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PubMed2005

Cardiac memory: mechanisms and clinical implications.

Cardiac memory (CM) is identified as an altered T wave on electrocardiogram and vectorcardiogram that is seen when sinus rhythm resumes after a period of abnormal myocardial activation. Specifically, the sinus rhythm T wave tracks the QRS vector of the abnormal impulse. CM frequently is induced by ventricular pacing or arrhythmias and historically has been considered of minor relevance to medical practice. Although it has long been known that CM can mimic the T-wave inversions of myocardial ischemia, we learned more recently that CM can alter the actions of antiarrhythmic drugs. Furthermore, it provides a template for investigating the mechanisms whereby ventricular pacing affects myocardial physiology. In this article we review the mechanisms believed responsible for induction of CM and some of its more recently recognized clinical manifestations. We also discuss the controversies regarding atrial memory and its potential clinical implications.

Animals↗
PubMed2006

Disruption of glucocorticoid action by environmental chemicals: potential mechanisms and relevance.

Glucocorticoids play an essential role in the regulation of key physiological processes, including immunomodulation, brain function, energy metabolism, electrolyte balance and blood pressure. Exposure to naturally occurring compounds or industrial chemicals that impair glucocorticoid action may contribute to the increasing incidence of cognitive deficits, immune disorders and metabolic diseases. Potentially, "glucocorticoid disruptors" can interfere with various steps of hormone action, e.g. hormone synthesis, binding to plasma proteins, delivery to target cells, pre-receptor regulation of the ratio of active versus inactive hormones, glucocorticoid receptor (GR) function, or export and degradation of glucocorticoids. Several recent studies indicate that such chemicals exist and that some of them can cause multiple toxic effects by interfering with different steps of hormone action. For example, increasing evidence suggests that organotins disturb glucocorticoid action by altering the function of factors that regulate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) pre-receptor enzymes, by direct inhibition of 11beta-HSD2-dependent inactivation of glucocorticoids, and by blocking GR activation. These observations emphasize on the complexity of the toxic effects caused by such compounds and on the need of suitable test systems to assess their effects on each relevant step.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2026

NSCLC in Vulnerable and Special Populations: Toward Personalized Care.

NSCLC encompasses a heterogeneous patient population whose clinical needs, biological features, and treatment outcomes differ substantially from those represented in pivotal studies. Adolescents and young adults, women, pregnant patients, individuals with actionable genomic alterations or constitutional pathogenic variants, immunocompromised patients, including those with chronic viral infections, older adults, patients with brain metastases, and survivors with second primary lung cancers remain consistently underrepresented in research programs. This limits the generalizability of current evidence and challenges the delivery of equitable precision oncology. Across these populations, distinct disease biology, differential genomic landscapes, sex- and age-related variations in pharmacology, and complex psychosocial or ethical considerations shape clinical decision-making. Advances in molecular testing and targeted therapies have improved outcomes for some subgroups; however, persistent disparities in diagnostic access, trial eligibility, and supportive care remain major barriers. In parallel, modern systemic agents including brain-penetrant targeted therapies, immunotherapy combinations, and antibody-drug conjugates have broadened therapeutic options, although their safety, effectiveness, and long-term consequences require dedicated evaluation in underrepresented populations. This review synthesizes contemporary evidence from these special NSCLC populations, highlighting shared challenges and unique considerations. We discuss implications for clinical practice, supportive care, survivorship, and research design and outline opportunities to strengthen inclusivity in precision oncology. Addressing longstanding gaps in representation, trial methodology, and structural inequities is essential to ensure that recent therapeutic advances translate into improved outcomes for the full spectrum of patients living with NSCLC.

