True Ischemia Research Articles

Ovarian conservation in a patient with a large ovarian cyst and adnexal torsion – a confirmatory video with intravenous indocyanine green

To share our experience of intravenous indocyanine green (ICG) application during conservative ovarian surgery in a young patient with adnexal torsion, a large ovarian cyst, and apparent ovarian necrosis. This confirmatory video of ovarian reperfusion uses footage from the laparoscopic treatment and ICG application in a young patient with adnexal torsion and apparent necrosis. Academic, multisite medical center. A 24-year-old patient with a 12-cm dermoid cyst, adnexal torsion, and apparent tissue necrosis. Five milligrams intravenous ICG, de-torsion, ovarian cystectomy, and ovarian reconstruction. The patient approved the ICG off-label use. Ovarian preservation and perioperative morbidity. This video demonstrates the surgical treatment of a patient with adnexal torsion. The perfusion patterns before and after the surgical treatment, i.e., cyst de-torsion and cyst removal are documented using intravenous ICG. The perfusion patterns guided the surgeon to perform ovarian conservation despite apparent initial ischemia. The patient recovered well, and no postoperative 30-day morbidity occurred. Intraoperative subjective overestimation of the true ovarian ischemia may lead to unnecessary oophorectomy. Per the American College of Obstetrics and Gynecology recommendation, patients with adnexal torsion should be treated surgically with ovarian conservation regardless of the appearance of the ovary. As demonstrated, ovaries reperfuse despite multiple twists along the infundibulopelvic pedicle, apparent necrosis, and large cysts. Unilateral salpingo-oophorectomies are avoidable even in these cases.

P76 Management of Giant Coronary Artery Aneurysms as a Coronary Sequelae of Kawasaki Disease – Surgical or Conservative Management?

Abstract Introduction Kawasaki Disease (KD) is the commonest childhood acquired heart disease in developed countries, predominantly affecting children younger than 5 years’ of age. These patients are at high risks of developing coronary arterial aneurysms (CAA) and CAA with absolute internal luminal diameters measuring ≥8mm or Z-score ≥10 are classified as giant coronary aneurysms (GCA). Case Report A 19-year-old girl with previous history of Kawasaki disease was diagnosed with giant coronary aneurysms on echocardiograms. Her subsequent CT coronary angiography showed large aneurysms in the right coronary artery (29mm x 25mm) and left anterior descending artery (10mm x 10mm) with signs of calcification. However, surprisingly, despite the evidence of large coronary aneurysms, she was completely asymptomatic and was physically active, participating in competitive sports. Her cardiac MRI scan 17 years after KD onset showed right coronary perfusion deficit in the distal right coronary territory but with no evidence of myocardial infarction. A repeated cardiac CT was performed and showed delayed filling of the distal right coronary artery. However, it was uncertain at this point if the aneurysm was causing true ischaemia or simply delayed perfusion. An ECG stress test was subsequently performed for further investigation which showed no significant abnormality. After having a detailed discussion in the MDT and with colleagues from San Diego, USA, a conservative approach was decided to be in the patient’s best interest. She has been advised to avoid competitive or strenuous exercise due to the associated risks. She is fit-and-well, and is currently on Warfarin variable dose and Aspirin 75mg OD, with annual cardiac MRI surveillance. Discussion 20% of KD patients develop CAA and approximately 5% of KD patients have evidence of GCA. Unlike small and medium CAA, GCA regress in a much slower and more constant rate, and they never achieve complete resolution. A Japanese retrospective study showed the 10-year coronary event-free survival rates in small, medium and giant CAA as 100%, 96% and 61% respectively (p<.001). Patients with GCA are at significantly increased risks of coronary complications and major cardiac events (48%). Despite maximal medical treatment, patients with GCA have high risks of aneurysm rupture which is associated with high mortality rates. These patients are also at lifelong risks of atherosclerosis and stenosis which may lead to myocardial ischaemia and even death. Therefore, it is absolutely essential to control for cardiovascular risk factors and adhere to strict treatment regime. These patients also require lifelong, uninterrupted cardiology follow-up in a specialist KD clinic. Catheter and surgical interventions may be indicated in some patients. There have been recent attempts in combining CABG with downsizing reconstruction for GCA in an attempt to decrease GCA diameter and improve the coronary flow rate to prevent thrombosis which has shown quite promising results. However, the decisions whether to undergo a surgical intervention should be tailored to each individual, taking into consideration all aspects of a patient, including their disease status and social life. Conclusion With an increasing prevalence of KD in UK, it is essential to always consider the diagnosis of KD in a febrile child with raised inflammatory markers, especially in patients presenting with prolonged fever (longer than 4-5 days) as a delay in commencing treatment poses a significantly increased risk of developing coronary complications which are associated with high morbidity and mortality rates.

