Biomedical subjects

Efstathios K Iliodromitis

Publications and source records attributed to Efstathios K Iliodromitis.

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↗

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

Protection from post-conditioning depends on the number of short ischemic insults in anesthetized pigs.

Post-conditioning in the early reperfusion period confers protection to the heart after a potentially lethal episode of prolonged ischemia. Protection from this novel intervention has been documented in rat, rabbit and canine hearts, but one group has reported that it is ineffective in pigs, a large-animal species that should be most relevant to humans. We hypothesized that this negative result was related to an inappropriate post-conditioning protocol rather than the species. The present study, therefore, tested whether an effective post-conditioning protocol could be identified that limits infarct size in anesthetized pigs. Domestic Landrace pigs weighing 25-29 kg were anesthetized, and after a mid-sternal thoracotomy and pericardiotomy the left anterior descending coronary artery was ligated for 60 min followed by 3 h of reperfusion. Three groups were studied: control group (n = 5) with no other intervention, 4-30 PostC group (n = 5) with 4 cycles of 30-s reperfusion/30-s ischemia, and 8-30 PostC group (n = 6) with 8 cycles of 30-s reperfusion/30-s ischemia. The two post-conditioning protocols started immediately after termination of the 60-min coronary occlusion. Region at risk and infarct size were delineated with the aid of pre-mortem monastral blue injection and postmortem staining with triphenyltetrazolium chloride, respectively. In control hearts 33.5 +/- 7.6% of the risk zone infarcted and 36.7 +/- 3.7% in the 4-30 PostC group (P = NS). But there was only 10.5 +/- 0.5% infarction in the 8-30 PostC group (P < 0.01 vs. the other two groups). Post-conditioning confers protection in pigs but requires more than 4 ischemia/reperfusion cycles. Post-conditioning may protect by inhibiting mitochondrial permeability transition pore formation by keeping the heart acidotic as it is reoxygenated. If true, then it would be difficult to employ too many occlusion cycles.

Animals↗

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

Effects of levosimendan versus dobutamine on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure.

A single levosimendan administration has recently been shown to result in clinical and hemodynamic improvement in patients with decompensated heart failure (HF), but without survival benefits. In this study, the effects of levosimendan and dobutamine on plasma levels of proinflammatory and proapoptotic mediators in decompensated HF were compared and correlated with the concomitant effects on cardiac function and prognosis. Sixty-nine patients were randomized to received 24-hour intravenous infusions of levosimendan (n = 23), dobutamine (n = 23), or placebo (n = 23). Echocardiographic, hemodynamic, and biochemical assessments were performed at baseline, immediately after treatment, and 48 hours later. Patients were subsequently followed for 4 months for disease progression. End-systolic wall stress, the left ventricular ejection fraction, pulmonary capillary wedge pressure, and cardiac index were significantly improved in the levosimendan group but remained practically unaffected in the other groups. Plasma N-terminal-pro-B-type natriuretic peptide, tumor necrosis factor-alpha, and soluble Fas ligand levels were significantly decreased only in the levosimendan group (from 1,900 +/- 223 to 1,378 +/- 170 pg/ml, 13.4 +/- 1.0 to 12.3 +/- 1.2 pg/ml, and 68.2 +/- 3.7 to 59.8 +/- 3.6 pg/ml, respectively; p <0.05 for all); interleukin-6 was also borderline reduced (p = 0.051). Levosimendan-induced reduction in end-systolic wall stress was significantly correlated with respective decreases in N-terminal-pro-B-type natriuretic peptide (r = 0.671, p <0.01), tumor necrosis factor-alpha (r = 0.586, p <0.01), soluble Fas (r = 0.441, p <0.05), and soluble Fas ligand (r = 0.614, p <0.01). Event-free survival was significantly longer in the levosimendan group (p <0.05). In conclusion, the superiority of levosimendan over dobutamine in improving central hemodynamics and left ventricular performance in decompensated HF seems to be related to its anti-inflammatory and antiapoptotic effects.

Aged↗

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

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 role of left ventricular long-axis contraction in patients with asymptomatic aortic regurgitation.

BACKGROUND: We aimed to investigate the role of long axis contraction in patients with asymptomatic chronic aorta regurgitation (AR). METHODS: In 84 consecutive patients (48 men, mean age 55.5 +/- 13.5 years) tissue Doppler imaging was performed. During catheterization, left ventricular end-diastolic pressure (LVEDP) and end-diastolic wall stress (EDWS) were calculated. RESULTS: The best predictor for group membership (exercise ejection fraction increase > or < of 5%) is the systolic wave maximal velocity (Sv) at the lateral mitral annulus (9 cm/s). Patients with Sv > 9 cm/s (45 patients) formed group I, while 39 patients with Sv < 9 cm/s formed group II. LVEDP and EDWS were higher in group II (15.5 +/- 1.9 mm Hg and 214.8 +/- 233.3 g/cm2) than in group I (10.3 +/- 1.7 mmHg and 111.8 +/- 40.8 g/cm2), P = .0001 and P = .01, respectively. CONCLUSION: In patients with asymptomatic AR, the estimation of left ventricular long axis contraction at rest, can unmask a subnormal left ventricular functional status.

