Infarct Size In Group Research Articles

Low-Intensity Ultrasound Reduces Brain Infarct Size by Upregulating Phosphorylated Endothelial Nitric Oxide in Mouse Model of Middle Cerebral Artery Occlusion.

There have been attempts to use therapeutic ultrasound (US) for the treatment of both experimental and clinical stroke. We hypothesized that low-intensity US has direct beneficial effects on the brain independent of cerebral blood flow (CBF) during middle cerebral artery occlusion (MCAO). Three groups of mice were studied. Group I included 84 mice with MCAO undergoing US treatment/no treatment at two US frequencies (0.25 and 1.05 MHz) with three different acoustic pressures at each frequency in which infarct size (IS) was measured 24 h later. Group II included 11 mice undergoing treatment based on best US results from group I animals in which the IS/risk area (RA) ratio was measured 24 h later. Group III included 38 normal mice undergoing US treatment/no treatment for assessment of CBF, tissue metabolite and protein expression and histopathology. Ultrasound at both frequencies and most acoustic pressures resulted in reduction in IS in group I animals, with the best results obtained with 0.25 MHz at 2.0 MPa: IS was reduced 4-fold in the cerebral cortex, 1.5-fold in the caudate putamen and 3.5-fold in the cerebral hemisphere compared with control. US application in group III animals elicited only a marginal increase in CBF despite a 2.6-fold increase in phosphorylated endothelial nitric oxide synthase (p-eNOS)-S1177 and a corresponding decrease in p-eNOS-T494. Histopathology revealed no evidence of hemorrhage, inflammation or necrosis. Low-intensity US at specific frequencies and acoustic pressures results in marked neuroprotection in a mouse model of stroke by modulation of p-eNOS independent of its effect on CBF.

Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model.

The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-l-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area. We aimed to evaluate IP therapy using a saline vehicle as a control (CON), a dose of 30 × 106 CDCs (CDCs) or APA microcapsules containing 30 × 106 CDCs (APA-CDCs) at 72 h in a porcine AMI model. Magnetic resonance imaging (MRI) was used to determine the left ventricular ejection fraction (LVEF), infarct size (IS), and indexed end diastolic and systolic volumes (EDVi; ESVi) pre- and 10 weeks post-injection. Programmed electrical stimulation (PES) was performed to test arrhythmia inducibility before euthanasia. Histopathological analysis was carried out afterwards. The IP infusion was successful in all animals. At 10 weeks, MRI revealed significantly higher LVEF in the APA-CDC group compared with CON. No significant differences were observed among groups in IS, EDVi, ESVi, PES and histopathological analyses. In conclusion, the IP injection of CDCs (microencapsulated or not) was feasible and safe 72 h post-AMI in the porcine model. Moreover, CDCs APA encapsulation could have a beneficial effect on cardiac function, reflected by a higher LVEF at 10 weeks.

The prognostic value of myocardial infarct size measured by cardiovascular magnetic resonance in patients with acute ST-segment elevation myocardial infarction

Objective: To investigate the prognostic value of infarct size (IS) in patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI). Methods: A total of 104 patients with acute STEMI who underwent primary PCI treatment in Shengjing Hospital of China Medical University from February 2017 to November 2018 were included in the present study. All patients underwent cardiovascular magnetic resonance (CMR) within one week after primary PCI treatment. The subjects were followed up for two years. Major adverse cardiac events (MACE) included new onset congestive heart failure and/or recurrent nonfatal myocardial infarction and/orcardiac death. The optimal IS cutoff value for MACE was determined by receiver operating character (ROC) curve. Based on the IS cutoff value, the patients were divided into the high IS group and the low IS group. Clinical characteristics between the two groups were compared. A cox regression model was used to analyze the prognostic value of IS in acute STEMI patients treated with primary PCI for the adverse events. Results: The IS cutoff value determined by ROC curve was 13.55%. 50 patients were in the high IS group (IS≥13.55%) and 54 patients were in the low IS group (IS<13.55%). More female patients [14 cases (28.0%) vs. 6 cases (11.1%)] were in the IS group, and a higher proportion of patients in the high IS group had anterior myocardial infarction [27 cases (54.0%) vs. 16 cases (29.6%)] or microvascular obstruction [32 cases (64.0%) vs. 16 cases (29.6%)]. White blood cell counts [11.25(8.90, 13.38) ×109/L vs. 9.25(7.58, 11.00) ×109/L], troponin I levels [50.63(16.56, 76.30)μg/L vs. 16.58(2.66, 38.42)μg/L] and brain natriuretic peptide levels [178.10(79.70, 281.95)μg/L vs. 79.60(42.83, 183.90)μg/L] in the high IS group were higher than those in the low IS group (P<0.05), and left ventricular ejection fraction [(45.15±10.65)% vs. (51.95±12.91)%] in the high IS group was lower than that in the low IS group (P<0.05). Multivariate Cox regression analyses showed that IS was independently associated with the risk of cardiac death in patients with acute STEMI two years after primary PCI(P=0.033, HR=1.075, 95%CI1.006-1.148). Every 1% increase in IS was associated with a 7.5% increase in cardiac death. Conclusions: Infarct size, measured by CMR within one week after primary PCI, is strongly associated with cardiac death in patients with acute STEMI two years after primary PCI. IS could be used as an index for the prognosis of patients with acute STEMI.

