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Biomedical subjects

Dimitrios Th Kremastinos

Publications and source records attributed to Dimitrios Th Kremastinos.

At least 19 recordsLinked to original sources
PubMed2007

Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress.

Oleuropein (oleu) is a natural phenolic antioxidant, which is present in elevated concentration in olives, olive oil and olive tree leaves. Doxorubicin (DXR) induced cardiotoxicity is mainly induced by oxidative stress but the precise mechanism remains obscure. However, there is evidence that high concentration of nitric oxide (NO) occurring as a result of iNOS induction and peroxynitrite formation may be involved in DXR cardiotoxicity. The aim of the present study was to evaluate a possible protective role of oleu in DXR induced cardiotoxicity in vivo. Fifty rats were divided into 6 groups and treated as follows: control group with a single injection of 2 ml normal saline intraperitoneally (i.p.), DXR group with a single dose of 20 mg/kg i.p, and DXR plus oleu groups with 20 mg/kg DXR i.p. and 100 or 200 mg/kg/BW of oleu i.p. for 5 or 3 consecutive days starting either 2 days before or on the day of DXR administration. Seventy-two hours after DXR treatment blood samples were collected for creatine phosphokinase (CPK), creatine phosphokinase-MB (CPK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) assessments and the rats were then sacrificed. Hearts were used for general histology, iNOS immunohistochemical and Western blot analysis, and for determination of tissue concentrations of lipid peroxidation products, protein carbonyls (PCs), and nitrotyrosine (NT). DXR treated animals demonstrated very extensive cytoplasmic vacuolisation whereas much less vacuolisation was found in oleu treated groups. They also revealed a significant elevation of cardiac enzymes release into systemic circulation (P<0.05 vs saline). Both doses of Oleu tested and both treatment protocols reduced DXR elevated serum levels of CPK, CPK-MB, LDH, AST and ALT (P<0.05). Furthermore, it reduced DXR induced lipid peroxidation, PCs content, NT concentration and iNOS induction in myocardial tissue (P<0.05). Oleu exerts a protective effect by eliminating DXR induced cardiotoxicity expressed by the alteration of intracellular and peripheral markers. Combined oleu and DXR treatment improves the therapeutic outcome by preventing undesirable toxicity.

Acute Disease↗
PubMed2007

Ischaemia modified albumin in radiofrequency catheter ablation.

UNLABELLED: Aim Ischaemia modified albumin (IMA) is considered a marker of myocardial ischaemia, in contrast to the biomarkers of myocardial injury [creatine kinase (CK), the MB isoenzyme of CK, and cardiac troponin I (Tn-I)] that are released when cardiac necrosis occurs. Ischaemia modified albumin has been reported to increase following percutaneous coronary intervention and in acute coronary syndromes. We sought to determine whether IMA increases following radiofrequency (RF) ablation. METHODS AND RESULTS: We studied 40 consecutive patients who underwent RF catheter ablation; 20 were men and 20 women and their age was 47 +/- 16 (16-77) years. All patients underwent electrophysiological study and subsequent RF ablation. Peripheral venous samples were collected before the procedure (baseline), immediately after the procedure, 2 h post-procedure and the following day (20 h post-procedure) and assayed for CK, the MB isoenzyme of CK, cardiac Tn-I and IMA. Ischaemia-modified albumin plasma levels did not differ significantly at all four time points, baseline, and following ablation (P = 0.5974), whereas CK, CK-MB, and Tn-I increased significantly at all time points compared with baseline (P < 0.0001). Post-ablation, all but three 3 CK measurements were in the normal range; 14 patients had CK-MB plasma levels above the upper limit of normal; all but one patient had Tn-I elevated. CONCLUSION: The IMA plasma levels do not change significantly following RF ablation, unlike biomarkers of myocardial injury, implying that myocardial necrosis occurs without preceding ischaemia.

Adolescent↗
PubMed2006

Application of NMR-based metabonomics in the investigation of myocardial ischemia-reperfusion, ischemic preconditioning and antioxidant intervention in rabbits.