Humans↗
PubMed2026

Large cell neuroendocrine carcinoma of the lung: Current standards, emerging targets, and translational foundations.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is one of the most complex and heterogenous clinical entities in thoracic oncology, sharing features with both non-small cell lung cancer (NSLC) and neuroendocrine lung cancers. LCNEC diagnosis and classification relies on evolving histopathological and molecular criteria that define its diagnostic boundaries. Recent advances have confirmed the dual nature of LCNEC, with distinct small cell-like and non-small cell-like molecular characteristics, which guide treatment decisions. In this review, we synthesize current evidence on the diagnosis, molecular characterization, and multimodality management of LCNEC to provide a comprehensive framework for clinical and translational decision-making. A comprehensive literature search was conducted using the PubMed database with no date restrictions, last updated on 12th of April 2026. Articles were selected based on relevance to the diagnosis, molecular characterization, and management of pulmonary LCNEC. Emphasis was placed on studies providing clinical, pathological, and molecular insights into the field. In this review, we summarize contemporary diagnostic approaches, including the expanding role of immunohistochemistry, next‑generation sequencing, and integrated morpho‑molecular assessment. This review represents a consolidated update on LCNEC genomic and transcriptional landscapes, and actionable molecular alterations that are anticipated to impact treatment decisions. Additionally, it provides a state-of-the-art overview of multimodality management, covering surgical approaches, radiotherapy, perioperative therapy, systemic treatment, and the emerging role of immunotherapy. Despite incremental progress, LCNEC remains constrained by limited prospective data and lack of consensus on optimal treatment pathways. By conducting literature review, we identified persistent gaps in LCNEC published data and hereby highlight key priorities for future research.

Humans↗
PubMed2004

Paroxetine alters KCl- or ATP-induced contractile responses of isolated vas deferens in rats chronically treated with ethanol.

Chronic ethanol administration affects many organ systems, including sexual organs. One of these organs is the vas deferens whose contractility can also be altered by selective serotonin re-uptake inhibitors (SSRIs). The aim of the present study, is to evaluate whether paroxetine (PX), a SSRI, can modify the contractile responses of isolated vas deferens obtained from rats chronically treated with ethanol to the contractile agents, potassium chloride (KCl) and adenosine triphosphate (ATP). For 21 days, alcohol was applied with a modified liquid diet to sexually mature male Sprague-Dawley rats (200-240 g). The vas deferens of the rats were excised at the end of day 21 and suspended in the organ baths by classical pharmacological methods. The responses to contractile agents tested were decreased by chronic ethanol treatment in all groups compared to their untreated matches. PX (10(-7) and 10(-6)M) potentiated the contractions to KCl (20-180 mM) and ATP (10(-6) to 10(-3)M) in epididymal portion but its higher concentrations (10(-5) and 10(-4)M) inhibited the responses, both in the control and chronically ethanol treated rat groups. Prazosin (PR), an alpha adrenergic receptor blocker, could not inhibit PX-induced potentiation in lower concentrations of KCl but could inhibit the potentiation occurred at higher concentrations of KCl in epididymal portion both in the control and chronically ethanol treated rat groups. PR also inhibited PX-induced potentiation on the responses to ATP in epididymal portion both in the control and chronically ethanol treated rat groups. In conclusion, all the results obtained in this study, suggest that chronic ethanol treatment decreased the contractility of vas deferens but did not alter the action pattern of PX on responses to KCl and ATP in rat vas deferens. On the other hand, the potentiation of responses to contractile agents induced by PX can be partially considered as the result of inhibition of noradrenaline re-uptake.

Adenosine Triphosphate↗
PubMed2006

In vitro exposure to environmental tobacco smoke induces CYP1B1 expression in human luteinized granulosa cells.

Women smokers and women exposed to environmental tobacco smoke (ETS) have reduced ovarian function as evidenced by an earlier menopause, reduced follicular numbers, decreased levels of circulating estradiol, and decreased conception rates; however, the mechanism of action of altered ovarian function by ETS is poorly understood. The direct effects of ETS were evaluated using human luteinized granulosa cells (HLGCs) exposed to ETS in primary cell culture. Exposure to ETS caused a decrease in both estradiol and progesterone production. There was a concentration dependent increase in CYP1B1 gene and protein expression without a change in catechol-O-methyltransferase (COMT) expression. This is the first report of CYP1B1 induction secondary to ETS exposure in cells from the human ovary. CYP1B1 metabolizes both endogenous estrogens and polyaromatic hydrocarbons in ETS to a variety of reactive species and may contribute to the complex effects of ETS on ovarian function.

Aryl Hydrocarbon Hydroxylases↗
PubMed2006

CXCR4 modulates contractility in adult cardiac myocytes.

