ubiquinone and Myocardial-Infarction

Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria, and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases, including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in people with heart failure, and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels, and in preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to people with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials was conducted prior to the original version of this Cochrane Review, in 2014.. To review the safety and efficacy of coenzyme Q10 in heart failure.. We searched CENTRAL, MEDLINE, Embase, Web of Science, CINAHL Plus, and AMED on 16 October 2020; ClinicalTrials.gov on 16 July 2020, and the ISRCTN Registry on 11 November 2019. We applied no language restrictions.. We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in people with heart failure. When we identified cross-over studies, we considered data only from the first phase.. We used standard Cochrane methods, assessed study risk of bias using the Cochrane 'Risk of bias' tool, and GRADE methods to assess the quality of the evidence. For dichotomous data, we calculated the risk ratio (RR); for continuous data, the mean difference (MD), both with 95% confidence intervals (CI). Where appropriate data were available, we conducted meta-analysis. When meta-analysis was not possible, we wrote a narrative synthesis. We provided a PRISMA flow chart to show the flow of study selection.. We included eleven studies, with 1573 participants, comparing coenzyme Q10 to placebo or conventional therapy (control). In the majority of the studies, sample size was relatively small. There were important differences among studies in daily coenzyme Q10 dose, follow-up period, and the measures of treatment effect. All studies had unclear, or high risk of bias, or both, in one or more bias domains. We were only able to conduct meta-analysis for some of the outcomes. None of the included trials considered quality of life, measured on a validated scale, exercise variables (exercise haemodynamics), or cost-effectiveness. Coenzyme Q10 probably reduces the risk of all-cause mortality more than control (RR 0.58, 95% CI 0.35 to 0.95; 1 study, 420 participants; number needed to treat for an additional beneficial outcome (NNTB) 13.3; moderate-quality evidence). There was low-quality evidence of inconclusive results between the coenzyme Q10 and control groups for the risk of myocardial infarction (RR 1.62, 95% CI 0.27 to 9.59; 1 study, 420 participants), and stroke (RR 0.18, 95% CI 0.02 to 1.48; 1 study, 420 participants). Coenzyme Q10 probably reduces hospitalisation related to heart failure (RR 0.62, 95% CI 0.49 to 0.78; 2 studies, 1061 participants; NNTB 9.7; moderate-quality evidence). Very low-quality evidence suggests that coenzyme Q10 may improve the left ventricular ejection fraction (MD 1.77, 95% CI 0.09 to 3.44; 7 studies, 650 participants), but the results are inconclusive for exercise capacity (MD 48.23, 95% CI -24.75 to 121.20; 3 studies, 91 participants); and the risk of developing adverse events (RR 0.70, 95% CI 0.45 to 1.10; 2 studies, 568 participants). We downgraded the quality of the evidence mainly due to high risk of bias and imprecision.. The included studies provide moderate-quality evidence that coenzyme Q10 probably reduces all-cause mortality and hospitalisation for heart failure. There is low-quality evidence of inconclusive results as to whether coenzyme Q10 has an effect on the risk of myocardial infarction, or stroke. Because of very low-quality evidence, it is very uncertain whether coenzyme Q10 has an effect on either left ventricular ejection fraction or exercise capacity. There is low-quality evidence that coenzyme Q10 may increase the risk of adverse effects, or have little to no difference. There is currently no convincing evidence to support or refute the use of coenzyme Q10 for heart failure. Future trials are needed to confirm our findings.

Topics: Ataxia; Heart Failure; Humans; Mitochondrial Diseases; Muscle Weakness; Myocardial Infarction; Quality of Life; Stroke; Stroke Volume; Ubiquinone; Ventricular Function, Left

Acute myocardial infarction (MI) is one of the most frequent causes of death in the United States. The evaluation and treatment of acute MI in conventional medicine has focused primarily on anatomical and physiological factors that lead to impaired blood flow. Less attention has been paid to metabolic factors that may influence the vulnerability of the myocardium to ischemia and to various stressors. There is evidence that in some cases inefficient cellular metabolism, rather than the availability of oxygen and other blood-borne nutrients, is an important factor determining whether cardiac pathology will develop. Metabolic dysfunction could result from intracellular deficiencies of magnesium, coenzyme Q10, carnitine, and certain B vitamins, nutrients which play a role in the synthesis of adenosine triphosphate (ATP; the body's main storage form of energy). In addition, increased oxidative stress may contribute to the pathogenesis of both MI-related myocardial damage and reperfusion injury. Consequently, administration of antioxidants might improve outcomes in patients with acute MI. Numerous clinical trials have found parenteral administration of magnesium in the early stages of acute MI can substantially reduce the death rate. In addition, several trials have shown L-carnitine is beneficial in the treatment of acute MI. Other nutrients, such as vitamin C, vitamin E, and various B vitamins, may also be of value.

Topics: Antioxidants; Ascorbic Acid; Carnitine; Dietary Supplements; Humans; Magnesium; Myocardial Infarction; Oxidative Stress; Primary Prevention; Ubiquinone; United States; Vitamin B Complex; Vitamin E

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

Topics: Acute Disease; Adult; Aged; Antioxidants; Humans; Male; Middle Aged; Myocardial Infarction; Ubiquinone

