coenzyme-q10 and Arrhythmias--Cardiac

Reperfusion arrhythmia following cardiac surgery has long been studied as part of myocardial damage. Reperfusion injury is thought to be exacerbated by oxygen-free radicals, whereas arrhythmogenic oscillations in membrane potential are mediated by reactive oxygen. Coenzyme Q10 is a lipid-soluble antioxidant that inhibits lipid peroxidation in biological membranes and supplies ATP cell synthesis, required as the organism's primary energy source. This process explains how Coenzyme Q10 helps stabilize membranes and avoids critical metabolite depletion that may relate to reperfusion arrhythmia. There is a reduction of iatrogenic Coenzyme Q10 after coronary artery bypass surgery (CABG). On the other hand, there is an increased inflammatory process and cellular demand post CABG procedure. It leads to ischemia that can be manifested as arrhythmia. Reperfusion arrhythmia was less common in patients who took Coenzyme Q10. These findings suggest that Coenzyme Q10 supplementation might help patients with heart surgery avoid reperfusion arrhythmia. However, a higher-quality randomized controlled study is needed to determine the effect of Coenzyme Q10 in preventing reperfusion arrhythmia in cardiac surgery patients.

Topics: Arrhythmias, Cardiac; Coronary Artery Bypass; Humans; Incidence; Reperfusion

The effects of oral treatment with coenzyme Q10 (120 mg/d) were compared for 28 days in 73 (intervention group A) and 71 (placebo group B) patients with acute myocardial infarction (AMI). After treatment, angina pectoris (9.5 vs. 28.1), total arrhythmias (9.5% vs. 25.3%), and poor left ventricular function (8.2% vs. 22.5%) were significantly (P < 0.05) reduced in the coenzyme Q group than placebo group. Total cardiac events, including cardiac deaths and nonfatal infarction, were also significantly reduced in the coenzyme Q10 group compared with the placebo group (15.0% vs. 30.9%, P < 0.02). The extent of cardiac disease, elevation in cardiac enzymes, and oxidative stress at entry to the study were comparable between the two groups. Lipid peroxides, diene conjugates, and malondialdehyde, which are indicators of oxidative stress, showed a greater reduction in the treatment group than in the placebo group. The antioxidants vitamin A, E, and C and beta-carotene, which were lower initially after AMI, increased more in the coenzyme Q10 group than in the placebo group. These findings suggest that coenzyme Q10 can provide rapid protective effects in patients with AMI if administered within 3 days of the onset of symptoms. More studies in a larger number of patients and long-term follow-up are needed to confirm our results.

Topics: Angina Pectoris; Antioxidants; Arrhythmias, Cardiac; Coenzymes; Double-Blind Method; Heart Ventricles; Humans; Male; Myocardial Infarction; Myocardium; Oxidative Stress; Placebos; Time Factors; Ubiquinone

Cardioprotective effects of coenzyme Q10 (CoQ10) injected intravenously 30 min before coronary artery occlusion were assessed on the model of myocardial ischemia/reperfusion in Wistar rats. Rats treated with CoQ10 after 30 min of ischemia and 120 min of reperfusion exhibited smaller (by 35%, p < 0.01) size of irreversibly damaged myocardium, shorter duration and decreased number of arrhythmias during reperfusion, and increased content of myocardial CoQ10 (by 210%, p < 0.01) as compared to saline-treated rats. Increased CoQ10 levels in myocardium were accompanied by smaller size of damaged myocardium (r = -0.77, p = 0.0002). Thus, there is evidence of the cardioprotective effect of CoQ10 injected intravenously before myocardial ischemia/reperfusion.

