No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
The use of coenzyme Q10 to protect ischemic heart muscle
... Coenzyme Q10 also appears to increase adenosine triphosphate levels by preventing the loss of adenine nucleotide pool from cardiac cells (Ito et al., 1991). Additionally, Coenzyme Q10 has demonstrated activity in preventing lipid peroxidation as an antioxidant scavenger and an indirect stabilizer of calcium channels to decrease calcium overload (Nayler, 1980;Sugiyama et al., 1980). In recent years, Coenzyme Q10 (CoQ10) has gained considerable attention as a dietary supplement capable of influencing cellular bioenergetics and counteracting some of the damage caused by free radicals (Linnane et al., 2002;Butler et al., 2003;Rosenfeldt et al., 2003;Zhou et al., 2005;Cooke et al., 2008). ...
Problem statement: Hyperlipidemia is well known to play a main role in the development of atherosclerosis. It is characterized by abnormally elevated cholesterol, triglyceride, low density lipoprotein cholesterol and very low density lipoprotein cholesterol levels in the blood. It has been recognized for many years that hypercholesterolemia is a major risk factor for cardiovascular diseases such as atherosclerosis, myocardial infraction, heart attacks and cerebrovascular diseases. In recent years, Coenzyme Q10 has gained considerable attention as a dietary supplement capable of influencing cellular bioenergetics and as a supplementary treatment for some chronic diseases. Approach: The present study was undertaken to evaluate whether Coenzyme Q10 supplementation would alter high cholesterol diet-induced hypercholesterolemic model in female rats. Sixty female albino rats of the Wistar strain weighing between 34.3 and 42.1 g were used. The experimental animals were divided into six groups. Rats of group 1 served as controls, fed with standard diet and had free access to water for three months. Rats of group 2 were daily supplemented with 1 mL of corn oil containing 10 mg of cholesterol/rat for two months. Animals of group 3 were daily supplemented with 1 mL of corn oil containing 10 mg of cholesterol/rat for two months and daily supplemented with 1 mg Coenzyme Q10/rat at third month. Rats of group 4 were daily supplemented with 1 mL of corn oil /rat for two months. The experimental rats of group 5 were daily supplemented with 1 mL of corn oil /rat for two months and daily supplemented with 1 mg Coenzyme Q10/rat at third month. Rats of group 6 were supplemented with 1 mg Coenzyme Q10/rat at third month. The body weight percentage changes were determined after second and third months in all experimental groups. Results: After 2 months, the maximum changes of body weight were noted in groups treated with high cholesterol diet and corn oil. After three months, the maximum percentage changes were observed in groups two and four and the minimum changes were noted in sixth group supplemented with only Coenzyme Q10 at last period. Serum triglycerides, cholesterol, High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), Atehrogenic Index (AI) and HDL Cholesterol (HDL-C) ratio were assessed at the end of experimental period. Significant increases in the levels of triglycerides, cholesterol, LDL-C VLDL-C were noted in rats supplemented with high cholesterol diet, while the level of HDL-C was significantly reduced. Similar observations were noted in rats treated with high cholesterol diet plus Coenzyme Q10. Statistically, the treatment of Coenzyme Q10 in rats subjected to high cholesterol diet showed a decrease in the change levels of these parameters. Also, the Atehrogenic Index (AI) value was significantly elevated in rats supplemented with high cholesterol diet compared with control value. Administration of Coenzyme Q10 for a period of one month to rats supplemented with high cholesterol diet significantly decreased the percentage change of the Atehrogenic Index (IA) value. HDL-C ratio value was significantly decreased in rats supplemented with high cholesterol diet compared with control value. Treatment with Coenzyme Q10 for a period of last month significantly decreased the percentage change of the HDL-C ratio value in rats fed with high cholesterol diet. Conclusion: The present results suggested that Coenzyme Q10 possesses hypolipidemic effects in rats supplemented with high cholesterol diet. Thus, use of Coenzyme Q10 may be useful in the treatment of cardiovascular diseases in which atherosclerosis plays a major role.