Early statin therapy after acute coronary syndrome reduces atherothrombotic vascular events. This study aimed to compare the effects of hydrophilic and hydrophobic statins on myocardial salvage and left ventricular (LV) function in patients with ST-elevated myocardial infarction (STEMI).. Seventy-five STEMI patients who had received emergency reperfusion therapy were enrolled and randomized into the hydrophilic statin group (rosuvastatin; 5 mg/day, n = 38) and hydrophobic statin group (atorvastatin; 10 mg/day, n = 37) for 6 months. LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) and co-enzyme Q10 (CoQ10) levels were measured at baseline and the end of treatment. The myocardial salvage index was assessed by single photon emission computed tomography with (123-)I-β-methyl-iodophenylpentadecanoic acid (ischemic area-at-risk at onset of STEMI: AAR) and (201-)thallium scintigraphy (area-at-infarction at 6 months: AAI) [myocardial salvage index = (AAR-AAI) × 100/AAR (%)].. Onset-to-balloon time and maximum creatine phosphokinase levels were comparable between the groups. After 6 months, rosuvastatin (-37.6% ± 17.2%) and atorvastatin (-32.4% ± 22.4%) equally reduced low-density lipoprotein-cholesterol (LDL-C) levels (p = 0.28). However, rosuvastatin (+3.1% ± 5.9%, p < 0.05), but not atorvastatin (+1.6% ± 5.7%, p = 0.15), improved LVEF. Rosuvastatin reduced BNP levels compared with atorvastatin (-53.3% ± 48.8% versus -13.8% ± 82.9%, p < 0.05). The myocardial salvage index was significantly higher in the rosuvastatin group than the atorvastatin group (78.6% ± 29.1% versus 52.5% ± 38.0%, p < 0.05). CoQ10/LDL-C levels at 6 months were increased in the rosuvastatin group (+23.5%, p < 0.01) and percent changes in CoQ10/LDL-C were correlated with the myocardial salvage index (r = 0.56, p < 0.01).. Rosuvastatin shows better beneficial effects on myocardial salvage than atorvastatin in STEMI patients, including long-term cardiac function, associated with increasing CoQ10/LDL-C.. URL http://www.umin.ac.jp/ctr/index.htm Unique Identifier: UMIN000003893.

Topics: Aged; Atorvastatin; Cholesterol, LDL; Echocardiography; Fatty Acids; Female; Fluorobenzenes; Heart; Heptanoic Acids; Humans; Hydrophobic and Hydrophilic Interactions; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Iodobenzenes; Male; Middle Aged; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Pilot Projects; Prospective Studies; Pyrimidines; Pyrroles; Radionuclide Imaging; Rosuvastatin Calcium; Sulfonamides; Thallium; Tomography, Emission-Computed, Single-Photon; Ubiquinone

In a randomized, double-blind, controlled trial, the effects of oral treatment with coenzyme Q10 (CoQ10, 120 mg/day), a bioenergetic and antioxidant cytoprotective agent, were compared for 1 year, on the risk factors of atherosclerosis, in 73 (CoQ, group A) and 71 (B vitamin group B) patients after acute myocardial infarction (AMI). After 1 year, total cardiac events (24.6 vs. 45.0%, p < 0.02) including non-fatal infarction (13.7 vs. 25.3%, p < 0.05) and cardiac deaths were significantly lower in the intervention group compared to control group. The extent of cardiac disease, elevation in cardiac enzymes, left ventricular enlargement, previous coronary artery disease and elapsed time from symptom onset to infarction at entry to study showed no significant differences between the two groups. Plasma level of vitamin E (32.4 +/- 4.3 vs. 22.1 +/- 3.6 umol/L) and high density lipoprotein cholesterol (1.26 +/- 0.43 vs. 1.12 +/- 0.32 mmol/L) showed significant (p < 0.05) increase whereas thiobarbituric acid reactive substances, malondialdehyde (1.9 + 0.31 vs. 3.1 + 0.32 pmol/L) and diene conjugates showed significant reduction respectively in the CoQ group compared to control group. Approximately half of the patients in each group (n = 36 vs. 31) were receiving lovastatin (10 mg/day) and both groups had a significant reduction in total and low density lipoprotein cholesterol compared to baseline levels. It is possible that treatment with CoQ10 in patients with recent MI may be beneficial in patients with high risk of atherothrombosis, despite optimal lipid lowering therapy during a follow-up of 1 year. Adverse effect of treatments showed that fatigue (40.8 vs. 6.8%, p < 0.01) was more common in the control group than CoQ group.

Topics: Adult; Antioxidants; Arteriosclerosis; Cholesterol, HDL; Coenzymes; Double-Blind Method; Female; Humans; Male; Malondialdehyde; Middle Aged; Myocardial Infarction; Risk Factors; Thiobarbituric Acid Reactive Substances; Ubiquinone; Vitamin E

Topics: Coenzymes; Female; Humans; Male; Myocardial Infarction; Taurine; Ubiquinone

Several noninvasive studies have shown the effect on heart failure of treatment with coenzyme Q10. In order to confirm this by invasive methods we studied 22 patients with mean left ventricular (LV) ejection fraction 26%, mean LV internal diameter 71 mm and in NYHA class 2-3. The patients received coenzyme Q10 100 mg twice daily or placebo for 12 weeks in a randomized double-blinded placebo controlled investigation. Before and after the treatment period, a right heart catheterisation was done including a 3 minute exercise test. The stroke index at rest and work improved significantly, the pulmonary artery pressure at rest and work decreased (significantly at rest), and the pulmonary capillary wedge pressure at rest and work decreased (significantly at 1 min work). These results suggest improvement in LV performance. Patients with congestive heart failure may thus benefit from adjunctive treatment with coenzyme Q10.

Topics: Adult; Aged; Antioxidants; Blood Pressure; Cardiac Catheterization; Cardiac Output; Cardiomyopathy, Dilated; Coenzymes; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Ubiquinone; Ventricular Function, Left

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

Sixty-one patients admitted with acute myocardial infarction, and a symptom's duration of less than 6 hr were randomized into two groups. Immediately after hospitalisation, members of the verum group (n = 32) received 500 mcg of selenium (as sodium selenite). Thereafter they received a daily dosage of 100 mg coenzyme Q10 (Bio-Quinone) and 100 mcg selenium (Bio-Selenium in the form of 1-seleno-methionine) for a period of one year. The control group (n = 29) were given matching placebo preparations. The groups were comparable as with respect to age, sex and medical treatment. Biochemical parameters showed a reduced concentration of CPK- and ASAT-level in the verum group during the acute phase (although not statistically significant). None of the patients in the verum group (i.e. on antioxidative treatment) showed prolongation of the frequency corrected QT-interval. In the control group, 40% revealed a prolongation of the QT-interval by more than 440 msec (p < 0.001). There were no significant differences, with respect to early complications. During the one-year follow-up period after myocardial infarction, six patients (20%) from the control group died from re-infarction whereas one patient from the verum group suffered a non-cardiac death.

