ECHOCARDIOGRAPHY, Issue 3 2008
Beibei Han M.D.
Background: The purpose of this study was to assess whether the dynamic changes in coronary flow velocity and coronary flow velocity reserve (CFVR) by intracardiac echocardiography (ICE) within proximal coronary arteries are related to myocardial perfusion status and infarct size in a myocardial ischemia-reperfusion injury model. Methods: In 14 dogs, left anterior descending coronary artery (LAD) was ligated for 2 hours followed by 2 hours reperfusion. Coronary flow velocity was obtained by ICE within coronary arteries at baseline, and at the end of both occlusion and reperfusion period. The CFVR was calculated as the ratio of hyperemic to resting peak diastolic velocity (PDV). Myocardial perfusion was evaluated by real time myocardial contrast echocardiography (MCE). The infarct area was detected by triphenyltetrazolium chloride (TTC) staining and expressed as the percentage of the whole left ventricular (LV) area. Results: CFVR significantly decreased both in proximal LAD and left circumflex (LCx) artery at the end of occlusion, and did not recover at the end of reperfusion. However, no significant difference in flow parameters was observed between dogs with myocardial perfusion defect and those without. CFVR in LAD at the end of reperfusion did not correlate with the infarct size (r =,0.182, P = NS) either. Conclusions: Decreased CFVR detected by ICE occurs both in ischemic and in nonischemic proximal arteries during myocardial ischemia and early stage of reperfusion. This change in CFVR has poor correlation with the extent of microvascular impairment and cannot be used to predict infarct size. [source]

Is Left Ventricular Diastolic Thickening Documented During Dobutamine and Pacing Stress Echocardiography Related to Myocardial Ischemia?

ECHOCARDIOGRAPHY, Issue 1 2002
An Animal Model Study
Transient increase in diastolic wall thickness (pseudohypertrophy) during pacing stress echocardiography has been reported in normal myocardium. To evaluate the occurrence of pseudohypertrophy and to investigate the contribution of myocardial ischemia on its production during pacing and dobutamine stress echocardiography, we produced a physiologically significant coronary stenosis in 14 open chest dogs. The stenosis in the circumflex artery was measured by quantitative coronary angiography (range: 50% to 89% reduction in luminal diameter), and no resting segmental wallmotion abnormalities were observed by epicardial echocardiography (short-axis, papillary level). In each study, dobutamine (5,40 ,g/kg/min) and pacing (up to 260 beats/min) were performed randomly. Positivity of stress echocardiography tests was quantitatively determined by a significant (P < 0.05) reduction or failure to increase in absolute and percent systolic wall thickening in the myocardial area supplied by the stenotic artery as compared to the left anterior descending (LAD) artery-related areas. Diastolic wall thickness and left ventricular diastolic area were compared before and after each stress test in the circumflex and LAD artery-related regions. Pseudohypertrophy was observed in 57% and 86% of dogs for pacing and dobutamine, respectively, in the circumflex region, and in 50% and 64% in the LAD region. Despite its increased incidence in the circumflex region, the augmented diastolic wall thickness did not correlate with coronary stenosis severity or stress test positivity, but correlated inversely with changes in left ventricular diastolic area. In addition, it correlated directly with changes in heart rate only for pacing. In conclusion, pseudohypertrophy was a frequent finding during pacing and dobutamine stress echocardiography tests but was not related to myocardial ischemia in this animal model. [source]

Elective coronary angioplasty with 60 s balloon inflation does not cause peroxidative injury

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2002
K. Cedro
Abstract Background The aim of this study was to evaluate the ongoing controversial issue of whether ischemia/reperfusion during elective coronary angioplasty evokes myocardial peroxidative injury. Design We measured indicators of free radical damage to lipids (free malondialdehyde) and proteins (sulphydryl groups) in coronary sinus blood in 19 patients with stable angina who were undergoing elective angioplasty for isolated stenosis of the proximal left anterior descending coronary artery. Ischemia induced by 60 s balloon inflations was confirmed by lactate washout into coronary sinus after deflation, with immediate and 1 min samples. Peroxidative injury was assessed from washout of (a) malondialdehyde measured directly by high performance liquid chromatography and (b) reduced sulphydryl groups, inverse marker of protein oxidative stress. Results Mean lactate concentration immediately after each deflation increased by 120,150% of the initial value, confirming ischemia and showing that blood originated largely from the ischemic region. Lack of myocardial production of malondialdehyde was confirmed by (a) no arteriovenous differences in individual basal concentrations (aortic, range 0·33,12·03 nmol mL,1, mean 7·82; coronary sinus blood, range 0·52,15·82 nmol mL,1, mean 8·18), and (b) after deflations, mean concentrations were not significantly different from preocclusion value. There was no decrease in concentration of sulphydryl groups throughout angioplasty. Conclusion Elective coronary angioplasty with 60 s balloon inflations is a safe procedure that does not induce peroxidative myocardial injury as assessed by methods used in the present study. [source]

Brain Hypoxia and Ischemia

EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2001
K A Jellinger
No abstract is available for this article. [source]

Do Diabetic Patients Have Higher In-hospital Complication Rates When Admitted from the Emergency Department for Possible Myocardial Ischemia?

