ubiquinone and Coronary-Disease

This review examines recent randomized clinical trials evaluating the role of coenzyme Q10 (CoQ10) in the management of coronary heart disease.. CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle. Although previous studies of CoQ10 for SAMS have produced mixed results, CoQ10 appears to be safe. Because CoQ10 is a cofactor in the generation of adenosine triphosphate, supplementation has also recently been studied in patients with heart failure, which is inherently an energy deprived state. The Q-SYMBIO trial found that CoQ10 supplementation in patients with heart failure not only improved functional capacity, but also significantly reduced cardiovascular events and mortality. Despite these positive findings, a larger prospective trial is warranted to support routine use of CoQ10. Less impressive are the effects of CoQ10 on specific cardiovascular risk factors such as blood pressure, dyslipidemia, and glycemic control. Current evidence does not support routine use of CoQ10 in patients with coronary heart disease. Additional studies are warranted to fully determine the benefit of CoQ10 in patients with heart failure before including it in guideline-directed medical therapy.

Topics: Antioxidants; Blood Glucose; Cardiovascular Diseases; Chronic Disease; Coronary Disease; Diabetes Mellitus; Dietary Supplements; Dyslipidemias; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Muscular Diseases; Randomized Controlled Trials as Topic; Risk Factors; Ubiquinone

The published evidence on strategies for avoiding the discontinuation of statin therapy due to muscular adverse effects is reviewed.. Statin medications are a cornerstone of the prevention and treatment of coronary heart disease, but about 20% of treated patients develop myalgia or other muscle-related adverse effects that can lead to the discontinuation of statin use. As there are no consensus guidelines or firm practice recommendations on continuing or reinitiating statin therapy in patients who experience statin-related muscular adverse effects, a literature search was conducted to evaluate a variety of strategies that have been studied. The search results indicated that the most widely used strategies are (1) alternative statin dosing, (2) co-enzyme Q10 supplementation, (3) vitamin D supplementation, (4) conversion to red yeast rice (RYR) therapy, and (5) conversion to a different statin. While positive results in some patients have been reported with all of the strategies reviewed, the available evidence is insufficient to support the routine use of any of the strategies in clinical practice. In particular, the use of RYR, which contains a naturally occurring statin, is not recommended due to limited and inconsistent study results and uncertainty about the contents of commercially available RYR products.. In patients intolerant to statin therapy due to myalgia or other muscular adverse effects, strategies such as alternative statin dosing schedules, coenzyme Q10 or vitamin D supplementation, and conversion to RYR or an alternative statin may allow some patients to continue to receive the benefits of lipid-lowering therapy.

Topics: Coronary Disease; Drug Administration Schedule; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Micronutrients; Muscular Diseases; Practice Guidelines as Topic; Ubiquinone; Vitamin D; Vitamins

There are a number of theoretical reasons as to why 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) should be prescribed to patients with chronic heart failure (CHF). These agents are proven to prevent coronary heart disease, the major etiological factor in the development of CHF. Potential additional effects of these agents include inhibition of proinflammatory cytokine activity and other potential beneficial effects on cardiac remodeling. However, there are also possible adverse effects of this strategy, supported by the overriding observation that low plasma lipid levels portend a poorer prognosis in patients with established CHF. Potential mechanisms by which statins may directly confer adverse effects include a reduction in levels of the antioxidant ubiquinone and an increase in blood endotoxin levels, both of which may contribute to CHF disease progression. Given these uncertainties, an answer to the question of whether or not therapy for CHF should include statins requires a definitive clinical trial. The importance of such a trial is further highlighted by the already commonplace usage of statins amongst patients with CHF.

Topics: Antioxidants; Coronary Disease; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Ubiquinone

This article provides a comprehensive review of 30 years of research on the use of coenzyme Q10 in prevention and treatment of cardiovascular disease. This endogenous antioxidant has potential for use in prevention and treatment of cardiovascular disease, particularly hypertension, hyperlipidemia, coronary artery disease, and heart failure. It appears that levels of coenzyme Q10 are decreased during therapy with HMG-CoA reductase inhibitors, gemfibrozil, Adriamycin, and certain beta blockers. Further clinical trials are warranted, but because of its low toxicity it may be appropriate to recommend coenzyme Q10 to select patients as an adjunct to conventional treatment.

Topics: Animals; Cardiomyopathies; Cardiovascular Diseases; Complementary Therapies; Coronary Disease; Heart Failure; Humans; Hypertension; Myocardial Infarction; Ubiquinone

There is evidence that coronary artery disease (CAD), hypertension, diabetes mellitus (DM) and hyperlipidemia develop due to interaction of genetic and environmental factors during transition from poverty to affluence. Rapid transition in diet and lifestyle factors may influence heritability of the variant phenotypes that are dependent on the nutrient environment for their expression. We are beginning to recognize the interaction of specific nutrients with the genetic code possessed by all nucleated cells. In the next millennium, the physician may be able to make nutrient intake recommendations not on physical characteristics but on the basis of the individual's phenotypic expression for health while suppressing his phenotypic expression for disease. We have demonstrated an increased susceptibility to CAD, diabetes, central obesity, hyperinsulinemia and lipoprotein(a) excess in Indians in younger age groups indicating a genetic predisposition to these problems due to interaction of gene and environment. Lipoprotein(a) is a genetic risk factor for CAD, diabetes and stroke and it is higher in South Indians than North Indians. Antioxidant vitamins, coenzyme Q10 and n-3 fatty acids may have a beneficial influence whereas linoleic acid, saturated fat and sugars may have adverse effects on phenotypic expression. There is significant evidence that genes are involved in determining enzymes, receptors, cofactors, structural components involved in regulation of blood pressure, the metabolism of lipids, lipoproteins and inflammatory and coagulation factors that are involved in determining an individual's risk. Majority of these genes are polymorphic. While some genes respond to nutritional modulation, others may not indicate any response.

Topics: Antioxidants; Coenzymes; Coronary Disease; Diet; Environment; Female; Humans; Lipoprotein(a); Male; Middle Aged; Phenotype; Polymorphism, Genetic; Risk Factors; Ubiquinone

Topics: Anticarcinogenic Agents; Antioxidants; Coronary Disease; Diet; Flavonoids; Humans; Neoplasms; Ubiquinone; Vitamins

Topics: Acetanilides; Carnitine; Clinical Trials as Topic; Coenzymes; Coronary Disease; Enzyme Inhibitors; Humans; Myocardial Ischemia; Piperazines; Ranolazine; Superoxide Dismutase; Trimetazidine; Ubiquinone; Vasodilator Agents

Topics: Antioxidants; Carotenoids; Coronary Disease; Humans; Lipid Peroxidation; Lipid Peroxides; Metabolic Diseases; Nutritional Requirements; Ubiquinone; Vitamin E

Topics: Animals; Antioxidants; Coronary Disease; Humans; Ubiquinone

A biochemical rationale for using CoQ in treating certain cardiovascular diseases has been established. CoQ subserves an endogenous function as an essential cofactor in several metabolic pathways, particularly oxidative respiration. As an exogenous source in supraphysiologic doses, CoQ may have pharmacologic effects that are beneficial to tissues rendered ischemic and then reperfused. Its mechanism of action appears to be that of a free radical scavenger and/or direct membrane stabilizer. Initial clinical studies performed abroad and in the United States indicate that CoQ may be effective in treating certain patients with ischemic heart disease, congestive heart failure, toxin-induced cardiotoxicity, and possibly hypertension. The most intriguing property of CoQ is its potential to protect and preserve ischemic myocardium during surgery. Currently, CoQ is still considered an experimental agent and only further studies will determine whether it will be useful therapy for human cardiovascular disease states.