... 87,88 These theoretical aspects have been clinically validated by a spate of recent studies. [315][316][317][318][319] Langsjoen et al. 320 reported a statistically significant improvement in myocardial function with daily doses of Q10 ranging from 75 to 600 milligrams, obtaining an average blood level of 2.92 mcg/ml (n=297 322 reported an overall NYHA functional class improvement from a mean of 2.4 to 1.36 (P<0.001) in their series of 109 patients with essential hypertension managed with Q10. The use of antihypertensive drugs was discontinued in more than half of the patients in this study. ...
... ATP is depleted during ischemia and experimental evidence indicates increased oxidative stress in stunned myocardium. Ex vivo work in a rabbit heart model of ischemia and reperfusion showed a relative maintenance of tissue stores of ATP, a relative preservation of ATP-generating capacity of mitochondria and a relative absence of calcium overload in CoQ 10 -pretreated rabbits [17]. We might reasonably hypothesize that in our clinical study, administration of 300 mg of CoQ 10 per day was capable of increasing, even slightly, myocardial ATP content, therefore, improving electron transport rate and ATP production. ...
For a number of years, coenzyme Q (CoQ10 in humans) was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in plasma, and extensively investigated its antioxidant role. These two functions constitute the basis on which research supporting the clinical use of CoQ10 is founded. Also at the inner mitochondrial membrane level, coenzyme Q is recognized as an obligatory co-factor for the function of uncoupling proteins and a modulator of the transition pore. Furthermore, recent data reveal that CoQ10 affects expression of genes involved in human cell signalling, metabolism, and transport and some of the effects of exogenously administered CoQ10 may be due to this property. Coenzyme Q is the only lipid soluble antioxidant synthesized endogenously. In its reduced form, CoQH2, ubiquinol, inhibits protein and DNA oxidation but it is the effect on lipid peroxidation that has been most deeply studied. Ubiquinol inhibits the peroxidation of cell membrane lipids and also that of lipoprotein lipids present in the circulation. Dietary supplementation with CoQ10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoproteins to the initiation of lipid peroxidation. Moreover, CoQ10 has a direct anti-atherogenic effect, which has been demonstrated in apolipoprotein E-deficient mice fed with a high-fat diet. In this model, supplementation with CoQ10 at pharmacological doses was capable of decreasing the absolute concentration of lipid hydroperoxides in atherosclerotic lesions and of minimizing the size of atherosclerotic lesions in the whole aorta. Whether these protective effects are only due to the antioxidant properties of coenzyme Q remains to be established; recent data point out that CoQ10 could have a direct effect on endothelial function. In patients with stable moderate CHF, oral CoQ10 supplementation was shown to ameliorate cardiac contractility and endothelial dysfunction. Recent data from our laboratory showed a strong correlation between endothelium bound extra cellular SOD (ecSOD) and flow-dependent endothelial-mediated dilation, a functional parameter commonly used as a biomarker of vascular function. The study also highlighted that supplementation with CoQ10 that significantly affects endothelium-bound ecSOD activity. Furthermore, we showed a significant correlation between increase in endothelial bound ecSOD activity and improvement in FMD after CoQ10 supplementation. The effect was more pronounced in patients with low basal values of ecSOD. Finally, we summarize the findings, also from our laboratory, on the implications of CoQ10 in seminal fluid integrity and sperm cell motility.