NMR based metabonomics was applied in rabbit plasma samples during myocardial ischemia-reperfusion injury, with the following interventions: (1) Control (no intervention); (2) ischemic preconditioning (IpC); (3) administration of melatonin; (4) IpC+administration of melatonin; (5) treatment of the indole derivative C6458. The (1)H NMR signal intensity ratio of lactate/glucose was found to increase in Control samples during reperfusion compared to baseline, while lactate+alanine/acetate was decreased suggesting impairment of aerobic glycolysis and concomitant lipid utilization. In contrast, after IpC or treatment with C6458, the lactate/glucose ratio was similar to baseline in accordance with the previously reported decrease in infarct size. Multivariate statistical methods such as Principal Component Analysis (PCA), and Discriminant Analysis (DA) were used for the discrimination of samples. The use of ANOVA variable preselection prior to PCA was advantageous in producing adequate models. PCA could classify the Control group in three clusters according to the condition of the heart (baseline-ischemia-reperfusion) while in the IpC groups no classification was evident. PCA discrimination upon treatment with melatonin and C6458 provided further evidence of their effect on the metabolic profile. The supervised DA resulted in fine discrimination between the different subgroups. Plasma NMR spectra in combination with pattern recognition techniques proved to be an efficient and simple method to depict the metabolic changes produced upon ischemia-reperfusion of the myocardium.

Acetates↗
PubMed2006

Ischemia-modified albumin in relation to exercise stress testing.

OBJECTIVES: We examined whether ischemia-modified albumin (IMA) plasma levels change during exercise stress testing (EST) in patients with known coronary artery disease and whether the induced changes differ between positive and negative exercise tests. BACKGROUND: Ischemia modified albumin is considered a marker of myocardial ischemia and increases after coronary angioplasty and in acute coronary syndromes. METHODS: We studied 40 consecutive patients with established coronary artery disease who underwent EST. Venous samples, for IMA measurement, were collected before the stress test (baseline), at peak exercise, and 60 min after the completion of the exercise test. RESULTS: There was significant difference in the IMA values at the 3 prespecified time points (p = 0.012), whereas there was no interaction between the IMA changes and the result of the stress test, whether positive or negative (p for the interaction term = 0.94). Baseline, peak EST, and post-EST IMA levels were similar in patients with positive and negative exercise tests (p = 0.61). The IMA significantly decreased at peak exercise compared with baseline values in positive (p < 0.0001) and in negative EST (p = 0.012). Moreover, IMA concentration increased 60 min after EST compared with peak-EST values in positive (p < 0.0001) and in negative tests (p = 0.003), returning to pre-EST levels in both groups. CONCLUSIONS: The IMA plasma levels change significantly during exercise testing in patients with coronary artery disease, but there is no difference between positive and negative stress tests; this possibly implies that the observed changes do not reflect myocardial ischemia.

Adult↗
PubMed2006

Effect of levosimendan on ventricular arrhythmias and prognostic autonomic indexes in patients with decompensated advanced heart failure secondary to ischemic or dilated cardiomyopathy.

Positive inotropes used for the treatment of heart failure have been arrhythmogenic. Levosimendan is a novel calcium sensitizer with vasodilating properties and a complex mechanism of action. Its effect on ventricular arrhythmias and 24-hour Holter electrocardiographically derived prognostic autonomic nervous system-related markers, because it occurs in parallel with changes in cardiac function and neurohormonal response, has not been systematically assessed. Forty-five patients (mean age 65 +/- 1.3 years) with heart failure refractory to conventional therapy and a mean ejection fraction of 23 +/- 1.2%, randomized to levosimendan or placebo, were studied. After Holter electrocardiographic recording, 1 drug was infused for 24 hours (levosimendan at a dose of 0.1 mug/kg/min). During this period, another Holter recording was performed to assess changes in ventricular arrhythmogenesis, 24-hour heart rate variability indexes, QTc, QT variability, and QT/RR slope. Clinical evaluation, echocardiography, and B-type natriuretic peptide measurements were performed at baseline and after treatment. After levosimendan, clinical and echocardiographic improvement was observed, associated with beneficial neurohormonal modulation (mean B-type natriuretic peptide level after levosimendan 668 +/- 108 vs 1,009 +/- 122 pg/ml at baseline, p <0.05). Episodes of nonsustained ventricular tachycardia increased with levosimendan (21.9 +/- 9.6 vs 3.0 +/- 1.2, p <0.05). Levosimendan and placebo exerted a neutral effect on all autonomic markers assessed. In conclusion, levosimendan at low doses increases nonsustained ventricular arrhythmias, without affecting Holter-derived, prognostically significant autonomic markers. At the same time, it is associated with improvements in cardiac function and neurohormonal response. These findings may have important clinical and prognostic implications.

Aged↗
PubMed2006

Rapid detection and successful treatment of esophageal perforation after radiofrequency ablation of atrial fibrillation: lessons from five cases.