Topics: Cardiovascular Diseases; Coenzymes; Coronary Disease; Humans; Ubiquinone

Contrast-induced nephropathy (CIN) is one of the common hospital-acquired acute renal failures. The purpose of this study was to investigate whether Coenzyme Q10 (CoQ10) and trimetazidine (TMZ) can prevent the occurrence of CIN after elective cardiac catheterization in patients with coronary artery disease complicated with renal dysfunction.. Consecutive coronary artery disease patients with renal insufficiency scheduled for coronary angiography were enrolled in randomized, paralleled, double-blind, controlled trial. The development of CIN was occurrence at the 48 or 72 h after the procedure. The changes of serum creatinine (SCr), eGFR, and Cys-C within 72 h after the procedure were measured and compared. In vivo contrast medium (CM)-induced acute kidney injury (AKI) animal model was established, and CoQ10 plus TMZ was orally administrated to evaluate its renal protective effect.. 150 patients with renal insufficiency were enrolled finally. CIN occurred in 21 (14.00%) of the 150 patients. 72 h after the procedure, the incidence of CIN was significantly lower in CoQ10 plus TMZ group compared with control group (6.67 vs. 21.3%, p = 0.01). No cardiac death occurred in this study. No side effects were observed after administration of CoQ10 and TMZ. In vivo test demonstrated that CoQ10 and TMZ could significantly reduce the concentration of blood urea nitrogen (BUN) and SCR induced by CM i.v. injection, as well as tubular pathological injuries. Meanwhile, CoQ10 and TMZ could significantly reduce the oxidation stress in kidneys from CM-AKI animals.. CoQ10 plus TMZ could decrease the incidence of CIN in patients with renal insufficiency undergoing elective cardiac catheterization, and their effect may be due to its strong anti-oxidation effect.

Topics: Acute Kidney Injury; Aged; Animals; Antioxidants; Cardiac Catheterization; Contrast Media; Coronary Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Trimetazidine; Ubiquinone

The subjects of the study were 43 patients with II- III functional class coronary heart disease (CHD) and dyslipidemia, who received conventional cardial therapy. The patients were divided into two groups: group I (26 subjects) received vasilip, a simvastatin generic, in a dose of 20 mg a day; group 11 (17 subjects) received vasilip in a dose of 20 mg a day plus cudesan in a dose of 1 ml a day, which contained 30 mg of ubiquinone Q 10 and 4.5 mg of alpha-tocopherol. Effects of the therapies on blood lipids, their peroxides, and the antioxidative status of blood were studied. After one month, vasilip was effective in achieving the target level of low-density lipoprotein cholesterol in 62% of group I patients and 65% of group II patients; at the same time, its use led to a significant increase in the level of primary and secondary lipid peroxidation (LP) products (25% and 29%, respectively), and lowering of the antioxidative status of blood, which consisted in a decrease in ceruloplasmin (CP) serum level and CP: transferrin (CP:TF) ratio by 6% in group I patients. The use of cudesan in combination with vasilip led to a significant decrease in the level of primary and secondary LP products (30% and 29%, respectively), and an increase in the level of serum CP by 25.7%, and CP: TF ratio by 12.5%.

Topics: Ceruloplasmin; Coenzymes; Coronary Disease; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hypolipidemic Agents; Lipid Peroxidation; Male; Middle Aged; Simvastatin; Transferrin; Ubiquinone

Previous clinical trials suggest that coenzyme Q(10) might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q(10) therapy on coenzyme Q(10) levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q(10) on mitochondrial function; to test the effect of coenzyme Q(10) in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q(10) therapy improves recovery of the heart after cardiac surgery.. Patients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q(10) (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed.. Patients receiving coenzyme Q(10) (n = 62) had increased coenzyme Q(10) levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q(10) than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q(10) exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% +/- 4.3% vs 64.0% +/- 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I.. Preoperative oral coenzyme Q(10) therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q(10) levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress.

Topics: Administration, Oral; Aged; Analysis of Variance; Biomarkers; Coenzymes; Coronary Artery Bypass; Coronary Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Elective Surgical Procedures; Female; Heart Function Tests; Hemodynamics; Humans; In Vitro Techniques; Length of Stay; Male; Middle Aged; Mitochondria, Heart; Myocardial Contraction; Preoperative Care; Probability; Reference Values; Risk Factors; Sensitivity and Specificity; Treatment Outcome; Troponin I; Ubiquinone

Coenzyme Q10 (CoQ10) is an antioxidant and plays an important role in the synthesis of adenosine triphosphate. Studies suggest that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce CoQ10 levels; however, no studies have directly compared HMG-CoA reductase inhibitors in a randomized crossover fashion.. Twelve healthy volunteers received either 20 mg pravastatin (P) or 10 mg atorvastatin (A) for 4 weeks in a randomized crossover fashion. There was a 4- to 8-week washout period between the 2 phases. CoQ10 levels and a lipid profile were obtained.. There was no difference in CoQ10 levels from baseline to post-drug therapy for either P or A (0.61 +/- 0.14 vs 0.62 +/- 0.2 microg/mL and 0.65 +/- 0.22 vs 0.6 +/- 0.12 microg/mL, respectively; P >.05). There was a significant difference in low-density lipoprotein (LDL) levels from baseline to post-drug therapy for both P and A (97 +/- 21 vs 66 +/- 19 mg/dL and 102 +/- 21 vs 52 +/- 14 mg/dL, respectively; P <.01). There was no significant correlation between LDL and CoQ10.. P and A did not decrease CoQ10 despite a significant decrease in LDL levels. These findings suggest that HMG-CoA reductase inhibitors do not significantly decrease the synthesis of circulating CoQ10 in healthy subjects. Routine supplementation of CoQ10 may not be necessary when HMG-CoA reductase inhibitor therapy is administered.

Topics: Adult; Atorvastatin; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chromatography, High Pressure Liquid; Coenzymes; Coronary Disease; Cross-Over Studies; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Pravastatin; Pyrroles; Reference Values; Triglycerides; Ubiquinone

To examine the effect of coenzyme Q10 supplementation on serum lipoprotein(a) in patients with acute coronary disease.. Randomized double blind placebo controlled trial.. Subjects with clinical diagnosis of acute myocardial infarction, unstable angina, angina pectoris (based on WHO criteria) with moderately raised lipoprotein(a) were randomized to either coenzyme Q10 as Q-Gel (60 mg twice daily) (coenzyme Q10 group, n=25) or placebo (placebo group, n=22) for a period of 28 days.. Serum lipoprotein(a) showed significant reduction in the coenzyme Q10 group compared with the placebo group (31.0% vs 8.2% P<0.001) with a net reduction of 22.6% attributed to coenzyme Q10. HDL cholesterol showed a significant increase in the intervention group without affecting total cholesterol, LDL cholesterol, and blood glucose showed a significant reduction in the coenzyme Q10 group. Coenzyme Q10 supplementation was also associated with significant reductions in thiobarbituric acid reactive substances, malon/dialdehyde and diene conjugates, indicating an overall decrease in oxidative stress.. Supplementation with hydrosoluble coenzyme Q10 (Q-Gel) decreases lipoprotein(a) concentration in patients with acute coronary disease.

Topics: Analysis of Variance; Antioxidants; Blood Glucose; Cholesterol; Coenzymes; Coronary Disease; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lipoprotein(a); Male; Oxidative Stress; Placebos; Ubiquinone

In a randomised, double-blind trial among patients receiving antihypertensive medication, the effects of the oral treatment with coenzyme Q10 (60 mg twice daily) were compared for 8 weeks in 30 (coenzyme Q10: group A) and 29 (B vitamin complex: group B) patients known to have essential hypertension and presenting with coronary artery disease (CAD). After 8 weeks of follow-up, the following indices were reduced in the coenzyme Q10 group: systolic and diastolic blood pressure, fasting and 2-h plasma insulin, glucose, triglycerides, lipid peroxides, malondialdehyde and diene conjugates. The following indices were increased: HDL-cholesterol, vitamins A, C, E and beta-carotene (all changes P<0.05). The only changes in the group taking the B vitamin complex were increases in vitamin C and beta-carotene (P<0.05). These findings indicate that treatment with coenzyme Q10 decreases blood pressure possibly by decreasing oxidative stress and insulin response in patients with known hypertension receiving conventional antihypertensive drugs.