Aortic Valve Insufficiency↗

PubMed2006

Primary stenting of an unprotected left main coronary artery total occlusion in a patient with acute myocardial infraction and cardiogenic shock.

Acute total occlusion of the left main coronary artery (LMCA) is a rare angiographic finding with very poor prognosis. We report a case of a 39-year-old man who presented with pulmonary edema and cardiogenic shock due to an acute anterior myocardial infarction. Coronary angiography, which was performed under the support of an intra-aortic balloon pump, revealed total occlusion of the LMCA. Prompt and successful percutaneous transluminal coronary angioplasty with sirolimus-stent deployment in the LMCA allowed for an uneventful recovery and discharge of the patient.

Adult↗

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↗

PubMed2006

Tissue Doppler imaging analysis at pre-cardioversion time predicts recurrent atrial fibrillation: a 12-month follow-up study.

INTRODUCTION: Tissue Doppler imaging (TDI) has been extensively used in several clinical settings. We aimed to investigate whether TDI can predict recurrent atrial fibrillation (AF). METHODS AND RESULTS: Seventy-four consecutive patients (aged 62.6 +/- 11.7 years) with AF (>48 hours and <6 months of duration) who underwent successful external electrical direct current cardioversion and 20 healthy individuals were enrolled. Conventional echocardiography and TDI were prospectively performed before cardioversion. Based on a cutoff point of 5.43 cm/sec for the negative systolic wave velocity (NSWV), derived by the normal controls (mean + 2 SD), patients were divided into Group I (36 patients) with a NSWV >5.43 cm/sec and Group II (38 patients) with NSWV 48 hours; all patients were in AF at 12 months. In Group II, all patients were in sinus rhythm at 12 months. However, those patients presenting with a NSWV less but near to 5 cm/sec had frequent episodes of asymptomatic paroxysmal AF lasting for <48 hours. CONCLUSION: One year after successful direct current cardioversion, TDI analysis at pre-cardioversion time may be a useful marker to identify a subgroup of patients with increased risk for AF recurrence.

Aged↗

PubMed2005

The effectiveness of postconditioning and preconditioning on infarct size in hypercholesterolemic and normal anesthetized rabbits.

BACKGROUND: Postconditioning with multiple very short coronary occlusions immediately after prolonged ischemia is a new endogenous mechanism for protection of the ischemic heart. We tested whether postconditioning is effective in limiting infarct size in hypercholesterolemic rabbits. METHODS: Male rabbits were fed a cholesterol-enriched diet for 6 weeks. Animals were subjected to 30 min of regional ischemia of the heart and 3h of reperfusion with the following additional interventions: Control group no additional intervention, ischemic preconditioning (IPC) group to two cycles of 5 min ischemia separated by 10 min reperfusion before the index ischemia, 6/10 IPostC group to six cycles of 10s ischemia separated by 10s reperfusion and 4/30 IPostC group to four cycles of 30s ischemia separated by 30s reperfusion immediately after the end of the index ischemia. In a second series of experiments the same interventions were applied to animals fed with a normal diet. Infarct size (I) was determined by triphenyltetrazolium chloride staining. RESULTS: The I/R in hypercholesterolemic rabbits was 55.2+/-5.9% in Control, 17.9+/-4.2% in IPC (P<0.01 versus Control), 63.4+/-4.8% in 6/10 IPostC and 55.6+/-8.2% in 4/30 IPostC (P=NS between them and the Control group). In the normal diet rabbits, the I/R was 48.2+/-4.3% in Control, 15.1+/-2.1% in IPC, 20.4+/-2.9% in 6/10 IPostC (P<0.01 versus Control) and 45.1+/-8.9% in 4/30 IPostC (P=NS versus Control). Blood cholesterol levels were increased and atheromatic lesions were present in the first series. CONCLUSION: Postconditioning is ineffective in limiting the infarct size in rabbits with hypercholesterolemia and atherosclerosis while preconditioning continued to be effective under the same conditions.

Animals↗

PubMed2005

The effects of 5-HT4 receptor blockade and stimulation, during six hours of atrial fibrillation.