INTRODUCTION: The aim of the study was to identify criteria for rapid recognition and successful treatment of esophageal perforation after radiofrequency ablation for atrial fibrillation (AF). METHODS AND RESULTS: Esophageal perforation occurred in five patients after intraoperative (n = 4) or percutaneous (n = 1) AF ablation. Patients presented with high fever (n = 3) or severe chest/epigastric pain (n = 2) 8-28 days after ablation. WBC count was elevated at presentation in all patients (15,460 +/- 2,910/muL), CRP showed a delayed rise. Thoracic CT detected free air in all. Neurologic complications occurred in three cases (60%) with a delay of 5-40 hours after first symptoms. Only one (20%) developed neurologic complications within the first 24 hours. Two patients (40%) died before surgery could be performed. In both, time from symptom onset to diagnosis was significant (24 and 36 hours). Three patients (60%) underwent esophageal resection and survived. In two of them, treatment was rapid with time from symptoms to surgery of 24 hours; they had favorable outcome. In the third surviving patient, surgery was late (5 days after first symptoms); permanent neurologic residues remained. CONCLUSION: The leading symptom of esophageal perforation is high fever or severe chest/epigastric pain. Fever is not necessarily present. Leukocytosis is the earliest and most sensitive laboratory marker, thoracic CT the most valuable diagnostic examination. The dramatic neurologic complications occur with a delay of at least a few hours after first symptoms. Immediate surgery may prevent neurologic complications and could possibly result in a high survival rate without residues. Delay of treatment seems to have devastating results.

Adult↗
PubMed2006

Pre-treatment with Irbesartan attenuates left atrial stunning after electrical cardioversion of atrial fibrillation.

AIMS: Left atrial (LA) stunning, the transient impairment of LA function, is responsible for an increased thrombo-embolic risk after cardioversion of atrial fibrillation (AF). Angiotensin receptor blockers (ARBs) attenuate atrial remodelling in AF and could theoretically influence LA stunning. We studied the effect of Irbesartan on LA stunning. METHODS AND RESULTS: We prospectively assigned 50 patients from the outpatient clinic undergoing electrical cardioversion for AF with duration of >4 weeks, into two matched groups: 25 patients were treated with Irbesartan (228+/-93 mg/day) for at least 2 weeks prior to cardioversion (Irbesartan group); 25 patients did not receive ARBs (control group). The groups did not differ concerning age (64+/-13 vs. 63+/-13 years, respectively), AF duration (20+/-18 vs. 20+/-19 weeks), underlying disease, LA diameter (46+/-7 vs. 47+/-9 mm), left ventricular dimensions, and ejection fraction (47.7+/-11.6 vs. 49.7+/-14.5%). We assessed LA appendage emptying velocities (LAAEV) and LA spontaneous echo contrast (LASEC) by transoesophageal echocardiography before and after cardioversion and at 2 weeks, and the A-wave by transthoracic echocardiography after cardioversion, at 2 and at 4 weeks. LA stunning was significantly attenuated in the Irbesartan group. The reduction of LAAEV immediately after cardioversion was significantly less in the Irbesartan group (LAAEV reduction of 9+/-49% from 28+/-9 cm/s before cardioversion to 25+/-13 cm/s immediately afterwards) than in the control group (reduction of 48+/-20% from 34+/-15 cm/s before cardioversion to 16+/-6 cm/s afterwards) (P = 0.048). New or increased LASEC occurred in eight patients (32%) in the Irbesartan vs. 16 patients (64%) in the control group (P = 0.046). CONCLUSION: Irbesartan significantly attenuates LA stunning after electrical cardioversion of AF. Therefore, ARBs may represent an important pharmacological supplementation in patients being prepared for cardioversion.

Adult↗
PubMed2006

Acute administration of vitamin E triggers preconditioning via K(ATP) channels and cyclic-GMP without inhibiting lipid peroxidation.