The inflammatory response is critical to the development and progression of heart failure. Chemokines and their receptors are a distinct class of inflammatory modulators that may play a role in mediating myocardial dysfunction in heart failure. Levels of the chemokine CXCL12, also known as stromal cell-derived factor (SDF), and its receptor, CXCR4, are elevated in patients with heart failure, and we undertook this study to determine whether this chemokine system can directly affect cardiac function in the absence of leukocytes. Murine papillary muscles and adult rat cardiac myocytes treated with CXCL12, the only identified ligand of CXCR4, demonstrate blunted inotropic responses to physiologic concentrations of calcium. The negative inotropic effects on cardiac myocytes are accompanied by a proportional diminution of calcium transients. The effects are abrogated by AMD3100, a specific CXCR4 inhibitor. Overexpression of the receptor through adenoviral infection with a CXCR4 construct accentuates the negative inotropic effects of CXCL12 on cardiac myocytes during calcium stimulation. CXCR4 activation also attenuates beta-adrenergic-mediated increases in calcium mobilization and fractional shortening in cardiac myocytes. In electrophysiologic studies, CXCL12 decreases forskolin- and isoproterenol-induced voltage-gated L-type calcium channel activation. These studies demonstrate that activation of CXCR4 results in a direct negative inotropic modulation of cardiac myocyte function. The specific mechanism of action involves alterations of calcium channel activity on the membrane. The presence of functional CXCR4 on cardiac myocytes introduces a new target for treating cardiac dysfunction.

Adenoviridae↗
PubMed2006

Analysis of FOXO1A as a candidate gene for type 2 diabetes.

The human forkhead box O1A (FOXO1A) gene on chromosome 13q14.1 is a key transcription factor in insulin signaling in liver and adipose tissue and plays a central role in the regulation of key pancreatic beta-cell genes including IPF1. We hypothesized that sequence variants of FOXO1A contribute to the observed defects in hepatic and peripheral insulin action and altered beta-cell compensation that characterize type 2 diabetes (T2DM). To test this hypothesis, we screened the three exons, 3' untranslated region, and 5' flanking region for sequence variants in Caucasian and African-American individuals with early onset (<45 years) T2DM. We identified only six variants; none altered the coding sequence, and except for one variant in the 3' untranslated region, they were rare or absent in Caucasians. To increase coverage of the gene, we selected seven additional variants in the large first intron and 5' flanking region, thus providing 13 variants that spanned 116.4kb. Based on frequency and linkage disequilibrium patterns in a subset of individuals, we selected eight SNPs to type in a Caucasian population comprising 192 unrelated nondiabetic control individuals and 192 individuals with T2DM, and 10 SNPs to type in 182 controls and 352 diabetic individuals of African-American ancestry. No variant was associated with T2DM (African-Americans, p>0.08; Caucasians, p>0.09). Of the 8 Caucasian SNPs, six comprised a single haplotype block spanning over 100kb and including most of the large first intron. In contrast, no block was observed among SNPs typed in African-Americans. No haplotype was associated with T2DM. FOXO1A variation is rare and is unlikely to contribute to T2DM in either Caucasian or African-American populations.

Black or African American↗
PubMed1985

Processing and transport of insulin by vascular endothelial cells. Effects of sulfonylureas on insulin receptors.

Polypeptide hormones such as insulin must cross the vascular barrier to mediate their biologic actions. A substantial vascular barrier may be encountered in muscle and fat tissues, which are supplied by continuous capillaries lined with tightly joined endothelial cells. Endothelial cells have previously been shown to bind and release insulin with minimal degradation. Because 125I-labeled insulin transport was demonstrated to be receptor-mediated, factors regulating insulin-receptor binding may also affect the insulin transport rate across the vascular barrier. Since sulfonylureas may have a glucose-lowering action by altering insulin receptors, the effects of tolazamide and glyburide on vascular endothelial cell insulin receptors were evaluated. Exposure of aortic endothelial cells in culture to insulin at 37 degrees C resulted in a 75 percent loss of receptors. Five to seven days of tolazamide exposure led to a 35 percent time-dependent increase in insulin binding. More strikingly, tolazamide altered the dose-receptor to insulin-induced down-regulation. Cells down-regulated with insulin (10 ng/ml) showed a 100 percent increase in binding in the presence of tolazamide; a dose-dependent effect occurred at the 75 to 200 micrograms/ml dosage level. Scatchard analysis indicated that the increase in 125I-labeled insulin binding was due to an increase in receptor number. When insulin receptors were identified with 125I-labeled insulin, tolazamide-treated cells clearly showed an increase of a band at Mr = 145 K, the alpha subunit of the receptor. Tolazamide may thus help normalize glucose in diabetes by preventing receptor down-regulation in endothelial cells.