Preproenkephalin-minimalistic immunological defined gene expression-nuclear localization sequence gene transfection reduced myocardial ischemia/reperfusion injury in rats

Objective Investigating the protective effects and expression level of the preproenkephalin(PPENK) by using Non-virus and Non-plasmids PPENK-minimalistic immunological defined gene expression(MIDGE)-nuclear localization sequence(NLS) construct on myocardial ischemia/reperfusion(I/R) injury in rats. Methods Forty eight SD rats were divided into four groups randomly as(n=12): sham operation group (group C), I/R group (group I/R), gene vector group (group P), and antagonist group (group D). Group C was treated identically as other groups except left anterior descending was not tied. Group I/R was treated with 30 min of occlusion and 24 h reperfusion. Group P was given PPENK-MIDGE-NLS gene vector by tail vein injection 24 h later and then established the rat model of myocardial I/R. Group D was injected with PPENK-MIDGE-NLS gene vector from tail vein 24 h before and was injected naltrindole(1g/kg) 30 min before the rat model of myocardial ischemia reperfusion was established. Hemodynamic indexes including MAP and HR were recorded at T1(before ischemia), T2(30 min after ischemia) and T3(30 min after reperfusion). According to the Lambeth conference standard, arrhythmia situation were recorded and scored within 30 min ischemia and 30 min reperfusion. At the end of reperfusion, the level of cardiac troponin I(cTnI) in plasma was measured by ELISA Kit. Myocardial infarction size was measured by Triphenyltetrazolium Chloride. The morphology change of cardiomyocyte was observed with lens microscope, and the protein expression level of proenkephalin(PENK) in the myocardial tissue was measured by western blotting. Results PPENK-MIDGE-NLS gene vector could reduce the drop extents of MAP and HR that induced by myocardial I/R in rats. The expression level of cTnI in group P was reduced compared with I/R proup and group D(P<0.05). The cardiac arrhythmia score in group P (2.0±0.9) was reduced compared with group I/R(4.1±0.6) and group D(4.0±1.0)(P<0.05). The myocardial infarction size in group P was decreased significantly compared with group I/R(P<0.05). The morphology change of myocardial injury was reduced obviously in group P. The expression of PENK protein was increased compared with other groups(P<0.05). Conclusions PPENK-MIDGE-NLS gene vector transfection enhanced the expression level of proenkephalin and had a protective effect on myocardial I/R injury in rats. Key words: Myocardial; Ischemia/reperfusion injury; Endogenous enkephalin; Gene vector

Effects of Different Limb Remote Ischaemic Preconditioning on Ischaemia Reperfusion Injury in an Acute Left Anterior Descending Artery Occlusion Rat Model