Topics: Antioxidants; Cardiovascular Agents; Coenzymes; Creatine Kinase; Electrocardiography; Female; Free Radical Scavengers; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Selenomethionine; Sodium Selenite; Ubiquinone

Ischemic heart disease (IHD) is a common diagnosis and a leading cause of death in both males and females. It accounts for 30% of deaths worldwide, including 40% in high-income countries and approximately 28% in developing nations. Several cardiac markers have been used to diagnose and manage cardiovascular diseases. The Coenzyme Q

Topics: Adult; Angina Pectoris; Biomarkers; C-Reactive Protein; Case-Control Studies; Female; Humans; Male; Myocardial Infarction; Troponin; Ubiquinone

Immunochromatography test strip (ICTS) displayed high advantages in screening acute myocardial infarction (AMI) biomarkers. However, the low sensitivity and nonquantitative results seriously limited its clinical application. Herein, we designed a highly sensitive, quantitative and dual-readout ICTS for assaying multiple AMI biomarkers based on magnetic nanoparticles (MNPs) quenching the fluorescence of Cy5, which was labeled on capture antibodies on test (T) lines. The changes of fluorescent intensity caused by MNPs nanoprobes enabled us to sensitively quantify cTnI and CK-MB for early diagnosis of AMI in 15 min with a corresponding detection limit of 0.049 ng/mL and 0.085 ng/mL, respectively. Meanwhile, the aggregations of MNPs on T lines allowed colorimetric readout in 2 min for rapid diagnosis of emergent and severe AMI patients. Furthermore, the detection results of 30 clinical serum samples were coincident with those by electrochemiluminescence immunoassay. So this approach is promising a new avenue for clinical diagnosis and prognosis of AMI.

Topics: Animals; Biomarkers; Chromatography, Affinity; Electron Spin Resonance Spectroscopy; Humans; Kinetics; Lactoferrin; Male; Myocardial Infarction; Oxidation-Reduction; Rats; Ubiquinone

Cardioprotective efficacy of coenzyme Q10 (CoQ10, ubidecarenone) and mexicor were evaluated on the 21st day of experimental myocardial infarction in Wistar rats. CoQ10 or mexicor were injected in a dose of 30 mg/kg intravenously 10 min after coronary artery occlusion. The observed cardioprotective effects of ubidecarenone and mexicor were close. Both drugs equally increased the survival of rats, prevented the development of dilatation and hypertrophy of the left ventricle, and improved the pump cardiac function.

Topics: Animals; Cardiotonic Agents; Disease Models, Animal; Male; Myocardial Infarction; Pyridines; Rats; Rats, Wistar; Ubiquinone; Vitamins

Myocardial infarction (MI) was induced by subcutaneous injection of isoproterenol (ISO) to investigate the effect of ISO on Coenzyme Q10 (CoQ10) content of myocardium and subsequent effects on lipid peroxidation, electrocardiogram pattern and hemodynamic parameters of the rat's heart.36 male Wistar rats were divided randomly into 6 groups. To induce heart failure (HF) and MI, 10 and 100 mg/kg of ISO was administered subcutaneously for 10 and 2 consecutive days, respectively. The effects of ISO on myocardium CoQ10 content, concentration of malondialdehyde, ECG pattern and hemodynamic parameters of heart were analyzed.ISO-treated rats showed significant alteration in heart hemodynamic parameters such as reduction of left-ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, besides increase of left ventricular end-diastolic pressure. Significant depletion of heart CoQ10 content (from 4.57 and 4.55 µg/100 mg tissue in control groups to 2.85 and 2.89 µg/100 mg tissue in ISO-induced HF and MI groups respectively) and increase in tissue levels of malondialdehyde (47.1 and 53.8 nmol/100 mg tissue in ISO-induced HF and MI groups, respectively) were also observed in ISO-treated animals compared with the normal animals (17.4 and 18.8 nmol/100 mg tissue in control groups, respectively). Additionally CoQ10 improved ISO effects on hemodynamic parameters and ECG pattern in ISO-induced HF and myocardial injury.The present findings have demonstrated that the cardiotoxic effects of ISO such as oxidative damage and hemodynamic declination might be related to depletion of CoQ10 concentration.

Topics: Animals; Heart Failure; Hemodynamics; Isoproterenol; Lipid Peroxidation; Male; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Ubiquinone

HDL and apolipoprotein A1 (apoA1) concentrations inversely correlate with risk of death from ischemic heart disease; however, the role of apoA1 in the myocardial response to ischemia has not been well defined. To test whether apoA1, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarction via direct left anterior descending coronary artery ligation in apoA1 null (apoA1(-/-)) and apoA1 heterozygous (apoA1(+/-)) mice. We observed that apoA1(+/-) and apoA1(-/-) mice had a 52% and 125% increase in infarct size as a percentage of area at risk, respectively, compared with wild-type (WT) C57BL/6 mice. Mitochondrial oxidation contributes to tissue damage in ischemia-reperfusion injury. A substantial defect was present at baseline in the electron transport chain of cardiac myocytes from apoA1(-/-) mice localized to the coenzyme Q (CoQ) pool with impaired electron transfer (67% decrease) from complex II to complex III. Administration of coenzyme Q10 (CoQ10) to apoA1 null mice normalized the cardiac mitochondrial CoQ pool and reduced infarct size to that observed in WT mice. CoQ10 administration did not significantly alter infarct size in WT mice. These data identify CoQ pool content leading to impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA1. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL and low apoA1 concentrations that can be corrected by CoQ10 supplementation and suggest populations of patients that may benefit particularly from CoQ10 supplementation.