Editors' note: Prognostic value of “tissue-based” definitions of TIA and minor stroke: Population-based study

In their post hoc analysis of the Oxford Vascular Study, Dr. Hurford and colleagues echoed the prognostic importance of the modern, “tissue-based” definition of acute stroke. The investigators observed that adult patients with diffusion-weighted imaging (DWI) changes were more likely to develop a subsequent cerebral infarction when compared with patients without DWI changes, regardless of the initial clinical diagnosis (TIA vs stroke). Compared to patients without DWI changes, those with DWI changes were also more likely to die by 90 days or to die at later follow-up. Although most patients (65%) were imaged within 5 days of symptoms, Dr. Cao et al. emphasized that some DWI lesions may be transient or reversible with antithrombotic or fibrinolytic therapy and some may not indicate true tissue ischemia. The authors of the OxVasc study agree that there is a declining appearance of DWI abnormalities with delayed scans; however, such patients with negative delayed scans may have a significantly lower risk of subsequent cerebral infarction as well. Also worth noting is that the diagnosis of “TIA” has long been plagued by a heterogeneous collection of mysterious mechanisms, in spite of the most sophisticated examination scales and neuroimaging. Drs. Gocan et al. question the final diagnoses of the more than 700 patients who were excluded from the OxVasc study because of a final diagnosis being one other than TIA. The authors affirm that all final diagnoses were validated by an experienced vascular neurologist using the criteria established by the World Health Organization. Irrespective of how one might define TIA, we may conclude that any new DWI lesion would be concerning in a patient with transient neurologic deficits because it may portend a significant risk of future cerebrovascular events and mortality. In their post hoc analysis of the Oxford Vascular Study, Dr. Hurford and colleagues echoed the prognostic importance of the modern, “tissue-based” definition of acute stroke. The investigators observed that adult patients with diffusion-weighted imaging (DWI) changes were more likely to develop a subsequent cerebral infarction when compared with patients without DWI changes, regardless of the initial clinical diagnosis (TIA vs stroke). Compared to patients without DWI changes, those with DWI changes were also more likely to die by 90 days or to die at later follow-up. Although most patients (65%) were imaged within 5 days of symptoms, Dr. Cao et al. emphasized that some DWI lesions may be transient or reversible with antithrombotic or fibrinolytic therapy and some may not indicate true tissue ischemia. The authors of the OxVasc study agree that there is a declining appearance of DWI abnormalities with delayed scans; however, such patients with negative delayed scans may have a significantly lower risk of subsequent cerebral infarction as well. Also worth noting is that the diagnosis of “TIA” has long been plagued by a heterogeneous collection of mysterious mechanisms, in spite of the most sophisticated examination scales and neuroimaging. Drs. Gocan et al. question the final diagnoses of the more than 700 patients who were excluded from the OxVasc study because of a final diagnosis being one other than TIA. The authors affirm that all final diagnoses were validated by an experienced vascular neurologist using the criteria established by the World Health Organization. Irrespective of how one might define TIA, we may conclude that any new DWI lesion would be concerning in a patient with transient neurologic deficits because it may portend a significant risk of future cerebrovascular events and mortality.

ST segment elevation following coronary artery bypass surgery

ST elevation on ECGs immediately after cardiac surgery is usually considered to be non-specific. However, these ST changes can be the first clues to serious condition such as graft occlusion and myocardial infarction. We present two patients with ST elevation on ECGs immediately following coronary artery bypass surgery to illustrate that ST changes early after surgery can represent significant pathology and true ischemia after cardiac surgery, which warrants prompt investigation. More studies are needed to see if different thresholds for ST elevation should be used for detecting STEMI after heart surgery.

