Effects Of Ischemia Research Articles

Early Weight-Based Aggressive vs. Non-Aggressive Goal-Directed Fluid Resuscitation in the Early Phase of Acute Pancreatitis: An Open-Label Multicenter Randomized Controlled Trial (The WATERFALL Trial), Design, and Rationale.

Treatment options are limited for acute pancreatitis (AP). Early aggressive fluid resuscitation (AFR) has been widely considered beneficial because of theoretical improvement in end-organ perfusion, including the pancreas and gut, with pancreatic necrosis and bacterial translocation as consequences of ischemia. There is scarce direct evidence for its association to improved outcomes. Furthermore, it has been described that AFR may be associated with poor outcomes in severe AP. WATERFALL is an investigator-initiated international multicenter open-label randomized controlled trial comparing AFR vs. moderate fluid resuscitation (MFR) in AP. The main outcome variable will be the incidence of moderate to severe AP (a clinically relevant outcome that has been validated). Aggressive fluid resuscitation will consist in lactated Ringer solution (LR) 20-mL/kg bolus (administered over 2 h) followed by LR 3 mL/kg per hour. Patients randomized to MFR will receive an LR bolus 10 mL/kg in case of hypovolemia or no bolus in patients with normal volemia, followed by LR 1.5 mL/kg per hour. The patients will be assessed at 3 (±1), 12 (±4), 24 (±4), 48 (±4), and 72 (±4) h from recruitment, and fluid resuscitation will be adjusted to the patient's clinical and analytical status according to a protocol. Based on a prospective multicenter study, the incidence of moderate to severe AP is 35%. Sample sizes of 372 patients per group (overall 744) achieve 80% power to detect a difference in the incidence of moderate to severe AP of 10%, at a significance level (α) of 0.05 using a two-sided z-test, assuming a 10% dropout rate. These results assume that three sequential tests are made using the O'Brien–Fleming spending function to determine the test boundaries.

An overview of the pathogenic mechanisms involved in severe cases of COVID-19 infection, and the proposal of salicyl-carnosine as a potential drug for its treatment

Multiple organ failure in COVID-19 patients is a serious problem which can result in a fatal outcome. Damage to organs and tissues, including general lung dysfunction, develops as a consequence of ischemia, which, in turn, is caused by thrombosis in small blood vessels and hypoxia, leading to oxidative stress and inflammation. Currently, research is underway to screen existing drugs for antioxidant, antiplatelet and anti-inflammatory properties. Having studied the available publications concerning the mechanisms of damage to tissues and organs of patients with COVID-19, as well as the available treatment strategies, we propose to investigate salicyl-carnosine as a potential drug for treating COVID-19 patients. In a recent study, we described the drug’s synthesis procedure, and showed that salicyl-carnosine possesses antioxidant, anti-inflammatory, and antiplatelet effects. Therefore, it can simultaneously act on the three pathogenetic factors involved in tissue and organ damage in COVID-19. Thus, we propose to consider salicyl-carnosine as a potential drug for the treatment of patients with severe cases of COVID-19 infection.

Learning experiences comprising central ethanol exposure in rat neonates: Impact upon respiratory plasticity and the activity of brain catalase.

Fetal ethanol exposure represents a risk factor for sudden infant death syndrome, and the respiratory effects of fetal ethanol exposure promote hypoxic ischemic consequences. This study analyzes central ethanol's effects upon breathing plasticity during an ontogenetic stage equivalent to the human third gestational trimester. Ethanol's unconditioned breathing effects and their intervention in learning processes were examined. Since central ethanol is primarily metabolized via the catalase system, we also examined the effects of early history with the drug upon this system. During postnatal days 3, 5, and 7 (PDs 3-7), pups were intracisternally administered with vehicle or ethanol (300mg%). They were tested in a plethysmograph scented or not scented with ethanol odor. The state of intoxication attenuated the onset of apneas, a phenomenon that is suggestive of ethanol's anxiolytic effects given the state of arousal caused by the novel environment and the stress of ethanol administration. At PD9, pups were evaluated when sober under sequential air conditions (initial-normoxia, hypoxia, and recovery-normoxia), with or without the presence of ethanol odor. Initial apneic episodes increased when ethanol intoxication was previously associated with the odor. Pups then ingested ethanol, and brain catalase activity was determined. Pre-exposure to ethanol intoxication paired with the odor of the drug resulted in heightened enzymatic activity. Central ethanol exposure appears to exert antianxiety effects that attenuate apneic disruptions. However, during withdrawal, the cues associated with such effects elicit an opposite reaction. The activity of the catalase system was also dependent upon learning processes that involved the association of environmental stimuli and ethanol intoxication.