Topics: Animals; Arrhythmias, Cardiac; Cardiotonic Agents; Drug Administration Schedule; Infusions, Intravenous; Male; Myocardial Reperfusion Injury; Myocardium; Oxygen Consumption; Rats; Rats, Wistar; Ubiquinone

Coenzyme Q10 (CoQ10) has been extensively studied as adjunctive therapy for ischemic heart disease, and its cardioprotective ability is well-established. The mitochondrial respiratory chain contains several coenzymes, including CoQ1, CoQ2, CoQ4, CoQ6, CoQ7, CoQ8, CoQ9, and CoQ10. It is not known whether other CoQs, especially CoQ9, is equally cardioprotective as CoQ10. The present study was designed to determine if CoQ 9 could protect guinea pig hearts from ischemia reperfusion injury. Guinea pigs were randomly divided into three groups: groups I and II were fed CoQ 9 and CoQ10, respectively, for 30 days while group III served as control. After 30 days, the guinea pigs were sacrificed and isolated hearts were perfused via working mode were subjected to 30 min ischemia followed by 2 h of reperfusion. Cardioprotection was assessed by evaluating left ventricular function, ventricular arrhythmias, myocardial infarct size, and cardiomyocyte apoptosis. Samples of hearts were examined for the presence of CoQ9 and CoQ10. The results demonstrated that both CoQ9 and CoQ10 were equally cardioprotective, as evidenced by their abilities to improve left ventricular performance and to reduce myocardial infarct size and cardiomyocyte apoptosis. High performance liquid chromatographic (HPLC) analysis revealed that a substantial portion of CoQ9 had been converted into CoQ10. The results indicate that CoQ9 by itself, or after being converted into CoQ10, reduced myocardial ischemia/reperfusion-induced injury.

Topics: Animals; Apoptosis; Arrhythmias, Cardiac; Biotransformation; Cardiotonic Agents; Drug Evaluation, Preclinical; Guinea Pigs; Humans; Male; Mass Spectrometry; Myocardial Reperfusion Injury; Random Allocation; Ubiquinone; Ventricular Function, Left

Anti-phospholipase (Plase) action of ubidecarenone (coenzyme Q10, CoQ10, E-0216) derivatives was investigated. CoQ10 and its derivatives prevented the release of fatty acids from canine heart mitochondrial phopholipids induced by PLase A2 and PLase C. The protective effects of the carboxyl derivatives of CoQ10 of the benzoquinone type (BQs) and of the methoxyl type (MPs) were stronger than that of CoQ10. MPs with 3 isoprenoid units (MP-3) was more effective than BQs with 3 isoprenoid units (BQ-3) with respect to PLase A2, while they showed similar protective effect against PLase C attack. The effects of BQ-3 and MP-3 on reperfusion arrhythmias were investigated in anesthetized dogs. Dogs were divided into three groups: the control group (n = 38), the BQ-3 group (n = 11), and the MP-3 group (n = 11). Physiological saline or 5 mg/kg of BQ-3 or MP-3 was premedicated in each group. 20 min after premedication, the left anterior descending coronary artery was occluded for 15 min followed by 5 min reperfusion. 32% of the controls developed reperfusion arrhythmias, while none of the dogs pretreated with CoQ10 derivatives developed arrhythmias. Immediately after 5 min of reperfusion, heart microsomes were prepared from normal and reperfused areas and the PLase activity in microsomes was measured by high performance liquid chromatography. In the arrhythmias cases of the control group, the endogenous PLase activity obtained from reperfused myocardium increased significantly compared with that from normal myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coenzymes; Coronary Circulation; Dogs; Fatty Acids, Nonesterified; Female; Heart Rate; Male; Microsomes; Mitochondria, Heart; Phospholipases; Structure-Activity Relationship; Ubiquinone

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.

Topics: Animals; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Cell Membrane; Coenzymes; Coronary Circulation; Coronary Disease; Dogs; Electrocardiography; Fatty Acids, Nonesterified; Female; Heart Rate; Male; Myocardium; Phospholipases; Phospholipids; Ubiquinone; Ventricular Fibrillation