ACADEMIC EMERGENCY MEDICINE, Issue 3 2000
Peter B. Richman MD
Abstract Objective: To compare in-hospital complication rates for diabetic and nondiabetic patients admitted from the emergency department (ED) for possible myocardial ischemia. Methods: This was a prospective, observational study of consecutive consenting patients presenting to a suburban university hospital ED during study hours with typical and atypical symptoms consistent with cardiac ischemia. Demographic, historical, and clinical data were recorded by trained research assistants using a standardized, closed-question, data collection instrument. Inpatient records were reviewed by trained data abstractors to ascertain hospital course and occurrence of complications. Final discharge diagnosis of acute myocardial infarction (AMI) was assigned by World Health Organization criteria. Categorical and continuous data were analyzed by chi-square and t-tests, respectively. All tests were two-tailed with alpha set at 0.05. Results: There were 1,543 patients enrolled who did not have complications at initial presentation; 283 were diabetic. The rule-in rate for AMI was 13.8% for nondiabetic patients and 17.7% for diabetic patients (p = 0.09). Times to presentation were similar for nondiabetic vs diabetic patients [248 minutes (95% CI = 231 to 266) vs 235 minutes (95% CI = 202 to 269); p = 0.32]. Nondiabetic patients tended to be younger [56.6 years (95% CI = 55.8 to 57.4) vs 61.6 years (95% CI = 60.2 to 63.1); p = 0.001] and were less likely to be female (34.3% vs 48.1%; p = 0.001). The two groups had similar prevalences for initial electrocardiograms diagnostic for AMI (5.5% vs 7.4%; p = 0.21). There was no significant difference between nondiabetic and diabetic patients for the occurrence of the following complications after admission to the hospital: congestive heart failure (1.3% vs 1.1%, p = 0.77); nonsustained ventricular tachycardia (VT) (1.3% vs 1.2%, p = 0.93); sustained VT (1.2% vs 1.1%, p = 0.85); supraventricular tachycardia (1.7% vs 3.2%, p = 0.12); bradydysrhythmias (1.9% vs 1.1%, p = 0.33); hypotension necessitating the use of pressors (0.9% vs 1.1%, p = 0.76); cardiopulmonary resuscitation (0.2% vs 0.7%, p = 0.10); and death (0.3% vs 0.7%, p = 0.34). One or more complications occurred with similar frequencies for patients in the two groups (6.3% vs 5.7%; p = 0.70). Conclusions: No statistically significant difference was found in the post-admission complication rates for initially stable diabetic vs nondiabetic patients admitted for possible myocardial ischemia. Based on these results, the presence or absence of diabetes as a comorbid condition does not indicate a need to alter admitting decisions with respect to risk for inpatient complications. [source]

Associations Between Lower Extremity Ischemia, Upper and Lower Extremity Strength, and Functional Impairment with Peripheral Arterial Disease

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2008
Mary M. McDermott MD
OBJECTIVES: To identify associations between lower extremity ischemia and leg strength, leg power, and hand grip in persons with and without lower extremity peripheral arterial disease (PAD). To determine whether poorer strength may mediate poorer lower extremity performance in persons with lower arterial brachial index (ABI) levels. DESIGN: Cross-sectional. SETTING: Academic medical centers. PARTICIPANTS: Four hundred twenty-four persons with PAD and 271 without PAD. MEASUREMENTS: Isometric knee extension and plantarflexion strength and handgrip strength were measured using a computer-linked strength chair. Knee extension power was measured using the Nottingham leg rig. ABI, 6-minute walk, and usual and fastest 4-m walking velocity were measured. Results were adjusted for potential confounders. RESULTS: Lower ABI values were associated with lower plantarflexion strength (P trend=.04) and lower knee extension power (P trend <.001). There were no significant associations between ABI and handgrip or knee extension isometric strength. Significant associations between ABI and measures of lower extremity performance were attenuated after additional adjustment for measures of strength. CONCLUSION: These results are consistent with the hypothesis that lower extremity ischemia impairs strength specifically in distal lower extremity muscles. Associations between lower extremity ischemia and impaired lower extremity strength may mediate associations between lower ABI values and greater functional impairment. [source]

Prevention of Limb Ischemia and Edema During Peripheral Venoarterial Extracorporeal Membrane Oxygenation in Adults

JOURNAL OF CARDIAC SURGERY, Issue 2 2009
Claudio F. Russo M.D.
The cannulation of the femoral vessels may be complicated by distal limb ischemia by arterial hypoperfusion and severe edema by venous obstruction. We describe a modified cannulation technique in order to prevent ischemia and edema of the inferior limb during VA-ECMO. [source]

Acute Effect of Cerivastatin on Cardiac Regional Ischemia in a Rat Model Mimicking Off-Pump Coronary Surgery

JOURNAL OF CARDIAC SURGERY, Issue 6 2005
Koki Nakamura M.D.
The aims of this study were to investigate the optimal duration of coronary occlusion for making reversible ischemia and to examine whether cerivastatin increases myocardial tolerance against prolonged coronary occlusion. Methods: Study 1,Male Sprague-Dawley rats (350 to 450 g) underwent temporary occlusion of either left anterior descending artery (LAD; for 3, 5, 7.5, 10, 12.5, 15, or 20 min) or circumflex artery (CX; for 5, 10, or 15 min). Study 2,Rats were divided into two groups, control and cerivastatin groups, which had 0.1 mg/kg cerivastatin intravenously after anesthesia. LAD was occluded for 10, 15, or 20 minutes. In the both studies, hearts were stained to determine the area at risk (AR) and infarcted (IF) area 24 hours after reperfusion. Results: In LAD occlusion, IF/AR increased in a time dependent manner: 4.5 ± 3.2%, 9.7 ± 5.2%, 17.2 ± 3.0%, 16.8 ± 2.7%, 23.9 ± 9.5% (p < 0.01 vs. 3 min), 62.4 ± 2.9% (p < 0.0001), and 63.4 ± 2.9% (p < 0.0001) at 3, 5, 7.5, 10, 12.5, 15, and 20 min, respectively. Also in CX, IF/AR increased with time: 14.3 ± 2.3%, 25.9 ± 2.1%, and 40.9 ± 6.2% (p < 0.001 vs. 5 min) at 5, 10, and 15 min, respectively. Cerivastatin significantly reduced IF/AR at 15 minutes (43.7 ± 6.2%) and at 20 minutes (44.6 ± 5.3%) compared to control (62.4 ± 2.9% and 60.6 ± 2.5%, respectively, p < 0.05). Conclusion: Cerivastatin increased myocardial tolerance after prolonged coronary occlusion over 10 minutes, which was considered to be the upper limit for creating a regional reversible ischemia in rats. [source]