Topics: Administration, Oral; Antioxidants; Blood Glucose; Blood Pressure; Coenzymes; Coronary Disease; Cytoprotection; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypertension; Insulin; Insulin Resistance; Lipid Peroxides; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Surveys and Questionnaires; Treatment Outcome; Triglycerides; Ubiquinone

Low blood levels of antioxidants are associated with an increased risk of developing coronary artery disease. Lipophilic antioxidants are transported in lipoproteins, and hypolipidaemic therapy may therefore alter their blood concentrations.. The present randomized, placebo-controlled cross-over study of 21 men with combined hyperlipidaemia examines whether 10-12 weeks of gemfibrozil treatment affects the serum concentrations of the antioxidants ubiquinone-10 or alpha- or gamma-tocopherol.. Gemfibrozil treatment lowered plasma triglycerides and both total and very low-density lipoprotein (VLDL)-cholesterol (P < 0.001 for all by ANOVA), whereas high-density lipoprotein (HDL)-cholesterol increased (P < 0.001). The median serum levels of ubiquinone-10 decreased from 1.30 mumol L-1 (interquartile range 0.87-1.71 mumol L-1) with placebo to 0.76 mumol L-1 (0.66-0.95) with gemfibrozil treatment (P < 0.001). Corresponding levels for alpha- and gamma-tocopherol were: 68.5 mumol L-1 (51.1-84.7) vs. 40.8 mumol L-1 (30.3-55.0) and 8.6 mumol L-1 (5.2-16.7) vs. 4.3 mumol L-1 (3.5-7.0) respectively (P < 0.001 for both). The decrease in serum antioxidants was also evident when standardized for total cholesterol (P < 0.05) or LDL-cholesterol (P < 0.001). Normolipaemic control subjects had significantly lower antioxidant levels than placebo-treated patients: ubiquinone 0.63 mumol L-1 (0.41-1.05), alpha-tocopherol 34.3 mumol L-1 (27.3-45.6) and gamma-tocopherol 3.2 mumol L-1 (2.5-4.2) (P < 0.001 for all). The association of antioxidants with lipoprotein lipids was further established by positive correlations between the levels of antioxidants and those of total cholesterol (r = 0.64, P < 0.001) or total triglycerides (r = 0.71, P < 0.001).. Gemfibrozil treatment of men with combined hyperlipidaemia reduces serum antioxidant levels to the levels seen in healthy normolipidaemic men. The mechanisms and the relevance of this finding remain unclear and need to be addressed in further studies.

Topics: Adult; Aged; Antioxidants; Apolipoproteins; Case-Control Studies; Coronary Disease; Cross-Over Studies; Gemfibrozil; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins; Male; Middle Aged; Ubiquinone; Vitamin E

A randomized, double-masked, placebo-controlled cross-over trial was carried out to evaluate whether ubiquinone supplementation (180 mg daily) corrects impaired defence against initiation of oxidation of low density lipoprotein (LDL) related to effective (60 mg daily) lovastatin treatment. Nineteen men with coronary heart disease and hypercholesterolemia received lovastatin with or without ubiquinone during 6-week periods after wash-out. The depletion times for LDL ubiquinol and reduced alpha-tocopherol were determined during oxidation induced by 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation phase of conjugated diene formation. Compared to mere lovastatin therapy, ubiquinone supplementation lead to a 4.4-fold concentration of LDL ubiquinol (P < 0.0001). In spite of the 49% lengthening in depletion time (P < 0.0001) of LDL ubiquinol, the lag time in copper-mediated oxidation increased only by 5% (P = 0.02). Ubiquinone loading had no statistically significant effect on LDL alpha-tocopherol redox kinetics during high radical flux ex vivo. The faster depletion of LDL ubiquinol and shortened lag time in conjugated diene formation during high-dose lovastatin therapy may, at least partially, be restored with ubiquinone supplementation. However, the observed improvement in LDL antioxidative capacity was scarce, and the clinical relevance of ubiquinone supplementation during statin therapy remains open.

Topics: Analysis of Variance; Anticholesteremic Agents; Antioxidants; Apolipoprotein A-I; Apolipoproteins B; Cholesterol; Copper Sulfate; Coronary Disease; Cross-Over Studies; Diet; Double-Blind Method; Humans; Hypercholesterolemia; Lipoproteins, HDL; Lipoproteins, LDL; Lovastatin; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Triglycerides; Ubiquinone

A double-blinded, placebo-controlled cross-over trial was carried out with 27 hypercholesterolemic men with coronary heart disease. During the 6-week treatment period lovastatin (60 mg/day) decreased fasting serum LDL cholesterol by 45%, LDL phosphorus by 38% and apoB by 33%. Ubiquinol content diminished by 13% as measured per LDL phosphorus. When LDL was oxidized ex vivo with AMVN both LDL ubiquinol and alpha-tocopherol were exhausted faster after lovastatin treatment compared to placebo, by 24% (P < 0.005) and 36% (P < 0.0001), respectively. Lag time in copper-induced oxidation of LDL decreased by 7% (P < 0.01). This suggests diminished antioxidant-dependent resistance of LDL to the early phase of oxidative stress.

Topics: Adult; Aged; Anticholesteremic Agents; Antioxidants; Apolipoproteins A; Apolipoproteins B; Cholesterol; Cholesterol, LDL; Copper; Coronary Disease; Cross-Over Studies; Double-Blind Method; Humans; Hypercholesterolemia; Lovastatin; Male; Middle Aged; Oxidation-Reduction; Triglycerides; Ubiquinone; Vitamin E

Coenzyme Q10 (ubiquinone) the essential mitochondrial redox-component and endogenous antioxidant, packaged into the LDL + VLDL fractions of cholesterol, has been suggested as an important anti-risk factor for the development of atherosclerosis as explained by the oxidative theory. Forty-five hypercholesterolemic patients were randomized in a double-blind trial in order to be treated with increasing dosages of either lovastatin (20-80 mg/day) or pravastatin (10-40 mg/day) over a period of 18 weeks. Serum levels of coenzyme Q10 were measured parallel to the levels of cholesterol at baseline on placebo and diet and during active treatment. A dose-related significant decline of the total serum level of coenzyme Q10 was found in the pravastatin group from 1.27 +/- 0.34 at baseline to 1.02 +/- 0.31 mmol/l at the end of the study period (mean +/- S.D.), P < 0.01. After lovastatin therapy the decrease was significant as well and more pronounced, from 1.18 +/- 0.36 to 0.84 +/- 0.17 mmol/l, P < 0.001. Although HMG-CoA reductase inhibitors are safe and effective within a limited time horizon, continued vigilance of a possible adverse consequence from coenzyme Q10 lowering seems important during long-term therapy.

Topics: Adult; Aged; Antioxidants; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Coenzymes; Coronary Disease; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lovastatin; Male; Middle Aged; Oxidation-Reduction; Pravastatin; Risk Factors; Ubiquinone

We compared the effect of oral administration of taurine (3 g/day) and coenzyme Q10 (CoQ10) (30 mg/day) in 17 patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy, whose ejection fraction assessed by echocardiography was less than 50%. The changes in echocardiographic parameters produced by 6 weeks of treatment were evaluated in a double-blind fashion. In the taurine-treated group significant treatment effect was observed on systolic left ventricular function after 6 weeks. Such an effect was not observed in the CoQ10-treated group.