AIMS: Stimulation of atrial 5-HT4 receptors is associated with arrhythmias. Their blockade prolongs atrial effective refractory period (ERP), following short runs of atrial fibrillation (AF). The role of 5-HT4 receptors during longer periods of AF is unknown. In this study, we investigated the effects of the selective 5-HT4 receptor stimulation and blockade on porcine atria, during 6 h of AF. METHODS: Atrial ERP, monophasic action potential (MAP) duration, time to sinus rhythm restoration (TSRR) and ERP/MAP ratio were assessed in 27 pigs, at baseline and every hour, during 6 h of AF, induced by rapid atrial pacing. Ten animals were used as controls, 10 were administered the selective 5-HT4 antagonist SB203186 and seven were administered the selective 5-HT4 agonist RS67333. RESULTS: During the first few hours of fibrillation, ERP, MAP and TSRR were preserved in SB203186-treated pigs, while they were shortened in controls and RS67333-treated animals. After 6 h of arrhythmia, ERP and MAP were shortened in all three groups, but the decrease was less in SB203186-treated pigs. ERP/MAP ratio increased in controls and RS67333-treated animals, while it remained unchanged in SB203186-treated pigs. Towards the end of the AF period, four of the SB203186-treated pigs developed sustained atrial tachycardia. CONCLUSION: Following short periods of AF, 5-HT4 receptors' blockade protects the porcine atria against ERP and MAP shortening, while their stimulation has the opposite result. This beneficial effect, though, is gradually diminished following longer periods of AF and atrial tachycardia may develop.

Aniline Compounds↗

PubMed2005

Repeated exercise stress testing identifies early and late preconditioning.

BACKGROUND: The warm-up phenomenon has been considered to trigger preconditioning. We investigated whether repeated exercise treadmill tests in humans are capable of inducing adaptation to ischemia by triggering both the early and late phase of preconditioning. METHODS: In 25 consecutive patients with stable coronary artery disease, four repeated treadmill tests were performed. Thirty minutes following the first test (T1) a second one was performed (T2), followed 6 h later by a third test (T3). Twenty-four hours later all patients were subjected to a fourth exercise test (T4). In every fifth patient, simultaneous echocardiographic examination was performed at the time of the exercise tests in an attempt to reveal ischemic abnormalities. RESULTS: At baseline there was no difference between the variables. At ST segment depression >1.5 mm, the rate-pressure product (RPP) was higher in T2 and T4 (231.3+/-17.9 and 232.6+/-15.8 mm Hg s 10(2)) than in T1 and T3 (210+/-17 and 210.2+/-16.7 mm Hg s 10(2)), p<0.001. Additionally, time to the onset of chest pain was longer in T2 and T4 (430.8+/-60.5 and 438+/-47 s) than in T1 and T3 (345.6+/-69 and 345.6+/-58 s), p<0.001. At peak exercise, the RPP was higher in T2 and T4 (278.6+/-21.6 and 278.3+/-19.6 mm Hg s 10(2)) than in T1 and T3 (255.6+/-23.1 and 256.6+/-23 mm Hg s 10(2)), p<0.001. The wall motion score index was higher in T1 and T3 (1.65+/-0.17 and 1.53+/-0.16) than in T2 and T4 (1.3+/-0.07 and 1.37+/-0.1), p<0.001. CONCLUSION: By using repeated exercise treadmill tests both the early and late phase of protection can be obtained.

Aged↗

PubMed2004

Deferoxamine infusion during coronary artery bypass grafting ameliorates lipid peroxidation and protects the myocardium against reperfusion injury: immediate and long-term significance.

AIMS: Previous reports have demonstrated enhanced myocardial protection and better post-ischaemic recovery using the oxygen free radical scavenger deferoxamine (DEF) during cardioplegia. The aim of this study was to test whether, in patients undergoing coronary artery bypass grafting (CABG), DEF i.v. infusion can reduce reperfusion injury on a short- and long-term basis. METHODS AND RESULTS: Forty-five consecutive male patients were randomly allocated to two groups: in group D (n=25, age 60.8+/-8.6 years), 4 g of DEF were infused for 8 h starting immediately after the induction of anaesthesia; in group C (n=20, age 62.2+/-6.4 years) dextrose solution was given for the same time as placebo. Haemodynamic monitoring and measurement of oxygen free radical production [by measuring thiobarbituric acid reactive substances (TBARS)] were carried out before and after CABG. Left ventricular ejection fraction (EF) and wall motion score index (WMSI) were measured before and after CABG and 12 months later. Haemodynamic measurements were similar in both groups before and after CABG. TBARS peaked at 4.8+/-1.1 nmol/mL in group C, but remained unchanged (2.4+/-0.9 nmol/mL) in group D (P=0.01). At baseline, both the EF and WMSI were similar between the groups. Following CABG, EF increased more in group D (8.8+/-8.4%) than in group C (1.3+/-6.7%), P=0.008, while WMSI decreased more in group D (-0.7+/-0.3) than in group C (-0.2+/-0.2), P=0.0001. Dividing group D according to the pre-operative median EF value (38%), we observed that after 1 year follow-up, DEF infusion conferred more protection in patients with a lower EF (EF increased by 19.3+/-6.2%, WMSI decreased by -1.1+/-0.2) than in those with a higher EF (EF increased by 7.7+/-4.5%, WMSI decreased by -0.8+/-0.2), P=0.001, respectively. CONCLUSION: In patients undergoing CABG, DEF i.v. infusion ameliorates oxygen free radical production and protects the myocardium against reperfusion injury. Patients with a lower EF seem to benefit more by DEF i.v. infusion.

