Animal Models Of Infarction Research Articles

Cardioprotective effects of nitrite during exercise

Exercise training has been shown to reduce many risk factors related to cardiovascular disease, including high blood pressure, high cholesterol, obesity, and insulin resistance. More importantly, exercise training has been consistently shown to confer sustainable protection against myocardial infarction in animal models and has been associated with improved survival following a heart attack in humans. It is still unclear how exercise training is able to protect the heart, but some studies have suggested that it increases a number of classical signalling molecules. For instance, exercise can increase components of the endogenous antioxidant defences (i.e. superoxide dismutase and catalase), increase the expression of heat shock proteins, activate ATP-sensitive potassium (K(ATP)) channels, and increase the expression and activity of endothelial nitric oxide (NO) synthase resulting in an increase in NO levels. This review article will provide a brief summary of the role that these signalling molecules play in mediating the cardioprotective effects of exercise. In particular, it will highlight the role that NO plays and introduce the idea that the stable NO metabolite, nitrite, may play a major role in mediating these cardioprotective effects.

Cosmic Implications of NXY-059

The SAINT studies on NXY-0591,2 have reinvigorated debate over the momentous issues of neuroprotection and the development of novel stroke therapeutics. Some may argue there is little new ground that NXY-059 has unearthed and, in fact, the clinical trials merely confirm that as a strategy, neuroprotection has not been shown to be effective. Editorials in high-profile journals have sent out the clarion call to terminate research on neuroprotection given decades of work, which has uniformly led to failure after failure in clinical studies.3 These sentiments are premature and ignore studies showing that hypothermia improves outcome in patients after cardiac arrest, a major cause of global cerebral ischemia.4,5 Proof for the neuroprotection concept has therefore already been established. Despite decades of neutral clinical trials, there still remains optimism among the stroke academic community. A majority of university-affiliated stroke neurologists in the United States in a recent survey still believe neuroprotection is a viable therapeutic strategy, although admittedly, that survey was conducted between the SAINT I and SAINT II publications.6 However, the question whether neuroprotection will ever work in stroke has been overshadowed by the larger issue of whether animal studies, which serve as the foundation for the development of stroke therapeutics, are even relevant to our patients with acute stroke. In the discussion section of the SAINT II article, the authors write, “it is possible that the animal models of acute focal infarction are not relevant to the patient population; they certainly are insufficient to guarantee a positive clinical-trial result.” Have all prior neuroprotective agents failed in clinical studies because rodent stroke is not relevant to human stroke? This is a key question. Substantial reductions in infarct size in rodents with stroke treated with various types of purported neuroprotective agents would seem to support this view. There …

Repetitive cortical spreading depolarizations in a case of severe brain trauma

Objective and importance: Cortical spreading depolarizations (CSD) are waves of mass tissue depolarization that mediate progressive development of cortical infarction in animal models and occur in ∼50% of patients with acute brain injury. Here we performed multi-modal cerebral monitoring to investigate pathologies associated with CSD occurrence in a case of severe traumatic brain injury.Clinical presentation: A 20 years old male suffering severe traumatic brain injury from a fall had extensive frontal subdural and intraparenchymal hemorrhage with mass effect. Craniectomy was performed for hematoma evacuation and decompression.Intervention: During surgery, a subdural electrocorticography (ECoG) electrode strip, along with microdialysis and PtiO2 probes, was placed beside injured cortex for CSD monitoring. Within 13–81 hours post-injury, 34 CSD occurred. CSD incidence increased during spontaneous hyperthermia and decreased during induced normothermia. Periods of CSD activity were also associated with low brain glucose (<0.10 mmol/l), elevated glutamate (>40 mmol/l) and lactate/pyruvate (>40), and PtiO2<10 mmHg. CSD caused progressive deterioration of ECoG activity only in regions with infarction at follow-up on day 27.Conclusion: Repetitive mass tissue depolarizations accompanied a negative course of hemorrhagic lesion progression in the presence of ischemic conditions after traumatic brain injury. Whether as cause or effect, CSD may represent an inherent component of progressive metabolic failure leading to tissue death, and temperature appears to be an important factor influencing their occurrence. Continuous ECoG is a valuable tool for monitoring subclinical events such as CSD and seizures and for translational research in acute brain injury mechanisms and therapeutics.