The aim is to compare effects of three different protocols of limb remote ischaemic preconditioning (LRIP) on ischaemia reperfusion injury in an acute left anterior descending artery (LAD) occlusion model rat. Forty adult male Wistar rats were randomly assigned into four groups: group A, control; group B, LRIP in bilateral upper-limb (BUL) IP; group C, LRIP in bilateral lower-limb (BLL) IP; group D, LRIP in bilateral upper and lower limbs (ULL) IP. The 60min ligation and 180min reperfusion in LAD were applied to all rats. Limb remote ischaemic preconditioning was performed using 5min occlusion and 15min reperfusion (six cycles). Heart rate, blood pressure and electrogastrography (EGG) were recorded. Creatine kinase isoenzyme (CK-MB) level and infarct size were measured. Limb remote ischaemic preconditioning did not significantly affect heart rate, systolic blood pressure and arrhythmia score. However, LRIP significantly increased DBP value and decreased CK-MB levels and infarct size in group B, C, and D. Moreover, LRIP in ULL had a significantly better effect on reducing infarct size than LRIP in BUL and BLL. Limb remote ischaemic preconditioning at limbs could significantly reduce reperfusion injury in the heart. Moreover, LRIP in ULL indicated a better effect in reducing infarct size than LRIP in BUL and BLL.

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker, in a porcine model of acute myocardial infarction.

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

Postconditioning during primary percutaneaous angioplasty: is the jury still out?

Enrico Favaretto Division of Cardiology, Department of Cardiac, Thoracic & Vascular Sciences, University Hospital of Padua, via Giustiniani, 2, 35128 Padua, Italy IS reduction. To this regard, it is well known that single-proton emission computed tomography is a relatively gross measurement of IS compared with cardiac magnetic resonance (CMR), which has proven to be superior to single-proton emission computed tomography with regard to detection and quantification of myocardial infarction. Moreover, all of these earlier experiences did not stratify the randomization for STEMI location nor related IS to the myocardial area at risk. These adjustments, although not definitive, might be important to reduce bias, in particular when studying a small population. More recently, five randomized trials assessing the impact of PostC on IS, as assessed by CMR, were published [14–19]. Among them, in the study by Lonborg et al., the absolute IS by CMR (3 months post-STEMI, manual delineation; study primary end point) did not differ significantly between groups and the potential benefit in IS reduction was inferred only after use of the infarct endocardial surface area to estimate the myocardial area at risk, in order to estimate myocardial salvage [14]. Although the authors found a good correlation between this parameter and CMR edema imaging, these data remain unpublished. In 2010, Sorensson et al. did not find significant differences between control and PostC groups in IS by CMR performed 6–9 days after index STEMI [15]. In this case, IS was quantified by an automatic CMR algorithm and related to the myocardial area at risk determined by left ventriculo graphy. Freixa et al. found that PostC, during percutaneous coronary intervention, did not reduce IS at both early and late follow-up and it might also have a potential harmful effect [17]. In the POST-AMI randomized trial (stratified for STEMI location), we evaluated the effect of PostC on IS in STEMI patients treating all ST-elevation acute myocardial infarction (STEMI) continues to represent a major cause of mortality and morbidity worldwide [1] and infarct size (IS) is a major determinant of prognosis in these patients [2]. Although rapid reperfusion is the mainstay definitive treatment for ischemic myocardium, it may exacerbate the ischemia-related injury (i.e., reperfusion injury) counteracting the benefit of early reperfusion [3]. Despite major therapeutic advances in STEMI treatment, adjunctive therapies to reduce reperfusion injury and, ultimately, IS are scant in humans [3]. In 1986, Murry et al. first reported the IS-limiting effect of ischemic preconditioning in a landmark study [4]. In 2003, Zhao et al. demonstrated in a dog model that repetitive brief ischemic episodes applied immediately at the onset of reperfusion after a prolonged ischemic insult also can afford cardioprotection, reducing IS and preserving endothelial function similarly to conventional preconditioning, and termed this phenomenon ischemic postconditioning (PostC) [5]. Unlike preconditioning, the experimental design of PostC allows direct application to clinical settings, especially during primary percutaneous coronary interventions. Inflation and deflation of the balloon after reopening the coronary artery can mimic repetitive coronary artery clamping in postconditioned animal models [6]. Notwithstanding, unlike animal models, clinical studies on the prognostic impact of PostC led to conflicting results [7–19]. In 2005, the first studies in humans testing PostC were published by Staat et al. [7] and Laskey [8]. Since then, other small clinical randomized trials have found a benefit of PostC on IS reduction [9–13]. However, these studies used release of biomarkers (serum creatinine kinase) or single-proton emission computed tomography as diagnostic tools for detection of