The distribution of coenzyme Q10 (CoQ10) in serum lipoprotein fractions was measured by high-speed liquid chromatography during myocardial infarction and cerebral infarction. In control subjects, the major part of CoQ10 was present in the LDL fraction, and the distribution of CoQ10 was correlated with that of cholesterol. The CoQ10 level was related to the phenotypes of hyperlipidemias: more CoQ10 was present in LDL in type IIa, and in VLDL in types IIb and IV. In myocardial infarctions, the CoQ10 concentration decreased on the 3rd day, then gradually returned to the initial level in the serum and LDL fraction, while it decreased gradually untill the 21st day in the HDL fraction. The CO10-cholesterol ratio decreased on the 3rd day in serum, and on the 3rd, 7th and 14th days in the LDL fraction. In contrast, there was no significant change in the HDL fraction. In cerebral infarctions, the CoQ10 concentration decreased on the 3rd and 7th days in serum, and on the 3rd day in the HDL fraction. These results suggest that part of the metabolism of CoQ10 is the same as that of cholesterol in serum lipoproteins, and that CoQ10 is carried from LDL and HDL to mitochondria-rich organs during repair.
Ubiquinone is a popular food supplement at present. This review is aimed at summarizing the available knowledge in relation to cardiovascular indications. Some clinical trials report positive results in relation to coronary heart disease, congestive heart failure and arterial hypertension. In the final analysis, however, these findings are not fully convincing. As far as we know today, Ubiquinone is not associated with severe adverse effects. In conclusion, Ubiquinone is a fascinating substance which has considerable therapeutic potential. It should be investigated in more detail.
We examined the effect of coenzyme Q10 (Co Q10) on superoxide radical (O2
Seventy-nine patients with stable chronic congestive heart failure were randomized into a double-blind, crossover placebo controlled study with 3-month treatment periods, where either 100 mg coenzyme Q10 (CoQ10) or placebo was added to conventional therapy. Mean patient age was 61 ± 10 years, ejection fraction at rest was 22% ± 10%, and maximal exercise tolerance was 91 ± 30 W. The follow-up examinations included ejection fraction (primary objective), exercise test, and quality of life questions. Ejection fraction at rest, during a slight volume load, and during a submaximal supine exercise increased slightly compared with placebo: 24% ± 12% versus 23% ± 12% (NS), 25% ± 13% versus 23% ± 12% (P < .05), and 23% ± 11% versus 22% ± 11% (NS). Maximal exercise capacity increased from 94 ± 31 W during the placebo period to 100 ± 34 W during the CoQ10 period (P < .05). Total score for the quality of life assessment increased significantly from 107 ± 23 during the placebo period to 113 ± 22 during the CoQ10 period (P < .05). The results indicate that oral long-term treatment with 100 mg CoQ10 in patients with congestive heart failure only slightly improves maximal exercise capacity and the quality of life and that the clinical importance of this needs to be further evaluated.
For a number of years, coenzyme Q (CoQ10 in humans), was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular
fractions and in plasma, and also extensively investigated its antioxidant role. This chapter discusses the relationship between
the acknowledged bioenergetic role of CoQ10 and some clinical effects. The antioxidant properties of CoQ10 are then analyzed especially for their consequences on protection of circulating human low-density lipoproteins and prevention
of atherogenesis. The relationship between CoQ10 and statins is also discussed in the light of possible involvement of CoQ10 deficiency in the issue of statin side effects. New aspects of the antioxidant involvement of coenzyme Q are also discussed
together with their relevance in cardiovascular disease. Data are reported on the efficacy of CoQ10 in ameliorating endothelial dysfunction in patients affected by ischemic heart disease. Many of the effects of CoQ10, which were classically ascribed to its bioenergetic properties, are now considered as the result of its biochemical interaction
with nitric oxide (NO), NO synthase and reactive oxygen species capable of inactivating NO. Clinical studies are reported
highlighting the effect of CoQ10 on extracellular SOD, which is deeply involved in endothelial dysfunction.
Previous studies have shown decreased levels of CoQ10 in the seminal plasma and sperm cells of infertile men with different kinds of asthenospermia. Research has been extended
to supplementation with CoQ10 of infertile men affected by idiopathic asthenozoospermia. CoQ10 levels increased significantly in seminal plasma and sperm cells after 6 months of treatment with concomitant improvement
of sperm cell motility.