Topics: Administration, Oral; Cardiomyopathy, Dilated; Chronic Disease; Coenzymes; Coronary Disease; Double-Blind Method; Drug Evaluation; Echocardiography; Female; Heart Failure; Humans; Male; Stroke Volume; Taurine; Ubiquinone; Ventricular Function, Left

Coenzyme Q10 (CoQ10) is indispensable in mitochondrial bioenergetics and for human life to exist. 88/115 patients completed a trial of therapy with CoQ10 for cardiomyopathy. Patients were selected on the basis of clinical criteria, X-rays, electrocardiograms, echocardiography, and coronary angiography. Responses were monitored by ejection fractions, cardiac output, and improvements in functional classifications (NYHA). Of the 88 patients 75%-85% showed statistically significant increases in two monitored cardiac parameters. Patients with the lowest ejection fractions (approx. 10%-30%) showed the highest increases (115 delta %-210 delta %) and those with higher ejection fractions (50%-80%) showed increases of approx. 10 delta %-25 delta % on therapy. By functional classification, 17/21 in class IV, 52/62 in class III, and 4/5 in class II improved to lower classes. Clinical responses appeared over variable times, and are presumably based on mechanisms of DNA-RNA-protein synthesis of apoenzymes which restore levels of CoQ10 enzymes in a deficiency state. 10/21 (48%) of patients in class IV, 26/62 (42%) in class III, and 2/5 (40%) in class II had exceptionally low control blood levels of CoQ10. Clinical responses on therapy with CoQ10 appear maximal with blood levels of approx. 2.5 micrograms CoQ10/ml and higher during therapy.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Output; Cardiomyopathies; Cardiomyopathy, Dilated; Clinical Trials as Topic; Coenzymes; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Stroke Volume; Ubiquinone

Topics: Coenzymes; Coronary Disease; Drug Evaluation; Humans; Ubiquinone

Reactive oxygen species seem to play an important role in vascular homeostasis. In conditions of high oxidative stress, such as chronic heart failure and multiple coronary risk factors, the rate of inactivation of nitric oxide to peroxynitrite by superoxide anions may be reduced by CoQ10, which can also protect against nitrosative damage. CoQ10 may also influence vascular function indirectly via inhibition of oxidative damage to LDL. Patients with lower levels of extracellular superoxide dismutase (ecSOD) demonstrate greater improvements than patients with normal ec-SOD levels, suggesting that the higher the oxidative stress the greater the improvement in the endothelium-dependent relaxation after the administration of a compound with antioxidant properties like CoQ10. Future studies are needed to inquire whether these effects may translate into benefits in clinical practice.

Topics: Coronary Disease; Endothelium, Vascular; Humans; Myocardial Ischemia; Oxidative Stress; Superoxide Dismutase; Ubiquinone

There is a growing body of evidence to suggest that low-density lipoprotein (LDL) cholesterol, inflammation and oxidative stress are pivotal in the development of cardiovascular disease, but their interconnections are not well known. The objective of this study was to determine whether immunological activation, reflected by the plasma levels of soluble CD40 (sCD40), interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-6 are associated with the antioxidant potential of LDL particles or with common lipid, immunological or thrombotic markers in 51 young healthy men.. We determined the coenzyme Q level from an oxidized LDL fraction, obtaining the concentration for ubiquinone, which indicates total coenzyme Q levels.. The plasma level of sCD40 was negatively correlated with LDL ubiquinone (r=-0.45, p=0.001) and E vitamin (r=-0.37, p=0.008) and positively correlated with plasma concentration of plasminogen activator inhibitor-1 (PAI-1, r=0.52, p=0.002) and caspase-1 (r=0.40, p=0.004). No correlation was detected between sCD40 and plasma lipid or C-reactive protein concentrations. As sCD40 was strongly correlated with the content of LDL ubiquinone and vitamin E, their values were compared according to groups formed by sCD40 tertiles. Analysis of variance showed that there were significant differences in LDL ubiquinone (p<0.0001) and vitamin E (p=0.004) concentrations between sCD40 tertiles.. The data indicate that increased activation of the CD40 system is related to low levels of LDL ubiquinone and vitamin E. This suggests that chronic or increased immunological activation may consume the antioxidant potential of LDL particles.

Topics: Adult; Biomarkers; CD40 Antigens; Coronary Disease; Humans; Inflammation; Lipoproteins, LDL; Male; Reference Values; Ubiquinone; Vitamin E

The goal of the present research was to assess the efficacy of combination treatment with antioxidant coenzyme Q10 and simvastatin as well as coenzyme Q10 without statin therapy in order to prevent coronary atherosclerosis. 42 outpatients were divided into 2 groups: receiving coenzyme Q10 (Hasco-Lek, Poland) 60mg daily and its combination with simvastatin (zocor, vasilip) 10mg daily for an 8-week period. The treatment with coenzyme Q10 demonstrated its potential independent role in positive modification of oxidative stress, antiatherogenic fraction of lipid profile, atherogenic ratio, platelet aggregability. Taking into consideration the obtained results the study supports the use of coenzyme Q10 in combination with statins. Suggested attractive approach may result in complete correction of dislipidemia, reverse of endothelial dysfunction, reduce degree of oxidative stress and platelet aggregability. Consequently such a combination may be beneficial in preventing of further development of atherosclerosis in native coronary arteries as well as in bypass grafts in all coronary heart disease patients with or without myocardial revascularization.

Topics: Antioxidants; Coenzymes; Coronary Artery Bypass; Coronary Artery Disease; Coronary Disease; Data Interpretation, Statistical; Drug Therapy, Combination; Female; Humans; Hypolipidemic Agents; Lipids; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Platelet Aggregation; Simvastatin; Time Factors; Treatment Outcome; Triglycerides; Ubiquinone

Indians or South Asians have been found to be particularly susceptible to coronary heart disease (CHD) in many countries. A novel risk factor for CHD may be coenzyme Q10 (CoQ10). In this study, plasma CoQ10 (including ubiquinol-10, CoQ10H2, and total CoQ10), various lipid parameters, and antioxidant levels were determined in a random sample of Indians and Chinese from the general population of Singapore. The reduced form of coenzyme Q10, CoQ10H2, and total Q10 concentrations in plasma were significantly lower in Indian males than Chinese males. Although no significant differences were found in plasma concentrations of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL) between the two ethnic groups, the ratios of ubiquinol and total CoQ10 to triglycerides, total cholesterol, and LDL were significantly lower in Indian males than Chinese males. There were no significant ethnic differences in other antioxidant levels, including trans-retinol, alpha-tocopherol, and ascorbic acid. The consistently lower values of coenzyme Q10, especially its reduced form, in Indian males may contribute to the higher susceptibility of this ethnic group to coronary heart disease.

Topics: Adult; Aged; alpha-Tocopherol; Ascorbic Acid; Cholesterol; Cholesterol, LDL; Coenzymes; Coronary Disease; Disease Susceptibility; Humans; Male; Middle Aged; Oxidation-Reduction; Risk Factors; Singapore; Tretinoin; Triglycerides; Ubiquinone

Ubiquinol-10 and ubiquinone-10 were measured in plasma of patients with several pathologies known to be associated with increased oxidative stress. Plasma ubiquinol-10, expressed as a percentage of total ubiquinol-10 + ubiquinone-10, was found to be significantly lower in hyperlipidaemic patients and in patients with liver diseases than in age-matched control subjects. In contrast, no decrease in ubiquinol-10 was detected in plasma of patients with coronary heart disease and Alzheimer's disease. Except for ubiquinol-10, no other lipophilic antioxidant was found to be decreased in patients with liver diseases. These data suggest that the level of ubiquinol-10 in human plasma may serve as a marker for liver dysfunction, reflecting its diminished reduction by the liver rather than increased consumption by oxidants.