Blood Vessels↗
PubMed2001

Effects of purified green and black tea polyphenols on cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues.

The effects of green and black tea polyphenols on cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid metabolism in normal human colon mucosa and colon cancers were investigated. At a concentration of 30 microg/mL, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin-3-gallate (ECG) from green tea and theaflavins from black tea inhibited LOX-dependent activity by 30-75%. The formation of 5-, 12-, and 15-LOX metabolites was inhibited to a similar extent. Tea polyphenols also inhibited COX-dependent arachidonic acid metabolism in microsomes from normal colon mucosa, with ECG showing the strongest inhibition. The formation of thromboxane (TBX) and 12-hydroxyheptadecatrienoic acid (HHT) was decreased to a greater extent than other metabolites. The inhibitory effects of tea polyphenols on COX activity, however, were less pronounced in tumor microsomes than in normal colon mucosal microsomes. Theaflavins strongly inhibited the formation of TBX and HHT, but increased the production of prostaglandin E(2) (PGE(2)) in tumor microsomes. The enhancing effect of theaflavins on PGE(2) production was related to the COX-2 level in the microsomes. Although theaflavin inhibited ovine COX-2, its activity in the formation of PGE(2) was stimulated by theaflavin when ovine COX-2 was mixed with microsomes, suggesting that theaflavin affects the interaction of COX-2 with other microsomal factors (e.g. PGE synthase). The present results indicate that tea polyphenols can affect arachidonic acid metabolism in human colon mucosa and colon tumors, and this action may alter the risk for colon cancer in humans.

Antioxidants↗
PubMed2001

Reproductive toxicology: current and future directions.

During the 20th century, there has been an increased risk from environmental by-products that may be harmful to reproductive function in humans. Therefore, as the 21st century begins, it is appropriate to evaluate future directions within the field of reproductive toxicology. This commentary identifies several approaches and developing technologies that would help research continue in a meaningful direction. Four areas for development are suggested, and selected examples of research involved in those areas are discussed: (1) Translational applications: workplace exposures thought to cause infertility in men (1,2-dibromo-3-chloropropane, DBCP) and menstrual disturbances in women (2-bromopropane, 2BP) are given as examples of human effects that have prompted animal studies. (2) Exposure paradigms: extrapolating dosing in animals to exposures in humans becomes complex. Two examples of surprising findings using lower doses are cited: ovotoxicity caused by polycyclic aromatic hydrocarbons (PAHs), and disrupted sexual differentiation caused by the fungicide vinclozolin. (3) Gender differences: predicting variable risk between women and men requires investigation of the effects of reproductive toxicants in both genders. The phthalates provide a good example for this comparison. Whereas di-(2-ethylhexyl)phthalate (DEHP) is a reproductive toxicant working by similar mechanisms in males and females, di-n-butyl phthalate (DBP) produces developmental effects in males and reproductive tract effects in females. (4) Endocrine disruptors: recent research has identified environmental chemicals that disrupt reproductive processes by altering the actions of endogenous steroid hormones. The endocrine disruptor issue is discussed in terms of evaluation of the actual risk these chemicals may pose in humans.

Animals↗
PubMed2003

Modification of intracellular free calcium in cultured A10 vascular smooth muscle cells by exogenous phosphatidic acid.

Exogenous phosphatidic acid (PA) was observed to produce a concentration-dependent increase in [Ca(2+)](i) in cultured A10 vascular smooth muscle cells. Preincubation of cells with sarcoplasmic reticulum Ca(2+)-ATPase inhibitors (cyclopiazonic acid and thapsigargin), a phospholipase C inhibitor (2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate), inositol 1,4,5-trisphosphate receptor antagonists (2-aminoethoxydiphenyl borate and xestospongin), and an activator of protein kinase C (PKC) (phorbol 12-myristate 13-acetate) depressed the PA-evoked increase in [Ca(2+)](i). Although EGTA, an extracellular Ca(2+) chelator, decreased the PA-induced increase in [Ca(2+)](i), sarcolemmal Ca(2+)-channel blockers (verapamil or diltiazem) did not alter the action of PA. On the other hand, inhibitors of PKC (bisindolylmaleimide I) and G(i)-protein (pertussis toxin) potentiated the increase in [Ca(2+)](i) evoked by PA significantly. These results suggest that the PA-induced increase in [Ca(2+)](i) in vascular smooth muscle cells may occur upon the activation of phospholipase C and the subsequent release of Ca(2+) from the inositol 1,4,5-trisphosphate-sensitive Ca(2+) pool in the sarcoplasmic reticulum. This action of PA may be mediated through the involvement of PKC.