Seventy-eight patients undergoing coronary artery bypass grafting (CABG) were compared retrospectively to evaluate whether pretreatment with coenzyme Q10 (CoQ) is effective in preventing left ventricular depression in early reperfusion following CABG. CoQ (5 mg/kg, intravenously) was given to 60 patients, 2 hours prior to the onset of cardiopulmonary bypass (CPB). CABG was performed using saphenous vein under CPB associated with cold cardioplegia in the standard fashion. Heart rate, mean arterial pressure, and cardiac index showed no significant difference between the CoQ and control groups. However, left ventricular stroke work index was significantly elevated at 6 and 10 hours of reperfusion following CABG in the CoQ-treated group compared with the controls. Serum MB-CK was lower at 0 and 6 hours of reperfusion in the CoQ group compared with the controls. These results suggest that pretreatment with intravenous CoQ is effective in preventing left ventricular depression in early reperfusion and in minimizing myocardial cellular injury during CABG followed by reperfusion.
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.
In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS] who had normal mitochondrial enzyme activity, high doses of coenzyme Q10 (CoQ) were administered. Clinical improvement with decreased serum lactate and pyruvate levels was observed. Though the mechanism of action of CoQ is not known, a trial is worthwhile in patients with MELAS.
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.
Coenzyme Q, an important component of the electron transfer system in mitochondria, plays a central role in energy production aerobically. The effect of pretreatment with coenzyme Q10 (Co Q) on myocardial slow action potentials (APs) and accompanying contractions and on myocardial high energy phosphate content was studied in perfused hearts subjected to decreased perfusion pressure-hypoxia-substrate-free. Post-hatched chicks were treated i.p. with 10 mg/kg of Co Q daily for 5 days. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated by elevated K+ (25 mM) Tyrode solution. The Ca++-dependent slow APs were induced by elevating [Ca]o to 5.4 mM; hearts were paced at a rate of 40 per min. Hearts which had been pretreated with Co Q were protected against the deleterious effect of decreased perfusion pressure - hypoxia - substrate-free perfusion on mechanical performance accompanying the slow Ca++-Na+ APs. The slow APs in hearts pretreated with Co Q were also less affected than were non-treated hearts. However, the myocardial ATP and total adenine nucleotides were not affected by exogenous Co Q. It was suggested that exogenous Co Q could protect against the decline of cardiac contractions via improved availability of slow APs during decreased perfusion pressure - hypoxia - substrate-free, independently of the cellular high energy phosphate level.
A randomized, prospective study of the effectiveness of preoperative administration of coenzyme Q10 on the prophylaxis of postoperative low cardiac output state was performed in 50 patients with acquired valvular diseases necessitating valve replacement. There were 25 patients in the treatment group and 25 in the control group. Patients in the treatment group received 30 to 60 mg of coenzyme Q10 orally for six days before operation. Preoperative clinical variables, operative procedures, total cardiopulmonary bypass time, and aortic cross-clamping time were similar for the two groups. Postoperatively, mild to severe low cardiac output state developed in 28 of 50 patients (56%) and necessitated the administration of considerable amounts of inotropic agent. The treatment group showed a significantly lower incidence of low cardiac output state during the recovery period than the control group (p less than 0.05). These results suggest that preoperative administration of coenzyme Q10 will increase the tolerance of human hearts to ischemia during aortic cross-clamping.
The electrophysiological and inotropic effects of Coenzyme Q10 (CoQ10) on isoproterenol or barium-induced slow responses in ventricular papillary muscle, depolarized by high K+ concentration (21.6 mM) under hypoxia (PO2 = 40 mmHg), were studied with microelectrode techniques. For the isoproterenol-induced slow response, application of CoQ10 (50 micrograms/ml), which was emulsified with the aid of a special solvent, increased the maximum rate of rise of action potentials (Vmax), an indicator of the slow inward current, by about 40%, with no consistent effect on the action potential duration and developed tension. Application of the solvent alone produced a significant decrease in both Vmax and developed tension. However, in these solvent-pretreated preparations, CoQ10 produced a significant (by about 50%) recovery in both Vmax and developed tension. The action potential duration was not changed by either the solvent alone or the application of CoQ10. The developed tension of the slow response consisted of early and late components. CoQ10 produced significantly more recovery in the late component than in the early one, suggesting that the recovery effect was due to increased slow inward Ca2+ current. CoQ10 did not reverse any parameter in the slow response induced by BaCl2 (0.2 mM). The results suggest that CoQ10 has significant but limited reversing effects on the hypoxia-induced deterioration of the slow response, and that the recovery is presumably due to increased availability of slow channels via increased production of ATP.