Topics: Adult; Aged; Alzheimer Disease; Biomarkers; Cholesterol; Coronary Disease; Humans; Hyperlipidemias; Liver Diseases; Middle Aged; Models, Biological; Oxidative Stress; Reference Values; Reproducibility of Results; Triglycerides; Ubiquinone

The purpose of the study was to investigate changes in serum ubiquinol/ubiquinone ratio with copper ion induced oxidative stress, and to assess the ubiquinol/ubiquinone ratio as marker of in vivo oxidative stress in patients with coronary artery disease (CAD). Plasma ubiquinol, ubiquinone, vitamin E (alpha-tocopherol) and total cholesterol (TC) concentrations were measured in 40 patients with angiographically confirmed coronary artery disease and 100 apparently healthy controls. The mean (SD) ubiquinol/ubiquinone ratio of 26.5 (7.5) of the CAD patients was significantly lower than the mean ratio of 30.2 (8.8) of the controls (p = 0.02). Our results indicate that the ubiquinol/ubiquinone ratio is a sensitive marker of oxidative stress and that an altered ubiquinol/ubiquinone ratio is the first sign of lipoprotein exposure to oxidative stress. The altered ratio in CAD patients cannot be explained by differences in plasma vitamin E levels. The vitamin E concentrations were in fact significantly higher in CAD patients, and did not appear to protect the ubiquinol from increased oxidation due to free radical reactions. These results may indicate that circulating lipoproteins of CAD patients are more exposed to, or are more susceptible to, free radical reactions compared with apparently healthy controls.

Topics: Adult; Aged; Biomarkers; Copper; Coronary Disease; Enzyme Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Ubiquinone; Vitamin E

Ubiquinol-10, the reduced form of ubiquinone-10 (coenzyme Q10), is a potent lipophilic antioxidant present in nearly all human tissues. The exceptional oxidative lability of ubiquinol-10 implies that it may represent a sensitive index of oxidative stress. The present study was undertaken to assess the hypothesis that the level of ubiquinol-10 in human plasma can discriminate between healthy subjects and patients who are expected to be subjected to an increased oxidative stress in vivo. Using a newly developed method, we measured plasma ubiquinol-10 in 38 hyperlipidaemic patients with and without further complications, such as coronary heart disease, hypertension, or liver disease, and in 30 healthy subjects. The oxidizability of plasma samples obtained from hyperlipidaemic patients was found to be increased in comparison with control subjects, suggesting that the patients were subjected to a higher oxidative stress in vivo than the controls. Plasma ubiquinol-10, expressed as a percentage of total ubiquinol-10 + ubiquinone-10 or normalized to plasma lipids, was lower in the patients than in controls (P = 0.001 and 0.008, respectively). The proportion of ubiquinol-10 decreased in the order young controls > aged controls > hyperlipidaemic patients without complications > hyperlipidaemic patients with complications (P = 0.003). A negative correlation was found between the proportion of ubiquinol-10 and plasma triglycerides. The hyperlipidaemic patients with hypertension had a lower proportion of ubiquinol-10 than subjects without. When the study population was divided into smokers and non-smokers, plasma ubiquinol-10 was found to be reduced amongst smokers, independently of whether it was expressed as a percentage of total ubiquinol-10 + ubiquinone-10 (P = 0.006) or normalized to plasma lipids (P = 0.009). These data suggest that the level of ubiquinol-10 in human plasma may represent a sensitive index of oxidative stress in vivo especially indicative of early oxidative damage. Measuring plasma ubiquinol-10 can be proposed as a practical approach to assess oxidative stress in humans.

Topics: Adult; Alcohol Drinking; Amidines; Antidotes; Body Mass Index; Coronary Disease; Female; Humans; Hyperlipidemias; Hypertension; Lipid Peroxidation; Lipoxygenase; Liver Diseases; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Regression Analysis; Risk Factors; Smoking; Spectrophotometry; Triglycerides; Ubiquinone

Topics: Animals; Coenzymes; Coronary Disease; Creatine Kinase; Humans; Myocardial Reperfusion Injury; Myocardial Revascularization; Prognosis; Ubiquinone

Oxidative modifications of blood serum in humans with and without coronary artery disease were investigated. Four parameters were analyzed: the intensity of serum fluorescence, which is indicative of the content of lipofuscine-like lipid peroxidation products; the content of thiobarbituric acid-reactive substances; the lag-phase of serum oxidation by azo-compounds; and the content of lipophilic natural antioxidants--alpha-tocopherol, beta-carotene and ubiquinol-9(10). It was found that coronary artery disease resulted in a significant increase of serum fluorescence and the content of TBARS. The atherogenic disorders in humans with coronary artery disease drastically decreased the lag-phase of serum oxidation in the presence of 2,2'-azo-bis-(2-amidinopropane) dihydrochloride. The oxidative modifications of serum were in close correlation with the balance of natural lipophilic antioxidants in blood serum, i.e. alpha-tocopherol, ubiquinols and beta-carotene. The contents of all antioxidants tested in serum were significantly decreased in patients with coronary artery disease.

Topics: Aged; Amidines; Analysis of Variance; beta Carotene; Biomarkers; Coronary Disease; Female; Free Radicals; Humans; Lipid Peroxidation; Lipid Peroxides; Male; Middle Aged; Oxidation-Reduction; Thiobarbituric Acid Reactive Substances; Ubiquinone; Vitamin E

It has been postulated that oxidatively modified low-density lipoprotein (LDL) contributes to the genesis of atherosclerosis. Ubiquinone has been suggested to be an important physiological lipid-soluble antioxidant and is found in LDL fractions in the blood. We measured plasma level of ubiquinone using high-performance liquid chromatography and plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in 245 normal subjects (186 males, 59 females) and in 104 patients (55 males, 49 females) who had coronary artery disease not receiving pravastatin and 29 patients (12 males, 17 females) receiving pravastatin. In the normal subjects, the plasma ubiquinone levels did not vary with age. In the patient groups, the plasma total cholesterol and LDL levels were higher and the plasma ubiquinone level lower than in the normal subject group. The LDL/ubiquinone ratio was higher in the patient groups. We found that ubiquinone level, either alone or when expressed in relation to LDL levels, was significantly lower in the patient groups compared with the normal subject group. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor is thought to prevent atherosclerosis, however, it also inhibits ubiquinone production. The present study revealed that HMG CoA reductase inhibitor decreased plasma cholesterol level, and that it did not improve either the ubiquinone level or the LDL/ubiquinone ratio. From these results, the LDL/ubiquinone ratio is likely to be a risk factor for atherogenesis, and administration of ubiquinone to patients at risk might be needed.

Topics: Coronary Disease; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins; Male; Pravastatin; Ubiquinone

Topics: Cardiovascular Diseases; Coenzymes; Coronary Disease; Humans; Ubiquinone

Twenty-eight male patients with ischaemic heart disease (IHD) performed OBLA (onset of blood lactate accumulation) exercise stress tests and had muscle biopsies taken from their vastus lateralis muscle the day before coronary bypass grafting. All 28 patients showed the same exercise performance pattern as compared to healthy sedentary, age-matched, controls: a low exercise intensity eliciting a blood lactate concentration of 2.0 mmol x l-1 (WOBLA), WOBLA corresponded to a high fraction (% WOBLA) of WSL (symptom limited or 'maximal' capacity), and a low peak blood lactate concentration. The high % WOBLA and low peak blood lactate indicated a reduced glycogenolytic capacity ('anaerobic' performance). Muscle fibre composition disclosed a high mean value of fast twitch (FT), type II or 'white' muscle fibres, as compared to sedentary healthy controls. This indicated that this patient group constituted an extreme subgroup of the age-matched population. The distorted muscle fibre composition in IHD could reflect both heredity as well as adaptation to physical inactivity, degenerative cytosolic properties, etc. Muscle and blood contents of a mitochondrial electron translocator and nonspecific radical scavenger, ubiquinone or coenzyme Q10(CoQ10), were low, which coincided with an elevated frequency of the fibre subgroup FT(c). The presence of the FT(c) fibre type is assumed to reflect histological trauma.