Topics: Animals; Antioxidants; Apolipoprotein A-I; Cardiotonic Agents; Dietary Supplements; Disease Models, Animal; Electron Transport; Electron Transport Complex II; Electron Transport Complex III; Heart; Hypoalphalipoproteinemias; Injections, Intraperitoneal; Intestinal Absorption; Male; Mice; Mice, Knockout; Mitochondria, Heart; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Tissue Distribution; Ubiquinone

The influence of coenzyme Q10 (CoQ10) on early ischemic deterioration was studied on Wistar rats with experimental myocardial infarction. CoQ10 (30 mg/kg) was injected intravenously 10 min after coronary artery occlusion, and morphometric analysis was performed for 72 h after the onset of ischemia. CoQ10-treated rats had restricted total myocardial damage (by 52%), including areas of necrosis (by 84%) and areas of cellular inflammatory infiltration (by 38%) as compared to saline-treated rats (p < 0.001).

Topics: Animals; Disease Models, Animal; Male; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Ubiquinone; Vitamins

Vitamin E and coenzyme Q10 (CoQ10) have antioxidant effects that may benefit cardiovascular health. Meta-analyses of randomized controlled trials have not shown a protective effect of supplementation with the vitamin E isomer α-tocopherol on the risk of acute myocardial infarction (AMI), but data on other isomers and CoQ10 are limited. Our objective was to examine the association of the plasma concentrations of vitamin E isomers (α-, γ-, and δ-tocopherol and α-, γ-, and δ-tocotrienol) and CoQ10 (ubiquinol and ubiquinone) with the incidence of AMI. We conducted a nested case-control study with 233 cases of incident AMI and 466 matched controls selected from the Singapore Chinese Health Study, aged 45-74 y at the time of recruitment and free of cardiovascular disease at the time of blood collection. We used conditional logistic regression to examine the association between vitamin E and CoQ10 and the risk of AMI adjusted for other risk factors. In the basic model, higher δ-tocopherol and ubiquinone concentrations were significantly associated with a higher risk of AMI, whereas there were no significant associations for the other vitamin E and CoQ10 isomers. After adjusting for lifestyle and other risk factors, only the association between δ-tocopherol and AMI risk remained significant [OR = 3.09 (95% CI: 1.53, 6.25) highest vs. lowest quintile; P-trend = 0.028]. We did not observe an inverse association between plasma concentrations of vitamin E isomers or CoQ10 and risk of AMI in Singapore Chinese. In contrast, plasma δ-tocopherol concentrations were associated with a higher risk of AMI. Our findings do not support a role of higher vitamin E or CoQ10 intakes in the prevention of AMI.

Topics: Aged; Asian People; Case-Control Studies; Female; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Risk Factors; Singapore; Ubiquinone; Vitamin E

Although arterial limb tourniquet is one of the first-line treatments to prevent exsanguinating hemorrhage in both civilian pre-hospital and battlefield casualty care, prolonged application of a limb tourniquet can lead to serious ischemia-reperfusion injury. However, the underlying pathomechanisms of tourniquet-induced ischemia-reperfusion injury are still poorly understood. Using a murine model of acute limb ischemia-reperfusion, we investigated if acute limb ischemia-reperfusion injury is mediated by superoxide overproduction and mitochondrial dysfunction. Hind limbs of C57/BL6 mice were subjected to 3h ischemia and 4h reperfusion via placement and release of a rubber tourniquet at the greater trochanter. Approximately 40% of the gastrocnemius muscle suffered infarction in this model. Activities of mitochondrial electron transport chain complexes including complex I, II, III, and IV in the gastrocnemius muscle were decreased in the ischemia-reperfusion group compared to sham. Superoxide production was increased while activity of manganese superoxide dismutase (MnSOD, the mitochondria-targeted SOD isoform) was decreased in the ischemia-reperfusion group compared to the sham group. Pretreatment with tempol (a SOD mimetic, 50mg/kg) or co-enzyme Q(10) (50mg/kg) not only decreased the superoxide production, but also reduced the infarct size and normalized mitochondrial dysfunction in the gastrocnemius muscle. Our results suggest that tourniquet-induced skeletal muscle ischemia-reperfusion injuries including infarct size and mitochondrial dysfunction may be mediated via superoxide overproduction and reduced antioxidant activity. In the future, this murine ischemia-reperfusion model can be adapted to mechanistically evaluate anti-ischemic molecules in tourniquet-induced skeletal muscle injury.

Topics: Animals; Cyclic N-Oxides; Electron Transport Chain Complex Proteins; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Mitochondria; Muscle, Skeletal; Myocardial Infarction; Reperfusion Injury; Spin Labels; Superoxide Dismutase; Superoxides; Tourniquets; Ubiquinone

Conditions of stress, such as myocardial infarction, stimulate up-regulation of heme oxygenase (HO-1) to provide cardioprotection. Here, we show that CO, a product of heme catabolism by HO-1, directly inhibits native rat cardiomyocyte L-type Ca2+ currents and the recombinant alpha1C subunit of the human cardiac L-type Ca2+ channel. CO (applied via a recognized CO donor molecule or as the dissolved gas) caused reversible, voltage-independent channel inhibition, which was dependent on the presence of a spliced insert in the cytoplasmic C-terminal region of the channel. Sequential molecular dissection and point mutagenesis identified three key cysteine residues within the proximal 31 amino acids of the splice insert required for CO sensitivity. CO-mediated inhibition was independent of nitric oxide and protein kinase G but was prevented by antioxidants and the reducing agent, dithiothreitol. Inhibition of NADPH oxidase and xanthine oxidase did not affect the inhibitory actions of CO. Instead, inhibitors of complex III (but not complex I) of the mitochondrial electron transport chain and a mitochondrially targeted antioxidant (Mito Q) fully prevented the effects of CO. Our data indicate that the cardioprotective effects of HO-1 activity may be attributable to an inhibitory action of CO on cardiac L-type Ca2+ channels. Inhibition arises from the ability of CO to promote generation of reactive oxygen species from complex III of mitochondria. This in turn leads to redox modulation of any or all of three critical cysteine residues in the channel's cytoplasmic C-terminal tail, resulting in channel inhibition.