Spontaneous coronary artery dissections

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic coronary artery pathology and an important cause of coronary artery disease in young women with an average age of 40 to 50 years with few or no cardiovascular risk factors. There has been a surge in the diagnosis of SCAD due to an increased use of coronary angiography and the clinical availability and application of high-resolution intracoronary imaging. SCAD is due to the separation of coronary wall layers with the formation of intramural hematoma, compression of the true lumen and secondary myocardial ischemia. Coronary angiography is the first-line imaging, also useful are intravascular ultrasound and optical coherence tomography. Therapy is conservative in most cases because of the high percentage of spontaneous healing of the vascular wall. The prognosis is good, although the disease is burdened by a high prevalence of major adverse coronary events, including recurrence of coronary dissection, thus making careful follow-up essential in survivors of the acute event. Given that the presence of SCAD may be associated with aneurysm formation and dissections of other arteries, screening of the arterial tree may be useful, especially of the supra-aortic trunks and splanchnic circulation.

Abstract 99: Diagnosis of Uncertain Origin Benign Transient Events (DOUBT)

Background and Aims: TIA and minor stroke offer a massive opportunity for stroke prevention. Patients with motor or speech symptoms have a higher risk of early recurrent stroke. Many patients with transient or mild neurological deficits do not have high-risk features (eg sensory symptoms). The aim of the DOUBT study was to assess what proportion of these lower risk patients have true brain ischemia and secondarily to establish whether clinically we can predict what clinical factors predict a higher risk of brain ischemia. Method: DOUBT was a multicentre, international, prospective, observational, cohort study assessing the diagnosis and prognosis of patients with lower risk focal neurological symptoms. Patients aged ≥ 40, with no previous stroke, with either very brief (<5 minutes) motor or speech symptoms, or non-motor or speech focal neurological symptoms were included. Patients had a detailed neurological assessment and an MRI brain within 7 days of onset. Proportion of patients with an acute DWI lesion on MRI was the primary outcome. Results: 1047 patients in Canada, Europe and Australia were prospectively enrolled in the study. All patients had a detailed neurological assessment prior to undergoing MRI brain. Preliminary analysis shows 13% true brain schema rate (DWI positive). Patients were less likely to have a DWI lesion if their symptoms were fully resolved at assessment (RR 0.57, 95%CI: 0.38-0.79, p <0.001), if they reported any psychological stress (RR 0.57: 0.33-0.99, p=0.04) or if male (RR 0.58, 0.42-0.81, p=0.001). Patients were more likely to have a DWI lesion if they had any motor or speech symptoms (RR 1.7 (0.17-2.55, p=0.009). Secondary analysis looking at detailed clinical predictors of DWI lesions status will be presented. Conclusion: We found a low but real risk of true brain ischemia in these lower risk patients. Further analysis is needed to explain why woman are more likely to have DWI lesions with low risk symptoms. Detailed neurological assessment may help us stratify these patients further.

Reciprocal ST-Segment Changes in Myocardial Infarction: Ischemia at Distance Versus Mirror Reflection of ST-Elevation

BackgroundReciprocal ST-depression in the electrocardiograms (ECGs) of patients with ST-elevation myocardial infarction (STEMI) results from either true ischemia at a distance via collateral circulation diverting blood to the infarcted region or an electrical phenomenon that results from a mirror reflection of ST-elevation. We aimed to identify the role of reciprocal ECG changes in predicting collateral circulation to the infarcted area determined angiographically. MethodsIn a retrospective study, ECG and angiography of 53 STEMI patients admitted to SUNY Upstate Medical University in 2014 were reviewed independently by experts blinded to the results of ECG and coronary angiography. ResultsReciprocal changes (RC) in ECG were present in 41 patients (77%) and on angiography, 14 patients (26%) exhibited collateral vessels to the ischemic areas. No correlation was found between the presence of RC and collateral circulation (P = 0.384), or between the depth of reciprocal ST-depression and the degree of the collateral circulation (P = 0.195). However, 84% of patients without collaterals exhibited resolution of RC after successful percutaneous coronary intervention (PCI) (P = 0.036), suggesting that the ST depressions that resolved after reperfusion were directly caused by the culprit vessel. Patients without RC presented late after symptom onset (9.25 versus 3.83 hours, P = 0.004), also suggesting time related resolution. ConclusionsRC had no relation to or predictive value for collaterals on angiography. Among late presenting patients, RC were less frequent. Thus, reciprocal ST-depression may represent subendocardial ischemia from the primary coronary event or simply an electrical phenomenon, rather than ischemia at distance from impaired collateral circulation.

