Myocardial ischemia and ventricular fibrillation: Pathophysiology and clinical implications

Luqman, Nazar; Sung, Ruey J.; Wang, Chunli; Kuo, Chi‐Tai

doi:10.1016/j.ijcard.2006.09.016

Cited by 86 publications

(62 citation statements)

References 53 publications

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“…These lethal disruptions have been linked to mutations in RyR2 and cause a reduction in the binding affinity of the channelstabilizing subunit FKBP12.6, which predisposes these mutant RyR2 channels to aberrant Ca 2+ release during diastole. Increased activity of the sympathetic nervous system, which leads to enhanced PKA phosphorylation of RyR2, further increases the risk of severe cardiac arrhythmias in patients with these RyR2 mutations (Luqman et al, 2007;Katra et al, 2007). In the present study, the results of PKA, RyR2 and FKBP12.6 also proved the point.…”

Section: Discussionsupporting

confidence: 75%

RetractedDecreased FKBP12.6 expression and enhanced endothelin receptor signaling associated with arrhymogenesis in myocardial infarction rats

Shi²,

Zeng

et al. 2008

Phytotherapy Research

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An increased propensity towards cardiac arrhythmias and aggravated heart function is observed in myocardial infarction (MI), the development of which is associated with the calcium handling system in the myocardium. It was hypothesized that the abnormal changes in the MI model may be a consequence of the abnormal expression and function of the RyR2-FKBP12.6 channel complex and that these abnormalities may be related to an over-activated endothelin (ET) system. Salvianolic acid B is expected to suppress life-threatening arrhythmias and to restore the abnormality of the RyR2-FKBP12.6 complex in rats. MI was produced by ligating the coronary artery for 4 weeks. Salvianolic acid B (100 mg/kg/day, p.o. for 4 weeks) was administered to rats 0.5 h before surgery. Measurements of cardiac arrhythmias, cardiac function, calcium transient, cardiac calcium release channel handling proteins and the endothelin system were conducted. The aggravated arrhythmia and compromised cardiac function in MI rats was accompanied by elevated diastolic Ca(2+) levels in the cytosol and a significant down-regulation of expression of RyR2-FKBP12.6. These were closely linked with an over-activated ET pathway in the myocardium. After a 4-week treatment with salvianolic acid B, all abnormalities were reversed significantly. Salvianolic acid B was capable of normalizing FKBP12.6 expression levels and decreasing the propensity towards arrhythmias by attenuating the up-regulated ET pathway.

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Section: Discussionsupporting

confidence: 75%

RetractedDecreased FKBP12.6 expression and enhanced endothelin receptor signaling associated with arrhymogenesis in myocardial infarction rats

Shi²,

Zeng

et al. 2008

Phytotherapy Research

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“…Myocardial perfusion abnormalities resulting in ischemia are well known to modulate automaticity, excitability, and refractoriness. These changes lead to heterogeneity of repolarization, thus creating a substrate for VA. 34, 35 Paganelli et al 36 demonstrated that residual ischemia in patients after a myocardial infarction, assessed with single photon emission computed tomographic, was associated with inducibility of VA, whereas LVEF and fixed perfusion defects were not. In particular, the extent of residual ischemia in the peri-infarction area was found to be of importance.…”

Section: Discussionmentioning

confidence: 99%

Impaired Hyperemic Myocardial Blood Flow Is Associated With Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy

Rijnierse

Haan

Harms

et al. 2014

Circ: Cardiovascular Imaging

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O]H 2 O positron-emission tomography was performed to quantify resting MBF, hyperemic MBF, and coronary flow reserve. Left ventricular dimensions, function, and scar burden were assessed with cardiovascular magnetic resonance imaging. An electrophysiological study was performed to test VA inducibility. Positive electrophysiological study patients (n=12) showed reduced hyperemic MBF (1.25±0.30 versus 1.66±0.38 mL•min ; P<0.01) and coronary flow reserve (1.59±0.49 versus 2.12±0.48; P<0.01) compared with electrophysiological study negative patients (n=18). In electrophysiological study positive patients, the number of scar segments >75% transmurality was higher (P<0.05), although scar size and border zone did not differ. Receiver-operating characteristic curve analysis indicated that impaired hyperemic MBF (area under the curve, 0.84; 95% confidence intervals [0.69-0.99 arrhythmias are an important and common cause of death in these classifications of cardiomyopathy, suggesting that quantitative assessment of MBF could be used not merely for risk stratification but specifically to identify patients prone to SCD. 14 The link between the occurrence of VA and impaired myocardial perfusion, however, remains to be elucidated.The aim of this pilot study was to assess whether hyperemic MBF and CFR as assessed with [15 O]H 2 O PET are associated with VA inducibility during an electrophysiological study (EPS) in patients with ischemic cardiomyopathy. Furthermore, the role of alternative risk factors such as LVEF, scar size, transmurality, and border zone as assessed with cardiovascular magnetic resonance (CMR) imaging was evaluated. Methods Study PopulationPatients with ischemic cardiomyopathy and LVEF ≤35%, who were referred for ICD implantation for primary prevention of SCD based on current guidelines, 4 were prospectively included. Exclusion criteria were a cardiac rhythm other than sinus rhythm and a previous history of sustained VA. During the study period, 581 ICD devices were implanted, of which 316 devices were combined with resynchronization therapy or implanted for secondary prevention indication. Of the remaining 265 patients, 109 had nonischemic cardiomyopathy, and another 19 patients did not have sinus rhythm. Of the remaining 137 eligible patients, 107 patients could not be included because of refusal of participation, logistical issues, or other contraindications for PET, CMR, or EPS. A total of 30 patients were included in the described study. None of the patients displayed residual ischemia at noninvasive testing amendable to revascularization before referral for ICD implantation. All patients underwent CMR, PET, and EPS for research purposes after inclusion in this study. The study was approved by the Ethics Committee of the VU University Medical Center, in accordance with the Declaration of Helsinki, and written informed consent was obtained from all patients. CMR Image AcquisitionCMR studies were performed on a clinical 1.5-T MRI scanner (Magnetom Avanto; Siemens, Erlangen, Germany) using a dedicated pha...

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“…Instead, ischemia causes a reduction in the transmembrane I Ca carried by VGCCs, which, together with prolonged inactivation of the channel, contributes to electrical instability and impairs excitation-contraction coupling (124,138). The effects of short-term IH on VGCC activity during I/R are unclear; however, long-term IH adaptation, which had no effect on basal I Ca , lessened L-type VGCC inactivation and facilitated I Ca during ischemic challenge (270), changes that might serve to increase electrical stability, improved myocardial contraction, and diminish cardiac electrical remodeling following an ischemic event (53).…”

Section: Circulatory Systemmentioning

confidence: 99%

Hypoxia. 4. Hypoxia and ion channel function

Shimoda

Polàk

2011

American Journal of Physiology-Cell Physiology

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The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes. oxygen deprivation; mammalian ion channels; oxygen homeostasis SENSING and appropriately responding to changes in O 2 concentration is of paramount importance for the survival of all organisms. Over time, O 2 homeostasis has evolved into a complex system to regulate O 2 delivery and use. While the rapid response to acute reductions in O 2 concentration typically results from processes that alter preexisting proteins, such as phosphorylation, stabilization, dimerization, or degradation, durable adaptation to prolonged hypoxic insult requires a coordinated response at the level of gene transcription. Since a deficit in O 2 is an important component of various physiological processes and the pathogenesis of numerous diseases, understanding the mechanisms by which changes in O 2 are linked to cell function is of great interest.Ion channels play a critical role in regulating a wide variety of biological processes, including neuronal transmission; control of ventillation; contraction of cardiac, skeletal, and smooth muscle; transport of nutrients and ions across the epithelium; T-cell activation; and glucose metabolism and pancreatic ␤-cell insulin release. To date, over 300 types of ion channels, differing in their mode of activation (voltage-dependent or -independent, ligand-gated, mechanosensitive, pH) and their ionic permeability (K ϩ , Ca 2ϩ , Cl Ϫ , Na ϩ ), have been identified. This heterogeneity in ion channel populations provides an astonishing array of variable responses within and between cell types. In 1988, a report demonstrating that rabbit carotid body glomus cells express an O 2 -sensitive potassium channel ushered in a new era of research exploring whether ion channel activity could be regulated in response to changes in O 2 availability (131). Since that initial description of an O 2 -regulated ion channel, an abundance of work has been produced indicating that a variety of ion channels spread across the different ion channel families are O 2 sensitive and exhibit changes in channel activity with acute hypoxia and alterations in channel quantity with prolonged hypoxic challenge. Although a great amount of work has been devoted to the study of hypoxia and ion channels in reptiles, amp...

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Myocardial ischemia and ventricular fibrillation: Pathophysiology and clinical implications

Cited by 86 publications

References 53 publications

RetractedDecreased FKBP12.6 expression and enhanced endothelin receptor signaling associated with arrhymogenesis in myocardial infarction rats

RetractedDecreased FKBP12.6 expression and enhanced endothelin receptor signaling associated with arrhymogenesis in myocardial infarction rats

Impaired Hyperemic Myocardial Blood Flow Is Associated With Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy

Hypoxia. 4. Hypoxia and ion channel function

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