Vitamin E (VitE) is considered an antioxidant agent. One or more brief periods of ischemia (isc), followed by short reperfusion (rep), increase the tolerance of the heart to a subsequent prolonged ischemia, a phenomenon known as ischemic preconditioning (PC). Mitochondrial KATP channels (mitoKATP), cyclic-GMP (cGMP), and free radicals are involved in the mechanism of PC, whereas some antioxidants abolish this benefit. The purpose of this study was to evaluate the effect of VitE on infarct size, PC, and the oxidative status in vivo. Male rabbits were divided into seven groups and were subjected to myocardial ischemia (isc) and reperfusion (rep) with the following interventions: (1) control (no intervention); (2) E150 (iv VitE at a dose of 150 mg/kg for 75 min, starting 40 min before index isc and lasting through 5 min of rep); (3) E300 (iv VitE 300 mg/kg as previously described); (4) PC (two cycles of 5 min isc and 10 min rep), (5) combined E150-PC; and (6) combined E300-PC. In the last two groups VitE was given 40 min before index ischemia. Blood samples were taken for malondialdehyde (MDA) and conjugated dienes (CDs) measurement. In a second series of experiments heart tissue samples were taken at the time of long ischemia for MDA and CD determination and for cGMP assay. In order to test whether combined treatment with VitE (as the E150 group) and the mitoKATP blocker 5-hydroxydecanoic acid (5-HD) changes the infarct size, an additional group was assessed in the first series of experiments. Tissue VitE concentration was evaluated in myocardium. VitE at both doses reduced the infarct size (19.7 +/- 2.8% for E150 and 18.8 +/- 4.9% for E300 vs 47.4 +/- 2.6% in control, P < 0.05) without attenuating the effect of PC (10.2 +/- 3.1% for E150-PC, 12.4 +/- 2.2% for E300-PC, vs 13.5 +/- 3.3% for PC). Combined VitE and 5-HD treatment abrogates this benefit (37.4 +/- 6.5%, P < 0.05 vs E150 and NS vs control). VitE increases intracellular cGMP and CDs levels (P < 0.05 vs control) to the same extent as PC (P < 0.05 vs control), with no effect on MDA (P = NS between all the groups). Peripheral markers of oxidative stress are increased during reperfusion in all groups (P < 0.05 vs baseline). Overall, VitE limits infarct size via mitoKATP and cGMP, while preserving the benefit of ischemic PC.

Animals↗
PubMed2006

Differential activation of mitogen-activated protein kinases in ischemic and nitroglycerin-induced preconditioning.

Previous studies have shown that the cardioprotective effect of ischemic preconditioning (IPC) can be mimicked pharmacologically with clinically relevant agents, including nitric oxide (NO) donors. However, whether pharmacological preconditioning shares the same molecular mechanism with IPC is not fully elucidated. The present study aimed to determine the activation of mitogen-activated protein kinases (MAPKs) (ERK1/2, p38 MAPK and p46/p54 JNKs) during ischemia and at reperfusion in nitroglycerin-induced preconditioning as compared to IPC and to correlate this with the conferred cardioprotection in anesthetized rabbits. Sixty minutes of intravenous administration of nitroglycerin was capable of inducing both early and late phase preconditioning in anesthetized rabbits, as it was expressed by the reduction of infarct size. Despite the cardioprotective effect conferred by both ischemic and nitroglycerin-induced preconditioning, there was a differential phosphorylation of MAPKs between the studied groups. p38 MAPK was activated early in ischemia in both ischemic and the early nitroglycerin-induced preconditioning while JNKs were markedly increased only after IPC. Furthermore, in these groups, ERK1/2 were activated during reperfusion. A different profile was observed in the late preconditioning induced by nitroglycerin with increased p38 MAPK and ERK1/2 phosphorylation during late ischemia. No activation of JNKs was observed at any time point in this group. It seems that activation of individual MAPK subfamilies depends on the nature of preconditioning stimulus.

Animals↗
PubMed2006

The effects of tirofiban on peripheral markers of oxidative stress and endothelial dysfunction in patients with acute coronary syndromes.

BACKGROUND: Endothelial dysfunction and oxidative stress are believed to be central mechanisms in atherogenesis. We aimed to determine the effects of tirofiban on oxidative stress and neutrophil-endothelium interaction markers in patients with acute coronary syndromes (ACS). MATERIALS AND METHODS: We measured malondialdehyde (MDA), interleukin-6 (IL-6) and soluble endothelial intercellular and vascular adhesion molecules (sICAM-1 and sVCAM-1) on admission, at 48 and 72 h and on 5th day of hospitalization in 34 patients (age 66.5+/-1.8 years) with ACS. Patients with recurrent angina, changes on the electrocardiogram and/or elevated troponin I received intravenously tirofiban for 48 h and the others received normal saline. RESULTS: Baseline concentrations of all markers did not differ significantly and compared with placebo, tirofiban infusion markedly reduced MDA, IL-6, sICAM-1 and sVCAM-1 at 48 h (-31+/-6% vs. 84+/-49%, p=0.007, -12+/-14% vs. 23+/-10%, p=0.05, -20+/-6% vs. 36+/-25%, p=0.04 and -10+/-5% vs. 6+/-5%, p=0.02, respectively). Relative to baseline, significant reductions were observed for all 4 markers at 72 h and day 5 (p<0.05). CONCLUSION: Tirofiban potentiates the decline in oxidative stress and may reverse abnormal endothelial activation in patients with ACS. This benefit seems to remain over the following 5 days.

