ischemia group (P ˂ 0.05). More prominent myocardial damage was observed in the PTZ + ischemia group than in the other groups (histopathological scores: PTZ + ischemia; 2.5 ± 0.5 versus ischemia; 1.2 ± 0.4, P ˂ 0.05). Conclusion: PTZ-induced seizure in rats increased myocardial injury and the incidence and number of VT episodes in myocardial ischemia. These results reveal that seizure in epilepsy patients may increase ventricular arrhythmia and myocardial injury during heart attack.

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“…At the same time, acute ischemia causes an increase in the frequency of Ca 2+ sparks that contributes to an increase in [Ca 2+ ] i (Mattiazzi et al, 2015a). The increase in [Ca 2+ ] i in ischemia is thought to be arrhythmogenic (Baumeister and Quinn, 2016) by driving excitatory after-depolarizations (Billman et al, 1991;Xing and Martins, 2004;Wu et al, 2011). Thus, if links exist between cell stretch and altered Ca 2+ handling in ischemia, they could represent important mechanisms for arrhythmogenesis.…”

Section: Mechanisms Of Ventricular Arrhythmias In Acute Regional Ischmentioning

confidence: 99%

“…Myocardial ischemia is also associated with an increase in [Ca 2+ ] i (Baumeister and Quinn, 2016), leading to a rise in Ca 2+ -calmodulin-dependent protein kinase II (CaMKII) activity (Mattiazzi et al, 2015b), which increases phosphorylation of RyR and the frequency of Ca 2+ sparks (Maier and Bers, 2007). Computational modeling has suggested that an elevation in [Ca 2+ ] i associated with hyperkalemia-induced membrane depolarization, along with a consequential reduction in NCXmediated Ca 2+ efflux and an increase in SR Ca 2+ content may also contribute to an increase in Ca 2+ spark rate in ischemia (Sato et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes

et al. 2020

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In ventricular myocytes, spontaneous release of calcium (Ca 2+) from the sarcoplasmic reticulum via ryanodine receptors ("Ca 2+ sparks") is acutely increased by stretch, due to a stretch-induced increase of reactive oxygen species (ROS). In acute regional ischemia there is stretch of ischemic tissue, along with an increase in Ca 2+ spark rate and ROS production, each of which has been implicated in arrhythmogenesis. Yet, whether there is an impact of ischemia on the stretch-induced increase in Ca 2+ sparks and ROS has not been investigated. We hypothesized that ischemia would enhance the increase of Ca 2+ sparks and ROS that occurs with stretch. Methods: Isolated ventricular myocytes from mice (male, C57BL/6J) were loaded with fluorescent dye to detect Ca 2+ sparks (4.6 µM Fluo-4, 10 min) or ROS (1 µM DCF, 20 min), exposed to normal Tyrode (NT) or simulated ischemia (SI) solution (hyperkalemia [15 mM potassium], acidosis [6.5 pH], and metabolic inhibition [1 mM sodium cyanide, 20 mM 2-deoxyglucose]), and subjected to sustained stretch by the carbon fiber technique (∼10% increase in sarcomere length, 15 s). Ca 2+ spark rate and rate of ROS production were measured by confocal microscopy. Results: Baseline Ca 2+ spark rate was greater in SI (2.54 ± 0.11 sparks•s −1 •100 µm −2 ; n = 103 cells, N = 10 mice) than NT (0.29 ± 0.05 sparks•s −1 •100 µm −2 ; n = 33 cells, N = 9 mice; p < 0.0001). Stretch resulted in an acute increase in Ca 2+ spark rate in both SI (3.03 ± 0.13 sparks•s −1 •100 µm −2 ; p < 0.0001) and NT (0.49 ± 0.07 sparks•s −1 •100 µm −2 ; p < 0.0001), with the increase in SI being greater than NT (+0.49 ± 0.04 vs. +0.20 ± 0.04 sparks•s −1 •100 µm −2 ; p < 0.0001). Baseline rate of ROS production was also greater in SI (1.01 ± 0.01 normalized slope; n = 11, N = 8 mice) than NT (0.98 ± 0.01 normalized slope; n = 12, N = 4 mice; p < 0.05), but there was an acute increase with stretch only in SI (+12.5 ± 2.6%; p < 0.001). Conclusion: Ischemia enhances the stretch-induced increase of Ca 2+ sparks in ventricular myocytes, with an associated enhancement of stretch-induced ROS production. This effect may be important for premature excitation and/or in the development of an arrhythmogenic substrate in acute regional ischemia.

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Altered Calcium Handling and Ventricular Arrhythmias in Acute Ischemia

Cited by 22 publications

References 129 publications

Energetic metabolism in cardiomyocytes: molecular basis of heart ischemia and arrhythmogenesis

Energetic metabolism in cardiomyocytes: molecular basis of heart ischemia and arrhythmogenesis

The effect of generalized seizure activity on ischemia-induced cardiac arrhythmias and myocardial injury with histopathological evaluation in anesthetized rats

Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes

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