Effects of a novel ascorbate-based protocol on infarct size and ventricle function in acute myocardial infarction patients undergoing percutaneous coronary angioplasty

Abstract

IntroductionThis study was designed to test the hypothesis that high-dose ascorbate prior to reperfusion followed by low chronic oral doses ameliorate myocardial reperfusion injury (MRI) in acute myocardial infarction patients subjected to primary percutaneous coronary angioplasty (PCA).Material and methodsA randomized double-blind placebo-controlled and multicenter clinical trial was performed on acute myocardial infarction (AMI) patients who underwent PCA. Sodium ascorbate (320 mmol/l, n = 53) or placebo (n = 46) was infused 30 min prior to PCA. Blood samples were drawn at enrolment (M1), after balloon deflation (M2), 6–8 h after M2 (M3) and at discharge (M4). Total antioxidant capacity of plasma (ferric reducing ability of plasma – FRAP), erythrocyte reduced glutathione (GSH) and plasma ascorbate levels were determined in blood samples. Cardiac magnetic resonance (CMR) was performed at 7–15 days and 2–3 months following PCA. Ninety-nine patients were enrolled. In 67 patients, the first CMR was performed, and 40 patients completed follow-up.ResultsThe ascorbate group showed significantly higher ascorbate and FRAP levels and a decrease in the GSH levels at M2 and M3 (p < 0.05). There were no significant differences in the infarct size, indexed end-systolic volume and ejection fraction at both CMRs. There was a significant amelioration in the decreased ejection fraction between the first and second CMR in the ascorbate group (p < 0.05).ConclusionsAscorbate given prior to reperfusion did not show a significant difference in infarct size or ejection fraction. However, it improved the change in ejection fraction determined between 7–15 days and 2–3 months. This result hints at a possible functional effect of ascorbate to ameliorate MRI.

Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities

“…In the clinical setting, impaired micro-circulatory reperfusion was improved by ascorbate infusion in patients undergoing elective PCA[ 74 ]. Similar results were recently reported by our group[ 75 ]. These results suggest a positive role of antioxidants in counteracting the deleterious effects of oxidative stress on microvascular function.…”

“…Our group recently developed a randomized clinical trial in patients with AMI undergoing PCA, where massive doses of ascorbate (or placebo) were administered prior to PCA. Patients treated with ascorbate prior to myocardial reperfusion showed a better recovery of ejection fraction at 2-3 mo (measured by cardiac magnetic resonance) and significantly higher myocardial perfusion after PCA ( TIMI -myocardial perfusion grade) than placebo patients, with no differences in infarct size[ 75 ] (Table 1 ).…”

Vitamin C in the critically ill - indications and controversies

“…One recent randomized multicenter clinical trial on patients with myocardial infarction undergoing percutaneous coronary angioplasty did not show a significant improvement in infarct size or ejection fraction at the time of the intervention with vitamin C administration. However, a decline in the LVEF between 7-15 d and 2-3 mo noted in the control group was not seen in the vitamin C group[ 63 ]. The authors of this study suggested that vitamin C may have ameliorated myocardial reperfusion injury[ 63 ].…”

“…However, a decline in the LVEF between 7-15 d and 2-3 mo noted in the control group was not seen in the vitamin C group[ 63 ]. The authors of this study suggested that vitamin C may have ameliorated myocardial reperfusion injury[ 63 ].…”

Vitamin C for Cardiac Protection during Percutaneous Coronary Intervention: A Systematic Review of Randomized Controlled Trials

“…The biologic plausibility of the cardioprotective effect of VC has been shown in clinical trials where VC reduced ROS when administered prior to PCI [33,34,42,43]. However, the outcomes are conflicting, with some studies showing reduction of the biomarkers of myocardial injury cTnI and CK-MB [39,41], whereas others fail to show a benefit [29,44]. Given these inconsistences, it is prudent to address the question whether or not VC administration is benefits following PCI.…”