Experiments were undertaken to determine if pretreating the animal with coenzyme Q10 (CoQ) protected the cardiac muscle of the isolated heart from the acute toxic injury induced by perfusion with adriamycin.CoQ (15 mg/kg/day) or vehicle alone was injected intraperitoneally into male rats for 7 days. Two hours after the last injection, the hearts were excised and perfused by Langendorff's technique. Perfusion with various concentrations of adriamycin (5, 10, 20, 30 or 50 μg of adriamycin/ml of perfusate) induced a dose-dependent decline in the contractile tension development and a dose-dependent elevation in the resting tension. When adriamycin in perfusate was 10 μg/ml or less than that, the coronary flow rate remained almost constant during the perfusion. No significant recovery in the contractile tension development and the resting tension was obtained by subsequent perfusion without adriamycin. The contractile tension development of the CoQ-pretreated hearts was significantly greater than that of the vehicle-pretreated hearts both during the perfusion with adriamycin (10 μg/ml) for 60 min and during the subsequent adriamycin-free perfusion for 30 min. After 60 min of perfusion with adriamycin, the cardiac stores of ATP, total adenine nucleotide and nicotinamide adenine dinucleotide in the CoQ-pretreated group were significantly higher than those in the vehicle-pretreated group.These results indicate that exogenous CoQ protects the cardiac muscle from the deterioraion in mechanical function induced by adriamycin. Better mechanical function of CoQ-pretreated hearts was attributable to relatively higher ATP stores presumably due to lesser loss of adenine nucleotide pool from the cardiac cells.
A defective myocardial energy supply--due to lack of substrates and/or essential cofactors and a poor utilization efficiency of oxygen--may be a common final pathway in the progression of myocardial diseases of various etiologies. The vitamin-like essential substance coenzyme Q10, or ubiquinone, is a natural antioxidant and has a key role in oxidative phosphorylation. A biochemical rationale for using coenzyme Q10 as a therapy in heart disease was established years ago by Folkers and associates; however, this has been further strengthened by investigations of viable myocardial tissue from the author's series of 45 patients with various cardiomyopathies. Myocardial tissue levels of coenzyme Q10 determined by high-performance lipid chromatography were found to be significantly lower in patients with more advanced heart failure compared with those in the milder stages of heart failure. Furthermore, the myocardial tissue coenzyme Q10 deficiency might be restored significantly by oral supplementation in selected cases. In the author's open clinical protocol study with coenzyme Q10 therapy (100 mg daily) nearly two-thirds of patients revealed clinical improvement, most pronounced in those with dilated cardiomyopathy. Double-blind placebo-controlled trials have definitely confirmed that coenzyme Q10 has a place as adjunctive treatment in heart failure with beneficial effects on the clinical outcome, the patients' physical activity, and their quality of life. The positive results have been above and beyond the clinical status obtained from treatment with traditional principles--including angiotensin-converting enzyme inhibitors.
Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism.