Animals↗
PubMed2000

Attenuated cardiac contractile responsiveness to insulin-like growth factor I in ventricular myocytes from biobreeding spontaneous diabetic rats.

OBJECTIVE: Insulin-like growth factor I (IGF-1) stimulates cardiac growth and contraction, but resistance to its action has been reported in diabetes. This study was to determine if IGF-1-induced cardiac contractile action is altered in rats genetically predisposed to diabetes. METHOD: Ventricular myocytes were isolated from spontaneously biobreeding diabetes-prone (BB/DP) rats and their diabetes-resistant littermates (BB/DR). Mechanical properties were evaluated in cardiomyocytes using a video-based edge-detection system. Myocytes were electrically stimulated at 0.5 Hz. Contractile properties analyzed included peak shortening (PS), time-to-PS (TPS) and time-to-90% relengthening (TR(90)). Intracellular Ca(2+) transients were measured as changes in fura-2 fluorescence intensity (DeltaFFI). RESULTS: Myocytes from BB/DP rats displayed increased PS, prolonged TPS and TR(90,) as well as reduced resting FFI compared to the BB/DR group. IGF-1 (10(-10)-10(-6) M) caused a dose-dependent increase in PS in myocytes from BB/DR but not BB/DP rats. The increase of PS was blunted by IGF-1 antagonist H-1356, phosphatidylinositol-3 (PI-3) kinase inhibitor wortmannin, but not tyrosine kinase inhibitor genistein. None of these agents affected responses to IGF-1 in BB/DP myocytes. Interestingly, IGF-1 elicited a comparable dose-dependent increase in Ca(2+) transients in myocytes from both BB/DR and BB/DP rats. CONCLUSION: These results suggest that the attenuation of IGF-1-induced cardiac contractile response in chemically-induced diabetes also exists in diabetes of genetic origin, possibly due to mechanisms involving PI-3 kinase and intracellular Ca(2+) sensitivity.

Androstadienes↗
PubMed2001

Neurovascular interactions between aldose reductase and angiotensin-converting enzyme inhibition in diabetic rats.

Increased polyol pathway flux has been linked to nerve complications in diabetic rats, which are attenuated by aldose reductase inhibitors, defective nitric oxide-mediated vasodilation being a particular target. Diabetes also elevates the endothelial angiotensin system, increasing vasa nervorum vasoconstriction. The aim was to assess whether promotion of vasodilation by treatment with the aldose reductase inhibitor, ZD5522 (3',5'-dimethyl-4'-nitromethylsulphonyl-2-(2-tolyl)acetanilide), coupled with reduced vasoconstriction using the angiotensin-converting enzyme inhibitor, lisinopril, interacted positively to improve neurovascular function. After 8 weeks of streptozotocin-induced diabetes, sciatic nerve blood flow and motor conduction velocity were 51% and 21% reduced, respectively. Two weeks of lisinopril treatment dose-dependently corrected the conduction deficit (ED(50) approximately 0.9 mg kg(-1)). Low-dose lisinopril (0.3 mg kg(-1)) or ZD5522 (0.25 mg kg(-1)) had modest corrective (10-20%) effects on nerve conduction and perfusion. However, when combined, blood flow and conduction velocity reached the nondiabetic range. The ZD5522 dose used gave a approximately 45% nerve sorbitol reduction but had no significant effect on fructose content; lisinopril co-treatment did not alter ZD5522 action on polyols. Thus, there was a marked neurovascular synergistic interaction between angiotensin-converting enzyme and aldose reductase inhibition in diabetic rats. This points to a potential therapeutic benefit, which requires evaluation in clinical trials.

Acetanilides↗
PubMed1998

Angiotensin AT1 receptors in Clone 9 rat liver cells: Ca2+ signaling and c-fos expression.