Topics: Adult; Aged; Coenzymes; Coronary Disease; Exercise Test; Humans; Lactates; Male; Muscles; Thigh; Ubiquinone

Low-temperature electron paramagnetic resonance (EPR) spectroscopy and spin traps were used to measure paramagnetic species generation in rat hearts and isolated mitochondria. The hearts were freeze-clamped at 77 K during control perfusion by the Langendorff procedure, after 20-30 min of normothermic ischemia or 10-30 s of reperfusion with oxygenated perfusate. All EPR spectra measured at 4.5-50 K exhibited signals of both mitochondrial free radical centers and FeS proteins. The analysis of spectral parameters measured at 243 K showed that free radicals in heart tissue were semiquinones of coenzyme Q10 and flavins. The appearance of a typical "doublet" signal at g = 1.99 in low-temperature spectra indicated that a part of ubisemiquinones formed a complex with a high potential FeS protein of succinate dehydrogenase. Ischemia decreased the free radical species in myocardium approximately 50%; the initiation of reflow of perfusate resulted in quick increase of the EPR signal. Mitochondria isolated from hearts during control perfusion and after 20-30 min of ischemia were able to produce superoxide radicals in both the NADH-coenzyme Q10 reductase and the bc1 segments of the respiratory chain. The rate of oxyradical generation was significantly higher in mitochondria isolated from ischemic heart.

Topics: Animals; Coronary Disease; Electron Spin Resonance Spectroscopy; Flavoproteins; Free Radicals; In Vitro Techniques; Male; Myocardial Reperfusion; Myocardium; Nitrogen Oxides; Rats; Rats, Inbred Strains; Superoxides; Triacetoneamine-N-Oxyl; Ubiquinone

Ubiquinone 6.2, 12.5 or 2.5 mg.kg-1 respectively twice iv 24 h and 30 min before coronary artery ligation, ameliorated the ischemic arrhythmia in conscious rats, and there was a close positive correlation between the ubiquinone concentration in myocardium and plasma and its anti-arrhythmic effect. Ubiquinone iv 3.1, 6.2, and 12.5 mg.kg-1 increased, while 25 mg.kg-1 decreased 6-keto-PGF1 alpha, and 12.5 and 25 mg.kg-1 decreased TXB2, which was in accordance with inhibitory effects on the synthesis of 6-keto-PGF1 alpha and TXB2 in vitro. But the ratio of metabolites of PGI2/TXA2 in vivo was increased in all ubiquinone groups. These results indicated that ubiquinone possesses protective effects on ischemic arrhythmia of conscious rats and the beneficial effects on myocardial ubiquinone content and PGI2/TXA2 seem to contribute to its myocardial protective action.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arrhythmias, Cardiac; Coronary Disease; Dose-Response Relationship, Drug; In Vitro Techniques; Male; Microsomes; Myocardium; Rats; Rats, Inbred Strains; Swine; Thromboxane B2; Ubiquinone

Topics: Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Humans; Middle Aged; Risk Factors; Triglycerides; Ubiquinone

The mechanism responsible for heterogeneity in tissue pH was investigated in perfused rat hearts subjected to ischemia/reperfusion insult, by correlating the time course of pH changes to the severity of vascular impairment. In 25 perfused hearts, myocardial pH was monitored by 31 P-NMR spectra. During ischemia, pH, which was 7.1 at the beginning of ischemia, progressively decreased and reached a steady level of 5.9 (5.9-compartment) after 40 minutes. In addition, another define peak of pH 7.1 (7.1-compartment) became evident after 50 min of ischemia. The 7.1-compartment grew higher with ischemic time and was only observed after 180 min of ischemia. Although reperfusion after 20 min of ischemia recovered pH, ATP, and creatine phosphate, reperfusion after 50 min left two Pi peaks, the 5.9- and 7.1-compartments; the former gradually decreased with a concomitant increase of the latter. Reperfusion after 180 min of ischemia with various pH levels did not shift the Pi peak from pH 7.1, suggesting that the perfusate did not reach that compartment, the impaired flow region. High coronary resistance and a heterogeneous staining pattern concomitant with a late appearance of the 7.1 component further supported this hypothesis. Myocardial coenzyme Q10 radical, an indicator of the tissue redox state, was also low in those hearts which were reperfused after 50 min of ischemia. Thus, the splitting of the Pi peak, caused by reperfusion after prolonged ischemia, represents the existence of a no-reflow region.

Topics: Animals; Coenzymes; Coronary Disease; Coronary Vessels; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Myocardial Reperfusion Injury; Myocardium; Oxidation-Reduction; Phosphocreatine; Rats; Rats, Inbred Strains; Ubiquinone; Vascular Resistance

Lovastatin is clinically used to treat patients with hypercholesterolemia and successfully lowers cholesterol levels. The mechanism of action of lovastatin is inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme involved in the biosynthesis of cholesterol from acetyl-CoA. Inhibition of this enzyme could also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), but there have not been definitive data on whether lovastatin reduces levels of CoQ10 as it does cholesterol. The clinical use of lovastatin is to reduce a risk of cardiac disease, and if lovastatin were to reduce levels of CoQ10, this reduction would constitute a new risk of cardiac disease, since it is established that CoQ10 is indispensable for cardiac function. We have conducted three related protocols to determine whether lovastatin does indeed inhibit the biosynthesis of CoQ10. One protocol was done on rats, and is reported in the preceding paper [Willis, R. A., Folkers, K., Tucker, J. L., Ye, C.-Q., Xia, L.-J. & Tamagawa, H. (1990) Proc. Natl. Acad. Sci. USA 87, 8928-8930]. The other two protocols are reported here. One involved patients in a hospital, and the other involved a volunteer who permitted extraordinary monitoring of CoQ10 and cholesterol levels and cardiac function. All data from the three protocols revealed that lovastatin does indeed lower levels of CoQ10. The five hospitalized patients, 43-72 years old, revealed increased cardiac disease from lovastatin, which was life-threatening for patients having class IV cardiomyopathy before lovastatin or after taking lovastatin. Oral administration of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function. Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10.

Topics: Adolescent; Cardiac Output; Coronary Disease; Female; Humans; Hypercholesterolemia; Lovastatin; Male; Middle Aged; Myocardial Contraction; Stroke Volume; Ubiquinone

The effects of coenzyme Q10 (CoQ10) on blood viscosity were studied in twelve patients (mean age 49 +/- 16 years) with ischemic heart disease. Twenty mg of CoQ10 was orally administered three times daily for two months (total dose 60 mg per day). Blood viscosity was measured with a cone-plate type viscometer at the shear rates of 37.5, 75, 150, and 375 s-1. Yield shear stress was calculated from Casson's plot. Blood viscosity decreased at each shear rate after the administration of CoQ10. Yield shear stress decreased significantly by the treatment with CoQ10. Hematocrit and fibrinogen were also measured, but showed no significant change. These results suggest that CoQ10 decreases the blood viscosity, i.e., improves the rheological properties of blood in ischemic heart disease.

Topics: Administration, Oral; Adult; Blood Viscosity; Coenzymes; Coronary Disease; Female; Hematocrit; Humans; Male; Middle Aged; Ubiquinone

1. The biosynthesis of ubiquinone (UQ) in isolated rat heart under ischemic and hypoxic conditions was investigated. 2. Under ischemic perfusion, a greater amount of biosynthetic intermediates, 3-nonaprenyl and 3-decaprenyl-4-hydroxybenzoate (PPHBs) was accumulated and a smaller amount of UQ-9 and -10 was synthesized when compared with normal conditions. 3. The accumulation of PPHBs was observed without forming UQs during anaerobic perfusion. 4. Hydroxylation which is the following reaction of PPHBs for the biosynthesis of UQ in rat heart, was proceeded by the monooxygenase(s) depending upon the oxygen concentrations.