Coenzyme Q
10 , which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q
10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q
10 , 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance ( 31 P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q
10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q
10 levels (133 ± 5 μg/gm ventricle versus 117 ± 4 μg/gm ventricle, p < 0.05). Developed pressure at end reperfusion was 62% ± 2% of equilibration in treatment group versus 37% ± 2% in control group, p < 0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 ± 0.08 mm Hg/(μl O
2 /min/gm ventricle) vs 1.00 ± 0.08 mm Hg/(μl O
2 /min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 ± 0.07 mm Hg/(μl O
2 /min/gm ventricle, p < 0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% ± 2% for the treatment group vs 33% ± 3% in the control group, p < 0.005; phosphocreatine 49% ± 3% in the treatment group vs 35% ± 3% in the control group, p < 0.005) and reperfusion (adenosine triphosphate 18% ± 3% in the treatment group vs 11% ± 2% in the control group, CTRL p < 0.05; phosphocreatine 45% ± 2% in the treatment group vs 23% ± 3% in the control group, p < 0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% ± 3% of equilibration activity vs 65% ± 2% in the control group, p < 0.05). Coenzyme Q
10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion. (J T HORAC C ARDIOVASC S URG 1996;111:443-50)
Recent research reveals that some patients with a normal coronary arteriogram present with myocardial ischemia in the late stages of Kawasaki disease (KD). The present paper reports a patient who developed ventricular arrhythmia and possible myocardial ischemia in the late stages of KD but whose coronary arteriogram was normal. The onset of KD was at 2 years of age but cardiac involvement including coronary arterial lesion was not detected during the acute stage. At 11 years of age, the Holter electrocardiogram showed both frequent ventricular premature contractions and ventricular tachycardia. The single photon emission computed tomogram demonstrated possible myocardial ischemia. Possible myocardial ischemia was considered to be one of the causes of the ventricular arrhythmia. Although the prognosis for the majority of patients without apparent coronary arterial lesion is excellent, regular follow up must be performed on patients with a history of KD.
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.
In vitro the antioxidative capacity of pooled and lyophilized human meconium, measured by chemiluminescence, was compared to that of three potent antioxidants: vitamin C, a vitamin E analogue and a synthetic antioxidant, butylated hydroxytoluene. Meconium showed a significant superoxide trapping and peroxidation prevention capacity, but its capacity to trap peroxyl radicals was minor. These effects of meconium were possibly due to bilirubin and ubiquinol-10, both found in high concentrations in meconium. It is speculated that human meconium may have a physiological role as an important endogenous antioxidant during perinatal transition.
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.
We examined the effect of coenzyme Q10 (Co Q10) on superoxide radical (O2-) production in a model of rat reperfusion injury. The chemiluminescence method using a derivative of luciferin was used to quantify O2- production by erythrocytes in the reperfused limb after a period of ischaemia. A total of 20 limbs from Lewis rats were preserved at 4 degrees C in Euro-Collins solution for 72 hours, and were grafted orthotopically to syngeneic rats by a microsurgical technique. In the treated group (n = 10), Co Q10 (10 mg/kg) was injected intraperitoneally into the recipients one hour before reperfusion. In the control group (n = 10), the same dose of solvent was given. To measure the extent of oxidative stress, heparinised blood from the treated and control recipients was collected before, and at 15, 30, and 60 minutes after reperfusion for the measurement of chemiluminescence. O2- production in the Co Q10-treated group was significantly lower than in the control group (p < 0.05). Although these findings suggest that Co Q10 scavenged O2- that was produced in the replanted limbs as a result of ischaemia-reperfusion injury, we should consider other possible mechanisms by which this agent may protect against ischaemia-induced reperfusion injury.
A 28-year-old woman presented with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The diagnosis was based on the results of molecular genetic analysis, which indicated a typical point mutation at the nucleotide pair 3243. Xenon computerized tomography scans obtained during the strokelike episodes revealed the lesion responsible for the symptoms to be an area of focal hyperperfusion, and scans obtained after the episodes revealed an area of hypoperfusion. Pathogenesis of the strokelike episodes appears to be metabolic dysfunction, although the involvement of a vascular event cannot be excluded.