What is the place of thrombolysis in acute stroke? A review of the literature and a current perspective

The global burden of stroke, the undisputed success of intravenous thrombolysis in the management of myocardial infarction and subsequent evidence from animal models of cerebral infarction have all fuelled intense interest in the potential role for thrombolytic agents in the acute management of stroke in clinical practice. Before any clinical treatment is introduced universally its safety and efficacy must be demonstrated in the routine clinical environment and not just within the ideal conditions of controlled clinical trials. Similarly, the cost effectiveness of a new treatment modality is an essential consideration before its use is promulgated. This paper reviews the current scientific evidence for thrombolysis in stroke with reference to issues of safety, efficacy and cost effectiveness.

Synthesis and preliminary biological evaluation of a 99mTc‐labeled hypericin derivative as a necrosis avid imaging agent

AbstractMono‐[123I]iodohypericin and mono‐[123I]iodohypericin monocarboxylic acid are iodine‐123‐labeled hypericin derivatives which have shown great promise in preclinical studies as necrosis avid imaging agents in animal models of infarction. In view of the more attractive properties of a 99mTc‐labeled hypericin derivative, we have synthesized a conjugate of protohypericin monocarboxylic acid with S‐benzoylmercaptoacetyldiglycyl‐diaminopentane in an overall yield of 15%. The conjugate was labeled with technetium‐99m by exchange labeling at pH 10 in a labeling yield of 95% followed by photocyclization to yield 99mTc‐mercaptoacetyldiglycyl‐1,5‐diaminopentylene hypericincarboxamide (99mTc‐13). The negatively charged 99mTc‐13 complex was purified by reversed phase high‐pressure liquid chromatography and the log P7.4 was determined to be 2.36. In normal NMRI mice, the complex showed slow hepatobiliary clearance while plasma clearance was rapid. The tracer was evaluated in rats with reperfused hepatic infarction by ex vivo autoradiography, gamma counting and histochemical techniques. Unlike the radioiodinated hypericin derivatives, the new tracer agent did not show preferential uptake in necrotic tissue on autoradiography and gamma counting techniques. Conjugation of hypericin with a 99mTc‐chelate, resulting in a change in size, charge and lipophilicity, had a profound effect on the necrosis avidity of the tracer agent. The results show that 99mTc‐13 is not suitable for imaging necrosis. Copyright © 2008 John Wiley &amp; Sons, Ltd.

Role of SDF-1/CXCR4 system in survival and migration of bone marrow stromal cells after transplantation into mice cerebral infarct

Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurological function when transplanted into animal models of cerebral infarction. However, it is still obscure how the transplanted BMSC restore the lost neurological function. In this study, therefore, we aimed to elucidate the role of stromal cell-derived factor-1 (SDF-1) and its specific receptor, CXCR4, in BMSC transplantation into the brain subjected to cerebral infarction. The BMSC were harvested from the wild type (WT) and CXCR4-knockout (CXCR4-KO) mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The WT or CXCR4-KO BMSC was injected into the ipsilateral striatum 7 days after the insult. Motor function of the animals was serially evaluated, using a rotarod treadmill. Using fluorescence immunohistochemistry, we evaluated the distribution and phenotype of the transplanted cells 4 weeks after transplantation. Recovery of motor function in the WT BMSC-transplanted mice was more pronounced than in the CXCR4-KO-transplanted mice and the vehicle-treated ones. SDF-1 was extensively expressed in peri-infarct area. In the WT BMSC-transplanted mice, the transplanted cells were extensively distributed in the ipsilateral hemisphere, and many of them migrated towards the peri-infarct area and expressed the proteins specific for neurons and astrocytes, although these findings were not observed in the CXCR4-KO-transplanted mice. The results suggest that the SDF-1/CXCR4 system may play a critical role in the survival, proliferation and migration of the transplanted BMSC and contribute to recovery of neurological function.