On "Acute Effect of Cerivastatin on Cardiac Regional Ischemia in a Rat Model Mimicking Off-pump Coronary Surgery"

JOURNAL OF CARDIAC SURGERY, Issue 6 2005
Michael A. Borger M.D., Ph.D.
No abstract is available for this article. [source]

The Diagnostic Evolution of the Cardiac Implantable Electronic Device: The Implantable Monitor of Ischemia

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2008
T. JARED BUNCH M.D.
No abstract is available for this article. [source]

Heterogeneity of Ventricular Fibrillation Dominant Frequency During Global Ischemia in Isolated Rabbit Hearts

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2007
Ch.B. , JANE CALDWELL M.B.
Introduction: Ventricular fibrillation (VF) studies show that ECG-dominant frequency (DF) decreases as ischemia develops. This study investigates the contribution of the principle ischemic metabolic components to this decline. Methods and Results: Rabbit hearts were Langendorff-perfused at 40 mL/min with Tyrode's solution and loaded with RH237. Epicardial optical action potentials were recorded with a photodiode array (256 sites, 15 × 15 mm). After 60 seconds of VF (induced by burst pacing), global ischemia was produced by low flow (6 mL/min), or the solution changed to impose hypoxia (95% N2/5% CO2), low pHo (6.7, 80% O2/20% CO2), or raised [K+]o (8 mM). DF of the optical signals was determined at each site. Conduction velocity (CV), action potential duration (APD90), effective refractory period (ERP), activation threshold, dV/dtmax, and membrane potential were measured in separate experiments during ventricular pacing. During VF, ischemia decreased DF in the left ventricle (LV) (to [58 ± 6]%, P < 0.001), but not the right (RV) ([93 ± 5]%). Raised [K+]o reproduced this DF pattern (LV: [67 ± 12]%, P < 0.001; RV: [95 ± 9]%). LV DF remained elevated in hypoxia or low pHo. During ventricular pacing, ischemia decreased CV in LV but not RV. Raised [K+]o did not change CV in either ventricle. Ischemia and raised [K+]o shortened APD90 without altering ERP. LV activation threshold increased in both ischemia and raised [K+]o and was associated with diastolic depolarization and decreased dV/dtmax. Conclusions: These results suggest that during VF, decreased ECG DF in global ischemia is largely due to elevated [K+]o affecting the activation thresholds in the LV rather than RV. [source]

Ischemia activates JNK/c-Jun/AP-1 pathway to up-regulate 14-3-3, in astrocyte

JOURNAL OF NEUROCHEMISTRY, Issue 2009
Yan Dong
Abstract Ischemia occurs in the brain as the result of stroke and other related injuries and few therapies are effective. If more is understood then potential treatments could be investigated. It was previously reported that 14-3-3, could be up-regulated by ischemia in astrocyte to protect cells from ischemia-induced apoptosis. In this study, we attempted to uncover the mechanism responsible for this 14-3-3, up-regulation in primary culture of astrocytes under ischemic-like conditions. It was found that in vitro ischemia may activate PI3K/Akt and MAPK signaling pathways. Astrocyte cultures were treated with LY294002 (PI3K inhibitor), U0126 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor). Only SP600125 could inhibit the ischemia-induced 14-3-3, up-regulation in astrocytes. At the same time, we observed an ischemia-induced nuclear translocation of p-c-Jun, a major downstream component of JNK. Inhibition of AP-1 with curcumin also inhibited 14-3-3, up-regulation indicating that ischemia-induced up-regulation of 14-3-3, in astrocyte involves activation of the JNK/p-c-Jun/AP-1 pathway. [source]

Regulation of A2A adenosine receptor expression and functioning following permanent focal ischemia in rat brain

JOURNAL OF NEUROCHEMISTRY, Issue 2 2008
Maria L. Trincavelli
Abstract Ischemia, through modulation of adenosine receptors (ARs), may influence adenosine-mediated-cellular responses. In the present study, we investigated the modulation of rat A2A receptor expression and functioning, in rat cerebral cortex and striatum, following in vivo focal ischemia (24 h). In cortex, middle cerebral artery occlusion did not induce any alterations in A2A receptor binding and functioning. On the contrary, in striatum, a significant decrease in A2A ligand affinity, associated with an increase in receptor density, were detected. In striatum, ischemia also induced a significant reduction both in G protein pool and in A2A receptor-G protein coupling. On the contrary, A2A receptor functional responsiveness, measured as stimulation of adenylyl cyclise, was not affected by ischemia, suggesting receptor up-regulation may represent a compensatory mechanism to maintain receptor functioning during cerebral damage. Immunohistochemical study showed that following 24 h middle cerebral artery occlusion, A2A ARs were definitely expressed both on neurons and activated microglia in ischemic striatum and cortex, but were not detected on astrocytes. In the non-ischemic hemisphere and in sham-operated rats A2A ARs were barely detected. Modifications of ARs may play a significant role in determining adenosine effects during ischemia and therefore should be taken into account when evaluating time-dependent protective effects of specific A2A active compounds. [source]

Supersensitivity of P2X7 receptors in cerebrocortical cell cultures after in vitro ischemia

