Coenzyme Q1O (COQ1O), with the chemical formula of 2, 3 dimethoxy-5-methyl-6- decamethylenedioxybenzoquinone, also known as ubiquinone and decaquinone, is an activator of cellular respiration and metabolism, and has a metabolic cardiac potentiating effect by participating in the process of cellular oxidative phosphorylation and adenosine triphosphate production[1] . Recent studies have shown that COQ1O has good therapeutic effects in the prevention of heart failure (HF). The progress of these studies is summarized as follows.
1 Clinical pharmacology
1.1 Pharmacokinetics[2, 3] COQ1O has a large molecular size and poor water solubility, and is absorbed slowly in the gastrointestinal tract, with peak concentrations reached 5~1Oh (mean 6.5h) after oral administration. The average plasma concentration of COQ1O after a single oral dose (1OOmg) was (1.OO4±O.37) μg/ml; the average steady state concentration after 3 doses of 1OOmg per dose was 5.4 μg/ml, which was 4-7 times higher than that of endogenous COQ1O. The average steady-state concentration of COQ1O is 5.4μg/ml, which is 4-7 times higher than that of endogenous COQ1O, and the blood concentration of COQ1O can reach 90% of the steady-state concentration after 4d of continuous administration. The drug is slowly metabolized with a biological half-life of (33.9±5.32) h. The drug is absorbed from the gastrointestinal tract. The drug is absorbed from the gastrointestinal tract by celiac disease and is bound to very low-density lipoproteins. Most of the drug is stored in the liver and is excreted mainly through the biliary tract, with about 62.5% excreted in the feces in its original form after prolonged administration.
1.2 Mechanisms of action
COQ1O has antioxidant and membrane stabilizing effects, and can improve myocardial metabolism. HF patients suffer from a disturbed balance between oxidation and antioxidant activity, increased lipid peroxidation, and weakened protective function of myocardial antioxidant enzymes[4] . Studies have shown that myocardial and blood levels of COQ1O are significantly lower in HF patients, and COQ1O supplementation significantly improves cardiac function in experimental HF animals and HF patients[5] . It has been demonstrated that mitochondrial hyperplasia and mitochondrial membrane phospholipid localization in peripheral lymphocytes of HF patients show different degrees of deletion, the degree of which is consistent with the state of cardiac function, and that cardiac myocytes show similar changes, and the correlation is good[6, 7] . With the improvement of cardiac function, the mitochondrial hyperplasia of lymphocytes and the damage of mitochondrial membrane phospholipids were significantly reduced after administration of COQ1O, and the beneficial effects of COQ1O might be achieved through the promotion of cellular oxidative phosphorylation, improvement of energy metabolism of the myocardium, and the direct antioxidant and membrane stabilizing effects that could protect and repair the damage of mitochondrial membrane phospholipids[8].
2 Clinical studies
2.1 Treatment of congestive heart failure
In 1970, FOlkers [2] analyzed more than 1,000 myocardial biopsy specimens and blood samples and proved that the endogenous COQ1O level in patients with congestive heart failure (CHF) was lower than that in normal subjects, and found that the more severe the CHF, the lower the level of myocardial COQ1O was, and the more effective the treatment of COQ1O was. LangsijeOn[5] and others also found that myocardial COQ1O levels were significantly lower in patients with CHF, and that supplementation with COQ1O significantly improved cardiac function in patients with CHF, further confirming the findings of FOlkers' study.
And observed 12 cases of CHF patients with unsatisfactory results of conventional digitalis and diuretics, daily oral COQ1O12Omg, 1 month later, clinical symptoms improved significantly 67%, echocardiography and other pioneering tests confirmed that the left atrial volume reduction and improved cardiac function. In China, Zhu Liyun et al[9] reported that COQ1O was used to treat 56 cases of CHF, and COQ1O9Omg/d was added on top of digoxin and diuretics, and was administered orally in 3 divided doses. 14 days were considered as one course of treatment, and 56 cases of CHF showed significant results in 10 cases, and 26 cases were effective, with an overall effective rate of 64%. The total effective rate was 64%. It showed that COQ1O was effective in treating CHF. It is especially effective in mild and moderate HF.
The COQ1O Clinical Trial Collaborative Group[1] reported that 114 HF patients were randomized and single-blindly compared with the addition of COQ1O and placebo on the basis of the original anti-HF treatment. 93 of the 114 patients were treated with COQ1O and 21 were treated with placebo, of which 33 underwent ECT cardiac blood pool imaging before and after treatment, and 12 underwent swan-Ganz-floating catheterization before and after treatment. The COQ1O dosage was 3O~6Omg/d for 8 weeks. The total effective rate of the COQ1O group was 90.4%, compared with 61.8% of the comfort group, and the difference was highly significant. In the COQ1O group, dyspnea and lower extremity edema were significantly reduced (P< O.O5), and hepatomegaly and jugular vein distension were also improved compared with the placebo group.
Ejection fraction (EF) and cardiac index (CI) increased significantly after COQ1O treatment. EF was 22.6±9.2 before treatment, but increased to 37.2±1O.1 after 2 months (P< O. O1), and CI increased from (2.O4±O.32) L/m2 to (2.48±O.52) L/m2 (P< O. O5). This suggests that the addition of COQ1O to conventional digitalis, diuretics and vasodilators in patients with HF is beneficial to increasing the contractility of the failing heart, increasing cardiac output and improving the symptoms of HF over a prolonged period of time. Wang Lizhi et al[1O] observed 84 cases of CHF patients in the original application of vasodilator, cardiotonic and diuretic anti-HF drugs, based on the treatment, static polarizing solution 5OOml ten COQ1O4Omg, 5~6h drip finished, once a day, 3 weeks for a course of treatment. The results showed that among the 84 cases, 34 cases (4O.8%) had obvious effect, 45 cases (53.57%) had effective effect, and the total effective rate was 94.O5%.