Sigmoid volvulus - an important cause of intestinal obstruction: how to deal with it?

Background: The objective of the study was to discuss the appropriate course of action in cases of sigmoid volvulus. It becomes important due to its high morbidity and mortality and its acute emergency presentation.Methods: This is a retrospective study of sigmoid volvulus admitted in the department of surgery at Late SBRKM Government Medical College, Jagdalpur. The study period was from January 2017 to August 2019. A total of 27 cases were under study. On admission, they were examined, investigated and treated surgically and the outcome noted.Results: Out of 27 patients 25 were male and 2 cases were female. The mean age group was 65 years. The co-morbidities consisted of previous abdominal surgeries, diabetes mellitus, hypertension, and renal complications. The common factor was chronic constipation and purgative abuse. All underwent a definitive surgical procedure like sigmoidectomy and colorectal anastamosis or sigmoidectomy and colostomy. In the second group colostomy closure and end to end anastamosis carried on at a later date. We have lost 5 patients in the post-operative period.Conclusions: The sigmoid volvulus presents with the features of intestinal obstruction. The real danger is the gangrene of the bowel, as a consequence of ischaemia. It requires an early surgical intervention for the maximum benefit of the patient.

Hyperbaric oxygenation protects the kidney against ischemia-reperfusion injury

Acute kidney injury (AKI) as a consequence of ischemia is a common clinical event that can lead to unacceptably high morbidity and mortality. Hyperbaric oxygen (HBO2) preconditioning has been shown to prevent ischemia-reperfusion injury (IRI) in different tissues. The aim of our study was to compare the effects of HBO2 preconditioning on renal hemodynamics, kidney function and oxidative stress in normotensive and spontaneously hypertensive rats that suffered kidney IRI. An experiment was performed on Wistar (normotensive) and spontaneously hypertensive rats (SHR). The animals were divided into the following experimental groups: sham-operated rats and rats with or without HBO2 preconditioning 24 hours before post-ischemic AKI induction. Treated rats were placed into experimental HBO2 chambers and exposed to pure oxygen twice a day for two consecutive days (2.026 bar of oxygen) for 60 minutes. AKI was performed the next morning. The right kidney was removed and the renal ischemia was performed by clamping the left renal artery for 45 minutes. In this study, HBO2 preconditioning significantly improved disturbed renal hemodynamics, major markers of kidney function in plasma (creatinine, urea and phosphate) as well as antioxidant enzymes (superoxide dismutase and catalase) activities in erythrocytes after AKI induction. Also, HBO2 preconditioning decreased lipid peroxidation in plasma after ischemic AKI. Positive effects were observed in both strains of rats. Our results suggest that HBO2 treatment improves renal hemodynamic and kidney function and decreases oxidative stress of Wistar and SHR rats with an AKI episode. Furthermore, it also implies that pre-existing hypertension does not affect the beneficial effects of HBO2 preconditioning.

Neuropathological findings suggestive for a stroke in an alpaca (Vicugna pacos)