JOURNAL OF NEUROCHEMISTRY, Issue 5 2005
Kerstin Wirkner
Abstract Neuronally enriched primary cerebrocortical cultures were exposed to glucose-free medium saturated with argon (in vitro ischemia) instead of oxygen (normoxia). Ischemia did not alter P2X7 receptor mRNA, although serum deprivation clearly increased it. Accordingly, P2X7 receptor immunoreactivity (IR) of microtubuline-associated protein 2 (MAP2)-IR neurons or of glial fibrillary acidic protein (GFAP)-IR astrocytes was not affected; serum deprivation augmented the P2X7 receptor IR only in the astrocytic, but not the neuronal cell population. However, ischemia markedly increased the ATP- and 2,-3,- O -(4-benzoylbenzoyl)-adenosine 5,-triphosphate (BzATP)-induced release of previously incorporated [3H]GABA. Both Brilliant Blue G and oxidized ATP inhibited the release of [3H]GABA caused by ATP application; the Brilliant Blue G-sensitive, P2X7 receptor-mediated fraction, was much larger after ischemia than after normoxia. Whereas ischemic stimulation failed to alter the amplitude of ATP- and BzATP-induced small inward currents recorded from a subset of non-pyramidal neurons, BzATP caused a more pronounced increase in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) after ischemia than after normoxia. Brilliant Blue G almost abolished the effect of BzATP in normoxic neurons. Since neither the amplitude of mIPSCs nor that of the muscimol-induced inward currents was affected by BzATP, it is assumed that BzATP acts at presynaptic P2X7 receptors. Finally, P2X7 receptors did not enhance the intracellular free Ca2+ concentration either in proximal dendrites or in astrocytes, irrespective of the normoxic or ischemic pre-incubation conditions. Hence, facilitatory P2X7 receptors may be situated at the axon terminals of GABAergic non-pyramidal neurons. When compared with normoxia, ischemia appears to markedly increase P2X7 receptor-mediated GABA release, which may limit the severity of the ischemic damage. At the same time we did not find an accompanying enhancement of P2X7 mRNA or protein expression, suggesting that receptors may become hypersensitive because of an increased efficiency of their transduction pathways. [source]

Increased phosphorylation and redistribution of NMDA receptors between synaptic lipid rafts and post-synaptic densities following transient global ischemia in the rat brain

JOURNAL OF NEUROCHEMISTRY, Issue 1 2005
Shintaro Besshoh
Abstract Ischemia results in increased phosphorylation of NMDA receptors. To investigate the possible role of lipid rafts in this increase, lipid rafts and post-synaptic densities (PSDs) were isolated by the extraction of rat brain synaptosomes with Triton X-100 followed by sucrose density gradient centrifugation. Lipid rafts accounted for the majority of PSD-95, whereas SAP102 was predominantly located in PSDs. Between 50 and 60% of NMDA receptors were associated with lipid rafts. Greater than 85,90% of Src and Fyn were present in lipid rafts, whereas Pyk2 was mainly associated with PSDs. Lipid rafts and PSDs were isolated from animals subjected to 15 min of global ischemia followed by 6 h of recovery. Ischemia did not affect the yield, density, flotillin-1 or cholesterol content of lipid rafts. Following ischemia, the phosphorylation of NR1 by protein kinase C and tyrosine phosphorylation of NR2A and NR2B was increased in both lipid rafts and PSDs, with a greater increase in tyrosine phosphorylation occurring in the raft fraction. Following ischemia, NR1, NR2A and NR2B levels were elevated in PSDs and reduced in lipid rafts. The findings are consistent with a model involving close interaction between lipid rafts and PSDs and a role for lipid rafts in ischemia-induced signaling pathways. [source]

Sphingolipids in rat model of transient focal cerebral ischemia: implication for stroke injury

JOURNAL OF NEUROCHEMISTRY, Issue 2002
M. Khan
Lipids are essential for signal transduction in response to trauma leading to neurodegeneration. Ceramide is an important mediator of apoptosis and cell proliferation. We studied the involvement of ceramide/sphingomyelin pathway in rat brain (stroke model) after 45 min ischemia followed by 24-h reperfusion. Ischemia was performed through occlusion of right middle cerebral artery (MCA). The level of ceramide was found increased (70,100% in ischemic side of brain v/s contralateral side of brain). Sphingomyelin levels were also decreased by 20,25% in ischemic brain v/s contralateral side of brain. Increase in ceramide and decrease in sphingomyelin were in good agreement with observed apoptotic cell loss (TUNEL assay) and decrease in the level of cardiolipin (a mitochondrian specific phospholipids) in affected ischemic brain. N-acetyl cysteine (NAC), a therapeutic agent recognized as potent antioxidant provided protective effect. Pretreatment with NAC before ischemia reduced the infarct volume size, suppressed apoptosis, restored cardiolipin level and decreased the levels of free fatty acids. However, NAC did not normalize the ceramide level. These interesting observations raise a question about the role of ceramide and its relationship with apoptosis and oxidative stress in rat brain ischemia. Acknowledgements:, Supported by NIH grants NS-40144, NS-40810, NS-22576, NS-34741 and NS-37766. [source]

Endogenously released DOPA is a causal factor for glutamate release and resultant delayed neuronal cell death by transient ischemia in rat striata

JOURNAL OF NEUROCHEMISTRY, Issue 3 2001
Nobuya Furukawa
Glutamate is implicated in neuronal cell death. Exogenously applied DOPA by itself releases neuronal glutamate and causes neuronal cell death in in vitro striatal systems. Herein, we attempt to clarify whether endogenous DOPA is released by 10 min transient ischemia due to four-vessel occlusion during rat striatal microdialysis and, further, whether DOPA, when released, functions to cause glutamate release and resultant delayed neuronal cell death. Ischemia increased extracellular DOPA, dopamine, and glutamate, and elicited neuronal cell death 96 h after ischemic insult. Inhibition of striatal l -aromatic amino acid decarboxylase 10 min before ischemia increased markedly basal DOPA, tripled glutamate release with a tendency of decrease in dopamine release by ischemia, and exaggerated neuronal cell death. Intrastriatal perfusion of 10,30 nm DOPA cyclohexyl ester, a competitive DOPA antagonist, 10 min before ischemia, concentration-dependently decreased glutamate release without modification of dopamine release by ischemia. At 100 nm, the antagonist elicited a slight ceiling effect on decreases in glutamate release by ischemia and protected neurons from cell death. Glutamate was released concentration-dependently by intrastriatal perfusion of 0.3,1 mm DOPA and stereoselectively by 0.6 mm DOPA. The antagonist elicited no hypothermia during and after ischemia. Endogenously released DOPA is an upstream causal factor for glutamate release and resultant delayed neuronal cell death by brain ischemia in rat striata. DOPA antagonist has a neuroprotective action. [source]