Topics: Animals; Calcium Channels, L-Type; Carbon Monoxide; Cell Line; Cyclic GMP-Dependent Protein Kinases; Electron Transport Complex III; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Mitochondria, Heart; Myocardial Infarction; Myocytes, Cardiac; NADPH Oxidases; Nitric Oxide; Organophosphorus Compounds; Point Mutation; Protein Structure, Tertiary; Rats; Reactive Oxygen Species; Ubiquinone; Xanthine Oxidase

We evaluated the impact of triple nutrient supplementation (TNS: carnitine, taurine and coenzyme Q(10)) vs. carnitine alone (CARN) or placebo on survival, infarct size, cardiac function and metabolic gene expression using a model of myocardial infarction (MI) in rats.. Male Wistar rats were randomized to three groups divided in two independent studies prior to ligation of the left anterior descending coronary artery (LAD): TNS vs. Placebo and TNS vs. CARN. Nutrient supplementation [L-carnitine (300 mg/day), coenzyme Q(10) (15 mg/kg body weight/day) and taurine (0.1M)] was administered daily for four weeks prior to and for 10 days after MI. At that time, cardiac function and infarct size were measured. Metabolic gene (mRNA) expression in the peri-infarct tissue of left ventricle from TNS, placebo or corresponding time-control rats (TNS or placebo without LAD ligation) was measured 10 days after MI. When compared to placebo, TNS significantly improved survival (60% vs. 34%, p<0.02), cardiac function, and reduced infarct size (30+/-7% vs. 42+/-9%, p<0.001). Although CARN improved survival like TNS (45% vs. 50%, not significant), it did not reduce infarct size (32+/-14% vs. 19+/-10%, p<0.05) or delay myocardial remodeling. In the placebo group, MI was associated with a significantly altered pattern of metabolic gene expression (glucose transporter 1, liver carnitine palmitoyl transferase 1, medium-chain acyl-CoA dehydrogenase; p<0.01 for all three) in the left ventricle peri-infarct tissue. In contrast, gene expression was normalized in the group receiving TNS.. Our results support the potential cardioprotective impact of TNS during myocardial ischemia. In contrast to carnitine supplementation alone, TNS improved survival as well as cardiac function, gene expression and delayed remodeling.

Topics: Acyl-CoA Dehydrogenase; Animals; Cardiac Output; Carnitine; Carnitine O-Palmitoyltransferase; Dietary Supplements; Glucose Transporter Type 1; Male; Myocardial Infarction; Rats; Rats, Wistar; RNA, Messenger; Taurine; Ubiquinone

Statins have been shown to be cardioprotective; however, their interaction with endogenous cardioprotection by ischemic preconditioning and postconditioning is not known. In the present study, we examined if acute and chronic administration of the 3-hydroxy-3-methylglutaryl CoA reductase inhibitor lovastatin affected the infarct size-limiting effect of ischemic preconditioning and postconditioning in rat hearts. Wistar rats were randomly assigned to the following three groups: 1) vehicle (1% methylcellulose per os for 12 days), 2) chronic lovastatin (15 mg.kg(-1).day(-1) per os for 12 days), and 3) acute lovastatin (1% methylcellulose per os for 12 days and 50 micromol/l lovastatin in the perfusate). Hearts isolated from the three groups were either subjected to a nonconditioning (aerobic perfusion followed by 30-min coronary occlusion and 120-min reperfusion, i.e., test ischemia-reperfusion), preconditioning (three intermittent periods of 5-min ischemia-reperfusion cycles before test ischemia-reperfusion), or postconditioning (six cycles of 10-s ischemia-reperfusion after test ischemia) perfusion protocol. Preconditioning and postconditioning significantly decreased infarct size in vehicle-treated hearts. However, preconditioning failed to decrease infarct size in acute lovastatin-treated hearts, but the effect of postconditioning remained unchanged. Chronic lovastatin treatment abolished postconditioning but not preconditioning; however, it decreased infarct size in the nonconditioned group. Myocardial levels of coenzyme Q9 were decreased in both acute and chronic lovastatin-treated rats. Western blot analysis revealed that both acute and chronic lovastatin treatment attenuated the phoshorylation of Akt; however, acute but not chronic lovastatin treatment increased the phosphorylation of p42 MAPK/ERK. We conclude that, although lovastatin may lead to cardioprotection, it interferes with the mechanisms of cardiac adaptation to ischemic stress.

Topics: Animals; Blotting, Western; Disease Models, Animal; Down-Regulation; Drug Administration Schedule; Enzyme Activation; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ischemic Preconditioning, Myocardial; Lovastatin; Male; Mitogen-Activated Protein Kinase 1; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Ubiquinone

Topics: Cholesterol; Coenzymes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Myocardial Infarction; Ubiquinone; Vitamins

The effect of chronic coronary artery occlusion on the content of rat myocardial coenzymes Q (CoQ) and evaluation of the applicability of CoQ(10) for limiting postinfarct remodeling have been investigated. Left ventricle myocardium hypertrophy was characterized by the decrease in CoQ(9) (-45%, p < 0.0001), CoQ(10) (-43%, p < 0.001), and alpha-tocopherol (-35%, p < 0.05). There were no differences between the parameters of postinfarction and sham-operated rats in plasma. Administration of CoQ(10) (10 mg/kg) via a gastric probe for 3 weeks before and 3 weeks after occlusion maintained higher levels of CoQ in the postinfarction myocardium: the decrease in CoQ(9) and CoQ(10) was 25% (p < 0.05) and 23% (p < 0.05), respectively (versus sham-operated animals). Plasma concentrations of CoQ(10) were more than 2 times higher (p < 0.05). In CoQ treated rats there was significant correlation between plasma levels of CoQ and the infarct size: r = -0.723 (p < 0.05) and r = -0.839 (p < 0.01) for CoQ(9) and CoQ(10). These animals were also characterized by earlier and more intensive scar tissue formation in the postinfarction myocardium and also by more pronounced cell regeneration processes. This resulted in the decrease in both the infarct size (16.2 +/- 8.1 vs. 27.8 +/- 12.1%) and also mass index of left ventricle (2.18 +/- 0.24 vs. 2.38 +/- 0.27 g/kg) versus untreated rats (p < 0.05). Thus, long-term treatment with ubiquinone increases plasma and myocardial CoQ content and this can improve the survival of myocardial cells during ischemia and limit postinfarct myocardial remodeling.