BackgroundThis case report describes a focal brain lesion in an alpaca (Vicugna pacos). Although this is a restricted study based on a single animal, neuropathological features are reported that are most likely attributed to a vascular event with either ischemic or hemorrhagic pathology. Concerning translational issues, these findings extend neurovascular unit concept to the alpacas’ brain and qualify a larger panel of stroke tissue markers for further exploration of ischemic or hemorrhagic consequences beyond the usually used small animal models in stroke research.Case presentationA brain lesion indicative of a stroke was diagnosed in a 3-year-old female alpaca as an incidental finding during a post mortem examination. The rostral portion of the right frontal lobe contained a 1.0 × 1.5 × 1.7 cm lesion that extended immediately to the overlying leptomeninges. Microscopically, it was composed of liquefactive necrosis with cholesterol crystal deposition and associated granulomatous inflammation as well as vascularized fibrous connective tissue rimmed by proliferated astrocytes. Multiple fluorescence labeling of the affected brain regions revealed strong microgliosis as shown by immunostaining of the ionized calcium binding adapter molecule 1 and astrogliosis as demonstrated by enhanced immunoreactivity for glial fibrillary acidic protein. In parallel, a drastic neuronal loss was detected by considerably diminished immunolabeling of neuronal nuclei. Concomitantly, up-regulated immunoreactivities for collagen IV and neurofilament light chains were found in the affected tissues, indicating vascular and cytoskeletal reactions.ConclusionsDriven by these neuropathological features, the incidental brain lesion found in this alpaca strongly suggests an ischemic or hemorrhagic etiology. However, since typical hallmarks became verifiable as previously described for other species affected by focal cerebral ischemia, the lesion is more likely related to an ischemic event. Nevertheless, as such cellular alterations might be difficult to distinguish from other brain lesions as for instance caused by inflammatory processes, adjuvant observations and species-related features need to be considered for etiological interpretations. Indeed, the lack of neurological deficits is likely attributed to the location of the lesion within the rostral aspect of the right frontal lobe of the alpacas’ brain. Further, fibroblast migration from the meninges likely caused the intralesional scar formation.

Continuous Positive Airway Pressure Treatment May Improve Optic Nerve Function in Obstructive Sleep Apnea: An Electrophysiological Study.

Obstructive sleep apnea (OSA) is a sleep disorder frequently associated with optic nerve diseases. Moreover, untreated patients with severe OSA may show optic nerve dysfunction as documented by electrophysiological studies using visual evoked potentials (VEP). Because continuous positive airway pressure (CPAP) treatment has proved to restore the physiologic nocturnal breathing, thus preventing nocturnal hypoxemia and reducing inflammation, in this study we tested whether 1-year CPAP treatment may modify VEP responses in patients with severe OSA. VEP were recorded at baseline and after 1 year of CPAP treatment in 20 patients with severe OSA, divided in two groups on the basis of CPAP adherence, and compared to a healthy control group. Patients with good adherence to CPAP therapy (CPAP+; n = 10) showed VEP P100 amplitude significantly higher than patients with poor adherence to CPAP therapy (CPAP-; n = 10). Moreover, the CPAP+ group showed VEP responses similar to those in the control group (n = 26). Considering the mean difference of VEP responses between baseline and follow-up, the CPAP+ group showed a significant increase in VEP P100 amplitude and a significant decrease in VEP P100 latency compared to the CPAP- group. This study documented that CPAP therapy significantly improves VEP in patients with OSA who are adherent to the treatment. We hypothesize that CPAP treatment, minimizing the metabolic, inflammatory and ischemic consequences of OSA, may normalize the altered VEP responses in patients with OSA by restoring and preserving optic nerve function.

Diagnostic Concordance and Clinical Outcomes in Patients Undergoing Fractional Flow Reserve and Stress Echocardiography for the Assessment of Coronary Stenosis of Intermediate Severity

The ischemic consequences of coronary artery stenosis can be assessed by invasive fractional flow reserve (FFR) or by noninvasive imaging. We sought to determine (1) the concordance between wall thickening assessment during clinically indicated stress echocardiography (SE) and FFR measurements and (2) the factors associated with hard events in these patients. Two hundred twenty-three consecutive patients who underwent SE and invasive FFR measurements in close succession were analyzed retrospectively for diagnostic concordance and clinical outcomes. At the vessel level, the sensitivity, specificity, positive predictive value, and negative predictive value of SE for identifying significant disease as assessed by FFR was 68%, 75%, 43%, and 89%, respectively. The greatest discordance was seen in patients with wall thickening abnormalities (WTAs) and negative FFR. During a follow-up of 3.6±2.2years, there were 23 cardiovascular (CV) events (death and nonfatal myocardial infarction). The number of wall segments with inducible WTAs emerged as the strongest factor associated with CV events (hazard ratio, 1.18 [1.05-1.34]; P=.008). FFR was not associated with outcome. There was a significant increase in event rate in patients with WTA/negative FFR versus no WTA/negative FFR (P=.01), but no significant difference versus WTA/positive FFR (P=.85). In a patient population with significant CV risk factors, a normal SE had a high negative predictive value for excluding abnormal FFR. WTAs were associated with outcomes regardless of FFR value, suggesting that this is a superior marker of ischemia to FFR.