Lipid Alterations in Transient Forebrain Ischemia

JOURNAL OF NEUROCHEMISTRY, Issue 6 2000
Possible New Mechanisms of CDP-Choline Neuroprotection
Abstract: We have previously demonstrated that cytidine5,-diphosphocholine (CDP-choline or citicoline) attenuated arachidonicacid (ArAc) release and provided significant protection for the vulnerablehippocampal CA1 neurons of the cornu ammonis after transientforebrain ischemia of gerbil. ArAc is released by the activation ofphospholipases and the alteration of phosphatidylcholine (PtdCho) synthesis.Released ArAc is metabolized by cyclooxygenases/lipoxygenases to formeicosanoids and reactive oxygen species (ROS). ROS contribute to neurotoxicitythrough generation of lipid peroxides and the cytotoxic byproducts4-hydroxynonenal and acrolein. ArAc can also stimulate sphingomyelinase toproduce ceramide, a potent pro-apoptotic agent. In the present study, weexamined the changes and effect of CDP-choline on ceramide and phospholipidsincluding PtdCho, phosphatidylethanolamine (PtdEtn), phosphatidylinositol(PtdIns), phosphatidylserine (PtdSer), sphingomyelin, and cardiolipin (anexclusive inner mitochondrial membrane lipid essential for electron transport)following ischemia/1-day reperfusion. Our studies indicated significantdecreases in total PtdCho, PtdIns, PtdSer, sphingomyelin, and cardiolipin andloss of ArAc from PtdEtn in gerbil hippocampus after 10-min forebrainischemia/1-day reperfusion. CDP-choline (500 mg/kg i.p. immediately afterischemia and at 3-h reperfusion) significantly restored the PtdCho,sphingomyelin, and cardiolipin levels as well as the ArAc content of PtdChoand PtdEtn but did not affect PtdIns and PtdSer. These data suggest multiplebeneficial effects of CDP-choline: (1) stabilizing the cell membrane byrestoring PtdCho and sphingomyelin (prominent components of outer cellmembrane), (2) attenuating the release of ArAc and limiting its oxidativemetabolism, and (3) restoring cardiolipin levels. [source]

Induction of Oxidative DNA Damage in the Peri-Infarct Region After Permanent Focal Cerebral Ischemia

JOURNAL OF NEUROCHEMISTRY, Issue 4 2000
Tetsuya Nagayama
Abstract: To address the role of oxidative DNA damage in focal cerebral ischemia lacking reperfusion, we investigated DNA base and strand damage in a rat model of permanent middle cerebral artery occlusion (MCAO). Contents of 8-hydroxyl-2,-deoxyguanosine (8-OHdG) and apurinic/apyrimidinic abasic sites (AP sites), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains obtained 4-72 h after MCAO. DNA single- and double-strand breaks were detected on coronal brain sections using in situ DNA polymerase I-mediated biotin-dATP nick-translation (PANT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), respectively. Levels of 8-OHdG and AP sites were markedly elevated 16-72 h following MCAO in the frontal cortex, representing the peri-infarct region, but levels did not significantly change within the ischemic core regions of the caudateputamen and parietal cortex. PANT- and TUNEL-positive cells began to be detectable 4-8 h following MCAO in the caudate-putamen and parietal cortex and reached maximal levels at 72 h. PANT- and TUNEL-positive cells were also detected 16-72 h after MCAO in the lateral frontal cortex within the infarct border, where many cells also showed colocalization of DNA single-strand breaks and DNA fragmentation. In contrast, levels of PANT-positive cells alone were transiently increased (16 h after MCAO) in the medial frontal cortex, an area distant from the infarct zone. These data suggest that within peri-infarct brain regions, oxidative injury to nuclear DNA in the form of base and strand damage may be a significant and contributory cause of secondary expansion of brain damage following permanent focal ischemia. [source]

Diazepam Promotes ATP Recovery and Prevents Cytochrome c Release in Hippocampal Slices After In Vitro Ischemia

JOURNAL OF NEUROCHEMISTRY, Issue 3 2000
Francesca Galeffi
Abstract: Benzodiazepines protect hippocampal neurons when administered within the first few hours after transient cerebral ischemia. Here, we examined the ability of diazepam to prevent early signals of cell injury (before cell death) after in vitro ischemia. Ischemia in vitro or in vivo causes a rapid depletion of ATP and the generation of cell death signals, such as the release of cytochrome c from mitochondria. Hippocampal slices from adult rats were subjected to 7 min of oxygen-glucose deprivation (OGD) and assessed histologically 3 h after reoxygenation. At this time, area CA1 neurons appeared viable, although slight abnormalities in structure were evident. Immediately following OGD, ATP levels in hippocampus were decreased by 70%, and they recovered partially over the next 3 h of reoxygenation. When diazepam was included in the reoxygenation buffer, ATP levels recovered completely by 3 h after OGD. The effects of diazepam were blocked by picrotoxin, indicating that the protection was mediated by an influx of Cl - through the GABAA receptor. It is interesting that the benzodiazepine antagonist flumazenil did not prevent the action of diazepam, as has been shown in other studies using the hippocampus. Two hours after OGD, the partial recovery of ATP levels occurred simultaneously with an increase of cytochrome c (,400%) in the cytosol. When diazepam was included in the reoxygenation buffer, it completely prevented the increase in cytosolic cytochrome c. Thus, complete recovery of ATP and prevention of cytochrome c release from mitochondria can be achieved when diazepam is given after the loss of ATP induced by OGD. [source]