VASCULAR ENDOTHELIAL GROWTH FACTOR GENE-TRANSFERRED BONE MARROW STROMAL CELLS ENGINEERED WITH A HERPES SIMPLEX VIRUS TYPE 1 VECTOR CAN IMPROVE NEUROLOGICAL DEFICITS AND REDUCE INFARCTION VOLUME IN RAT BRAIN ISCHEMIA

Several reports recently suggested that vascular endothelial growth factor (VEGF) may have a therapeutic benefit against experimental cerebral infarction animal models. In addition, bone marrow stromal cells (BMSCs) are known to have therapeutic potency in improving neurological deficits after occlusive cerebrovascular diseases. In the present study, we evaluated the hypothesis that intracerebral transplantation of VEGF gene-transferred BMSCs could provide a greater therapeutic effect than intracerebral transplantation of native (non-gene-transformed) BMSCs by using a transient middle cerebral artery occlusion (MCAO) rat model. Adult Wistar rats (Japan SLC, Inc., Hamamatsu, Japan) were anesthetized. VEGF gene-transferred BMSCs engineered with a replication-deficient herpes simplex virus type 1 1764/4-/pR19-hVEGF165 vector, native BMSCs, or phosphate-buffered saline were administered intracerebrally 24 hours after transient MCAO. All animals underwent behavioral testing for 28 days, and the infarction volume was determined 14 days after MCAO. The brain water contents in the ipsilateral and contralateral hemispheres of the MCAO were measured 2 and 7 days after the MCAO. Fourteen days after MCAO, immunohistochemical staining for VEGF was performed. The group receiving VEGF-modified BMSCs demonstrated significant functional recovery compared with those receiving native BMSCs. Fourteen days after the MCAO, there was a significantly lower infarct volume without aggravating cerebral edema in the group treated with VEGF gene-modified BMSCs compared with the control groups. The transplanted VEGF gene-modified BMSCs strongly expressed VEGF protein for at least 14 days. Our data suggest that the intracerebral transplantation of VEGF gene-transferred BMSCs may provide a more potent autologous cell transplantation therapy for stroke than the transplantation of native BMSCs alone.

Myocardial extracellular matrix remodeling in ischemic heart failure

Left ventricular (LV) remodeling is a process whereby structural alterations attempt to compensate altered hemodynamic load. In the chronic setting this process becomes maladaptive, self-sustaining and is associated with worsened survival. The extracellular matrix (ECM) of the heart, once believed an inert scaffold for cardiomyocytes, is now known to play an important role in LV remodeling. The enzyme system primarily responsible for ECM turnover is the matrix metalloproteinases (MMPs), and these enzymes are robustly altered in cardiovascular pathologies, including myocardial infarction (MI) and ischemic heart failure. A cause-and-effect relationship has been established between MMPs and LV remodeling post MI, as MMP inhibition prevents LV dilation and preserves cardiac function in animal models of infarction. In spite of this, initial clinical experience with MMP inhibition post MI has been disappointing. This review examines the structural and functional roles of the myocardial ECM, the evidence for MMP involvement in LV remodeling, and recent investigations into MMPs as prognostic markers and therapeutic targets.

RANKL Inhibition: A Novel Strategy to Decrease Femoral Head Deformity After Ischemic Osteonecrosis

A novel therapeutic strategy to decrease the development of femoral head deformity after ischemic osteonecrosis was studied in a large animal model of total head infarction. RANKL inhibition through exogenous osteoprotegerin administration significantly decreased pathologic bone resorption and deformity during repair of the infarcted head. Legg-Calvé-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that can produce permanent femoral head deformity (FHD) and premature osteoarthritis. The development of FHD in LCPD is closely associated with the repair process, characterized by a predominance of bone resorption in its early stage that produces a fragmented appearance and collapse of the femoral head. We present here a novel strategy to preserve the femoral head structure after ischemic osteonecrosis based on inhibition of interaction between RANK and RANKL using exogenous administration of osteoprotegerin (OPG-Fc) in a large animal model of ischemic osteonecrosis. Ischemic osteonecrosis was surgically induced in 18 male piglets by placing a ligature tightly around the right femoral neck to disrupt the blood flow to the right femoral head. Two weeks after the induction of total head infarction, OPG-Fc or saline was administered subcutaneously to nine animals per group for 6 weeks. The contralateral, normal (left) femoral heads from the animals treated with saline served as normal, nondisease controls. All animals were killed at 8 weeks when severe FHD has been previously shown to occur because of the repair process dominated by osteoclastic bone resorption. Radiographic, histomorphometric, and immunohistochemical assessments were performed. Radiographic assessment showed significantly better preservation of the femoral head structure in the OPG-Fc group compared with the saline group. Epiphyseal quotient (the ratio of epiphyseal height to diameter) was significantly higher in the OPG-Fc group (0.41 +/- 0.09) compared with the saline group (0.24 +/- 0.08, p < 0.001). Histomorphometric assessment revealed a significant reduction in the number of osteoclasts present in the OPG-Fc group (5.9 +/- 5.3mm(-2)) compared with the saline group (39.6 +/- 13.8 mm(-2), p < 0.001). Trabecular bone volume, number, and separation were significantly better preserved in the OPG-Fc group compared with the saline group (p < 0.001). No significant difference in femoral length was observed between the OPG-Fc and saline groups. Immunostaining revealed the presence of OPG-Fc only within the blood vessels, with no apparent staining of bone matrix or trabecular bone surfaces. To our knowledge, this is the first study to show that RANKL inhibition decreases bone resorption and FHD after ischemic osteonecrosis. Because RANKL inhibitors do not bind to bone, their effects on resorption are reversible as the drug is cleared from circulation. The reversible nature of RANKL inhibitors is very appealing for treating pediatric bone diseases such as LCPD, where the resorptive stage of the disease lasts for 1-2 years.