Acute Disease↗
PubMed2006

Coronary angioplasty in identical twins.

We report coronary angioplasty of the same coronary artery in identical twin sisters. The patients had similar risk factors but differed in their coronary anatomy. The angioplasties were carried out on the same day and by the same cardiologist. To our knowledge, this is the first reported follow-up of such a case.

Aged↗
PubMed2006

Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study.

AIMS: To compare the therapeutic efficacy of placebo, propranolol, and fluoxetine in patients with vasovagal syncope (VVS). METHODS AND RESULTS: Ninety-six consecutive patients with VVS were randomized to treatment with placebo, propranolol, or fluoxetine and followed-up for 6 months. Before and during treatment, they reported their syncopal and presyncopal episodes and graded their well-being, expressed as the general evaluation of life, general activities, and everyday activities (each scaled from 1 = very good to 5 = very bad). Two patients refused follow-up. Among the remaining 94, no difference between groups was observed regarding the distribution of time of vasovagal events (syncopes or presyncopes) during follow-up (log-rank test). No difference was also observed when syncopes and presyncopes were assessed separately. Eighteen patients discontinued therapy. Among the remaining 76 ('on-treatment' analysis), the mean time to a vasovagal episode (syncope or presyncope) was significantly longer in the fluoxetine group when compared with the two other groups (log-rank test, P < 0.05). A significant difference in favour of fluoxetine was also observed regarding presyncopes. The difference between groups regarding the syncope-free period was not significant. During therapy, patients' well-being was improved (decreased) only in the fluoxetine-group (13.4 +/- 0.7 vs. 15.4 +/- 0.9 before treatment, P < 0.01). CONCLUSION: Fluoxetine seems to be equivalent to propranolol and placebo in the treatment of VVS. However, it improves patients' well-being and might be more effective in reducing presyncopes and total vasovagal events in some patients with recurrent VVS.

Adrenergic beta-Antagonists↗
PubMed2006

A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy.

The sarcoplasmic reticulum Ca(2+)-cycling proteins are key regulators of cardiac contractility, and alterations in sarcoplasmic reticulum Ca(2+)-cycling properties have been shown to be causal of familial cardiomyopathies. Through genetic screening of dilated cardiomyopathy patients, we identified a previously uncharacterized deletion of arginine 14 (PLN-R14Del) in the coding region of the phospholamban (PLN) gene in a large family with hereditary heart failure. No homozygous individuals were identified. By middle age, heterozygous individuals developed left ventricular dilation, contractile dysfunction, and episodic ventricular arrhythmias, with overt heart failure in some cases. Transgenic mice overexpressing the mutant PLN-R14Del recapitulated human cardiomyopathy exhibiting similar histopathologic abnormalities and premature death. Coexpression of the normal and mutant-PLN in HEK-293 cells resulted in sarcoplasmic reticulum Ca(2+)-ATPase superinhibition. The dominant effect of the PLN-R14Del mutation could not be fully removed, even upon phosphorylation by protein kinase A. Thus, by chronic suppression of sarcoplasmic reticulum Ca(2+)-ATPase activity, the nonreversible superinhibitory function of mutant PLN-R14Del may lead to inherited dilated cardiomyopathy and premature death in both humans and mice.

Adult↗
PubMed2006

The effect of the phytoestrogen genistein on myocardial protection, preconditioning and oxidative stress.