Self-thrombosing anterior cerebral artery aneurysm leading to a caudate infarct

Abstract Self-thrombosing intracranial aneurysms are relatively uncommon and the conditions that lead to their formation are unknown, although they can be seen following subarachnoid hemorrhage and in autopsy specimens. We seek to raise awareness of the unintended iatrogenic thrombosis of intracranial aneurysms, its ischemic consequences, and the use of mechanical thrombectomy in its treatment. A 50-year-old hypertensive woman presented with a sudden onset of severe headache concerning for a ruptured cerebral aneurysm (Hunt-Hess 2). HCT showed diffuse subarachnoid hemorrhage (modified Fisher grade 3), and CTA showed two aneurysms arising from an anterior communicating (ACOM) complex fenestration and one aneurysm arising from the proximal left anterior cerebral artery (ACA) A1 segment. Successful coil embolization of the distal ACOM aneurysm was followed by an attempted balloon-assisted coil embolization of a left ACA A1 aneurysm that led to self-thrombosis and partial occlusion of the A1 segment. After mechanical thrombectomy, there was significant reduction in left A1 thrombus burden. The patient developed an asymptomatic small infarct of the left caudate, likely by occlusion of an anatomic variant of the recurrent artery of Heubner arising from the A1 segment. To our knowledge, this is the first reported case of a self-thrombosing aneurysm during attempted balloon-assisted embolization. Propagation of the thrombus can lead to parent vessel occlusion and ischemia, and, in this case, an anatomic variant of the recurrent artery of Heubner from A1 made this more likely. Intra-arterial mechanical thrombectomy may be used in the treatment of an iatrogenic vessel thrombosis.

MANAGING THE EARLY PHASE OF REHABILITATION AFTER ISCHEMIC CEREBROVASCULAR ACCIDENT

Objective: Ischemic cerebrovascular accident (ICA) is characterised by the rapid deterioration of brain function due to vascularization disorders. The ischemic cerebrovascular accident may arise as a consequence of ischemia or hemhorrage in brain tissue, but the optimal treatment approach is unclear. In this study, we examined ICA rehabilitation goals, implementation of rehabilitation plans, management of sensomotor deficits and functional status, improvement of independence, prevention and treatment of complications, functional status monitoring, and planning recommendations, as well as education of ICA patients and their families.Methods: This study considered 69 ICA patients who were classified as suitable for rehabilitation intervention among a total of 231 patients who were evaluated for a diagnosis of ICA following hospitalization at the Clinic of Neurology, University Clinical Center of Kosovo (UCCK) in Prishtina. From the statistical parameters, we used the structure index, whereas testing results were evaluated using the Chi-square test with significance established at p<0.05.Results: For the 69 ICA patients, most ICA incidents occurred in patients who were older than 40 y-old. Mobility decreased from 42.9% to 8.6% when rehabilitation began at release instead of admission. Meanwhile, the ability to perform daily activities decreased from 48.6% to 11.4% when rehabilitation began after release as opposed to immediately after stabilization. Transfers and balance showed similar decreases (48.6% to 11.4% and 48.6% to 11.4%, respectively Chi-test=59.7, p<0.001.). The rehabilitation of patients in the early acute stage after ICA should begin as soon as possible after the diagnosis is made and the patient's condition is stable. During rehabilitation intervention, priority should be given to preventing complications and recurrent stroke, as well as enhancing patient mobility and improving patient morale.Conclusion: ICA is a medical emergency that can cause permanent neurological lesions and other complications that may be fatal or associated with permanent disability. The most affected age group is individuals older than 40 y old. Neurological deficits can cause motor, sensory, functional and emotional disability in ICA patients. Rehabilitation after ICA should begin immediately after the patient has stabilized to minimze functional losses.