Topics: Animals; Chromatography, High Pressure Liquid; Coronary Disease; Hydroxylation; Hypoxia; Male; Mitochondria, Heart; Myocardium; Oxygen; Parabens; Pyridines; Rats; Rats, Inbred Strains; Rotenone; Terpenes; Ubiquinone

Topics: Acetylglucosaminidase; Animals; Coenzymes; Coronary Disease; Dogs; Female; Male; Malondialdehyde; Mitochondria, Heart; Myocardial Reperfusion Injury; Myocardium; Ubiquinone

Pharmacological protection of acute ischemic myocardial injury was studied using diltiazem, bunazosin, coenzyme-Q10 (Co-Q), and nicorandil, in dogs of which the left anterior descending coronary artery was ligated for 60 min. Drugs were given intravenously prior to and/or during coronary ligation. Co-Q, bunazosin and diltiazem suppressed degradation of sarcoplasmic reticulum (SR) expressed as inhibitions of reduction in Ca++-dependent ATPase activity and degradation of major ATPase protein. Fine structures of ischemic myocardial cells were simultaneously retained as well. On the contrary, the effects of nicorandil on ischemic myocardial injury were few. It is likely that protection of ischemic myocardial injury could be expected with drugs which react with ischemic myocardium directly and inhibit excess inflow of extracellular Ca++ in ischemic myocardium.

Topics: Adenosine Triphosphatases; Adrenergic alpha-Antagonists; Animals; Calcium; Calcium-Transporting ATPases; Coenzymes; Coronary Disease; Diltiazem; Dogs; Myocardium; Niacinamide; Nicorandil; Quinazolines; Sarcoplasmic Reticulum; Ubiquinone; Vasodilator Agents

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Coronary Disease; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Specimen Handling; Ubiquinone

Complex I (nicotinamide adenine dinucleotide-ubiquinone reductase) is a complex enzyme system located in the inner mitochondrial membrane. It has the ability to catalyze several different enzymatic reactions in electron transport, and is known to be one of the respiratory chain components most sensitive to ischaemia. Mitochondria and two complexes I (complex IA and complex IB) were isolated from normal and ischaemic myocardial tissue. Enzymatic activities, polypeptide composition, as well as other components such as non-haem iron, acid-labile sulphur and ubiquinone, were determined. The results indicated that complex IB reflected the enzymatic changes in the mitochondria during myocardial ischaemia, but complex IA did not. The lesion that resulted from ischaemia was localised as altered enzymatic activities due to a different polypeptide composition, as well as loss of ubiquinone and non-haem iron from complex IB.

Topics: Animals; Coronary Disease; Electron Transport; Female; Ferricyanides; Glutamates; Glutamic Acid; Kinetics; Male; Mitochondria, Heart; NAD; NAD(P)H Dehydrogenase (Quinone); NADP; Oxidative Phosphorylation; Oxygen Consumption; Peptides; Perissodactyla; Quinone Reductases; Ubiquinone; Vitamin K

Topics: Animals; Coenzymes; Coronary Disease; Electrocardiography; In Vitro Techniques; Male; Myocardial Contraction; Myocardial Reperfusion; Rabbits; Time Factors; Ubiquinone; Ventricular Fibrillation

The effect of pretreatment on the 3 hrs globally ischemic heart assessed from the myocardial enzymes, lysosomal enzymes and cyclic nucleotides in coronary sinus blood was studied in mongrel dogs. Combined administration of CoQ10, Aprotinin, Betamethasone and Nifedipine was done as pretreatment.. m-AST, NAG and beta-Glucuronidase were significantly lower in the pretreatment group. Significant positive correlations were obtained in order between beta-Glucuronidase and NAG (r = 0.6869), m-AST and beta-Glucuronidase (r = 0.6590), m-AST and NAG (r = 0.5381), m-AST and CK-MB (r = 0.49), respectively. Significant increase in cAMP/cGMP ratio was observed in the control group after reperfusion. Before aortic occlusion, significant negative correlations were obtained between cAMP and beta-Glucuronidase, NAG, m-AST, and after 5 min of reperfusion, significant negative correlations were obtained between cGMP and NAG, m-AST and significant positive correlations between cAMP/cGMP ratio and NAG, m-AST. These data suggested the effectiveness of pretreatment, the relation between lysosomal enzyme release and the ischemic myocardial injury, and the usefulness of m-AST to evaluate the degree of myocardial injury. Moreover, the increase of cAMP/cGMP ratio suggested the ischemic myocardial injury, and cGMP in the ischemic condition, and cAMP in the non-ischemic condition affected lysosomal enzyme release.

Topics: Animals; Aprotinin; Betamethasone; Coronary Disease; Creatine Kinase; Cyclic AMP; Cyclic GMP; Dogs; Heart Arrest, Induced; Isoenzymes; Lysosomes; Myocardium; Nifedipine; Perfusion; 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

Complex I (NADH-ubiquinone reductase) is a complex system located in the inner mitochondrial membrane and has the ability to catalyse several different enzymatic reactions concerned in electron transport. It is known to be one of the first components of the respiratory chain to be damaged by ischemia. Our results, using autolysis in the rat heart as experimental model, indicate that the NADH dehydrogenase system was impaired relatively early during ischemia while transhydrogenation and NADPH dehydrogenation appeared to be relatively resistant.

Topics: 2,6-Dichloroindophenol; Animals; Autolysis; Coronary Disease; Female; Ferrocyanides; Mitochondria, Heart; NAD(P)H Dehydrogenase (Quinone); NADH, NADPH Oxidoreductases; Oxygen; Oxygen Consumption; Phosphorylation; Quinone Reductases; Rats; Rats, Inbred Strains; Ubiquinone; Vitamin K

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

Topics: Aged; Angina Pectoris; Coenzymes; Coronary Disease; Female; Heart Diseases; Humans; Male; Middle Aged; Ubiquinone; Urologic Diseases

Topics: Aged; Coenzymes; Coronary Disease; Female; Heart Diseases; Humans; Male; Middle Aged; Ubiquinone

This study tests the hypothesis that the oxygen radical scavenger coenzyme Q10 can be given both intravenously and in the cardioplegic solution and can improve muscle salvage following surgical revascularization. Pilot studies were carried out in dogs undergoing 40 minutes of coronary artery ligation with reperfusion with normal blood, with the heart in the beating, working state. Intravenous infusions of coenzyme Q10 (10 mg/kg) 5 minutes before reperfusion resulted in improved recovery of creatine phosphate, adenosine triphosphate, total adenine nucleotide, and myocardial function reverse estimated by postextrasystolic potentiation, in comparison with the degree of recovery in untreated dogs. Experimental studies were done on 27 dogs undergoing 2 hours of left anterior descending coronary artery occlusion and subsequent reperfusion with and without total vented bypass. Thirteen dogs received intravenous coenzyme Q10 10 minutes before extracorporeal circulation, six received substrate-enriched blood cardioplegic solution with added coenzyme Q10, and six received normal blood reperfusate. Six others had cardioplegic reperfusion without coenzyme Q10. The systolic bulging that occurred during ischemia (ultrasonic crystals) persisted after reperfusion with normal blood (-25% systolic shortening, p less than 0.05), and 44% transmural triphenyltetrazolium chloride nonstaining occurred in the area at risk. Conversely, hearts receiving substrate-enriched blood cardioplegic solution recovered 37% contractility (p less than 0.05), with the least, and only, subendocardial triphenyltetrazolium chloride nonstaining (25% of area at risk) occurring with intravenous coenzyme Q10 before bypass and coenzyme Q10 supplementation of the cardioplegic solution. Intravenous coenzyme Q10, given just before reperfusion (possibly in transit to the operating room), enhances the role of substrate-enriched blood cardioplegic solution (especially when added to the cardioplegic solution) in salvaging ischemic myocardium and allowing immediate functional recovery.