Inhalation of hydrogen gas protects against myocardial stunning and infarction in swine

Objectives. The present study was carried out to determine whether inhalation of hydrogen (H2) gas protects myocardium against ischemia-reperfusion (I/R) injury in swine. Design. In anesthetized open-chest swine, myocardial stunning was produced by 12-minute occlusion of left anterior descending coronary artery (LAD) followed by 90-minute reperfusion in the first study. Group A inhaled 100% oxygen, and group B inhaled 2% H2 plus 98% oxygen during ischemia and reperfusion. In the second study, myocardial infarction was produced by 40-minute occlusion of LAD followed by 120-minute reperfusion. Group C inhaled 100% oxygen during ischemia and reperfusion. Group D inhaled 2% H2 plus 98% oxygen. Group E inhaled 4% H2 plus 96% oxygen. Results. The change of segment shortening (%SS) from baseline at 90 minutes after reperfusion in group B was 74 ± 13 (mean ± SD) %, which was significantly higher than that in group A (48 ± 15%). Myocardial infarct size in group E (32 ± 10%), but not in group D (40 ± 9%) was smaller than that in group C (46 ± 6%). Conclusions. Inhalation of 2% H2 gas improves myocardial stunning, and inhalation of 4% but not 2% H2 gas reduces myocardial infarct size in swine.

Effect of electroacupuncture preconditioning at “Nèiguān” ( PC 6) on gene expression of myocardial opioid receptors in rats with ischemia-reperfusion

ObjectiveTo explore protective effects of electroacupuncture at “Nèiguān” (▪ PC 6) for preconditioning on myocardial ischemia-reperfusion injury (MIRI) and the mechanisms involved. MethodsForty-eight male Wistar rats were randomly divided into a sham operation group (Group N), a MIRI group (Group M) and an electroacupuncture (EA) group (Group E). The MIRI model was established by ligating the left anterior descending artery (LAD) for 30 min followed by reperfusion for 120 min. Partition sutures were passed under LAD without ligation for rats in Group N. Rats in Group E were pretreated with electroacupuncture (EA) applied at bilateral “Nèiguān” (▪ PC 6) for 20 min once a day for 3 consecutive days before ischemia. The infarct size plus the area at risk was evaluated by 2,3,5-triphenyltetrazolium chloride staining, and serum isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) levels were measured by biochemical methods. Myocardium morphological changes were observed under light microscopy. The mRNA expressions of myocardial δ and κ opioid receptors (DOR and KOR) were tested by real-time RT-PCR measurements. ResultsThe myocardial infarct size in Group E was more significantly decreased than that in Group M (P<0.05). The levels of CK-MB [(980 ± 92) U/L] and LDH [(2743 ± 124) U/L] in Group M were significantly higher than those in Group N [(312±41) U/L] and [(530 ± 56) U/L], respectively (both P<0.01). The levels of CK-MB [(572±70) U/L] and LDH [(1819±97) U/L] in Group E were significantly lower than those in Group M (both P<0.01). There were no significant differences in mRNA expressions of DOR and KOR between Group M and Group N (both P>0.05), but DOR expression in Group E was significantly higher than that either in Group M or in Group N (both P<0.01). No significant differences were found in KOR expression among the three groups (all P>0.05). ConclusionUp-regulation of expression of δ opioid receptors may be involved in protective effects of EA at Nèiguān (▪ PC 6) for preconditioning on MIRI.

Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction

BackgroundIn reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI. MethodsAdult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8mg plus intravenous EPO 1000IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8). ResultsFifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF+EPO: 8±1%; pVEGF: 16±5%; EPO: 13±4%) compared to placebo (25±7%, p<0.001). However, in the EPO+VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect. ConclusionsCombined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction.