Association of Pretreatment ASPECTS Scores with tPA-Induced Arterial Recanalization in Acute Middle Cerebral Artery Occlusion

JOURNAL OF NEUROIMAGING, Issue 1 2008
Georgios Tsivgoulis MD
ABSTRACT BACKGROUND AND PURPOSE The Alberta Stroke Program Early CT-Score (ASPECTS) assesses early ischemic changes within the middle cerebral artery (MCA) and predicts poor outcome and increased risk for thrombolysis-related symptomatic ICH. We evaluated the potential relationship between pretreatment ASPECTS and tPA-induced recanalization in patients with MCA occlusions. SUBJECTS & METHODS Consecutive patients with acute ischemic stroke due to MCA occlusion were treated with standard IV-tPA and assessed with transcranial Doppler (TCD) for arterial recanalization. Early recanalization was determined with previously validated Thrombolysis in Brain Ischemia (TIBI) flow-grading system at 120 minutes after tPA-bolus. All pretreatment CT-scans were prospectively scored by trained investigators blinded to TCD findings. Functional outcome at 3 months was evaluated using the modified Rankin Scale (mRS). RESULTS IV-tPA was administered in 192 patients (mean age 68 ± 14 years, median NIHSS-score 17). Patients with complete recanalization (n= 51) had higher median pretreatment ASPECTS (10, interquartile range 2) than patients with incomplete or absent recanalization (n= 141; median ASPECTS 9, interquartile range 3, P= .034 Mann-Whitney U-test). An ASPECTS ,6 was documented in 4% and 17% of patients with present and absent recanalization, respectively (P= .019). Pretreatment ASPECTS was associated with complete recanalization (OR per 1-point increase: 1.54; 95% CI 1.06,2.22, P= .023) after adjustment for baseline characteristics, risk factors, NIHSS-score, pretreatment TIBI grades and site of arterial occlusion on baseline TCD. Complete recanalization (OR: 33.97, 95% CI 5.95,185.99, P < .001) and higher ASPECTS (OR per 1-point increase: 1.91; 95% CI 1.17,3.14, P= .010) were independent predictors of good functional outcome (mRS 0,2). CONCLUSIONS Higher pretreatment ASPECT-scores are associated with a greater chance of complete recanalization and favorable long-term outcome in tPA-treated patients with acute MCA occlusion. [source]

Echocardiographic Findings of Patients With Retinal Ischemia or Embolism

JOURNAL OF NEUROIMAGING, Issue 3 2002
Mikael Mouradian MD
ABSTRACT Background and Purpose. A potential source of emboli is not detected in more than 50% of patients with retinal arterial occlusive events. Echocardiographic studies are not always included in the diagnostic workup of these patients. The authors studied the diagnostic yield of transthoracic (TTE) and/or transesophageal (TEE) echocardiography in identifying potential sources of emboli in patients with retinal ischemia or embolism. Methods. In a prospective study, 73 consecutive patients with clinically diagnosed retinal ischemia or embolism received a standardized diagnostic workup including retinal photography, echocardiography, and imaging studies of the internal carotid arteries. TTE was performed in 83.6% of patients, TEE was performed in 5.5% of patients, and both TTE and TEE were per-formed in 11.0% of patients. Ophthalmological diagnoses consisted of amaurosis fugax (n= 28), asymptomatic cholesterol embolism to the retina (n= 34), and branch or central retinal artery occlusion (n= 11). Results. Echocardiography identified a potential cardiac or proximal aortic source for embolism in 16 of 73 (21.9%) patients, including 8 who also had either atrial fibrillation or internal carotid artery stenosis of more than 50% on the side of interest. Thus, 8 of 73 (11.0%) patients had lesions detected only by echocardiography. The most commonly identified lesions were proximal aortic plaque of more than 4 mm thickness (n= 7, 9.6%) and left ventricular ejection fraction of less than 30% (n= 6, 8.2%). TEE was particularly helpful in identifying prominent aortic plaques. Conclusion. Echocardiography frequently identifies lesions of the heart or aortic arch that can act as potential sources for retinal ischemia or embolism. Further studies are needed to evaluate the prognostic and therapeutic relevance of these findings. [source]

Effect of mivazerol, a ,2 -agonist, on striatal norepinephrine concentration during transient forebrain ischemia in rats,

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2008
T. KIMURA
Background: We have previously reported that mivazerol, a ,2 -agonist, possibly provides neuroprotection against transient forebrain ischemia in rats. This study was designed to investigate the ability of mivazerol to attenuate ischemia-induced increase in striatal norepinephrine concentration after transient forebrain ischemia in rats. Methods: Male Sprague,Dawley rats, anesthetized with halothane, were assigned to one of three groups (n=10 each); control (C, normal saline 1 ml/kg), mivazerol 20 ,g/kg (M20), and 40 ,g/kg (M40) groups. Monitored variables included temporal muscle temperature (maintained at 37.5±0.1 °C), electroencephalogram, systolic/diastolic blood pressure, heart rate, arterial blood gases, and blood glucose concentrations. Thirty minutes after subcutaneous drug administration, forebrain ischemia was induced with hemorrhagic hypotension (systolic arterial pressure: 40,50 mmHg) and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. Norepinephrine concentration in the interstitial fluids in the striatum was analyzed using in vivo microdialysis in combination with high-performance liquid chromatography. Results: Ischemia resulted in a prompt increase in norepinephrine concentrations in the striatum in all groups. However, there were no significant differences in norepinephrine concentrations in the striatum between the three groups at any period. Conclusions: Our results indicate that mivazerol did not attenuate ischemia-induced increase in striatal norepinephrine concentration. This suggests that the possible neuroprotective property of mivazerol is not related to inhibition of norepinephrine release in the brain. [source]