The influence of coenzyme Q10 (CoQ10) in cold stress test (-15 degrees C for 4 hours) cardiac functional impairment was studied in isolated isovolumic heart of control rats (C; n=12) and of placebo (P; n=11) and treated rats (CoQ10; n=10). In addition, electron microscopic evaluation of left ventricular (LV) slices (n=3 in each group) allowed us to analyze the myocardial ultrastructure. Maximal values of developed pressure (DPmax) were similarly decreased in cold stressed animals (C=129+/-3.9 mmHg; P=106+/-6.7 mmHg; CoQ10=91+/-3.9 mmHg); however, volume-induced enhancement of pressure generation (slope of DP volume relations: C=0.248+/-0.0203 mmHg / microl; P=0.2831+/-0.0187 mmHg / microl; CoQ10=0.2387 ( 0.0225 mmHg / microl; p > 0.05), and the duration of systole (C=80+/-1.6 ms; P=78+/-1.3 ms; CoQ10=80+/-2.7 ms) were not altered. Myocardial relaxation, evaluated by the relaxation constant (C=39+/-1.9 ms; P=42+/-3.4 ms; CoQ10=51+/-6.0 ms), as well as resting stress / strain relations were unaffected by cold stress. Myocardial samples showed that pretreatment with CoQ10 attenuates myofibrillar and mitochondrial lesions, and prevents mitochondrial fractional area increase (P: 53.11%>CoQ10: 38.78%=C: 33.87%; p< 0.005) indicating that the exogenous administration of CoQ10 can reduce cold stress myocardial injury.
Background:
Coenzyme Q10 (CoQ10) protects myocardium from ischemia-reperfusion (IR) injury as evidenced by improved recovery of mechanical function, ATP, and phosphocreatine during reperfusion. This protection may result from CoQ10's bioenergetic effects on the mitochondria, from its antioxidant properties, or both. The purpose of this study was to elucidate the effects of CoQ10 supplementation on mitochondrial function during myocardial ischemia-reperfusion using an isolated mitochondrial preparation.
Methods:
Isolated hearts (n = 6/group) from rats pretreated with liposomal CoQ10 (10 mg/kg iv, CoQ10), vehicle (liposomal only, Vehicle), or saline (Saline) 30 min before the experiments were subjected to 15 min of equilibration (EQ), 25 min of ischemia (I), and 40 min of reperfusion (RP). Left ventricular-developed pressure (DP) was measured. Mitochondria were isolated at end-equilibration (end-EQ), at end-ischemia (end-I), and at end-reperfusion (end-RP). Mitochondrial respiratory function (State 2, 3, and 4, respiratory control index (RCI, ratio of State 3 to 4), and ADP:O ratio) was measured by polarography using NADH (alpha-ketoglutarate, alpha-KG)- or FADH (succinate, SA)-dependent substrates.
Results:
CoQ10 improved recovery of DP at end-RP (67 +/- 11% in CoQ10 vs 47 +/- 5% in Vehicle and 50 +/- 11% in Saline, P < 0.05 vs Vehicle and Saline). CoQ10 did not change preischemic mitochondrial function. IR decreased State 3 and RCI in all groups using either substrate. CoQ10 had no effect in the mitochondrial oxidation of alpha-KG at end-I. CoQ10 improved State 3 at end-I when SA was used (167 +/- 21 in CoQ10 vs 120 +/- 10 in Saline and 111 +/- 10 ng-atoms O/min/mg protein in Vehicle, P < 0.05). Using alpha-KG as a substrate, CoQ10 improved RCI at end-RP (4.2 +/- 0.2 in CoQ10 vs 3.2 +/- 0.2 in Saline and 3.0 +/- 0.3 in Vehicle, P < 0.05). Using SA, CoQ10 improved State 3 (181 +/- 10 in CoQ10 vs 142 +/- 9 in Saline and 140 +/- 12 ng-atoms O/min/mg protein in Vehicle, P < 0.05) and RCI (2.21 +/- 0.06 in CoQ10 vs 1.85 +/- 0.11 in Saline and 1.72 +/- 0.08 in Vehicle, P < 0.05) at end-RP.
Conclusions:
The cardioprotective effects of CoQ10 can be attributed to the preservation of mitochondrial function during reperfusion as evidenced by improved FADH-dependent oxidation.