The application of optical coherence tomography angiography in uveitis and inflammatory eye diseases

Since its introduction in the early 1990s, optical coherence tomography (OCT) has evolved in resolution and technological advances, and in recent years its initial application of assessing the morphology of a tissue has been implemented by the study of its functional blood flow, through optical coherence tomography angiography (OCTA). This novel technique details capillary networks by comparing the amount of light returned from static and moving targets without the need for intravenous dye administration. While this imaging modality has been used for various ocular conditions, the application OCTA to uveitis conditions remains sparse. This review aims to establish the basis of OCTA and its current application to ocular inflammatory disorders, with an emphasis on monitoring progression and response to treatment, as well as predicting visual complications. In particular, this review explores the use of OCTA in iris vessel dilation seen in various forms of iritis, as a predictive factor for further episodes of inflammation. OCTA can also depict ischemia in the deep plexus layers of the retina and identify true choroicapillaris ischemia in cases of placoid diseases or masking of the indocyanine green dye, as in multiple evanescent white dot syndrome. In addition, OCTA can depict neovascularization in granulomatous disease of the retina or choroid not previously depicted with previous imaging methods. While OCTA provides several advancements in the imaging, management and prognosis of uveitis diseases, we emphasize that further studies are required to fully understand its application to these conditions.

122 Relationship Between Coronary Microvascular Dysfunction, Myocardial Oxygenation and Abnormal Myocardial Energetics at Rest and Stress in Patients with Type 2 Diabetes Mellitus

Background We and others have previously shown impaired myocardial energetics (decreased PCr/ATP using cardiac 31P Magnetic Resonance Spectroscopy [MRS]) in patients with type 2 diabetes mellitus (T2DM) at rest. Diabetic patients are known to have impaired myocardial perfusion reserve due to microvascular dysfunction even in the absence of epicardial coronary artery disease (CAD). There is yet no evidence whether this hypoperfusion is translated to myocardial deoxygenation and further energetic derangement at stress, i.e. true tissue ischaemia. We aimed to assess if the pre-existing energetic deficit in patients with uncomplicated T2DM is further exacerbated during exercise and to establish its relationship to myocardial perfusion and oxygenation during adenosine stress. Methods 31 patients (mean age 55 ± 2 years; BMI 29 ± 1.0 kg/m 2 ) with T2DM and 24 matching controls (mean age 50 ± 3 years; BMI 27 ± 3 kg/m 2 ) were studied. Patients were on oral antidiabetic therapies only, with mean HBA1c 7.7 ± 0.3%. Obstructive CAD (>50% lumen diameter obstruction) was excluded in all patients by CT coronary angiography. Cardiac 31P-MRS (3T) was performed at rest and during 8 min of leg exercise lying prone, with 2.5 kg weights attached to both legs. Oxygenation-sensitive CMR (using a T2-prepared sequence) and first-pass perfusion images (using a saturation recovery fast-gradient echo sequence and 0.03 mmol/kg bolus of Gadoterate meglumine were also acquired at stress (3–6 min i.v. adenosine, 140 μg/kg/min) and rest. Signal intensity change (SIΔ) and myocardial perfusion reserve index (MPRI) were measured from oxygenation and perfusion images, respectively. Results Left ventricular ejection fraction (LVEF) and mass index (LVMI) were similar in patients and controls (LVEF 69 ± 2 vs 70 ± 1%, P = ns; LVMI 60 ± 2 vs 52 ± 4 g/m 2 , P = ns). Increases in rate pressure product with exercise (T2DM 46 ± 36%, controls 42 ± 26%, P = 0.825) and adenosine stress (T2DM 40 ± 3%, controls 39 ± 3%, P = 0.89) were similar. There was no change in PCr/ATP during exercise in controls (rest: 2.07 ± 0.1, exercise: 2.25 ± 0.1, P = 0.098). Resting PCr/ATP was reduced in patients (1.74 ± 0.1, P = 0.001) compared to controls, and during exercise, there was a further reduction in PCr/ATP (1.54 ± 0.1, P = 0.005) vs rest. As expected, myocardial perfusion reserve was significantly reduced in diabetic patients (1.61 ± 0.1 vs 2.19 ± 0.2 in controls, P = 0.002). Myocardial oxygenation was also impaired (SIΔ: T2DM 7.3 ± 1.4%; normal 17.1 ± 1.8%, P Conclusions During exercise, the pre-existing energetic deficit in patients with T2DM is further exacerbated. While myocardial energetics at rest is not related to coronary microvascular dysfunction and is primarily a result of metabolic dysfunction, during exercise, microvascular dysfunction exacerbates the energetic deficit.