INTRODUCTION: We have previously shown that estrogen administered in ovariectomized female rabbits significantly reduce myocardial infarct size. We now investigated whether the phytoestrogen genistein similarly protects ischemic myocardium and whether this is associated with its antioxidant properties. In addition, we examined whether genistein abolishes preconditioning, since at high doses, it inhibits tyrosine kinase. MATERIALS AND METHODS: We studied five groups of New Zealand white female rabbits. Group A (n = 12) were normal controls, group B (n = 14) were ovariectomized 4 weeks prior to the experiment, group C (n = 10) were ovariectomized and treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment, group D (n = 12) had intact gonads and were treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment and group E (n = 8) were ovariectomized 4 weeks prior to the experiment and treated with a single dose of genistein (0.2 mg kg(-1) day(-1) subcutaneously) just prior to the experiment. All animals underwent 30 min of heart ischemia and 120 min of reperfusion, with (subgroup I) or without (subgroup II) preconditioning. Malondialdehyde (MDA) concentration just before the experiment was determined. RESULTS: We found significant differences between the groups-p < 0.0001 in factorial ANOVA. The groups with preconditioning had significant smaller infarcts compared to those without-AI vs AII (10.66 +/- 1.42% vs 43.22 +/- 2.67%), BI vs BII (18.53 +/- 2.36% vs 43.05 +/- 8.37%), CI vs CII (10.17 +/- 2.07% vs 44.5 +/- 5.47%), DI vs DII (14.98 +/- 2.36% vs 37.79 +/- 3.92%) and EI vs EII (17.11 +/- 3.24% vs 42.08 +/- 3.42%), p < 0.0005. Ovariectomy was not associated with larger myocardial infarctions-AII vs BII, p = NS. Genistein, for 4 weeks, did not protect ischemic myocardium in either ovariectomized or non-ovariectomized animals-BII vs CII and AII vs DII, p = NS. There was no significant difference between the preconditioned animals, with intact gonads or ovariectomized (AI vs BI, p = NS), ovariectomized with or without genistein (BI vs CI, p = NS) and non-ovariectomized whether treated with genistein or not (AI vs DI, p = NS). A single dose of genistein did not offer any protection (EII vs BII, p = NS), nor did it modify the preconditioning effect (EI vs BI, p = NS). We found no significant difference in MDA plasma levels between the groups. CONCLUSION: Genistein, at this dose, does not reduce infarct size per se nor abolishes the protection induced by preconditioning, in both ovariectomized and non-ovariectomized animals. Preconditioning offers myocardial protection in animals with intact gonads as well as estrogen deprived; bilateral ovariectomy, at least during short-term, is not associated with larger myocardial infarcts compared to control animals. In addition estrogen deprivation, during short term, as well as genistein do not modify oxidative stress.

Animals↗
PubMed2006

The olive constituent oleuropein exhibits anti-ischemic, antioxidative, and hypolipidemic effects in anesthetized rabbits.

Thgoal of this study was to evaluate the efficacy of the antioxidant olive constituent, oleuropein, on infarct size, oxidative damage, and the metabolic profile in rabbits subjected to ischemia. Oleuropein, 10 or 20 mg/(kg x d), was administered to 8 groups that consumed a normal or hypercholesterolemic diet for 6 wk or only the higher dose for 3 wk. Circulating levels of malondialdehyde, protein carbonyl, nitrite+nitrate, cholesterol, triglycerides, SOD activity, and the metabolic profile were measured using 1H NMR spectra. In rabbits that consumed the normal diet, the infarct size (percentage of infarct to risk areas) was reduced by the administration of 10 mg oleuropein/(kg x d) (16.1 +/- 2.9%) or 20 mg oleuropein/(kg x d) for 3 wk (21.7 +/- 2.2%) or for 6 wk (24.3 +/- 1.3%) compared with the control group (48.05 +/- 2.0%, P < 0.05). Only the higher dose of 20 mg/(kg x d) reduced the infarct size in hypercholesterolemic rabbits (34.7 +/- 4.4% for 6 wk and 34.8 +/- 6.1% for 3 wk) compared with the cholesterol-fed control group (52.8 +/- 2.4%, P < 0.05). Oleuropein decreased the plasma lipid peroxidation product and protein carbonyl concentrations compared with the control groups, in which these factors increased relative to baseline due to ischemia and reperfusion. Furthermore, in rabbits administered oleuropein, RBC superoxide dismutase activity did not change during ischemia and reperfusion. This activity was significantly higher than in both control groups in which it was reduced by ischemia and reperfusion compared with baseline. Treatment for 6 wk with both doses of oleuropein reduced total cholesterol and triglyceride concentrations. 1H NMR spectra revealed a different profile of glycolysis metabolites in the oleuropein-treated groups compared with the controls. Oleuropein, for 3 or 6 wk, reduced the infarct size, conferred strong antioxidant protection and reduced the circulating lipids. This is the first experimental study in vivo that suggests the possibility of using an olive constituent in the treatment of ischemia.

Animals↗