| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1996;61:829-833
© 1996 The Society of Thoracic Surgeons
Departments of Cardiothoracic Surgery and Biochemistry, Royal Brompton Hospital, London, England
Accepted for publication November 2, 1995.
 |
Abstract |
|---|
 TopFootnotes Abstract IntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
Methods. To determine whether short-term oral supplementation with large doses of CoQ10 (600 mg in divided doses 12 hours before operation) was effective in myocardial protection, 20 patients with well-preserved left ventricular function (ejection fraction greater than 0.50) undergoing elective coronary revascularization were enrolled in a prospective, double-blind, placebo-controlled, randomized trial. Serial concentrations of CoQ10, myoglobin, creatine kinase MB fraction, and cardiac troponin T were measured preoperatively and 1, 6, 24, 72, and 120 hours postoperatively. Efficacy of myocardial protection was also assessed by clinical out-come and serial changes in electrocardiographic indices.
Results. The patient groups were similar with respect to preoperative and intraoperative characteristics. There was no significant difference in the preoperative plasma levels of CoQ10. These levels fell significantly in both groups after operation, although the magnitude of the decrease was less in the CoQ10-supplemented group (43% versus 60%). In both groups, there were significant postoperative increases in myoglobin, creatine kinase MB fraction, and cardiac troponin T. The magnitude of increases in cardiac troponin T was greater in the CoQ10-supplemented group, reaching marginal overall statistical significance (p = 0.06).
Conclusions. Short-term supplementation with large doses of CoQ10 does not lead to improved myocardial protection in patients undergoing coronary revascularization with well-preserved ventricular function and relatively short ischemic times.
|
Introduction |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
A number of groups have reported beneficial effects of CoQ10 in operative myocardial ischemia-reperfusion injury, both in the experimental [2–5] and clinical settings [6–10]. As an additive to cardioplegia, CoQ10 has been shown to increase the levels of adenosine triphosphate, reduce the production of free radicals, promote ultrastructural preservation, and improve cardiac function [2–5]. In the clinical setting, oral supplementation with CoQ10 for the week before operation has been reported to improve cardiac function, reduce the release of cardiac enzymes, and improve preservation of ventricular architecture as judged by electron micrography [6–9]. In one study, CoQ10 was administered intravenously to 60 patients a few hours before operation; CoQ10 improved the postoperative left ventricular stroke work index and reduced the release of cardiac enzymes [10]. The aim of our study was to determine whether short-term oral supplementation with large doses of CoQ10 (600 mg over 12 hours) could achieve similar benefits as intravenous administration.
In a prospective, double-blind, placebo-controlled, randomized trial, 20 patients undergoing elective coronary revascularization received high-dose oral supplementation with CoQ10 (300 mg at 6 PM the evening before operation and a further 300 mg at 6 AM on the morning of operation). Outcome was assessed based on clinical events, electrocardiographic changes, and serial measurements of three biochemical markers of myocardial injury.
|
Material and Methods |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
Trial Design
This was a prospective, randomized, double-blind, placebo-controlled trial. Patients were randomized by a computer-generated program to receive active preparation or placebo (Pharma Nord, Morpeth, UK). All patients were administered the active preparation or placebo at 6 PM the evening before and at 6 AM on the morning of operation. The nature of the preparation administered to each patient was unknown to the medical staff.
Patients
To keep the study as homogeneous as possible, we included only patients undergoing elective coronary artery bypass grafting. We excluded patients with unstable symptoms and those with concomitant medical illness, ejection fractions less than 0.30, or requirement for combined procedures or endarterectomy.
Operations
All operations were done by one surgeon. Cardiopulmonary bypass was performed with nonpulsatile flow at 2.4 L•min–1•m–2 of surface area per minute at normothermia, with a reduction to 1.8 L•min–1•m–2 at 28°C. Patients received 1 L of St. Thomas's Hospital formula cardioplegic solution at 4°C infused into the aortic root. Systemic hypothermia of 28° to 30°C was used during completion of the distal anastomoses.
Blood Samples
Blood samples were collected for plasma levels of CoQ10, cardiac troponin T (cTnT), creatine kinase MB fraction (CK-MB), and myoglobin before anesthesia and at 1, 6, 24, 72, and 120 hours after the end of the ischemic period. Samples were collected in tubes containing lithium heparin and were centrifuged within 30 minutes. The plasma was separated from the cells and stored at –20°C until analysis.
Biochemical Analyses
Plasma CoQ10 concentration was measured by coupled-column liquid chromatography (Prof K. Folkers, University of Texas). We measured cTnT by an enzyme-linked immunosorbent assay technique (ELISA Troponin T Kit; Boehringer Mannheim, Lewes, UK). Creatine kinase was measured by microparticle enzyme immunoassay with an Abbott IMX CK-MB kit and an Abbott IMX analyzer (Abbott Diagnostics Division, Maidenhead, UK). Myoglobin was assayed by a double antibody radioimmunoassay (Myoglobin RIA Test Kit; Biogenesis, Bournemouth, UK).