Topics: Adenosine Triphosphate; Animals; Coenzymes; Coronary Circulation; Coronary Disease; Dogs; Heart Arrest, Induced; Infusions, Parenteral; Myocardial Revascularization; Phosphocreatine; Ubiquinone

This study tests the hypothesis that improved muscle salvage after prolonged ischemia (4 hours) occurs when the substrate-enriched blood cardioplegic solution is markedly hyperglycemic (greater than 400 mg/dl) and markedly hyperosmotic (greater than 400 mOsm). Thirty-five dogs underwent 4 hours of occlusion of the left anterior descending coronary artery and reperfusion during total vented bypass with substrate-enriched blood cardioplegic solution, in which the glucose concentration and osmolarity were varied in relation to one another. Spontaneous systolic shortening recovered consistently (31 +/- 6%) only when glucose was greater than 400 mg/dl and osmolarity was greater than 400 mOsm. The least recovery occurred (only one of six dogs recovering spontaneous shortening) when cardioplegic glucose was greater than 400 mg/dl and osmolarity was greater than 400 mOsm. Regional segments reperfused with our standard substrate-enriched blood cardioplegic solution had lower transmural flow rates following reperfusion (56 versus 87 ml/100 gm/min, p less than 0.05), markedly reduced mitochondrial State 3 and State 4 respiration in epicardial and endocardial muscle (p less than 0.05), and the most extensive histochemical evidence of damage (63% area of nonstaining versus area at risk, p less than 0.05). We conclude that markedly increased levels of osmolarity (greater than 400 mOsm) and glucose (greater than 400 mg/dl) improve the capacity of substrate-enriched blood cardioplegic solution to salvage myocardium after prolonged ischemia.

Topics: Animals; Aspartic Acid; Citrates; Citric Acid; Coenzymes; Coronary Circulation; Coronary Disease; Diltiazem; Dogs; Glucose; Glutamates; Heart Arrest, Induced; Myocardial Contraction; Osmolar Concentration; Phosphates; Potassium; Tromethamine; Ubiquinone

To evaluate effects of coenzyme Q10 added to a potassium cardioplegic solution for myocardial protection, 17 mongrel dogs underwent 60 minutes of ischemic cardiac arrest under cardiopulmonary bypass. Cardiac arrest was induced by infusing the cardioplegic solution into the aortic root every 20 minutes. Experimental animals were divided into three groups according to the cardioplegic solution used. In Group 1, we used our clinical potassium cardioplegic solution (K+, 22.31 mEq/L); in Group 2, potassium cardioplegic solution with coenzyme Q10 added (coenzyme Q10, 30 mg/500 ml of solution); and in Group 3, cardioplegic solution with coenzyme Q10 solvent. Exogenous coenzyme Q10 in the cardioplegic solution provided significantly high myocardial stores of adenosine triphosphate and creatine phosphate and a low level of lactate during induced ischemia and reperfusion. Furthermore, percent recovery of the aortic flow in Group 2 was significantly higher than that in the other two groups. Ultrastructures of the ischemic myocardium in Group 2 were better preserved than those in Group 1. Addition of coenzyme Q10 to potassium cardioplegia resulted in improved myocardial oxygen utilization and accelerated recovery of myocardial energy metabolism after reestablishment of circulation.

Topics: Adenosine Triphosphate; Animals; Cardiopulmonary Bypass; Coenzymes; Coronary Disease; Creatine Kinase; Dogs; Female; Heart Arrest, Induced; Hemodynamics; Isoenzymes; Lactates; Male; Myocardium; Oxygen; Phosphocreatine; Potassium; Potassium Compounds; Ubiquinone

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

Topics: Aged; Coenzymes; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Ubiquinone

Topics: Animals; Cardiac Output; Coenzymes; Coronary Disease; Halothane; Heart Rate; Hemodynamics; In Vitro Techniques; Male; Rats; Rats, Inbred Strains; Ubiquinone

Topics: Animals; Coronary Disease; Dogs; Heart Arrest, Induced; Mitochondria, Heart; Myocardium; Potassium; Ubiquinone; Vitamin E

Topics: Animals; Coenzymes; Coronary Circulation; Coronary Disease; In Vitro Techniques; Preoperative Care; Rats; Rats, Inbred Strains; Ubiquinone

Topics: Aprotinin; Coenzymes; Coronary Artery Bypass; Coronary Disease; Heart Arrest, Induced; Humans; Lidocaine; Ubiquinone

Protection of the ischaemic myocardium with Coenzyme Q10 (COQ10) following constriction of left anterior descending coronary artery was studied in 38 open-chest mongrel dogs. Left anterior descending coronary artery blood flow was independently reduced by tightening a constrictor around the vessel. Aortic pressure and left ventricular pressure were measured, and the Tension Time Index (TTI) was calculated. Myocardial segment shortening in the ischaemic area was measured with an ultrasonic dimension gauge. After obtaining haemodynamic data, the ischaemic myocardium was biopsied and the tissue sample was frozen in liquid nitrogen for adenosine triphosphate (ATP) analysis. Animals premedicated with COQ10 (20 mg . kg-1 iv) had a significantly higher ATP content in ischaemic myocardium (3.25 +/- 0.35 mumol . g-1 wet weight) compared with that in ischaemic myocardium of control animals (2.96 +/- 0.19) (P less than 0.05), when coronary blood flow was reduced by 50 to 74%. There were failure of ATP preservation by COQ10 with a further reduction in coronary blood flow. Changes in the pattern of myocardial segment shortening in the ischemic area induced by a 50 to 74% coronary blood flow reduction were less in COQ10 treated animals than in control animals. Since there were no haemodynamic differences between control and COQ10 treated animals, these effects were considered not to be due to a decrease in myocardial oxygen consumption secondary to haemodynamic changes.

Topics: Adenosine Triphosphate; Animals; Coenzymes; Coronary Circulation; Coronary Disease; Dogs; Hemodynamics; Myocardial Contraction; Myocardium; Ubiquinone

Topics: Animals; Benzoquinones; Cardiovascular Agents; Citric Acid Cycle; Coronary Circulation; Coronary Disease; Electron Transport; Hypoxia; Malates; Mice; Myocardium; Quinones; Rats; Succinates; Ubiquinone

Topics: Adenosine Triphosphate; Animals; Coenzymes; Coronary Disease; Dogs; Hemodynamics; Ligation; Perfusion; Phosphocreatine; Tissue Survival; Ubiquinone

Topics: Animals; Cardiomegaly; Coronary Disease; Dogs; Heart; Myocardium; Ubiquinone

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Coenzymes; Coronary Circulation; Coronary Disease; Heart; Male; Myocardial Contraction; Perfusion; Rats; Ubiquinone

Topics: Animals; Coronary Disease; Dogs; Electron Transport; Female; Male; Mitochondria, Heart; Myocardium; NAD; Ubiquinone

Topics: Animals; Aorta; Coronary Disease; Dogs; Energy Metabolism; Myocardium; Time Factors; Ubiquinone

The effect of KoQ4 on the energetics, contractility, and electrogram of the ischemized myocardium was studied in acute experiments on dogs with induced myocardial ischemia. Intracornoary administration of KoQ4, 1.3 mg/kg, directly into the focus of ischemia for 15 min promoted a decrease in the lactate level in blood draining from the ischemic zone as compared to the control data in the absence of a difference in the dynamics of the pyruvic acid content. In distinction to the control experimental series, there was no decrease in the concentration of glucose in samples of venous blood draining from the focus of ischemia. Under the effect of KoQ4 the amplitude of left ventricular pressure and the maximum rate of its growth (dp/dt) increased moderately and the ST segment and ST/R coefficient of the epicardial electrogram from the border zone of ischemia decreased. It was shown in the rat experiments that preliminary intravenous administration of KoQ4 (14 mg/kg) increased myocardial resistance to oxygen deficiency under conditions of diacetylcholine-induced apnoe.

Topics: Acute Disease; Animals; Blood Glucose; Blood Pressure; Coronary Disease; Dogs; Drug Evaluation, Preclinical; Energy Metabolism; Heart; Heart Rate; Lactates; Myocardial Contraction; Myocardium; Pyruvates; Time Factors; Ubiquinone

Topics: Accidents; Adolescent; Adult; Aged; Aging; Animals; Child; Child, Preschool; Coronary Disease; Female; Heart Diseases; Humans; Infant; Infant, Newborn; Liver; Male; Middle Aged; Neoplasms; Rats; Refrigeration; Ubiquinone; Vitamin A