Coronary Artery Bypass↗

PubMed2004

Intravenous atenolol and esmolol maintain the protective effect of ischemic preconditioning in vivo.

Catecholamines bind to alpha- and beta-adrenoreceptors and are capable of preconditioning ischemic myocardium. Our purpose was to investigate the effect of acute either short or prolonged i.v. administration of beta-adrenoreceptor antagonists on ischemic preconditioning in vivo. Fifty-five anesthetized rabbits were divided into 10 groups (n=5-7 per group) and were subjected to 30-min regional ischemia of the heart after ligation of a prominent left coronary artery and 3-h reperfusion after releasing the snare. Ischemic preconditioning was obtained by three cycles of 5-min ischemia separated by 10-min reperfusion. beta-Adrenoreceptor blockade was obtained by the long acting beta-adrenoreceptor antagonist atenolol or by the short acting esmolol, which were given as a short 5-min infusion or as a prolonged 45-min infusion, starting respectively 20 min before and ending 15 min before the beginning of sustained ischemia, or starting 45 min before and ending immediately before the beginning of sustained ischemia. Atenolol was given at a rate of 0.2 mg min(-1) during 5 min or at a rate of 0.088 mg min(-1) as a 45-min infusion. Esmolol was given as an initial dose of 500 microg kg(-1) within 1 min, followed by a 4-min infusion at a rate of 50 microg kg(-1) min(-1) or as an initial dose of 3.4 mg within 1 min, followed by a 44-min infusion at a rate of 0.15 mg min(-1). Blood pressure and heart rate were continuously monitored. The infarcted and risk areas were delineated with the aid of tetrazolium chloride staining and fluorescent Zn-Cd particles. Infarct size was expressed in percent of the area at risk. All the animals without preconditioning developed an infarct size ranging between 36.3+/-2.4% and 49.6+/-7.6% (P=NS) and all the preconditioning groups developed an infarct size ranging between 14.9+/-1.2% and 21.0+/-2.2% (P=NS). All the preconditioning groups, independently of the use of beta-adrenoreceptor antagonists, had a smaller infarct size than the control group, which developed an infarct size of 47.3+/-2.5% (P<0.01). Intravenous atenolol and esmolol, independent of timing and mode of administration, does not seem to interfere with protection afforded by ischemic preconditioning in vivo.

Adrenergic beta-Antagonists↗

PubMed2004

Melatonin does not prevent the protection of ischemic preconditioning in vivo despite its antioxidant effect against oxidative stress.

Free radicals are involved in the protective mechanism of preconditioning (PC), whereas antioxidant compounds abolish this benefit. Melatonin is a hormone with antioxidant properties. The aim of our study was to evaluate the effect of melatonin on infarct size in ischemic preconditioning in vivo. We randomly divided 33 male rabbits into four groups and subjected them to 30 min of myocardial ischemia and 3 h of reperfusion with the following prior interventions: (i) no intervention, (ii) iv melatonin at a total dose of 50 mg/kg, (iii) PC with two cycles of 5 min ischemia and 10 min reperfusion, and (iv) combined melatonin and PC. In a second series of experiments, another antioxidant agent N-acetylcysteine (NAC) was used in a control and in a PC group. Myocardial infarct size was determined and blood samples were drawn at different time points for the determination of lipid peroxidation products, total superoxide dismutase (SOD) activity, and (1)H-NMR spectra to evaluate the changes in the metabolic profile. Melatonin showed no effect on myocardial infarct size in the group of sustained ischemia (42.9 +/- 3.6% vs 47.4 +/- 4.9%) and it did not attenuate the reduction of myocardial infarct size in the PC group (13.6 +/- 2.4% vs 14.0 +/- 1.7%). A similar effect was found in NAC-treated groups (44.8 +/- 3.4% vs 14.3 +/- 1.3%). Lipid peroxidation product levels were significantly elevated in the control and PC groups, whereas melatonin decreased them in both groups. The SOD activity was enhanced in the PC group compared to controls; melatonin kept SOD activity unchanged during ischemia/reperfusion and enhanced its activity when it was combined with PC. Melatonin did not change the metabolic profile of the control and PC groups. Melatonin does not prevent the beneficial effect of ischemic PC on infarct size despite its antioxidant properties.

Acetylcysteine↗