Effects of cardiac patches engineered with bone marrow-derived mononuclear cells and PGCL scaffolds in a rat myocardial infarction model

Little is known about the cardioprotective effects against heart failure (HF), the effects on differentiation of bone marrow-derived mononuclear cell (BMMNC), and the biocompatibility of BMMNC-seeded biodegradable poly-glycolide- co-caprolactone (PGCL) scaffolds in a myocardial infarction (MI) animal model. This study hypothesized that implantation of a BMMNC-seeded PGCL scaffold into the epicardial surface in a rat MI model would be biocompatible, induce BMMNC migration into infarcted myocardium, and effectively improve left ventricular (LV) systolic dysfunction. One week after the implantation of a BMMNC-seeded PGCL scaffold, BMMMC showed migration into the epicardial region. Four weeks after implantation, augmented neovascularization was observed in infarcted areas and in infarct border zones. Some BMMNCs exhibited the presence of α-MHC and troponin I, markers of differentiation into cardiomyocytes. In echocardiographic examinations, BMMNC-seeded PGCL scaffold and non-cell-seeded simple PGCL scaffold groups effectively reduced progressive LV dilatation and preserved LV systolic function as compared to control rat MI groups. Thus, BMMNC-seeded PGCL scaffolding influences BMMNC migration, differentiation to cardiomyocytes, and induction of neovascularization, ultimately effectively lessening LV remodeling and progressive LV systolic dysfunction. PGCL scaffolding can be considered as an effective treatment alternative in MI-induced advanced HF.

Transient Body Fluid Accumulation and Enhanced NKCC2 Expression in Gerbils with Brain Infarction

Background: Enhanced expression of a kidney-specific sodium co-transporter (NKCC2: Na-K-2Cl co-transporter) in the thick ascending limb of Henle has been identified in rat models of congestive heart failure and liver cirrhosis, suggesting that high NKCC2 expression underlies edema formation. An increased abundance of NKCC2, however, has also been noted in rats with the syndrome of inappropriate secretion of antidiuretic hormone; hyponatremia without edema. In the present study, we examined NKCC2 expression in non-edematous disease, such as a brain infarction, and investigated the physiological and/or pathological characterization of NKCC2 expression. Methods:We initially examined NKCC2 expression in an animal model of brain infarction. Mongolian gerbils (around 60 g body weight) underwent bilateral clamping of the common carotid arteries for 5 min for the induction of brain infarction. NKCC2 and apical water channel (AQP2) protein levels in the collecting duct were examined by Western blotting in kidney tissues 2, 7, and 14 days after the brain infarction. Gerbils with brain infarction were then fed either a normal low-sodium diet (0.3 g/kg/day) or a high-sodium diet (3.0 g/kg/day), and body weight, urine volume and urinary osmolality were examined daily. Blood parameters were measured on day 14 after the brain infarction. Results: Histochemical examination of the brain confirmed the presence of brain infarction, as manifested by altered cresyl violet staining in the hippocampus. Protein levels of NKCC2 were significantly increased in gerbils with brain infarction on days 2 and 7 after brain infarction, whereas AQP2 protein signals remained unaltered. However, the increased NKCC2 intensity disappeared on day 14. Body weight gain was slightly, but significantly greater in gerbils with brain infarction than in sham-operated gerbils up to 7 days after the brain infarction. The high-sodium diet resulted in significant urinary concentration and enhanced weight gain in infarcted gerbils. Conclusion: We noted increased NKCC2 abundance in non-edematous disease, which enhanced body fluid accumulation, likely via the sodium loading-dependent concentration of the urine. These results suggest that the physiological process of edema formation is based on specific NKCC2 expression. The transient duration of these findings in the present animal model suggests two different characteristics of specific NKCC2 expression, an immediate, transient appearance as a common response in serious conditions and more chronic expression that leads to edema formation.