Topics: alpha-Tocopherol; Animals; Cardiomegaly; Chromatography, High Pressure Liquid; Coenzymes; Male; Microscopy, Electron; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Ubiquinone; Ventricular Remodeling; Vitamins

We assessed whether the infusion of Coenzyme Q10-loaded liposomes (CoQ10-L) in rabbits with an experimental myocardial infarction can result in increased intracellular delivery of CoQ10 and thus limit the fraction of the irreversibly damaged myocardium.. CoQ10-L, empty liposomes (EL), or Krebs-Henseleit (KH) buffer were administered by intracoronary infusion, followed by 30 min of occlusion and 3 h of reperfusion. Unisperse Blue dye was used to demarcate the net size of the occlusion-induced ischemic zone ("area at risk") while nitroblue tetrazolium staining was used to detect the final fraction of the irreversibly damaged myocardium within the total area at risk.. The total size of the area at risk in all experimental animals was approx. 20% wt. of the left ventricle (LV). The final irreversible damage in CoQ10-L-treated animals was only ca. 30% of the total area at risk as compared with ca. 60% in the group treated with EL (p < 0.006) and ca. 70% in the KH buffer-treated group (p < 0.001).. CoQ10-L effectively protected the ischemic heart muscle by enhancing the intracellular delivery of CoQ10 in hypoxic cardiocytes in rabbits with an experimental myocardial infarction as evidenced by a significantly decreased fraction of the irreversibly damaged heart within the total area at risk. CoQ10-L may provide an effective exogenous source of the CoQ10 in vivo to protect ischemic cells.

Topics: Animals; Coenzymes; Cytoprotection; Liposomes; Myocardial Infarction; Myocardial Reperfusion Injury; Rabbits; Ubiquinone

Reactive oxygen species (ROS) mediate volatile anesthetic preconditioning. We tested the hypothesis that isoflurane (ISO) generates ROS from electron transport chain complexes I and III. Rabbits (n = 55) underwent 30 min coronary artery occlusion followed by 3 h reperfusion and received 0.9% saline, the complex I inhibitor diphenyleneiodonium (DPI; 1.5 mg/kg bolus followed by 1.5 mg/kg over 1 h), or the complex III inhibitor myxothiazol (MYX; 0.1 mg/kg bolus followed by 0.3 mg/kg over 1 h) in the absence and presence of 1.0 minimum alveolar concentration ISO. ISO was administered for 30 min and discontinued 15 min before coronary occlusion. Infarct size and ROS production (n = 32) were determined using triphenyltetrazolium staining and ethidium-DNA fluorescence, respectively. Adenosine triphosphate (ATP) synthesis in mitochondria obtained from rabbit hearts (n = 24) subjected to drug interventions was measured by luciferin-luciferase luminometry. ISO significantly (P < 0.05) reduced infarct size (19% +/- 4%) as compared with control (39% +/- 4%). MYX (35% +/- 4%), but not DPI (24% +/- 2%), abolished this protection. ISO increased ethidium-DNA fluorescence (83 +/- 11 U) as compared with control (40 +/- 12 U). MYX (35 +/- 3 U), but not DPI (78 +/- 9 U), abolished ROS generation. DPI and MYX selectively reduced complex I- and complex III-mediated ATP synthesis, respectively. ROS generated from electron transport chain complex III mediate ISO-induced cardioprotection.

Topics: Adenosine Triphosphate; Anesthetics, Inhalation; Animals; Coenzymes; Electron Transport; Enzyme Inhibitors; Hemodynamics; In Vitro Techniques; Ischemic Preconditioning, Myocardial; Isoflurane; Male; Methacrylates; Mitochondria, Heart; Myocardial Infarction; NADH Dehydrogenase; Onium Compounds; Rabbits; Reactive Oxygen Species; Thiazoles; Ubiquinone; Ventricular Function, Left

To examine whether nutritional supplementation of coenzyme Q(10) (CoQ(10)) can reduce myocardial ischemia-reperfusion injury, a group of swine was fed a regular diet supplemented with CoQ(10) (5 mg x kg(-1) x day(-1)) for 30 days. Another group of pigs that were fed a regular diet supplemented with placebo served as a control. After 30 days, isolated in situ pig hearts were prepared and hearts were perfused with a cardiopulmonary pump system. Each heart was subjected to 15 min of regional ischemia by snaring of the left anterior descending coronary artery, followed by 60 min of hypothermic cardioplegic global ischemia and 120 min of reperfusion. After the experiments were completed, myocardial infarct size was measured by triphenyltrazolium chloride staining methods. Postischemic left ventricular contractile function was better recovered in the CoQ(10) group than in the control group of pigs. CoQ(10)-fed pigs revealed less myocardial infarction and less creatine kinase release from the coronary effluent compared with control pigs. The experimental group also demonstrated a smaller amount of malonaldehyde in the coronary effluent and a higher content of the endogenous antioxidants ascorbate and thiol. Significant induction of the expression of ubiquitin mRNA was also found in the hearts of the CoQ(10)-fed group. The results of this study demonstrate that nutritional supplementation of CoQ(10) renders the hearts resistant to ischemia-reperfusion injury, probably by reducing the oxidative stress.