The Evidence for Nonoperative Management of Visceral Artery Dissections: A Single-Center Experience

Spontaneous isolated visceral artery dissection is an uncommon condition encountered by clinicians. Presentation may vary from asymptomatic to acute intestinal ischemia, although a clear natural history has yet to be elucidated. No consensus exists on how best to manage these patients in the absence of true intestinal ischemia; however, much of the literature suggests that intervention is required. We present our institution's experience with 10 patients, both symptomatic and asymptomatic, all but 1 of whom was managed medically. From September 2009 to August 2013, 10 patients presented to our institution with celiac or mesenteric artery dissection. We retrospectively reviewed these patients' clinical presentation, treatment, and follow-up. The mean age of the patients was 61.5 ± 10.3 (standard deviation [SD]) years (range, 41-77 years), and the mean follow-up period was 14.7 ± 11.6 (SD) months (range, 1-31 months). Four (40%) patients had abdominal pain and no ischemic changes of the bowel. There were 1 type I, 6 type II, 2 type III, and 1 type IV dissections according to Sakamoto classification. Treatments included observation without anticoagulation treatment in 8 patients (80%), anticoagulation treatment in 1 patient (10%), and endovascular stenting in 1 patient (10%) with unremitting abdominal pain. Anticoagulation was used in the 1 symptomatic patient with radiographic evidence of associated thrombus. The disease stabilized in all patients during follow-up. Most authors tend to advocate an endovascular or even operative repair for these processes. In our experience, most of these patients have a self-limited course of symptoms or their dissections are found incidentally. We believe that the results of conservative management in our cohort of patients support the conservative approach over the once recommended operative repair.

Vasopressors and Reconstructive Flap Perfusion

Use of intraoperative vasopressors is of debate in microvascular surgery. Anesthesia is an important factor in maintaining the rate of success of flap transfer by affecting regional blood flow and global hemodynamics. We conducted a review of the literature comparing the use of different vasoactive agents on different flaps in various human and animal models. A systematic review of the literature was performed. Bibliographies of key articles were also reviewed for additional resources. Analysis was done to determine the overall trend of how flap perfusion is affected by the use of intraoperative vasoactive medication. The literature search identified 16 relevant articles. Flaps were studied in pigs in 7 studies, rats in 5, and humans in 4. The most common flap was the rectus abdominis musculocutaneous flap. Phenylephrine and norepinephrine were the most common pressor agents used. No significant statistical changes were noted in 8 of the 16 studies; initial ischemia followed by delayed improved perfusion was observed in 4 studies, "true ischemia" and hypoperfusion of the skin flaps was noted in 3. There was no consistency in their effect on flap perfusion: initial ischemia followed by delayed improved perfusion was observed in 4 studies, whereas true ischemia and hypoperfusion of the skin flaps was noted in 3. To date, there is no reliable prospective clinical evidence that supports the absolute contraindication of pressor agents during free flap surgery. This topic will continue to be a matter for debate until more definitive data can be obtained.

The Evaluation Criteria in Diagnosing Ischemia with Stress and Rest Myocardial Perfusion Gated SPECT

The Evaluation Criteria in Diagnosing Ischemia with Stress and Rest Myocardial Perfusion Gated SPECT