Electrocardiographic Diagnosis of Myocardial Infarction
Serial electrocardiograms were performed before and 1, 24, and 72 hours after operation, and as clinically indicated. A new Q wave (greater than 0.04 ms) or loss of more than 25% of R-wave progression in at least two leads was considered diagnostic of myocardial infarction. Minor ST-T wave changes and changes in conduction were not by themselves considered diagnostic of infarction.
Statistical Analyses
Data were analyzed with the STATGRAPHICS statistical program (Statgraphics, version 6.0, Manugistics, Inc.). Analysis of continuous data was performed with the Student's t test, and two-way analysis of variance was employed for repeated measures. The 
2 test was used to compare categoric data. Results are expressed as mean ± standard error.
|
Results |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
, the groups were well matched with respect to age, ejection fraction, number of grafts, and ischemic times. In particular, both groups of patients had well-preserved ventricular function (ejection fraction greater than 0.50) and relatively short ischemic times (approximately 45 minutes).
|
). The magnitude of fall in the placebo group (2.35 ± 0.27 µg/mL to 0.95 ± 0.13 µg/mL, ie, 60%) was greater than that in the supplemented group (2.01 ± 0.18 µg/mL to 1.14 ± 0.15 µg/mL, ie, 43%), although this did not reach statistical significance.
|
, respectively). The peak increase in myoglobin was at 1 hour, that of CK-MB was between 1 and 6 hours, and that of cTnT was at 6 hours. There was no significant difference in the magnitude of increase in myoglobin and CK-MB between the groups. In contrast, cTnT levels were greater in the CoQ10-supplemented group for most of the postoperative period, and these differences reached marginal statistical significance (p = 0.06).
|
|
|
Clinical Outcome
All patients survived, and there was no case of low cardiac output as judged by the need for mechanical or substantial inotropic support. Atrial fibrillation requiring administration of digitalis occurred in 2 patients in the control group and 3 in the supplemented group. There were no apparent adverse side effects of CoQ10 supplementation.
|
Comment |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
In the clinical setting, oral supplementation with CoQ10 for up to 1 week before operation [6–9] or intravenous supplementation a few hours before operation [10] has been reported to improve cardiac function and to reduce the release of cardiac enzymes. One particularly attractive feature of CoQ10 is the absence of any important adverse effects with supplementation [1].
However, CoQ10 is not currently available in parenteral form, and long-term oral supplementation before operation may be difficult to achieve because of geographic distance or urgency of operation. To investigate whether short-term oral supplementation with a large dose of CoQ10 might have equally beneficial actions on cardiac function and release of cardiac enzymes as are obtained with short-term parenteral supplementation [10], we administered 600 mg of CoQ10 in two divided doses over a 12-hour period before operation. Accepting that approximately 50% of an orally ingested dose of CoQ10 is absorbed and that peak plasma levels are reached 5 to 10 hours later, we prescribed a dose of CoQ10 calculated to achieve a plasma concentration equivalent to that used by Sunamori and colleagues [10], who administered 5 mg/kg CoQ10 intravenously 2 hours before operation.
Despite oral supplementation, there was no significant difference in the immediate preoperative plasma levels of CoQ10 in the two groups. Exogenously administered CoQ10 may not necessarily alter endogenous plasma levels because after absorption, CoQ10 is taken up by chylomicrons and then concentrated in specific sites, including the liver and myocardium [1]. The subsequent decrease in the plasma concentration of CoQ10 was lower in the supplemented group (by 43%) than in the placebo group (by 60%), although this just failed to reach statistical significance.
Both the temporal pattern and the magnitude of responses of myoglobin, CK-MB, and cTnT (a more specific marker of myocardial injury than myoglobin and CK-MB [11], which are derived from sources other than myocardium after cardiac operations) were very similar to those we have described previously in patients undergoing coronary revascularization with [12] and without [13] cardioplegia. The most surprising observation in the current study, however, was a suggestion of less favorable myocardial protection in the patients receiving supplementation with CoQ10. In a study with relatively small patient numbers, such conclusions must be interpreted cautiously because of the possibility that statistical power is too small to detect clinically important differences between the groups. Nevertheless, whereas there were no significant changes in myoglobin and CK-MB between the groups, the cTnT levels were greater in the CoQ10 group between 1 and 72 hours, reaching marginal statistical significance (p = 0.06).