Ischemia,reperfusion injury pathophysiology, part I

JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2004
DACVECC, Maureen McMichael DVM
Abstract Objective: To review the current scientific literature on ischemia,reperfusion (IR) injury in both human and veterinary medicine. To describe the normal antioxidant defense mechanisms, the pathophysiology of IR injury, and the role of neutrophils in IR injury. Data sources: Data sources include scientific reviews and original research publications in both human and veterinary medicine. Summary: IR injury is a complex pathophysiological process involving numerous pathways and body systems. Normal antioxidant defense mechanisms function to limit oxidative injury during times of health. Ischemia is the period that occurs before oxygenated blood is re-introduced and the severity of injury has been shown to correlate with the magnitude and length of ischemia in dogs. During ischemia, there is a buildup of substances (i.e., xanthine oxidase, hypoxanthine, etc.) that, upon re-introduction of oxygen, form reactive oxygen species (ROS). ROS, produced in large part upon reperfusion, can cause extensive damage to DNA, proteins, carbohydrates, and lipids. Although mammalian systems are endowed with abundant antioxidant defenses, the generation of large amounts of ROS can overwhelm these mechanisms leading to cell dysfunction and death. Neutrophils play a critical role in IR injury and may mediate the majority of mucosal and microvascular injury that occurs by releasing ROS and proteolytic enzymes. Although experimental studies have been carried out on cats, dogs, and horses there are few clinical studies on companion animals. Conclusions: The pathophysiology of IR injury is complex and involves damage by ROS to all biological membranes. Neutrophils play a major role in IR injury and initiate and propogate much of the damage. This article is intended as a review of the pathophysiology of IR injury. [source]

Ischemia,reperfusion injury: assessment and treatment, part II

JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2004
DACVECC, Maureen McMichael DVM
Abstract Objective: To review the current scientific literature on ischemia,reperfusion (IR) injury in both human and veterinary medicine and to describe the assessment of IR injury, the available testing methods, and the options available for treatment. Data sources: Data sources include scientific reviews and original research publications in both human and veterinary medicine. Summary: The assessment of IR injury includes measuring products formed by the reaction of reactive oxygen species (ROS) with biological membranes, measuring levels of endogenous antioxidants, and measuring ROS themselves. Testing depends on the laboratory used, the test method chosen, the sample submitted (i.e., plasma, urine, tissue, etc.), and the timing of the test in relation to sample collection. For this reason, testing is not standardized and pharmacological data on antioxidant effectiveness are not available. Antioxidants and drugs tested have included single agents as well as ,cocktails' consisting of several agents working at different key points in the injury cascade. Conclusions: There are several new testing methods as well as new strategies for attempting to ameliorate the damage inflicted upon reperfusion and this article is intended as a review of the assessment and treatment of IR injury. [source]

Long-term effects of hypothermia on neuronal cell death and the concentration of apoptotic proteins after incomplete cerebral ischemia and reperfusion in rats

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2005
E. Eberspächer
Background:, The present study investigates the long-term effects of postischemic hypothermia on neuronal cell damage and concentration changes of apoptotic proteins after cerebral ischemia. Methods: Sixty-four Sprague-Dawley rats were anesthetized, intubated and ventilated with 2.0 Vol% isoflurane and 70% N2O/O2. After preparation the animals were randomly assigned to the following groups: group 1 (n = 32, fentanyl-N2O/normothermia 37.5°C), and group 2 (n = 32, fentanyl-N2O/hypothermia 34.0°C. Ischemia (45 min) was induced by common carotid artery occlusion plus hemorrhagic hypotension (MAP = 40 mmHg). Arterial blood gases and pH were maintained constant. After 1, 3, 7, or 28 days (each n = 8) the brains were removed, frozen and cut. Neuronal damage was assessed by analyzing Bax, Bcl-2, p53, and Mdm-2 proteins, activated caspases-3-positive and eosinophilic cells. A third group (n = 8) of untreated animals served as naive controls. Results:, In hypothermic animals, Bax concentration was decreased by 50,70% over time compared to normothermia. On days 1 and 3, Bcl-2 was increased by 50% with hypothermia. The amount of activated caspase-3-positive cells in the ischemic hemisphere was 0.5% in the hypothermic and 1,2% in the normothermic animals. Of the hippocampal cells, 10,25% were eosinophilic in both groups over time. Conclusion:, The present data show that hypothermia prevents an ischemia-induced increase of the pro-apoptotic protein Bax for as long as 28 days and increases the concentration of the antiapoptotic protein Bcl-2 up to 3 days compared to normothermic animals. Therefore, after cerebral ischemia, hypothermia has the sustained neuroprotective potential to shift apoptosis-related proteins towards neuronal cell survival. [source]

Reactivity of Brain Parenchymal Arterioles after Ischemia and Reperfusion

MICROCIRCULATION, Issue 6 2008
MARILYN J. CIPOLLA
ABSTRACT Objective: We investigated the effect of ischemia and reperfusion on the vasoactive function of penetrating brain parenchymal arterioles under pressurized conditions. Methods: Parenchymal arterioles (<50 ,m in diameter) from within the middle cerebral artery territory were dissected from male Wistar rats that were either nonischemic control (n = 16) or ischemic for one hour and reperfused for 24 hours (n = 16) by temporary filament occlusion of the middle cerebral artery. Arterioles were mounted on glass cannulas within an arteriograph chamber that allowed for the measurement of lumen diameter and control over intravascular pressure. Results: After one hour of equilibration at 10 mmHg, spontaneous myogenic tone developed in both groups of animals, constricting control arterioles from 69 ± 9 to 49 ± 11 ,m (29.5 ± 10.2%) and ischemic arterioles from 66 ± 9 to 45 ± 11 ,m (33.1 ± 14.1%); p > 0.05. Contraction to the nitric oxide synthase inhibitor nitro-L-arginine (10,4M) was significantly diminished in ischemic arterioles, constricting only 3.2 ± 3.3 vs. 15.6 ± 12.5% in control arterioles (p = 0.017). Both groups dilated to nifedipine; however, the response was significantly diminished after ischemia. The EC50 for nifedipine in control arterioles was 3.54 ± 0.11 vs. 9.90 ± 0.71 nM for ischemic arterioles (p = 0.024). Conclusions: These findings demonstrate that functional changes occur in brain parenchymal arterioles after ischemia and reperfusion, a result that may significantly influence stroke outcome by altering blood flow to an ischemic region. [source]