Electrocardiographic Electrode Misplacement, Misconnection, and Artifact

BackgroundElectrocardiograms (ECGs) are performed by humans, and thus are subject to human error. An underappreciated source of electrocardiographic abnormality is electrode misconnection, both limb and precordial, and improper placement, which is principally an issue with the precordial electrodes due to anatomic variation. Patterns of abnormality exist; recognition allows the emergency physician to avoid mistaking the resulting electrocardiographic findings for true pathology. ObjectivesThe purpose of this clinical review is to describe the patterns of electrocardiographic electrode reversal, misplacement, and artifact and thus make them recognizable to the Emergency Physician. DiscussionCommon limb electrode reversals feature distinctive patterns manifesting as unexpected morphologic and frontal plane axis changes in the QRS complexes in the limb and augmented leads. Precordial electrode misplacement (improper positioning of the electrodes on the chest) is common and may mimic a pseudoinfarction pattern, or ST-segment/T-wave changes, which must be recognized as the result of the misplacement rather than true cardiac ischemia. Precordial electrode reversal should be suspected when the normal R/S wave amplitude transition is violated. Electrocardiographic artifact must be distinguished from dysrhythmia to avoid a potentially hazardous progression to unnecessary diagnostics and therapeutics. ConclusionsThe hallmarks of electrode misconnection, misplacement, and electrocardiographic artifact can be easily mastered by the Emergency Physician; recognition of these findings can positively impact patient care by avoiding unnecessary intervention secondary to misattribution of findings on the 12-lead ECG to cardiac pathology.

Kidney transplantation with grafts from type III Maastricht non-beating-heart donors.

Kidney transplantation (KT) with kidneys from non-beating-heart donors (NBHD) is a growing trend in Spain. The majority of these kidneys come from type II Maastricht patients, although in recent years, organ donations from patients awaiting cardiac arrest following limitation of life-sustaining therapy has already been in practice in certain European and North American countries, involving type III Maastricht patients. We present a series of 6 KT using kidneys from NHBD as a consequence of limitation of life-sustaining therapy in three different hospitals in the sector of Malaga. After agreeing upon a protocol for evaluating the potential of a patient for organ donation after the decision for limiting life-sustaining therapy, the patients’ families were given the option of organ donation. Kidneys were preserved using a Porges double balloon catheter, which was placed prior to cardiac arrest. In two cases, the limitation of life-sustaining therapy took place in the intensive care unit, and in the third case, in the operating room. The interval between limitation of life-sustaining therapy and cardiac arrest ranged between 15 minutes and 40 minutes, with an interval of circulatory arrest prior to perfusion of 5-11 minutes. Perfusion-cooling of the kidneys was initially carried out using saline solution, followed by organ preservation solution (Celsior or Belzer) and extraction of the kidney using a rapid surgical technique. True or functional hot ischaemia times were 60 minutes, 59 minutes, and 50 minutes, respectively, for each of the three donors. Kidneys were evaluated for viability using time intervals for the procedure (including hypotension prior to cardiac arrest), macroscopic appearance, and histopathology of a sample taken from each kidney. The recipients of these 6 kidneys had given their consent to receive organs from expanded-criteria donors. Cold ischaemia lasted between 9 hours and 20 hours (mean: 14.6 hours). One recipient developed haemorrhagic complications during the immediate postoperative period and required a transplantectomy. The other five currently retain functioning grafts. All had delayed graft function, necessitating haemodialysis. The range of estimated glomerular filtration rates at the most recent follow-up evaluation was 23.0-106 ml/min/1.73 m(2). In conclusion, type III Maastricht donors provide valid kidneys for transplantation, although this series showed that supported functional hot ischaemia was very important, the consequence of accumulated ischaemic damage starting in the agonal phase, circulatory arrest, and organ preservation using cold solutions. As such, to improve the quality of results obtained using kidneys from these types of donors would involve a very careful selection of optimal donors and minimisation of total functional ischaemia times.

Prevalence and risk factors accounting for true silent myocardial ischemia: a pilot case-control study comparing type 2 diabetic with non-diabetic control subjects

BackgroundGiven the elevated risk of cardiovascular events and the higher prevalence of silent coronary artery disease (CAD) in diabetic versus non-diabetic patients, the need to screen asymptomatic diabetic patients for CAD assumes increasing importante. The aims of the study were to assess prospectively the prevalence and risk factor predictors of true silent myocardial ischemia (myocardial perfusion defects in the absence of both angina and ST-segment depression) in asymptomatic type 2 diabetic patients.MethodsStress myocardial perfusion gated SPECT (Single Photon Emission Computed Tomography) was carried out in 41 type 2 diabetic patients without history of cardiovascular disease (CVD) and 41 nondiabetic patients matched by age and gender.ResultsThere were no significant differences between the two groups regarding either the classic CVD risk factors or left ventricular function. True silent ischemia was detected in 21.9% of diabetic patients but only in 2.4% of controls (p < 0.01). The presence of myocardial perfusion defects was independently associated with male gender and the presence of diabetic retinopathy (DR). The probability of having myocardial perfusion defects in an asymptomatic diabetic patient with DR in comparison with diabetic patients without DR was 11.7 [IC95%: 3.7-37].ConclusionsTrue silent myocardial ischemia is a high prevalent condition in asymptomatic type 2 diabetic patients. Male gender and the presence of DR are the risk factors related to its development.