First preclinical evaluation of mono-[123I]iodohypericin as a necrosis-avid tracer agent

We have labelled hypericin, a polyphenolic polycyclic quinone found in St. John's wort (Hypericum perforatum), with( 123)I and evaluated mono-[(123)I]iodohypericin (MIH) as a potential necrosis-avid diagnostic tracer agent. MIH was prepared by an electrophilic radioiodination method. The new tracer agent was evaluated in animal models of liver infarction in the rat and heart infarction in the rabbit using single-photon emission computed tomography (SPECT), triphenyltetrazolium chloride (TTC) histochemical staining, serial sectional autoradiography and microscopy, and radioactivity counting techniques. Using in vivo SPECT imaging, hepatic and cardiac infarctions were persistently visualised as well-defined hot spots over 48 h. Preferential uptake of the tracer agent in necrotic tissue was confirmed by perfect match of images from post-mortem TTC staining, autoradiography (ARX) and histology. Radioactivity concentration in infarcted tissues was over 10 times (liver; 3.51% ID/g in necrotic tissue vs 0.38% ID/g in normal tissue at 60 h p.i.) and over 6 times (myocardium; 0.36% ID/g in necrotic tissue vs 0.054% ID/g in normal tissue; ratios up to 18 for selected parts on ARX images) higher than in normal tissues. The results suggest that hypericin derivatives may serve as powerful necrosis-avid diagnostic agents for assessment of tissue viability.

Risk factors for coronary artery disease, circulating endothelial progenitor cells, and the role of HMG-CoA reductase inhibitors

Recent studies suggest that postnatal neovascularization relies not exclusively on sprouting of preexisting vessels ("angiogenesis"), but also involves the contribution of bone marrow-derived circulating endothelial progenitor cells (EPCs). EPCs can be isolated from peripheral blood or bone marrow mononuclear cells, CD34(+) or CD133(+) hematopoietic progenitors. Infusion of EPCs was shown to promote postnatal neovascularization of ischemic tissue after myocardial infarction in animal models and initial clinical trials. Moreover, circulating endothelial precursor cells can home to denuded arteries after balloon injury and contribute to endothelial regeneration, thereby limiting the development of restenosis. Thus, circulating endothelial cells may exert an important function as endogenous repair mechanism to maintain the integrity of the endothelial monolayer and to promote ischemia-induced neovascularization. However, risk factors for coronary artery disease, such as diabetes, hypercholesterolemia, and hypertension are associated with impaired number and function of EPC in patients with coronary artery disease. Therapeutically, the reduction of EPC number and the decreased functional activity in patients with coronary artery disease was counteracted by 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase inhibitors (statins), vascular endothelial growth factor (VEGF), estrogen, or exercise. At the molecular level, these factors are well established to activate the phosphatidyl-inositol-3-kinase (PI3K)-Akt-dependent activation of the endothelial nitric oxide synthase (eNOS), suggesting that the PI3K-Akt-eNOS signaling pathway may be involved in the transduction of atheroprotective factors. Taken together, the balance of atheroprotective and proatherosclerotic factors may influence EPC levels and their functional capacity to improve neovascularization and endothelial regeneration.