Topics: Animals; Antioxidants; Coenzymes; Creatine Kinase; Diet; Free Radicals; Gene Expression; Heart; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Swine; Ubiquinone; Ubiquitins; Ventricular Function, Left

Topics: Antioxidants; Coenzymes; Eicosapentaenoic Acid; Fish Oils; Humans; India; Myocardial Infarction; Survival Analysis; Ubiquinone

Coenzyme Q10 has been found to enhance recovery of function after reperfusion in numerous experimental acute ischemia-reperfusion models. We assessed whether coenzyme Q10, administered intravenously either during or 1 h before ischemia, can limit infarct size in the rabbit.. Anesthetized open-chest rabbits were subjected to 30 min of coronary artery occlusion and 4 h of reperfusion. In Protocol 1, 12 min after beginning of ischemia rabbits were randomized to intravenous infusion of 30 mg coenzyme Q10 (Eisai Co., Japan) (n = 10) or vehicle (n = 10). In Protocol 2, rabbits were randomized to 30 mg coenzyme Q10 (n = 6) or vehicle (n = 6) treatment 60 min before ischemia. Ischemic zone at risk (IZ) was assessed by blue dye and necrotic zone (NZ) by tetrazolium staining.. In both protocols, coenzyme Q10 did not alter heart rate, mean blood pressure, or regional myocardial blood flows in either the ischemic or non-ischemic zones during ischemia or reperfusion. No difference was found in IZ (as fraction of LV weight) (Protocol 1: 0.24 +/- 0.02 vs. 0.25 +/- 0.02; Protocol 2: 0.28 +/- 0.02 vs. 0.28 +/- 0.03, in the control vs. coenzyme Q10 groups, respectively). The NZ/IZ ratio was comparable between the groups in both protocols (Protocol 1: 0.22 +/- 0.04 vs. 0.26 +/- 0.04; Protocol 2: 0.21 +/- 0.06 vs. 0.30 +/- 0.06, in the control vs. coenzyme Q10 groups, respectively).. Coenzyme Q10, administered acutely either during or 60 min before myocardial ischemia, does not attenuate infarct size in the rabbit.

Topics: Animals; Coenzymes; Disease Models, Animal; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Rabbits; Random Allocation; Ubiquinone

The effects of long-term treatment with coenzyme Q10 (CoQ10) on myocardial energy metabolism of rats with chronic heart failure (CHF) were examined. Left coronary artery ligation resulted in decreases in blood pressure, left ventricular developed pressure, the first derivative of left ventricular developed pressure, cardiac output and stroke volume indices and caused an increase in left ventricular end-diastolic pressure 12 weeks after the operation. Significant decreases in adenosine-5'-triphosphate, creatine phosphate, creatine and inorganic phosphate contents and the mitochondrial oxygen consumption rate of the viable left and right ventricles were detected in the CHF rat. Oral administration of 5 mg/kg/day CoQ10 for 12 weeks attenuated the changes in the first derivative of left ventricular developed pressure, cardiac output and stroke volume indices of the CHF rat but did not significantly improve the survival of CHF animals. The developed infarct area was approximately 40% of the whole left ventricle, irrespective of treatment with or without CoQ10. There was no reversal in the decreased myocardial CoQ9 and CoQ10 contents of the CHF rat after treatment with exogenous CoQ10. In the right ventricle of CoQ10-treated animals, a significant recovery of creatine, inorganic phosphate and mitochondrial oxygen consumption rate, and a small restoration of creatine phosphate but not of adenosine-5'-triphosphate, were observed, which suggests an appreciable recovery of energy-producing ability in the right ventricle. In contrast, a significant restoration of tissue creatine and inorganic phosphate, but not of other variables, was detected in the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cardiac Output, Low; Chronic Disease; Coenzymes; Energy Metabolism; Heart; Heart Ventricles; Hemodynamics; Male; Mitochondria, Heart; Myocardial Infarction; Myocardium; Organ Size; Oxygen Consumption; Rats; Rats, Wistar; Time Factors; Ubiquinone

Effects of coenzyme Q9 (25 mg/kg), N6-cyclohexyl adenosine (CHA, 100 micrograms/kg) and their combination were compared in rats with short-term or permanent ligation of the left coronary artery. The following parameters were evaluated in three series of experiments: 1) incidence and duration of ventricular fibrillation and tachycardia during coronary occlusion (10 min) and consecutive reperfusion (5 min); 2) contractility and electrical stability of the heart (ventricular fibrillation threshold) in animals with 2-day myocardial infarction; 3) ischemic myocardial mass after coronary occlusion (5 min) and necrotic tissue mass in 2-day myocardial infarction. The rats were given oral drugs 5 days and 2 hours before the study. All the experiments were performed in open-chest anesthetized (nembutal, 50 mg/kg) rats exposed to ventilation at room air. Both the coenzyme Q9 and CHA significantly reduced the incidence and duration of coronary occlusion and reperfusion arrhythmias, prevented cardiac contractile depression (heart rate.developed pressure) and increased ventricular fibrillation threshold). The effect of coenzyme Q9 was more marked than that of CHA. Coenzyme Q9 substantially reduced necrotic tissue mass while CHA diminished ischemic tissue mass. At the same time the total cardioprotective action of the Q9 + CHA combination was more pronounced than that of them used alone.

Topics: Adenosine; Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Heart Arrest, Induced; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Rats; Rats, Inbred Strains; Ubiquinone

The authors have studied the behaviour of ubidecorenone (Co Q10) in the acute phase of myocardial infarction in 24 patients, 19 male and 5 female, mean age 56.8 +/- 3.3. Ubidecorenone level was determined on admittance, after 48 hours and on the 7th and 30th days. A significant decrease was observed from the first to the 3rd day (mean values 0.90 +/- 0.18 microgram/ml vs 0.72 +/- 0.22, p less than 0.01). Thereafter a progressive rise was observed, but at the 30th day mean values were still below the basal ones. No significant differences were observed between patients treated with fibrinolytic agents and those not so treated, nor between those in whom reperfusion was obtained and the others. Nor was there a proven correlation with changes in creatinkinase. The behaviour of ubidecorenone may be associated with increased consumption for metabolic needs and increased destruction in scavenger action, and also to a lesser extent to decreased production due to lower food intake.