The difference in the cTnT response cannot be ascribed to different carriers, as the same substance (soy bean oil solution in a gelatin capsule) was used in both the supplemented and placebo groups. Another possible explanation-perioperative infarction in the CoQ10-supplemented group-was excluded by the absence of specific diagnostic criteria on serial postoperative electrocardiograms. Furthermore, although our trial contained relatively small numbers of patients, careful preoperative selection to produce a homogeneous population, accompanied by randomization, resulted in well-matched groups comparable to the patient populations in other studies, in which beneficial effects of CoQ10 have been reported.
The majority of experimental and clinical studies reporting beneficial effects of CoQ10 supplementation have used indices of cardiac function as the predominant outcome measurements. Only two other clinical studies examined myocardial CK-MB release after CoQ10 supplementation and, in contrast to our findings, reported beneficial effects of CoQ10 supplementation. Chello and associates [8] demonstrated a significant reduction in plasma levels of CK-MB during a mean ischemic period of 71 minutes in 20 patients supplemented with 150 mg of CoQ10 for 7 days before operation. Because biochemical comparisons were stopped after protamine administration, it is not possible to say whether this beneficial effect would have persisted into the postoperative period. Sunamori and colleagues [10] reported a significant reduction in CK-MB release for up to 6 hours after reperfusion in 60 patients given intravenous supplementation of 5 mg CoQ10/kg 2 hours before operation when compared with historic controls. Unfortunately, this study exhibits the limitations of all retrospective, nonrandomized studies, and the conclusions must be interpreted cautiously.
The most likely explanation for the discrepancy between our results and those of others demonstrating beneficial effects of CoQ10 is that in the other studies, oral supplementation with CoQ10 was given for up to 1 week before operation. This could be advantageous in producing a steady-state concentration of plasma CoQ10, as 90% of the steady-state concentration is achieved after 4 days of oral dosing [1]. Two other factors may be relevant. First, our patients had well-preserved ventricular function and relatively short ischemic times. Indeed, endogenous plasma levels of CoQ10 taken from more than 1,000 patients with general cardiac disease were significantly lower in those with evidence of heart failure [14]. It is conceivable that such patients would have the most to gain from CoQ10 supplementation. This finding also may explain the observations of Tanaka and co-workers [6] that CoQ10 administration to patients undergoing valve replacement (who frequently have greater myocardial dysfunction) reduced the postoperative incidence of low cardiac output.
In summary, our study suggests that short-term supplementation with large doses of CoQ10 does not result in improved myocardial protection, at least in patients with well-preserved ventricular function undergoing myocardial revascularization with relatively short ischemic times. In view of the consistently beneficial effects of CoQ10 reported in the literature, however, long-term supplementation should still be considered in patients with impaired ventricular function.
|
Acknowledgments |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
|
Footnotes |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
|
References |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  J. B. Selvanayagam, I. Porto, K. Channon, S. E. Petersen, J. M. Francis, S. Neubauer, and A. P. Banning Troponin Elevation After Percutaneous Coronary Intervention Directly Represents the Extent of Irreversible Myocardial Injury: Insights From Cardiovascular Magnetic Resonance Imaging Circulation, March 1, 2005; 111(8): 1027 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Rosenfeldt, S. Marasco, W. Lyon, M. Wowk, F. Sheeran, M. Bailey, D. Esmore, B. Davis, A. Pick, M. Rabinov, et al. Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue J. Thorac. Cardiovasc. Surg., January 1, 2005; 129(1): 25 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Taggart Biochemical assessment of myocardial injury after cardiac surgery: Effects of a platelet activating factor antagonist, bilateral internal thoracic artery grafts, and coronary endarterectomy J. Thorac. Cardiovasc. Surg., October 1, 2000; 120(4): 651 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Vento, J. Aittomaki, K. A. Verkkala, L. J. Heikkila, J. A. Salo, J. Sipponen, and O. J. Ramo Nitecapone as an additive to crystalloid cardioplegia in patients who had coronary artery bypass grafting Ann. Thorac. Surg., August 1, 1999; 68(2): 413 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K Singal, N. Khaper, V. Palace, and D. Kumar On the role of coenzyme Q10 in cardiovascular diseases Cardiovasc Res, July 1, 1999; 43(1): 250 - 251. [Full Text] [PDF]
|
|
|
|
|
|
D. P. Taggart, L. Hadjinikolas, J. Hooper, J. Albert, M. Kemp, D. Hue, M. Yacoub, and J. C. Lincoln EFFECTS OF AGE AND ISCHEMIC TIMES ON BIOCHEMICAL EVIDENCE OF MYOCARDIAL INJURY AFTER PEDIATRIC CARDIAC OPERATIONS J. Thorac. Cardiovasc. Surg., April 1, 1997; 113(4): 728 - 735. [Abstract] [Full Text]
|
|
|
|
|
|
S. A. Mortensen and D. P. Taggart Coenzyme Q10 Treatment May Be Protective During Coronary Artery Bypass Operations Ann. Thorac. Surg., October 1, 1996; 62(4): 1243 - 1244. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
