ascorbic-acid and Ventricular-Fibrillation

In this study, we aimed to compare the myocardial protective effects of high dose ascorbic acid with the effects obtained by adding diltiazem to high dose ascorbic acid. We studied 30 elective cardiac surgery patients prospectively. In ascorbic acid group (group AA), ascorbic acid was given after induction and just before aortic declamping, 50 mg.kg-1 each time. In ascorbic acid + diltiazem group (group AA + D), diltiazem was added to ascorbic acid (0.3 mg.kg-1, i.v. after induction and then 2 micrograms.kg-1 min-1 i.v. infusion until declamping). Group C was the control group. There was no significant difference between groups in terms of cardiac enzyme levels. After declamping, the arterial and coronary sinus malondialdehyde levels, measured as a marker of lipid peroxidation, were increased significantly in the group C while remained stable in the other two groups. Ventricular fibrillation (VF) after declamping was positive in 3, 1 and 6 patients in the groups AA, AA + D and C respectively. In this study, we observed the prevention of lipid peroxidation in the group AA and group AA + D. The only positive result obtained by addition of diltiazem to high dose ascorbic acid was the decrease in the frequency of VF after declamping. We concluded that the prevention of lipid peroxidation in the groups AA and AA + D provided no measurable protection over myocardial ischaemia-reperfusion injury.

Topics: Adult; Aged; Ascorbic Acid; Calcium Channel Blockers; Coronary Artery Bypass; Diltiazem; Female; Hemodynamics; Humans; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Myocardial Reperfusion Injury; Myocardium; Postoperative Complications; Prospective Studies; Ventricular Fibrillation

Accumulating evidence demonstrated that administration of ω-3 polyunsaturated fatty acid (ω-3 PUFA) or ascorbic acid (AA) following cardiac arrest (CA) improves survival. Therefore, we investigate the effects of ω-3 PUFA combined with AA on myocardial function after CA and cardiopulmonary resuscitation (CPR) in a rat model. Thirty male rats were randomized into 5 groups: (1) sham; (2) control; (3) ω-3 PUFA; (4) AA; (5) ω-3 PUFA + AA. Ventricular fibrillation (VF) was induced and untreated for 6 min followed by defibrillation after 8 min of CPR. Infusion of drug or vehicle occurred at the start of CPR. Myocardial function and sublingual microcirculation were measured at baseline and after return of spontaneous circulation (ROSC). Heart tissues and blood were collected 6 h after ROSC. Myocardial function and sublingual microcirculation improvements were seen with ω-3 PUFA or AA compared to control after ROSC (p < 0.05). ω-3 PUFA + AA shows a better myocardial function than ω-3 PUFA or AA (p < 0.05). ω-3 PUFA or AA decreases pro-inflammatory cytokines, cTnI, myocardium malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) modified proteins compared to control (p < 0.05). ω-3 PUFA and AA combined have lower MDA and 4-HNE modified proteins than alone (p < 0.05). ω-3 PUFA or AA treatment reduces the severity of post-resuscitation myocardial dysfunction, improves sublingual microcirculation, decreases lipid peroxidation and systemic inflammation in the early phase of recovery following CA and resuscitation. A combination of ω-3 PUFA and AA treatment confers an additive effect in suppressing lipid peroxidation and improving myocardial function.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Biomarkers; Blood Circulation; Cardiopulmonary Resuscitation; Disease Models, Animal; Fatty Acids, Omega-3; Heart Arrest; Inflammation Mediators; Lipid Peroxidation; Male; Myocardium; Oxidative Stress; Rats, Sprague-Dawley; Recovery of Function; Ventricular Fibrillation