Reduction of Cerebral Infarct Size by Dronedarone

In the ATHENA trial, dronedarone reduced the incidence of stroke in patients with atrial fibrillation. Since smaller cerebral infarcts are sometimes asymptomatic, the reduced incidence of stroke might reflect reduction of infarct size (IS) by dronedarone. However, no data on this effect of dronedarone are available. In 60 rats, the middle cerebral artery was occluded (MCAO) for 1h followed by reperfusion. IS was assessed at day 7. Animals were examined using a neurological 5 points score. Twelve animals served as controls (group A), 12 animals received 30mg/kg (group B) and 100mg/kg (group C) dronedarone daily starting 3days before MCAO; 12 animals received 30mg/kg (group D) starting 2h after MCAO. In all groups treatment was maintained until day 7. In 12 additional animals (6 controls, 6 pretreated animals) fractional anisotropy (FA) was assessed using magnetic resonance imaging (MRI). IS in group A was 151 ± 45mm(3) versus 94 ± 42mm(3) in group B, 79 ± 29mm(3) in group C, and 127 ± 51mm(3) in group D, respectively (B,C,D P < 0.05 vs. A). Neuroscores and weight loss (expressed as percent of initial weight) were less in treatment groups: 1.8 ± 0.6 and 91% in group B, 1.4 ± 0.5 and 93% in group C, and 2.1 ± 0.6 and 89% in group D compared to 2.4 ± 0.5 and 83% in controls (B,C,D P < 0.05 vs. A). FA in the ischemic penumbra was significantly higher in treated than in control animals (0.44 ± 0.2 vs. 0.35 ± 0.17; P < 0.05). Dronedarone administered before and after MCAO reduces IS and improves FA and neurological outcome in transient cerebral ischemia.

Effect of Physiologic Ischemic Training on Protection of Myocardial Infarction in Rabbits

The aim of this study was to investigate the protective effect of physiologic ischemic training of normal skeletal muscle against myocardial infarction. Thirty-five rabbits were implanted with water balloon constrictors in the left ventricular branch to cause myocardial ischemia and an electrode near the left sciatic nerve for electric muscle stimulation for physiologic ischemic training. Three groups were randomly selected: the pure ischemia (PI) group received myocardial ischemia for 2 mins, two times a day, five times a week; the exercise training (ET) group received myocardial ischemia as did the PI group, plus 4 mins of physiologic ischemic training, two times a day, five times a week; and the sham-operated (SO) group was the sedentary controls. After 4 wks of training, the left ventricular branch was occluded to cause infarction. Infarct size was measured by magnetic resonance imaging; left ventricular ejection fraction, by echocardiogram; capillary density, by immunohistochemistry; and collateral circulation blood flow, by a microsphere technique. The ET group's infarct size was significantly smaller than that of the PI group (P < 0.01) and the SO group (P < 0.01). Change in left ventricular ejection fraction in the ET group was significantly lower than in the SO group (P < 0.01), and capillary density in the ET group was significantly higher than in the PI group (P< 0.01) and the SO group (P < 0.01). Collateral circulation blood flow in the ET group was significantly higher than in the PI group (P < 0.01) and the SO group (P< 0.01). Capillary density was significantly correlated with endpoint collateral circulation blood flow (r = 0.91, P = 0.000), infarct size (r = -0.91, P = 0.000), and change in left ventricular ejection fraction (r = -0.94, P = 0.000). Physiologic ischemic training of skeletal muscle may induce collateral circulation development in the myocardium, thus decreasing infarct size when infarction occurs.

E0648 Effects of pretreatment with simvastatin on the area of myocardial infarction in reperfusion injury rabbits after acute myocardial infarction

ObjectiveTo investigate the effects and mechanism of the pretreatment with simvastatin on the area of myocardial infarction in reperfusion injury rabbits after acute myocardial infarction (AMI).Method20 New Zealand white rabbits...

Effects of Intra-arterial Urokinase on a Non-human Primate Thromboembolic Stroke Model

One of the most important prognostic factors in the thrombolytic treatment of acute ischemic stroke is to re-canalize. The purpose of this study was to evaluate the effectiveness and safety of urokinase in a primate thromboembolic stroke model. Thromboembolic stroke was accomplished via occlusion of the middle cerebral artery (MCA) obtained by injecting an autologous blood clot into the left internal carotid artery in 21 male cynomolgus monkeys. Animals were randomly assigned to the following treatment groups: Group 1: vehicle (saline), Group 2: urokinase (40,000 IU), Group 3: urokinase (120,000 IU,) over 2 or 6 h via intra-internal carotid catheter starting 1 h after embolization, respectively. In the urokinase-treated groups, neurologic deficits were improved in consciousness and skeletal muscle coordination, but not sensory and motor systems. The infarction size in Group 2 (11.9 +/- 3.9% of the hemisphere) and 3 (7.6 +/- 2.5%) were significantly smaller than that (24.7 +/- 3.5%) in Group 1. However, 2 of 5 animals in Group 3 died. In conclusion, urokinase improved neurologic deficits and reduced cerebral infarction on thromboembolic stroke in the cynomolgus monkey.

Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion ? results of the Austrian multi-centre randomized ReoPro-BRIDGING Study

The aim of the ReoPro-BRIDGING Austrian multi-centre study was to investigate the effects of abciximab (ReoPro) on early reperfusion in ST-elevation myocardial infarction prior to or during primary percutaneous coronary angioplasty (pPCI). Fifty-five patients with STEMI were randomized either to start abciximab (0.25 mg/kg bolus followed by 10 microg/min infusion) during the organization phase for pPCI (Group 1, n=28) or immediately before pPCI (Group 2, n=27). The time between first bolus of abciximab and first balloon inflation of pPCI was 83+/-18 vs 21+/-13 min in Group 1 vs 2. The pre-pPCI ST-segment resolution (55+/-21.4% vs 42.4+/-18.2%, p=0.005), TIMI flow grade 3 (29% vs 7%, p=0.042), corrected TIMI frame count (58.4+/-32.7 vs 78.9+/-28.4 frame, p=0.018) %diameter stenosis (76.3 /63.5-100/ vs 100 /73.5-100/; median /interquartile range/, p=0.023), were significantly higher in Group 1 vs Group 2. Quantitative myocardial dye intensity measurement revealed a significantly higher grade of myocardial tissue perfusion (1 /0-9.25/ vs 0 /0-3.0/ grey pixel unit, p=0.048) in Group 1 before pPCI. Rapid release of cardiac enzymes was observed in Group 1 as compared with Group 2: rate of rise of CK was 210+/-209 vs 97+/-95 U/l/h (p=0.015). QRS score indicated a smaller infarct size in Group 1 (4.8+/-3.8 vs 7.6+/-3.5, p=0.011) on day 7. The use of abciximab in the organization phase for pPCI results in signs of early recanalization of the infarct-related artery and a subsequent improved myocardial tissue reperfusion.

Decompressive craniectomy in acute cerebral ischemia in ratsIs there any benefit in smaller thromboembolic infarcts?

Early craniectomy has shown to reduce infarction size in experimental large MCA infarction probably due to improved leptomeningeal perfusion. Based on the hypothesis that craniectomy may also be beneficial in smaller MCA infarction we evaluated the effects of craniectomy on infarction size in small thromboembolic cerebral infarction in rats. Therefore, thromboembolic cerebral ischemia was induced in 40 rats by endovascular injection of autologous, fibrin-rich emboli. Twenty-one animals with a diffusion-weighted MR imaging (DWI)-derived infarction size of 50–100 mm3 (involving one- to two-third of the MCA territory) at 1 h after injection were randomly assigned to two groups. Eleven animals of group 1 immediately underwent craniectomy, ten animals of group 2 (controls) were not treated. Serial DWI was performed at 4 and 24 h. Infarction size was assessed by TTC-staining at 48 h after emboli injection. As result, prior to treatment, at 1 h after emboli injection, infarction size in groups 1 and 2 was 65.9 ± 16.0 mm3 and 67.9 ± 17.8 mm3, respectively. At 4 and 24 h, infarction size in group 1 was 73.5 ± 22.1 mm3 and 85.2 ± 24.7 mm3, and 76.3 ± 21.0 mm3 and 83.4 ± 22.9 mm3 in group 2, respectively. TTC-derived infarction size was 84.0 ± 23.3 mm3 and 82.7 ± 21.5 mm3, respectively. There was no significant difference between the two groups (P > 0.79). In conclusion, our results demonstrate that for small thromboembolic MCA infarction early craniectomy is not beneficial.

Decompressive craniectomy in acute cerebral ischemia in rats: Is there any benefit in smaller thromboembolic infarcts?