A series of 38 patients with solid tumours (N=29) and haematological malignancies (N=9) and with suspicion of cardiotoxicity (CTX) due to antineoplastic drugs was studied. The series comprised 22 females and 16 males (mean age 52 years). The patients were examined clinically by ECG, chest X-ray and echocardiography. Seventeen patients were classified as having moderate or severe chronic CTX; 16 patients developed either arrhythmias shortly after the administration of chemotherapy (acute CTX) or arrhythmias and/or signs of myocardial dysfunction (without overt congestive heart failure) at a later date, after chemotherapy had been suspended (latent CTX). In 5 cases the suspicion of CTX could not be confirmed. Weak and non-specific symptoms such as unexplained tachycardia or coughing at night should alert the clinician and result in ECG control and further non-invasive cardiological investigations (including radionuclide angiocardiography) before additional anthracycline is administered. Chest X-ray is a very insensitive method with respect to early diagnosis of chronic CTX; in cases of doubt heart catheterization with endomyocardial biopsy should be carried out to obtain a reliable estimate of the extent of morphological damage. As anthracycline CTX may present without prominent clinical symptoms or as latent disease, one should be aware of potential precipitating factors such as volume load (during i.v. chemotherapy), surgical trauma and general anaesthesia and alcohol abuse. Further effects to lessen CTX should be made, using supposed cardio-protective substances in randomized clinical trials. Promising research on coenzyme Q10 and carnitine may usher in a new era in the prevention of anthracycline cardiotoxicity.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Biopsy; Cardiac Catheterization; Carnitine; Coenzymes; Electrocardiography; Endocardium; Female; Follow-Up Studies; Heart; Heart Diseases; Humans; Male; Middle Aged; Myocardium; Naphthacenes; Risk; Ubiquinone

Topics: Anesthesia; Animals; Arrhythmias, Cardiac; Coenzymes; Coronary Circulation; Coronary Disease; Male; Rats; Rats, Inbred Strains; Superoxide Dismutase; Ubiquinone; Vitamin E

Topics: Adult; Arrhythmias, Cardiac; Coenzymes; Female; Fetal Diseases; Humans; Maternal-Fetal Exchange; Pregnancy; Prenatal Diagnosis; Ubiquinone

The mechanism of mitochondrial damage during reperfusion injury of ischemic myocardium was studied using mongrel dogs in vivo and isolated mitochondria in vitro. Seventy-seven adult dogs were divided into three groups: the control group (n = 38), the Coenzyme Q10 (CoQ10)-5 mg group (n = 24), and the CoQ10-15 mg group (n = 15). In the control group, the left anterior descending coronary artery (LAD) of the dog was occluded for 15 min followed by 5 min of reperfusion after 40 min of premedication with physiological saline. In both CoQ10 groups, 5 mg/kg or 15 mg/kg of CoQ10 was infused intravenously for 20 min and then physiological saline was administered for 20 min before 15 min occlusion of the LAD. Subsequently, reperfusion was allowed for 5 min. Each group was further divided into two subgroups depending on the presence (arrhythmia group) or the absence (non-arrhythmia group) of ventricular arrhythmias. Immediately after 15 min occlusion, myocardial samples were taken from the normal and reperfused areas to measure CoQ10 content of myocardium. Heart mitochondria were prepared after 5 min of reperfusion from both areas. Arrhythmias appeared in 12 of 38 dogs in the control group (32%), two of 24 dogs in the CoQ10-5 mg group (8%) and none of 15 dogs in the CoQ10-15 mg group (0%). Premedication with CoQ10 increased tissue CoQ10 content in a dose-dependent manner. In the CoQ10-5 mg group, the increase in CoQ10 content of dogs with reperfusion arrhythmias was relatively less than that of dogs without reperfusion arrhythmias. In each group, mitochondrial function was decreased in the arrhythmia group compared to that of the non-arrhythmia group. The increase in free fatty acid (FFA) content and the decrease in phospholipid content were also observed in mitochondria from the reperfused area of each arrhythmia group. The increase in FFA and mitochondrial dysfunction were induced by the incubation of mitochondria in vitro with phospholipase (PLase) A2 or PLase C, and protected by the addition of CoQ10. These results suggest that PLase plays an important role in the development of mitochondrial damage associated with reperfusion.