In C9 (Clone 9) liver cells, angiotensin 11 increased the intracellular Ca2+ content, inositol phosphate production and c-fos mRNA expression. Other angiotensins were also active with the order of potency being angiotensin II = angiotensin III >> angiotensin I > angiotensin IV. Losartan, but not PD 123177 (1-(4-amino-3-methyl)-5-diphenylacetyl-4,5,6,7-tetrahydro-1H-imida zo [4,5c]pyridine-6-carboxylic acid), blocked the effects of angiotensin II. Pertussis toxin did not alter these actions of angiotensin II. These data indicate that the effects were mediated through angiotensin AT1 receptors involving pertussis toxin-insensitive G-proteins. Phorbol myristate acetate was also able to increase c-fos mRNA expression. The action of angiotensin II was consistently greater than that of the active phorbol ester. Staurosporine but not genistein inhibited this effect of angiotensin II. Angiotensin II- and phorbol myristate acetate-induced proto-oncogene mRNA expression was attenuated in cells incubated overnight with the active phorbol ester, which suggests a major role of protein kinase C.

Angiotensin II↗
PubMed1999

Inhibition by adrenomedullin of amine release from adrenergic nerves in dog mesenteric arteries.

Adrenomedullin and calcitonin gene-related peptide (CGRP) inhibited the pressor response to transmural electrical stimulation in perfused isolated canine mesenteric arteries. The response was abolished by treatment with either prazosin or tetrodotoxin. Adrenomedullin-(22-52), an adrenomedullin receptor antagonist, reduced the inhibitory effect of adrenomedullin (10(-10) to 10(-8) mol/l), but did not alter the action of CGRP. CGRP-(8-37), a CGRP(1) receptor antagonist, did not affect the inhibition induced by adrenomedullin, but reversed the CGRP-induced inhibition. In helical strips of the arteries, adrenomedullin (up to 10(-8) mol/l) did not influence the contraction induced by noradrenaline, whereas CGRP attenuated the response. Adrenomedullin decreased the release of noradrenaline from adrenergic nerves elicited by transmural electrical stimulation, but CGRP had no effect. Adrenomedullin-(22-52) reversed the decrease in noradrenaline release induced by adrenomedullin. The adrenomedullin-induced relaxation of vascular strips precontracted with prostaglandin F(2alpha) was suppressed by CGRP-(8-37) but was unaffected by adrenomedullin-(22-52). These findings suggest that adrenomedullin impairs noradrenaline release from adrenergic nerves by acting on adrenomedullin receptors located in the nerve terminals, whereas arterial relaxation caused by adrenomedullin and CGRP is due to activation of CGRP(1) receptors in vascular smooth muscle.

Adrenergic Fibers↗
PubMed1986

The role of phospholipase in the genesis of reperfusion arrhythmia.

To clarify the mechanism of reperfusion arrhythmia, the following experiments were performed. In vivo study: Using anesthetized mongrel dogs, the left anterior descending coronary artery was occluded for 15 min and the ligation was released. The dogs were divided into two groups depending on whether the pretreatment was with saline or coenzyme Q10 (CoQ10), 15 mg/kg, before the ligation, i.e., the control and the CoQ10 groups. Each group was further divided into two subgroups depending on the presence or the absence of reperfusion arrhythmia. Reperfusion arrhythmia was observed in 12 out of 38 dogs in the control, whereas in the CoQ10 group none developed arrhythmia. Nine species of free fatty acids (FFA) were detected in the plasma membrane in each group. In the dogs in the control group with arrhythmia, all species of detected FFA increased, and phospholipid content in plasma membrane decreased. These changes were not observed in the dogs without arrhythmia in both the control and the CoQ10 groups. In vitro study: Incubation of myocardial plasma membrane with phospholipase (PLase) A2 increased only unsaturated FFA, while PLase C increased all detected FFA. Premedication with CoQ10 prevented the increase in FFA caused by PLases. Perfusion with PLase A2 or C altered membrane action potential. Premedication with CoQ10 also prevented changes in membrane action potential. PLase liberates fatty acids from phospholipids, and CoQ10 is known to protect the membrane phospholipids from the attack of PLase. These facts and results suggest that activation of PLase associated with coronary reperfusion is closely related to the development of reperfusion arrhythmia.

Animals↗