Early craniectomy has shown to reduce infarction size in experimental large MCA infarction probably due to improved leptomeningeal perfusion. Based on the hypothesis that craniectomy may also be beneficial in smaller MCA infarction we evaluated the effects of craniectomy on infarction size in small thromboembolic cerebral infarction in rats. Therefore, thromboembolic cerebral ischemia was induced in 40 rats by endovascular injection of autologous, fibrin-rich emboli. Twenty-one animals with a diffusion-weighted MR imaging (DWI)-derived infarction size of 50–100 mm 3 (involving one- to two-third of the MCA territory) at 1 h after injection were randomly assigned to two groups. Eleven animals of group 1 immediately underwent craniectomy, ten animals of group 2 (controls) were not treated. Serial DWI was performed at 4 and 24 h. Infarction size was assessed by TTC-staining at 48 h after emboli injection. As result, prior to treatment, at 1 h after emboli injection, infarction size in groups 1 and 2 was 65.9 ± 16.0 mm 3 and 67.9 ± 17.8 mm 3, respectively. At 4 and 24 h, infarction size in group 1 was 73.5 ± 22.1 mm 3 and 85.2 ± 24.7 mm 3, and 76.3 ± 21.0 mm 3 and 83.4 ± 22.9 mm 3 in group 2, respectively. TTC-derived infarction size was 84.0 ± 23.3 mm 3 and 82.7 ± 21.5 mm 3, respectively. There was no significant difference between the two groups ( P > 0.79). In conclusion, our results demonstrate that for small thromboembolic MCA infarction early craniectomy is not beneficial.

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 1H-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.

TNF-alpha antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits.

Pretreatment with tumor necrosis factor-alpha (TNF-alpha) antibodies abolishes myocardial infarct size reduction by late ischemic preconditioning (IP). Whether or not TNF-alpha is also important for myocardial infarct size reduction by classic IP is unknown. Anesthetized rabbits were untreated (group 1, n = 7), classically preconditioned by 5 min left coronary artery occlusion/10 min reperfusion (group 2, n = 6), or pretreated with TNF-alpha antibodies without (group 3, n = 6) or with IP (group 4, n = 6) before undergoing 30 min of occlusion and 180 min of reperfusion. Infarct size in group 1 was 44 +/- 11 (means +/- SD)% of the area at risk. With a comparable area at risk, infarct size was reduced to 13 +/- 7%, 23 +/- 8%, and 19 +/- 12% (all P < 0.05) in groups 2, 3, and 4, respectively. The circulating TNF-alpha concentration was increased during ischemia in group 1 from 752 +/- 403 to 1,542 +/- 482 U/ml (P < 0.05) but remained unchanged in all other groups. Circulating TNF-alpha concentration during ischemia and infarct size correlated in all groups (r = 0.76). IP, TNF-alpha antibodies, and the combined approach reduced infarct size to a comparable extent. Therefore, the question of whether or not TNF-alpha is causally involved in the infarct size reduction by IP in rabbits could not be answered.

Prediction of the Final Infarct Volume within 6 h of Stroke Using Single Photon Emission Computed Tomography with Technetium-99m Hexamethylpropylene Amine Oxime

Background: A simple method to predict the final infarct volume within 6 h of onset of hemispheric ischemic stroke based on the measurement of cerebral blood flow (CBF) using single photon emission computed tomography (SPECT) with techneticum-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) was investigated in a clinical model involving patients without definite early reperfusion or clinical recovery. Methods: A group of 16 patients (group 1) was used to establish the methodology, which was then validated in a second group of 14 patients (group 2). The final infarct volume was defined using computed tomography (CT) performed at least 7 days after stroke. The relative CBF threshold value, expressed as a percentage of the mean contralateral hemispheric value, which most closely estimated the final infarct size on coregistered CT was established for each patient. Results: The mean threshold CBF value for group 1 was 63.7%. When this value was used to predict infarct size in group 2, a close correlation was observed between the actual and the estimated sizes (r = 0.973, p < 0.0001). This value was not time dependent. Conclusions: If no significant early reperfusion or clinical recovery occurs, a CBF threshold value of 63.7% on ^99mTc-HMPAO SPECT performed within 6 h of stroke onset will reliably predict the final infarct size.