Intravenous (IV) administration of ascorbic acid during cardiopulmonary resuscitation (CPR) was reported to facilitate defibrillation and improves survival in ventricular fibrillation (VF) cardiac arrest. We investigated whether IV administration of ascorbic acid after return of spontaneous circulation (ROSC) can improve outcomes in VF cardiac arrest in a rat model and its interaction with therapeutic hypothermia.. Ventricular fibrillation-induced cardiac arrest followed by CPR and defibrillation was performed in male Wistar rats. After ROSC, the animals were equally randomized to the normothermia (NormoT), hypothermia (HypoT), ascorbic acid (AA+NormoT), and ascorbic acid plus hypothermia (AA+HypoT) groups. The AA+NormoT and AA+HypoT groups received IV ascorbic acid (100 mg/kg). In the HypoT and AA+HypoT groups, therapeutic hypothermia was maintained at 32°C for 2 hours.. There were 12 rats in each group. Within 4 hours after ROSC, the HypoT, AA+NormoT, and AA+HypoT groups had significantly lower myocardial lipid peroxidation than the NormoT group. Within 4 hours following ROSC, the AA+NormoT group had a significantly better systolic function (dp/dt40 ) than the NormoT group (6887.9 mm Hg/sec, SD ± 1049.7 mm Hg/sec vs. 5953.6 mm Hg/sec, SD ± 1161.9 mm Hg/sec; p < 0.05). The AA+HypoT group also showed a significantly better diastolic function (-dp/dtmax ) than the HypoT group (dp/dt40 : 8524.8, SD ± 1166.7 mm Hg/sec vs. 7399.8 mm Hg/sec, SD ± 1114.5 mmHg/sec; dp/dtmax : -8183.4 mm Hg/sec, SD ± 1359.0 mm Hg/sec vs. -6573.7 mm Hg/sec, SD ± 1110.9 mm Hg/sec; p < 0.05) at the fourth hour following ROSC. Also at 4 hours, there was less myocytolysis in the HypoT, AA+NormoT, and AA+HypoT groups than the NormoT group. The HypoT, AA+NormoT, and AA+HypoT groups had significantly better survival rates and neurologic outcomes than the NormoT group. Compared with only five surviving animals in the NormoT group, there were nine, eight, and 10 in the HypoT, AA+NormoT, and AA+HypoT groups, respectively, with good neurologic outcomes at 72 hours.. Intravenous ascorbic acid administration after ROSC in normothermia may mitigate myocardial damage and improve systolic function, survival rate, and neurologic outcomes in VF cardiac arrest of rat. Combination of ascorbic acid and hypothermia showed an additive effect in improving both systolic and diastolic functions after ROSC.

Topics: Animals; Ascorbic Acid; Cardiopulmonary Resuscitation; Diastole; Disease Models, Animal; Electric Countershock; Heart Arrest; Hemodynamics; Hypothermia; Hypothermia, Induced; Infusions, Intravenous; Lipid Peroxidation; Male; Myocardial Contraction; Myocardium; Rats; Rats, Wistar; Survival Analysis; Systole; Ventricular Fibrillation

To examine the effects of ascorbic acid (AA) administrated during cardiopulmonary resuscitation (CPR) on the myocardial injury in a rat model of ventricular fibrillation (VF) and electrical shock (ES).. VF was induced in male Wistar rats and left untreated for 5 min, followed by 1 min of CPR, and then one ES of 5 J. At the start of CPR, animals received either intravenous administration of AA (100 mg/kg) or Tempol (30 mg/kg), two antioxidants, or 0.9% saline (VF + ES group). After ES, animals were immediately killed. Myocardial lipoxidation was determined by malondialdehyde (MDA) assay. The histology and ultrastructural changes of myocardium were also evaluated. The mitochondrial permeability transition pore (mPTP) opening was measured based on the mitochondrial swelling rate. The complex activities and respiration of mitochondria were assessed, too.. Increased myocardial injury and mitochondrial damage in the VF + ES group were noted. AA and Tempol alleviated such damages. Both AA and Tempol improved accelerated mitochondrial swelling; decreased complex activities and respiratory dysfunction occurred in the VF + ES group. The animals receiving AA and Tempol during CPR had better successful resuscitation rates and 72-h survival than the VF + ES group.. Intravenous administration of AA and Tempol at the start of CPR may reduce lipid peroxidation and myocardial necrosis, diminish mitochondrial damage, facilitate resuscitation, and improve outcomes after VF + ES.

Topics: Animals; Antioxidants; Ascorbic Acid; Cardiopulmonary Resuscitation; Electric Countershock; Heart Arrest; Heart Injuries; Male; Rats; Rats, Wistar; Taiwan; Ventricular Fibrillation

The present experiment determined the effects of glutathione and ascorbic acid, the two most important hydrophilic antioxidants, on myocardial ischemia-reperfusion injury and evaluated their relative therapeutic values. Isolated rat hearts were subjected to ischemia (30 min) and reperfusion (120 min) and treated with ascorbic acid, glutathione monoethyl ester (GSHme), or their combination at the onset of reperfusion. Administration of 1 mM GSHme alone, but not 1 mM ascorbic acid alone, significantly attenuated postischemic injury (P < 0.05 versus vehicle). Most interestingly, coadministration of ascorbic acid with GSHme markedly enhanced the protective effects of GSHme (P < 0.01 versus vehicle). The protection exerted by the combination of GSHme and ascorbic acid at 1 mM each was significantly greater than that observed with 1 mM GSHme alone (P < 0.05). Moreover, treatment with GSHme alone or GSHme plus ascorbic acid markedly reduced myocardial nitrotyrosine levels, suggesting that these treatments attenuated myocardial peroxynitrite formation. These results demonstrated that 1) GSHme, but not ascorbic acid, exerted protective effects against ischemia-reperfusion injury; and 2) the protective effects of GSHme were further enhanced by coadministration with ascorbic acid, suggesting a synergistic effect between GSHme and ascorbic acid.

Topics: Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Glutathione; Heart; Heart Rate; Incidence; Lipid Peroxidation; Myocardial Reperfusion Injury; Myocardium; Protective Agents; Rats; Reperfusion Injury; Tachycardia; Tyrosine; Ventricular Fibrillation