Topics: Animals; Arrhythmias, Cardiac; Coenzymes; Coronary Circulation; Dogs; Fatty Acids; Mitochondria, Heart; Myocardial Infarction; Oxygen Consumption; Phospholipases; Phospholipases A; Ubiquinone

Adriamycin (ADR), one of the anthracycline derivatives, has the most strong cardiotoxicity. We studied the cardiotoxicity caused by ADR in New Zealand white rabbits and its protection by the medication of CoQ10. The findings of ECG and the myocardial tissue examined by the electron microscope showed the effectiveness of the injection of CoQ10 to prevent the cardiotoxicity caused by ADR. The concomitant injection of CoQ10 dissolved in saline was tried in patients with various kinds of neoplasm who were given more than 200 mg of ADR or DM. Only one patient showed the ST-T change. On the contrary, 3 of patients given more than 200 mg ADR or DM alone showed abnormal change of ECG.

Topics: Acute Disease; Adult; Aged; Animals; Arrhythmias, Cardiac; Cardiomyopathies; Coenzymes; Doxorubicin; Electrocardiography; Female; Heart; Humans; Leukemia; Lymphoma; Male; Middle Aged; Rabbits; Ubiquinone

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Coenzymes; Coronary Disease; Heart Valve Diseases; Humans; Middle Aged; Postoperative Complications; Postoperative Period; Premedication; Ubiquinone

An investigation was undertaken to evaluate the antiarrhythmic effect of CoQ10 on VPBs using the Holter ECG, in 27 patients with no clinical findings of organic cardiopathies. As a result, the effect of CoQ10 on VPBs was considered beneficial in 6 (22%) of 27 cases, consisting of 1 patient with hypertension and 5 patients with DM. Even in the remaining 2 patients with DM, the frequency of VPBs was reduced by 50% or more during treatment with CoQ10. The mean reduction of VPBs frequency in the 5 responders plus these 2 patients with DM was 85.7%. These findings suggest that CoQ10 exhibits an effective antiarrhythmic action not merely on organic heart disease but also on VPBs supervening on DM.

Topics: Adult; Aged; Arrhythmias, Cardiac; Child, Preschool; Coenzymes; Diabetes Complications; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Monitoring, Physiologic; Ubiquinone

In this study, we investigated the mechanism of the arrhythmogenic action of chlorpromazine (CPZ). Thirty-two anesthetized mongrel dogs were used. In each, the chest was opened and a stimulating electrode was attached to the apex of the left ventricle and the ventricular multiple response threshold (VMRT) was measured. The carotid artery was cannulated to measure aortic pressure. The dogs were divided into four groups, and the time course of VMRT, blood pressure, and heart rate were determined. All groups were placed under observation for 30 min after CPZ infusion. In the control group, only saline (2ml/kg) was infused; CPZ group: CPZ (Img/kg) was infused 10 min after saline (2ml/kg) infusion; CoQ10 group: Coenzyme Q10 (CoQ10) (5mg/kg) was infused 10 min before CPZ (Img/kg) infusion; FAD group: Flavin-adenine-dinucleotide (FAD) (2mg/kg) was infused 10 min before CPZ (Img/kg) infusion. In each group, myocardial mitochondria were prepared 30 min after CPZ infusion. The mitochondrial functions, respiratory control index, AdP/O, State III rate of oxygen consumption, and activities of two segments of the electron-transport chain (NADH leads to CoQ leads to cyt.c and cyt.c leads to cyt.a,a3 leads to O2) were measured separately. Ca++--binding activity of the mitochondria was also determined. CPZ administration decreased VMRT and blood pressure, and caused mitochondrial dysfunction which derived from a disturbance in the first segment of the electron transport chain. Decreased Ca++--binding activity was observed when mitochondrial function was disturbed. CoQ10 prevented significantly the decrease in VMRT and the disturbance of mitochondrial function induced by CPZ, but did not prevent the hypotensive effect of CPZ. FAD prevented not only the decrease in VMRT and the disturbance of mitochondrial function, but also the hypotensive effect of CPZ. These results suggest that the decrease in VMRT is closely related to mitochondrial dysfunction induced by CPZ. Moreover, it is suggested that the arrhythmogenic effect of CPZ is derived from the decreased mitochondrial Ca++--binding activity.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Cardiac Complexes, Premature; Chlorpromazine; Coenzymes; Dogs; Electric Stimulation; Female; Flavin-Adenine Dinucleotide; Heart Ventricles; Hemodynamics; Humans; Male; Mitochondria, Heart; Ubiquinone