Is there a transitional zone between brain infarcts and the surrounding brain? A histological study.

Twenty-eight recent brain infarcts were studied histologically for the presence of zones of partial tissue destruction between the infarct border and the surrounding normal brain. Such transitional zones have been demonstrated in animals and might be suspected in humans from the broad zones of reduced blood flow that have been demonstrated around brain infarcts. Necrotic neurons were observed outside the infarct borders in 20 of 28 cases. However, the width of the peri-infarct border zone was less than 5 mm in 17 of 20 cases and between 7 and 10 mm in 2 cases. Only one section from one case showed necrotic neurons more than 20 mm from the infarct border. It is concluded that the large majority of the brain infarcts in man are sharply delimited and that the broad zones of reduced flow around the infarcts may be due to functional inactivity following partial denervation of the cortex rather than to true ischemia.

A Novel Murine Island Skin Flap for Ischemic Preconditioning

Ischemia reperfusion injury is a well-known phenomenon affecting skin flap viability. One method to improve flap viability is ischemic preconditioning. Previous murine flap models used random flaps. We developed a single pedicle island skin flap which allows us to create true ischemia by clamping the single pedicle. Our first aim was to describe a novel murine skin flap model with a definable, reproducible injury. Our second aim was to test the usefulness of this model by demonstrating mitigation of injury via ischemic preconditioning. Dorsal lateral thoracic artery pedicle island skin flaps (3.5 x 1.5 cm) were elevated in 39 male C57/BL6 mice: a Control group (n = 7), 10 h of ischemia (n = 21), and Preconditioning (2 cycles of 20 min ischemia: 20 minutes reperfusion) + 10-h ischemia (n = 11). After flap elevation, a silicon sheet barrier was placed. The axial pedicles were occluded, and the flaps were inset with 6-0 prolene. In all mice, ischemia was followed by 1 wk of reperfusion. At 1 wk, percent necrosis was measured and an analysis of variance was performed. The percent of flap necrosis was 1.1% +/- 1.11% in controls. Animals that were subjected to 10 h of ischemia developed 33.14% +/- 7.23% necrosis. Preconditioned animals that underwent 10 h of ischemia demonstrated a 43% reduction in necrosis (18.82% +/- 5.68%). There was a statistically significant difference among all groups (P < or = 0.001). Rat models have been the standard for skin flap experiments. We have developed a novel murine single pedicle island skin flap model with reproducible injury. This model has numerous advantages, including ease of handling, low cost, appropriateness for biomedical studies, and the availability of genetically altered animals. We also confirmed this model's usefulness in a study of mitigation of ischemia reperfusion injury through ischemic preconditioning.

The Role of RIP2 in p38 MAPK Activation in the Stressed Heart

The activation of p38 MAPK by dual phosphorylation aggravates myocardial ischemic injury and depresses cardiac contractile function. SB203580, an ATP-competitive inhibitor of p38 MAPK and other kinases, prevents this dual phosphorylation during ischemia. Studies in non-cardiac tissue have shown receptor-interacting protein 2 (RIP2) lies upstream of p38 MAPK, is SB203580-sensitive and ischemia-responsive, and aggravates ischemic injury. We therefore examined the RIP2-p38 MAPK signaling axis in the heart. Adenovirus-driven expression of wild-type RIP2 in adult rat ventricular myocytes caused robust, SB203580-sensitive dual phosphorylation of p38 MAPK associated with activation of p38 MAPK kinases MKK3, MKK4, and MKK6. The effect of SB203580 was recapitulated by unrelated inhibitors of RIP2 or the downstream MAPK kinase kinase, TAK1. However, overexpression of wild-type, kinase-dead, caspase recruitment domain-deleted, or kinase-dead and caspase recruitment domain-deleted forms of RIP2 had no effect on the activating dual phosphorylation of p38 MAPK during simulated ischemia. Similarly, p38 MAPK activation and myocardial infarction size in response to true ischemia did not differ between hearts from wild-type and RIP2 null mice. However, both p38 MAPK activation and the contractile depression caused by the endotoxin component muramyl dipeptide were attenuated by SB203580 and in RIP2 null hearts. Although RIP2 can cause myocardial p38 MAPK dual phosphorylation in the heart under some circumstances, it is not responsible for the SB203580-sensitive pattern of activation during ischemia.