Temporary focal ischemia in the mouse: Technical aspects and patterns of Fluoro-Jade evident neurodegeneration

Animal models of cerebral infarction are crucial to understanding the mechanisms of neuronal survival following ischemic brain injury and to the development of therapeutic interventions for victims of all types of stroke. Rodents have been used extensively in such research. One rodent model of stroke utilizes either permanent or temporary occlusion of the middle cerebral artery (MCAO) to produce ischemia. Since the development of an endovascular method for this was published in 1989, MCAO has been applied commonly to the rat, and often paired with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining for stroke volume measurement. Meanwhile, advances in the ability to genetically alter mice have allowed exciting lines of research into ischemia. Because of technical demands and issues with survival, relatively few laboratories have investigated the MCAO method in the mouse. Our present work utilizes a mouse middle cerebral occlusion (MCAO) model of embolic stroke to study neuronal degeneration following temporary focal cerebral ischemia. C57Bl/6J mice were used to examine the exact effects of MCAO using Fluoro-Jade, a marker of neurodegeneration that allows observation of specific brain regions and cells destined to die. A time course of escalating neuronal degeneration from 10 min to 7 days following MCAO was established. Technical aspects of this popular method for transient focal ischemia as it applies to the mouse are discussed.

Mode entropy and dynamical analysis of irregularity for HFECG

A new algorithm—ModEn (mode entropy) is proposed by analyzing and modifying ApEn (approximate entropy), so that the irregular analysis can be applied to the time series of short-term signals with broad amplitude and slow fluctuation (SBS signals); and the ModEn is introduced in the irregular dynamic analysis of high frequency electrocardiogram (HFECG) on a myocardium infarction (MI) animal model. It is shown that the ModEn has a considerable dynamic change in MI. Hence there are potential application values of the algorithm in the early stage diagnosis of heart disease.

Validation of a simple and inexpensive method for the quantitation of infarct in the rat brain.

A gravimetric method was evaluated as a simple, sensitive, reproducible, low-cost alternative to quantify the extent of brain infarct after occlusion of the medial cerebral artery in rats. In ether-anesthetized rats, the left medial cerebral artery was occluded for 1, 1.5 or 2 h by inserting a 4-0 nylon monofilament suture into the internal carotid artery. Twenty-four hours later, the brains were processed for histochemical triphenyltetrazolium chloride (TTC) staining and quantitation of the schemic infarct. In each TTC-stained brain section, the ischemic tissue was dissected with a scalpel and fixed in 10% formalin at 0 masculine C until its total mass could be estimated. The mass (mg) of the ischemic tissue was weighed on an analytical balance and compared to its volume (mm(3)), estimated either by plethysmometry using platinum electrodes or by computer-assisted image analysis. Infarct size as measured by the weighing method (mg), and reported as a percent (%) of the affected (left) hemisphere, correlated closely with volume (mm(3), also reported as %) estimated by computerized image analysis (r = 0.88; P < 0.001; N = 10) or by plethysmography (r = 0.97-0.98; P < 0.0001; N = 41). This degree of correlation was maintained between different experimenters. The method was also sensitive for detecting the effect of different ischemia durations on infarct size (P < 0.005; N = 23), and the effect of drug treatments in reducing the extent of brain damage (P < 0.005; N = 24). The data suggest that, in addition to being simple and low cost, the weighing method is a reliable alternative for quantifying brain infarct in animal models of stroke.

A new animal model of cerebral venous infarction: ligation of the posterior part of the superior sagittal sinus in the cat.

Dural sinus occlusion is an infrequent but potentially devastating cause of stroke. The pathophysiological course of events underlying it is, as yet incompletely understood. In a cat model, regional cerebral blood flow (CBF) was measured during control and 2, and 24 hours after superior sagittal sinus occlusion. Around 48 hours after superior sagittal sinus occlusion, experimental settings were terminated by perfusion fixation with 4% paraformaldehyde solution, and haematoxylin and eosin histology. CBF was significantly reduced over the time-period of measurement (p < 0.05) covering about 45% of the brain in planes that were affected by occlusion. Histologically, in all cases signs of subacute venous infarction could be demonstrated. Based on the newly-developed model of microsurgical ligation of the superior sagittal sinus in cats, we present for the first time an animal model for cerebral venous infarction that leads to a histologically proven subacute venous infarction with a good reproducibility. The further advantage of this model is the fact that it mimics the clinical situation as far as possible by its inter- and intra-individual variance of extension of the venous infarction and by the slow reduction of CBF over 24 hours. Sequential PET imaging is a favourable, non-invasive method to gain further insight into the pathophysiological characteristics of experimental cerebral venous infarction. Therefore, the new-developed cat-model as demonstrated in this study will be of great value for further and more detailed investigations of cerebral-venous infarctions, and for the experimental evaluation of therapeutic strategies.