Abstract 115: Microvascular Response to Ramipril in Peripheral Artery Disease

Background: The myopathy of Peripheral Artery Disease (PAD), a consequence of ischemia caused by atherosclerotic plaques in arteries supplying the legs, is characterized by myofiber degeneration and fibrosis of the vascular walls and extramyofiber matrix. In association with fibrosis we have found a robust expression of the profibrotic cytokine TGFβ1 in vascular smooth muscle cells. Additionally, we have observed microvascular endothelial “swelling” in PAD muscle. Published data indicate that inhibitors of the angiotensin system reduce fibrosis in multiple organ systems and improve walking performance, in diverse patient populations. We hypothesize that “swelling” of microvasculature endothelial cells represents abnormal accumulation of basement membrane Collagen Type IV (Col-IV) and that treatment with Ramipril will improve the microvasculature. Methods and Results: Gastrocnemius biopsies of PAD patients at Fontaine Stage II (N=5) before and after six months of Ramipril intervention and control patients (N=4) were labeled with an antibody specific for Col-IV. Images were acquired with an automated wide-field microscope and then processed with Image Pro Plus® and AutoQuant® deconvolution software. We used Col IV label to measure wall thickness and lumen diameter of 230 to 360 microvessels per patient, with a custom MatLab program based on the Expectation Maximization algorithm coupled with a Gaussian Mixture Model. Microvessel wall thickness was significantly greater (p < 0.04) in PAD patients before (1.54 ± 0.04 μ) and after (1.61 ± 0.06 μ) Ramipril treatment compared to control (1.42 ± 0.02). Lumen diameter was significantly greater (p < 0.02) in Post-Ramipril (3.49 ± 0.04 μ) compared to Pre-Ramipril (3.18 ± 0.08 μ) and control (3.00 ± 0.11 μ) patients. Conclusions: The increase of microvessel lumen diameter with Ramipril treatment is expected to increase microvascular perfusion and thereby improve walking distance. Our study will be expanded to increase cohort size and evaluate the association of microvascular measurements with microperfusion determined by Contrast Enhanced Ultrasonography and with walking performance.

Abstract 211: Implications of the PEGASUS-TIMI 54 Trial for U.S. Clinical Practice

Background: The PEGASUS trial demonstrated a reduction in ischemic events following P2Y 12 inhibition with ticagrelor among patients with a prior MI. The implications of these findings for clinical practice are unknown. Methods: We sought to determine the proportion of real-world myocardial infarction (MI) patients who would have been eligible for the PEGASUS-TIMI 54 trial, to characterize their current use of P2Y12 inhibitors, and to explore the estimated costs and ischemic event consequences of increasing P2Y12 inhibitor use among these patients. In the U.S. national ACTION Registry-GWTG, We identified 273,328 MI patients and determined the proportion that would have met the eligibility criteria for the PEGASUS trial. We described longitudinal P2Y 12 inhibitor use among PEGASUS eligible patients and estimated the cost and ischemic consequences of increasing P2Y 12 use among eligible patients. Results: A total of 112,222 (41.1%) MI patients in ACTION Registry-GWTG met eligibility for the PEGASUS trial. Among 83,871 eligible patients with pharmacy claims data, 23,042 (27.5%) were on a P2Y 12 inhibitor at 1 year, 9,661 (11.5%) at 2 years, and 5,246 (6.3%) at 3 years (see Figure), with the majority (79.2%) of these patients on clopidogrel. Use of ticagrelor in eligible patients not already on a P2Y 12 inhibitor at 1-year post MI would cost an estimated $885,000 per myocardial infarction, stroke, or cardiovascular death averted over a 3-year time horizon, while use of clopidogrel would cost an estimated $19,800 per ischemic event averted. Conclusions: In contemporary clinical practice, a minority of patients are on a P2Y 12 inhibitor beyond 1-year post-MI. Applying PEGASUS trial findings to clinical practice would result in a large increase in P2Y 12 inhibitor use with a cost per ischemic event averted that is strongly influenced by the choice of therapy.

Brain damage resulting from postnatal hypoxic-ischemic brain injury is reduced in C57BL/6J mice as compared to C57BL/6N mice