TNFα and IL-1 induce IL-6 expression in human cardiac fibroblasts: Role of p38 MAP kinase subtypes

No. 7 The role of RIP2 in p38 MAPK activation in the stressed heart S. Jacquet⁎, Y. Nishino, S. Kumphune, P. Sicard, J.E. Clark, K.S. Kobayashi, R.A. Flavell, J. Eickhoff, M. Cotten, M.S. Marber. Cardiovascular Division, KCL, UK ⁎ Corresponding author. Department of Cardiology, Kings College London, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK. Tel.: +44 20 7188 8349; fax: +44 20 7188 0970. E-mail address: sebastien.jacquet@kcl.ac.uk The activation of p38 MAPK by dual phosphorylation aggravates myocardial ischemic injury and depresses cardiac contractile function. SB203580, an ATP-competitive inhibitor of p38 MAPK and other kinases, prevents this dual phosphorylation during ischemia. Studies in non-cardiac tissue have shown that Receptor Interacting Protein 2 (RIP2) lies upstream of p38 MAPK, is SB203580-sensitive, ischemia-responsive and aggravates ischemic injury. We therefore examined the RIP2– p38 MAPK signaling axis in the heart. Adenoviral-driven expression of wild type RIP2 in adult rat ventricular myocytes caused robust, SB203580-sensitive, dual phosphorylation of p38 MAPK associated with activation of the p38 MAPK kinases, MKKs 3, 4 and 6. The effect of SB203580 was recapitulated by unrelated inhibitors of RIP2 or the downstream MKKK, TAK1. However, overexpression of wild type, kinase dead, CARD-deleted or kinase dead and CARD-deleted, forms ofRIP2 had no effect on the activating dual phosphorylation of p38 MAPK during simulated ischemia. Similarly, p38 MAPK activation and myocardial infarction size in response to true ischemia did not differ between hearts from wild type and RIP2 null mice. However, both the p38 MAPK activation and the contractile depression caused by the endotoxin component muramyl dipeptide were attenuated in RIP2 null hearts. Although RIP2 can cause myocardial p38 MAPK dual phosphorylation in the heart under some circumstances it is not responsible for the SB203580-sensitive pattern of activation during ischemia.

The role of RIP2 in p38 MAPK activation in the stressed heart

The activation of p38 MAPK by dual phosphorylation aggravates myocardial ischemic injury and depresses cardiac contractile function. SB203580, an ATP-competitive inhibitor of p38 MAPK and other kinases, prevents this dual phosphorylation during ischemia. Studies in non-cardiac tissue have shown receptor-interacting protein 2 (RIP2) lies upstream of p38 MAPK, is SB203580-sensitive and ischemia-responsive, and aggravates ischemic injury. We therefore examined the RIP2-p38 MAPK signaling axis in the heart. Adenovirus-driven expression of wild-type RIP2 in adult rat ventricular myocytes caused robust, SB203580-sensitive dual phosphorylation of p38 MAPK associated with activation of p38 MAPK kinases MKK3, MKK4, and MKK6. The effect of SB203580 was recapitulated by unrelated inhibitors of RIP2 or the downstream MAPK kinase kinase, TAK1. However, overexpression of wild-type, kinase-dead, caspase recruitment domain-deleted, or kinase-dead and caspase recruitment domain-deleted forms of RIP2 had no effect on the activating dual phosphorylation of p38 MAPK during simulated ischemia. Similarly, p38 MAPK activation and myocardial infarction size in response to true ischemia did not differ between hearts from wild-type and RIP2 null mice. However, both p38 MAPK activation and the contractile depression caused by the endotoxin component muramyl dipeptide were attenuated by SB203580 and in RIP2 null hearts. Although RIP2 can cause myocardial p38 MAPK dual phosphorylation in the heart under some circumstances, it is not responsible for the SB203580-sensitive pattern of activation during ischemia.