Topics: Aged; Clinical Enzyme Tests; Female; Humans; Male; Middle Aged; Myocardial Infarction; Recombinant Proteins; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Ubiquinone; Urokinase-Type Plasminogen Activator

The effects of coenzyme Q10 (CoQ) and captopril on functional capacity, hemodynamics and survival were studied in 154 rats that recovered after experimental myocardial infarction. Rats were randomized into four groups receiving either CoQ, captopril, a combination of the two drugs or 1 ml of tap water once daily for 12 weeks from the day of coronary artery ligation. CoQ as well as captopril and the combined treatment significantly improved exercise capacity as evaluated by lactate production during a standardized treadmill exercise test. No significant changes in heart rate or mean blood pressure were observed during the study in the captopril-treated group. CoQ treatment increased the maximum heart rate significantly, whereas no effect on mean blood pressure was observed. Both captopril and CoQ decreased pulmonary congestion. Furthermore, the data may suggest that captopril prevents right ventricular hypertrophy seen in placebo-treated rats with large infarcts. This was not observed after CoQ treatment. Captopril treatment improved 3-month probability of survival (93%) as compared with placebo (74%) (P less than .05). CoQ and the combined treatment tended to improve survival, but this was, however, not statistically significant.

Topics: Animals; Body Weight; Captopril; Coenzymes; Drug Synergism; Energy Metabolism; Female; Heart Failure; Hemodynamics; Myocardial Infarction; Organ Size; Rats; Survival Rate; Ubiquinone

This study tests the hypothesis that metabolic support of remote "nonischemic" myocardium during acute infarction will reverse the trend toward cardiogenic shock. Thirty-seven dogs underwent ligation of the left anterior descending coronary artery and 50% stenosis of the circumflex coronary artery. Irreversible ventricular fibrillation developed in 11 of them. The 26 survivors were observed for up to 6 hours; global and regional left ventricular function (cardiac index, stroke work index, ultrasonic crystals) and regional blood flow (radioactive microspheres) were measured. After 2 hours, eight dogs received an intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, coenzyme Q10, and 2-mercapto-propionyl-glycine for 4 hours. Five dogs received the mannitol infusion to raise serum osmolarity 30 mOsm. Four additional dogs received the intravenous substrate infusions over 4 hours without undergoing ischemia. The substrate infusion for 4 hours caused no change in regional or global cardiac function in the four control dogs. Three of nine untreated dogs died of cardiogenic shock, and progressive left ventricular power failure occurred in the six others (40% decrease in cardiac index, 50% decrease in stroke work index, p less than 0.05) because of persistent dyskinesia in the left anterior descending region (-40% of systolic shortening, p less than 0.05) and hypocontractility in the circumflex region (48% of control systolic shortening, p less than 0.05), despite normal transmural blood flow in the posterior left ventricular wall (76 ml/100 gm/min). In contrast, in treated dogs, hypercontractility recovered in the circumflex segment (138% of systolic shortening) and stroke work index rose to control levels (91%) without a change in regional blood flow. Mannitol infusion did not improve hemodynamics or avoid the development of progressive left ventricular power failure. We conclude that cardiogenic shock after myocardial infarction is due, in large part, to impaired ability of "nonischemic" myocardium to maintain hypercontractility. This limitation can be prevented by metabolic support of viable muscle, and the data imply that intravenous substrate infusions may be helpful before definitive treatment (i.e., coronary artery bypass grafting) is undertaken.

Topics: Animals; Aspartic Acid; Coronary Circulation; Dogs; Glucose; Glutamates; Hemodynamics; Infusions, Intravenous; Insulin; Mannitol; Myocardial Contraction; Myocardial Infarction; Myocardium; Potassium; Shock, Cardiogenic; Tiopronin; Ubiquinone; Ventricular Fibrillation

We studied the irreversible change of myocardium on coronary artery occlusion using mongrel dogs. These dogs were divided into 2 groups. One group was administered CoQ10 before and after coronary artery occlusion and the other received placebo. Results are summarized as follows. 1) In both groups the hemodynamic change showed no significant change. 2) In the biochemical studies there was no significant difference between both groups, but in the infarction group, serum GPT and pyruvic acid in a sampling of blood taken from the coronary sinus were significantly higher than in the non-infarction group (P less than 0.05, 0.025). 3) By the triphenyl tetrazolium chloride (TTC) technique for the myocardial infarction, infarction did not appear in the CoQ10 group until 90 minutes after coronary occlusion but in the placebo group infarction appeared as early as 60 minutes. 4) In the ultrastructural studies of myocardium the electron microscopy detected irreversible change of mitochondrias when the TTC technique identified infarction. In conclusion, the administration of CoQ10 has a protective effect for the irreversible change of ischemic myocardium.

Topics: Alanine Transaminase; Animals; Coenzymes; Dogs; Hemodynamics; Mitochondria, Heart; Myocardial Infarction; Myocardium; Pyruvates; Pyruvic Acid; Staining and Labeling; Time Factors; Ubiquinone

Topics: Animals; Dogs; Electrocardiography; Female; Hemodynamics; Male; Myocardial Infarction; Myocardium; Ubiquinone

Coenzyme Q10 (CoQ10) is a redox component in the respiratory chain. CoQ10 is necessary for human life to exist; and a deficiency can be contributory to ill health and disease. A deficiency of CoQ10 in myocardial disease has been found and controlled therapeutic trials have established CoQ10 as a major advance in the therapy of resistant myocardial failure. The cardiotoxicity of adriamycin, used in treatment modalities of cancer, is significantly reduced by CoQ10, apparently because the side-effects of adriamycin include inhibition of mitochondrial CoQ10 enzymes. Models of the immune system including phagocytic rate, circulating antibody level, neoplasia, viral and parasitic infections were used to demonstrate that CoQ10 is an immunomodulating agent. It was concluded that CoQ10, at the mitochondrial level, is essential for the optimal function of the immune system.

Topics: Aged; Aging; Cardiac Output; Coenzymes; Double-Blind Method; Doxorubicin; Female; Heart Diseases; Heart Failure; Humans; Immunity; Male; Middle Aged; Myocardial Infarction; Stroke Volume; 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

Topics: Animals; Chromatography; Diet, Atherogenic; Fats, Unsaturated; Fatty Acids, Essential; Linoleic Acids; Myocardial Infarction; Oils; Rats; Spectrophotometry; Sterols; Thrombosis; Ubiquinone; Vitamin E; Zea mays