A new animal model of cerebral venous infarction: ligation of the posterior part of the superior sagittal sinus in the cat.

Dural sinus occlusion is an infrequent but potentially devastating cause of stroke. The pathophysiological course of events underlying it is, as yet incompletely understood. In a cat model, regional cerebral blood flow (CBF) was measured during control and 2, and 24 hours after superior sagittal sinus occlusion. Around 48 hours after superior sagittal sinus occlusion, experimental settings were terminated by perfusion fixation with 4% paraformaldehyde solution, and haematoxylin and eosin histology. CBF was significantly reduced over the time-period of measurement (p < 0.05) covering about 45% of the brain in planes that were affected by occlusion. Histologically, in all cases signs of subacute venous infarction could be demonstrated. Based on the newly-developed model of microsurgical ligation of the superior sagittal sinus in cats, we present for the first time an animal model for cerebral venous infarction that leads to a histologically proven subacute venous infarction with a good reproducibility. The further advantage of this model is the fact that it mimics the clinical situation as far as possible by its inter- and intra-individual variance of extension of the venous infarction and by the slow reduction of CBF over 24 hours. Sequential PET imaging is a favourable, non-invasive method to gain further insight into the pathophysiological characteristics of experimental cerebral venous infarction. Therefore, the new-developed cat-model as demonstrated in this study will be of great value for further and more detailed investigations of cerebral-venous infarctions, and for the experimental evaluation of therapeutic strategies.

Clinical Outcome and ECG Change in Patients with Acute Myocardial Infarction and Prodromal Angina

Background and Objectives:Ischemic preconditioning reduces the size of myocardial infarct in animal models, however its role in humans remains unclear. Clinical data suggests that episodes of angina immediately before acute myocardial infarction may be associated with a protective effect on the human myocardium. We performed an analysis on the effect of prodromal angina on infarct size, in-hospital outcome and newly developed Q-wave in patients with acute myocardial infarction. Subjects and Methods:65 patients who had received thrombolytic therapy were enrolled in the study. Eleven patients (17%) had experienced previous angina within 24 hours prior to acute myocardial infarction (group I), and the remaining 54 patients (83%) did not have a history of previous angina (group II). Killip class, cardiac enzyme, ECG findings, echocardiographic data and in-hospital outcomes were compared between the two groups. Results:Group I tended to have lower peak creatine kinase (CK) and CK-MB levels, although the difference between the two groups in regards to the level of cardiac enzyme was statistically insignificant. Despite similar patient characteristics, Group I showed a lower incidence of heart failure during hospitalization than group II. 6/11 patients (55%) in group I and 47/54 (87%) in group II had a Q-wave at discharge ECG. Group I showed better left ventricular systolic function during admission. None of the DM patients (14 patients) had prodromal angina and 13 of 14 patients (93%) demonstrated Q-wave infarction. Conclusion:Prodromal angina prior to acute myocardial infarction as a marker of ischemic preconditioning may also confer beneficial effects in terms of in-hospital outcomes. Further studies concerning the long term outcomes of such cases are needed. (Korean Circulation J 2002; 32(1):47-52)

Epi and endomyocardial pH allows the detection of acute right ventricular ischemia in pigs: a new evaluation method.

Techniques which identify acute right ventricular (RV) ischemia may help elucidate the pathophysiology of RV dysfunction. This study's goal was to validate an acute RV ischemia or infarction detection technique. Could RV endomyocardial and epimyocardial (interstitial) pH electrodes detect RV pH changes in an animal model of RV infarction produced by right coronary artery ligation? In ten adult anesthetized pigs, RV interstitial (pHepi) and transmural endomyocardial pH (pHendo) were measured before and serially after right coronary occlusion. pHendo and pHepi fell significantly following coronary occlusion. The absolute and relative rates of change were greater for pHendo (mean pH decreased from 7.36 to 7.04) compared to pHepi ( mean pH of 7.28 vs 7.08; P <0.002). pH was unchanged in control experiments where the electrode was placed in the right atrial or ventricular chamber, and in sham-operated animals. These data suggest that coronary ligation induced RV ischemia produces RV myocardial pH changes, which can be recorded from an electrode placed against the RV wall via a central vein, or in the interstitium. This newly described technique may be helpful in developing more discriminating tools to identify acute RV ischemia.