Liu Sufen et al[11] reported that 32 cases of ischemic cardiomyopathy were treated with potassium, magnesium solution and COQ1O, which could improve the cardiac function, greatly shorten the course of treatment, and significantly improve the efficacy of treatment. Gao Yan et al[12] observed 33 cases of diabetic heart disease treated with COQ1O for 3 months, echocardiography confirmed that the left ventricular internal diameter decreased from (5.13±O.56) cm to (4.87±O.34) cm (P< O.O5), of which 3 cases of left ventricular enlargement was obvious, but the left ventricular internal diameter was basically restored to the normal range after treatment. Li Shuzheng et al[13] treated 32 patients with dilated cardiomyopathy HF with captopril and COQ1O, with an effective rate of 93.7%. Zhao Pitian et al[14] treated 22 patients with dilated cardiomyopathy HF with the combination of oxalic acid, astragalus, and COQ1O on the basis of conventional therapy, and the results were satisfactory. The results were satisfactory. Compared with the conventional therapy, the cardiac function improved significantly, and the heart-chest ratio decreased significantly. This indicates that after long-term application of COQ1O in patients with dilated cardiomyopathy, the EF of most patients increased. Survival time is prolonged, and it is safe and effective[5] .
2.2 Treatment of refractory heart failure
Cao Guangzhi et al[15] included 30 cases of refractory HF with unsatisfactory therapeutic effects after 2 weeks of cardiotonic, diuretic and vasodilator treatment in the treatment group of patients with chronic CHF due to various etiologies who were hospitalized in the same period. After enrollment, on the basis of continuing to apply cardiotonic, diuretic and vasodilator, add COQ1O 1O~2Omg, twice a day intramuscular injection, 4 weeks for a course of treatment. Before and after the application of COQ1O 1, 2, 4 weeks, we did blood and urine routine, liver and kidney function, 12-lead electrocardiogram and open heart function test and X-ray cardiac telemetry. Other routine clinical methods were used to observe the condition.
As a result, most of the symptoms such as palpitation and shortness of breath improved within 1 week, and a few improved significantly within 2-3 weeks. Changes in cardiac function: hypertensive heart disease patients had the effect within 3 days; rheumatic heart valve disease patients had the slowest effect, within 2 weeks; the rest had the effect within 1 week. All cases were effective after 4 weeks of treatment, of which 26 cases (86.7%) showed significant effect and 4 cases (13.3%) were effective. 18 cases showed reduction of cardiac shadow in 4 weeks on X-ray cardiac telecardiogram. Cardiovascular function tests showed significant improvement, with a mean CI increase of 52.4%, total peripheral resistance decreased by 47.7%, and pulmonary capillary wedge pressure decreased by 34%.
Guo Fushan et al[16] treated 33 patients with refractory heart failure of cardiac function grade 3~4, on the basis of conventional digitalis, diuretic and vasodilator therapy, CoQ1O 6Omg was added to 5% dextrose 5OOml and placed on IV drip for 3~5h, once a day, for 15 days as a course of treatment. After that, CoQ1O1Omg was injected intramuscularly once a day; or CoQ1O1Omg was administered orally 3 times a day. After treatment, cardiac function improved, with an overall effective rate of 84.8%. Compared with 30 patients treated with digitalis, diuretics and vasodilators, the former was found to have significant efficacy, with a significant increase in partial oxygen pressure (P< O.O1), and a significant improvement in stroke volume and EF (P< O.O1). After discontinuing CoQ1O treatment, most patients (83.O%) had a recurrence of symptoms, and re-treatment was still effective without serious side effects. Xia Dejun et al[17] applied milrinone and CoQ1O to treat 50 cases of refractory heart failure, with an overall effective rate of 50%, compared with 25% in the control group, with a significant difference. Xiong Wansheng [18] used shenmai injection combined with CoQ1O to treat 31 cases of refractory heart failure, 11 cases (35. 5%), the total effective rate of 83. 9%, while the control group only 2 cases (8%), the total effective rate of 48. O%, the two groups of apparent efficiency and the total effective rate of the significant difference (P < O. O5). It is suggested that CoQ1O is an effective drug in the treatment of refractory heart failure, and the high dose of intravenous drip, the effect is rapid[15] .
3 Adverse reactions
Adverse reactions to CoQ1O are rare. Epigastric discomfort (O.39%), loss of appetite (O.23%), nausea (O.16%), diarrhea (O.12%), asymptomatic elevation of lactate dehydrogenase and ghrelin in patients who consume more than 3OOmg per day, and mild itching in a very small number of patients may occur.
In summary, CoQ1O has the following characteristics in the treatment of CHF: (1) the efficacy of CoQ1O is basically similar between different underlying cardiac diseases and different cardiac functions; (2) it does not affect the serum electrolytes and renal function; (3) it can reduce the dosage of digitalis and diuretics by combining it with other antichthonous drugs; (4) it can slow down the progression of HF, reduce the death rate, and prolong the life of patients; (5) it has better antichthonous efficacy, no matter it is injected orally or intravenously. (5) The drug has good anti-CHF efficacy both orally and intravenously, and the intravenous application has a short course of treatment, quick effect, and overcomes the shortcomings of inconsistent absorption rate of different individuals orally, thus the intravenous application is more reliable.
CoQ1O is a new endogenous biodynamic drug after cardiotonic, diuretic and vasodilator, which is an important progress and breakthrough in the history of HF treatment.
bibliography
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