Perinatal hypoxia is a critical complication during delivery and is mostly studied in animal models of postnatal hypoxic-ischemic brain injury. We here studied the effects of postnatal hypoxic-ischemic brain injury in two different sub-strains of C57BL/6 mice, i.e. C57BL/6J and C57BL/6N mice. These two sub-strains show different metabolic properties, for instance an impaired glucose tolerance in C57BL/6J mice. Genetically, this was linked to differences in their nicotinamide nucleotide transhydrogenase (Nnt) genes: In C57BL/6J mice, exons 7–11 of the Nnt gene are deleted, resulting in the absence of functional Nnt protein.The mitochondrial Nnt-protein is one of several enzymes that catalyses the generation of NADPH, which in turn is important for the elimination of reactive oxygen species (ROS). As ROS is thought to contribute to the pathophysiology of hypoxia-ischemia, the lack of Nnt might indirectly increase ROS levels and therefore result in increased brain damage. We therefore hypothesize that lesion score and lesion size will increase in C57BL/6J mice as compared to C57BL/6N mice. Surprisingly, the results showed exactly the opposite: C57BL/6J mice showed a decrease in lesion score and size, associated with a reduced number of apoptotic cells and activated microglia. In contrast, the number of cells with ROS-induced DNA modifications (detected by 8OHdG) was higher in C57BL/6J than C57BL/6N mice. In conclusion, C57BL/6J mice showed reduced ischemic consequences after postnatal hypoxic-ischemic brain injury compared to C57BL/6N mice, with the exception of the amount of ROS-induced DNA-damage. These differences might relate to the lack of Nnt, but also to a modified metabolic setting (cardiovascular parameters, oxygen and glucose metabolism, immune function) in C57BL/6J mice.

Plasminogen and stroke: more is better

Plasminogen and stroke: more is better

Enhanced Endothelin-1 Mediated Vasoconstriction of the Ophthalmic Artery May Exacerbate Retinal Damage after Transient Global Cerebral Ischemia in Rat.

Cerebral vasculature is often the target of stroke studies. However, the vasculature supplying the eye might also be affected by ischemia. The aim of the present study was to investigate if the transient global cerebral ischemia (GCI) enhances vascular effect of endothelin-1 (ET-1) and 5-hydroxytryptamine/serotonin (5-HT) on the ophthalmic artery in rats, leading to delayed retinal damage. This was preformed using myography on the ophthalmic artery, coupled with immunohistochemistry and electroretinogram (ERG) to assess the ischemic consequences on the retina. Results showed a significant increase of ET-1 mediated vasoconstriction at 48 hours post ischemia. The retina did not exhibit any morphological changes throughout the study. However, we found an increase of GFAP and vimentin expression at 72 hours and 7 days after ischemia, indicating Müller cell mediated gliosis. ERG revealed significantly decreased function at 72 hours, but recovered almost completely after 7 days. In conclusion, we propose that the increased contractile response via ET-1 receptors in the ophthalmic artery after 48 hours may elicit negative retinal consequences due to a second ischemic period. This may exacerbate retinal damage after ischemia as illustrated by the decreased retinal function and Müller cell activation. The ophthalmic artery and ET-1 mediated vasoconstriction may be a valid and novel therapeutic target after longer periods of ischemic insults.

Parthenolide-Induced Cytotoxicity in H9c2 Cardiomyoblasts Involves Oxidative Stress.

Cardiac cellular injury as a consequence of ischemia and reperfusion involves nuclear factor-κB (NF-κ B), amongst other factors, and NF-κ B inhibitors could substantially reduce myocardial infarct size. Parthenolide, a sesquiterpene lactone compound which could inhibit NF-κ B, has been shown to ameliorate myocardial reperfusion injury but may also produce toxic effects in cardiomyocytes at high concentrations. The aim of this study was to examine the cytotoxic effects of this drug on H9c2 cardiomyoblasts, which are precursor cells of cardiomyocytes. Cell viability and apoptosis were examined by MTT and TUNEL assay, respectively, and protein expression was analyzed by western blot. Reactive oxygen species (ROS) production was measured using DCFH-DA as dye. Cytosolic Ca(2+) concentration and mitochondrial membrane potential were measured microfluorimetrically using, respectively, fura 2 and rhodamine 123 as dyes. Parthenolide caused apoptosis at 30 μ M, as judged by TUNEL assay and Bax and cytochrome c translocation. It also caused collapse of mitochondrial membrane potential and endoplasmic reticulum stress. Parthenolide triggered ROS formation, and vitamin C (antioxidant) partially alleviated parthenolide-induced cell death. The results suggested that parthenolide at high concentrations caused cytotoxicity in cardiomyoblasts in part by inducing oxidative stress, and demonstrated the imperative for cautious and appropriate use of this agent in cardioprotection. Cardiomyoblast; Endoplasmic reticulum stress; Oxidative stress; Parthenolide; Reperfusion injury.