Inflammatory and Hemodynamic Changes in the Cerebral Microcirculation of Aged Rats after Global Cerebral Ischemia and Reperfusion

MICROCIRCULATION, Issue 4 2008
Leslie Ritter
ABSTRACT Effects of aging on inflammation and blood flow in the brain are unclear. Young (three to six months) and aged (19,22 months) male Brown Norway Fisher rats were used to compare (i) leukocyte function in nonischemic conditions and (ii) leukocyte function and hemodynamic changes after ischemia-reperfusion (I-R). In nonischemic studies, polymorphonuclear (PMN) CD11b expression and reactive oxygen species (ROS) production were measured with flow cytometry and PMN chemotaxis was measured with a Boyden chamber (+/-fMLP). In I-R studies, ischemia was induced by bilateral carotid artery occlusion and hypotension (20 minutes). During early reperfusion (30 minutes), leukocyte adhesion and rolling and blood-shear rates were measured using fluorescence microscopy. During late reperfusion (48 hours), mortality, neurological function, and leukocyte infiltration were measured. Stimulated PMN chemotaxis was increased in nonischemic aged rats (p < 0.05). In early reperfusion, there was a significant increase in leukocyte rolling and adhesion in the cerebral microcirculation and a significant decrease in shear rate in aged rats, compared to the young (p < 0.05). During late reperfusion, neurologic function was worse in aged vs. young rats (p < 0.05). These findings suggest that increased intravascular PMN adhesion and vascular dysfunction may contribute to poor neurologic outcome after cerebral I-R in the aged brain. [source]

Protective Effects of Ischemic Preconditioning on the Intestinal Mucosal Microcirculation Following Ischemia,Reperfusion of the Intestine

MICROCIRCULATION, Issue 8 2005
ISMAIL H. MALLICK
ABSTRACT Objective: The small bowel villi are extremely sensitive to ischemia,reperfusion (IR) injury and a range of microcirculatory disturbances contribute to structural and functional changes. The aim of this study was to determine the protective effects of ischemic preconditioning (IPC) of the intestine on the mucosal villous microcirculation during IR injury of the intestine and whether heme oxygenase (HO) is involved in the protection. Methods: Rats were allocated into 4 groups: (1) sham, (2) IR consisting of 30 min of ischemia followed by 2 h of reperfusion, (3) IPC, as in IR group, but preceded by 10 min of ischemia and 10 min of reperfusion, and (4) with administration of zinc protoporphyrin, an HO inhibitor before IPC and IR. The mucosa of an exteriorized segment of ileum was visualized. Mucosal perfusion index (MPI), red blood cell (RBC) velocity and leukocyte,endothelial interactions during reperfusion were assessed continuously using in vivo fluorescence microscopy. HO activity in the ileum was assessed at the end of the reperfusion period. Results: IPC improved the MPI by 26% and the RBC velocity by 29% on comparison to IR. IR led to a 52% increase in leukocyte,endothelial interactions on comparison to IPC. The administration of zinc protoporphyrin reversed the beneficial effects of IPC. There was a two fold increase of HO activity in IPC compared to IR, whereas zinc protoporphyrin significantly reduced the HO activity. Conclusions: IPC conferred a protective effect on the villous microcirculation possibly via HO and might prove to be an effective strategy for the amelioration of IR injury. [source]

Ischemia,Reperfusion Impairs Ascending Vasodilation in Feed Arteries of Hamster Skeletal Muscle

MICROCIRCULATION, Issue 7 2005
MIRIAM C. J. DE WITH
ABSTRACT Objective: Vasodilation originating within the microcirculation ascends into proximal feed arteries during muscle contraction to attain peak levels of muscle blood flow. Ascending vasodilation (AVD) requires an intact endothelium, as does conducted vasodilation in response to acetylcholine (ACh). Whereas ischemia,reperfusion (I-R) can affect endothelial cell function, the effect of I-R on AVD is unknown. The authors tested the hypothesis that I-R (1h,1h) would impair AVD. Methods: Using the retractor muscle of anesthetized hamsters, contractions were evoked using field stimulation (200 ms at 40 Hz every 2 s for 1 min) and ACh was delivered using microiontophoresis (1 ,m tip, 500,4000 ms pulse at 800 nA). Feed artery responses were monitored 500,1500 ,m upstream. Results: Neither resting (51 ± 4 ,m) nor maximal diameter (81 ± 5 ,m; 10 ,m sodium nitroprusside) following I-R (n = 8) were different from time-matched controls (n = 10). With peak active tension of 23 ± 4 mN · mm,2, control AVD was 26 ± 2 ,m. Following I-R, active tension fell by 48% (p < .05) and AVD by 57% (p < .05). Stimulation at 70 Hz restored active tension but AVD remained depressed by nearly half (p < .05), as did local and conducted responses to ACh. Nevertheless, control responses to 500 ms ACh were restored by increasing stimulus duration to 4000 ms. Conclusions: Ischemia,reperfusion impairs the initiation of feed artery dilation with muscle contraction and with ACh while conduction along the vessel wall is preserved. Respective components of endothelial cell signaling events may differ in their susceptibility to I-R. [source]