Coenzyme Q10 (CoQ10) or ubiquinone, a redox component of the mitochondrial electron transport chains, is a powerful antioxidant and membrane stabilizer that may prevent cellular damage during myocardial ischemia and reperfusion therapy. Coenzyme Q10 has been used primarily as an adjuvant therapy for some cardiomyopathies. However, one of the main problems in CoQ10 administration is the high variability of endogenous plasma and tissue levels, which seems to be dependent on several factors. This work explores temporal 24h and seasonal variation as well as gender and racial differences in endogenous plasma ubiquinone concentration. Coenzyme Q10 measurements (quantified by HPLC-UV) of 16 healthy volunteers were done during the daytime hours of activity beginning at 09:00h one day and ending at 09:00h the next day (13 different determinations) in two distinct months. April and October, of the year. A statistically significant circadian rhythm in plasma ubiquinone concentration that includes only the fundamental 24h component was demonstrated both in the April and October data. Furthermore, the time-point means of the ubiquinone concentration in the October study were invariably higher than those obtained in the April study. No statistically significant differences were found in CoQ10 concentration between male and female subjects, both in April and in October. In addition, racial differences were demonstrated; lower plasma ubiquinone levels were found in Caucasian compared to African subjects. However, the latter small group of subjects failed to demonstrate a circadian rhythm, neither in the April nor in the October analysis.
Coenzyme Q10 is a vitamin-like substance used in the treatment of a variety of disorders primarily related to suboptimal cellular energy metabolism and oxidative injury. Studies supporting the efficacy of coenzyme Q10 appear most promising for neurodegenerative disorders such as Parkinson's disease and certain encephalomyopathies for which coenzyme Q10 has gained orphan drug status. Results in other areas of research, induding treatment of congestive heart failure and diabetes, appear to be contradictory or need further clarification before proceeding with recommendations. Coenzyme Q10 appears to be a safe supplement with minimal side effects and low drug interaction potential.
In this review we summarise the current state of knowledge of the therapeutic efficacy and mechanisms of action of CoQ(10) in cardiovascular disease. Our conclusions are: 1. There is promising evidence of a beneficial effect of CoQ(10) when given alone or in addition to standard therapies in hypertension and in heart failure, but less extensive evidence in ischemic heart disease. 2. Large scale multi-centre prospective randomised trials are indicated in all these areas but there are difficulties in funding such trials. 3. Presently, due to the notable absence of clinically significant side effects and likely therapeutic benefit, CoQ(10) can be considered a safe adjunct to standard therapies in cardiovascular disease.
We investigated the association of idiopathic sudden sensorineural hearing loss (ISSNHL) with coenzyme Q (CoQ) and cardiovascular risk factors.
A prospective study.
Hospital center.
Thirty Italian patients with ISSNHL and 60 healthy Italian subjects.
Diagnostic.
Evaluation of serum CoQ levels and cardiovascular risk factors (total cholesterol, low-density lipoprotein [LDL], homocysteine [HCY]). The results were compared with variance analysis and Student's t test. Univariate and multivariate analysis were used to evaluate the association between ISSNHL and CoQ, total cholesterol, LDL, and HCY levels.
In our series, we found a significant association between ISSNHL and high total cholesterol (p < 0.05), high LDL (p = 0.021), and low CoQ (p < 0.05) levels. We did not find a significant association between ISSNHL and HCY levels. In the univariate analysis, low levels of CoQ, high levels of total cholesterol, and LDL were found to be significantly associated with ISSNHL. In the multivariate analysis, only high levels of total cholesterol and low levels of CoQ remained significantly associated with a high risk of sudden sensorineural hearing loss.
The studies regarding the role of cardiovascular risk factors in ISSNHL are not conclusive. This is the first report regarding the association of ISSNHL and low serum levels of the antioxidant CoQ. Further studies are needed to investigate the role of antioxidants, including CoQ, in ISSNHL.
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.
ResearchGate has not been able to resolve any references for this publication.