Book Review: “Cerebral Small Vessel Disease”. What’s the Big Deal about Small Vessels?

Book Review: “Cerebral Small Vessel Disease”. What’s the Big Deal about Small Vessels?

Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel.

Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric chloride injury is now a well-established technique to rapidly and accurately induce the formation of thrombi in exposed veins or artery of small and large diameter. This model has played a key role in the study of the pathophysiology of thrombosis, in the discovery and validation of novel antithrombotic drugs and in the understanding of the mechanism of action of these new agents. Here, the implementation of this technique on a mesenteric vessel and carotid artery in mice is presented. The method describes how to label circulating leukocytes and platelets with a fluorescent dye and to observe, by intravital microscopy on the exposed mesentery, their accumulation at the injured vessel wall which leads to the formation of a thrombus. On the carotid artery, the occlusion caused by the clot formation is measured by monitoring the blood flow with a Doppler probe.

Urinary Allantoin Is Elevated in Severe Intraventricular Hemorrhage in the Preterm Newborn.

Germinal matrix intraventricular hemorrhage (IVH) is the most common type of intracranial hemorrhage observed in preterm neonates. It is a precursor of poor neurocognitive development, cerebral palsy, and death. The pathophysiology is not well defined, but damage to the fragile germinal matrix vasculature may be due to free radicals generated during inflammation and as a consequence of ischemia followed by reperfusion. Assessment of the oxidative stress status in these infants is therefore important. Urinary allantoin concentration was measured in preterm neonates as a marker of oxidative stress associated with IVH. Urine was collected from 44 preterm neonates at four time points between 24 and 72 hours of life (HOL), and the allantoin content was determined by gas chromatography mass spectrometry (GCMS). Records were retrospectively reviewed, and the incidence and severity of IVH was categorized as follows: no IVH (n = 24), mild (grade 1-2) IVH (n = 13), and severe (grade 3-4) IVH (n = 7). Neonates with severe IVH showed significantly elevated allantoin levels vs subjects with no IVH from 36 HOL (0.098 ± 0.013 μmol and 0.043 ± 0.007 μmol, respectively, p = 0.002). The allantoin concentration remained elevated even at 72 HOL (0.079 ± 0.014 μmol and 0.033 ± 0.008 μmol, respectively, p = 0.021). There were no significant differences in allantoin levels in the no IVH and mild IVH groups. IVH was diagnosed by head imaging on average at about 11th postnatal day. Urinary allantoin levels were significantly elevated during the first 3 days of life in the neonates subsequently diagnosed with severe IVH, suggesting that oxidative stress might be a crucial factor in IVH pathogenesis. Further studies are needed to assess the usefulness of urinary allantoin in early identification of preterm infants at risk for or with severe IVH and monitoring of the response to interventions designed to prevent or treat it.

TOWARD THE QUESTION OF ISCHEMIC MYOCARDIAL DYSFUNCTION

The authors of the review have analyzed papers published on the problem of ischemic myocardial dysfunction. They begin with a definition of the term “ischemia” (derived from two Greek words: isch ō , meaning to hold back, and haima, meaning blood) - a condition at which the arterial blood flow is insufficient to provide enough oxygen to prevent intracellular respiration from shifting from the aerobic to the anaerobic form. The poor rate of ATP generation from this process causes a decrease in cellular ATP, a concomitant rise in ADP, and ultimately, to depression inotropic (systolic) and lusitropic (diastolic) function of the affected segments of the myocardium. But with such simplicity of basic concepts, the consequences of ischemia so diverse. Influence of an ischemia on myocardial function so unequally at different patients, which is almost impossible to find two identical cases (as in the case of fingerprints). It depends on the infinite variety of lesions of coronary arteries, reperfusion (time and completeness of restoration of blood flow) and reactions of a myocardium which, apparently, has considerable flexibility in its response. Ischemic myocardial dysfunction includes a number of discrete states, such as acute left ventricular failure in angina, acute myocardial infarction, ischemic cardiomyopathy, stunning, hibernation, pre- and postconditioning. There are widely differing underlying pathophysiologic states. The possibility exists that several of these states can coexist.