Insufficient Blood Flow Research Articles

Hypoxia Responsive, Tumor Penetrating Lipid Nanoparticles for Delivery of Chemotherapeutics to Pancreatic Cancer Cell Spheroids.

Solid tumors are often poorly irrigated due to structurally compromised microcirculation. Uncontrolled multiplication of cancer cells, insufficient blood flow, and the lack of enough oxygen and nutrients lead to the development of hypoxic regions in the tumor tissues. As the partial pressure of oxygen drops below the necessary level (10 psi), the cancer cells modulate their genetic makeup to survive. Hypoxia triggers tumor progression by enhancing angiogenesis, cancer stem cell production, remodeling of the extracellular matrix, and epigenetic changes in the cancer cells. However, the hypoxic regions are usually located deep in the tumors and are usually inaccessible to the intravenously injected drug carrier or the drug. Considering the designs of the reported nanoparticles, it is likely that the drug is delivered to the peripheral tumor tissues, close to the blood vessels. In this study, we prepared lipid nanoparticles (LNs) comprising the synthesized hypoxia-responsive lipid and a peptide-lipid conjugate. We observed that the resultant LNs penetrated to the hypoxic regions of the tumors. Under low oxygen partial pressure, the hypoxia-responsive lipid undergoes reduction, destabilizing the lipid membrane, and releasing encapsulated drugs from the nanoparticles. We demonstrated the results employing spheroidal cultures of the pancreatic cancer cells BxPC-3. We observed that the peptide-decorated, drug encapsulated LNs reduced the viability of pancreatic cancer cells of the spheroids to 35% under hypoxic conditions.

Blood flow speed of the gastric conduit assessed by indocyanine green fluorescence: New predictive evaluation of anastomotic leakage after esophagectomy.

Anastomotic leakage is considered as an independent risk factor for postoperative mortality after esophagectomy, and an insufficient blood flow in the reconstructed conduit may be a risk factor of anastomotic leakage. We investigated the clinical significance of blood flow visualization by indocyanine green (ICG) fluorescence in the gastric conduit as a means of predicting the leakage of esophagogastric anastomosis after esophagectomy.Forty patients who underwent an esophagectomy with gastric conduit reconstruction were prospectively investigated. ICG fluorescence imaging of the gastric conduit was detected by a near-infrared camera system during esophagectomy and correlated with clinical parameters or surgical outcomes.In 25 patients, the flow speed of ICG fluorescence in the gastric conduit wall was simultaneous with that of the greater curvature vessels (simultaneous group), whereas in 15 patients this was slower than that of the greater curvature vessels (delayed group). The reduced speed of ICG fluorescence stream in the gastric conduit wall was associated with intraoperative blood loss (P = 0.008). Although anastomotic leakage was not found in the simultaneous group, it occurred in 7 patients of the delayed group (P < 0.001). A flow speed of ICG fluorescence in the gastric conduit wall of 1.76 cm/s or less was determined by a receiver operating characteristic (ROC) curve, identified as a significant independent predictor of anastomotic leakage after esophagectomy (P = 0.004).This preliminary study demonstrates that intraoperative evaluation of blood flow speed by ICG fluorescence in the gastric conduit wall is a useful means to predict the risk of anastomotic leakage after esophagectomy.

Safety and Efficacy of Repeated Bone Marrow Mononuclear Cell Therapy in Patients with Critical Limb Ischemia in a Pilot Randomized Controlled Trial.

Critical limb ischemia is a manifestation of peripheral arterial disease characterized by insufficient arterial blood flow for maintaining tissue viability in the lower extremities. Therapeutic angiogenesis is used for peripheral arterial disease patients who are not candidates for surgical revascularization or radiological intervention. There is accumulating evidence for the beneficial impact of autologous bone marrow mononuclear cell transplantation for treatment of critical limb ischemia in humans. This study aims to investigate the safety and efficacy of repeated bone marrow mononuclear cell injections in comparison with a single bone marrow mononuclear cell injection in critical limb ischemia patients. Patients with critical limb ischemia (n = 22) were randomized (http://clinicaltrials.gov/ct2 show/NCT01480414) to receive either a single (n = 11) or four (n = 11) intramuscular injections of bone marrow mononuclear cells as a cell therapy product. There were no reported adverse events during the 24-week follow-up period after cell delivery. Efficacy assessment indicated that after cell injections, there was significant improvement in Ankle-Brachial Index, Visual Analog Scale, pain-free walking distance, and Wagner stage as well as reduction in ulcer size. There was no significant difference between the two groups in terms of clinical parameters. However, by the 24th week the pain-free walking distance improved significantly in the group who received four injections of cells. Favorable clinical outcomes strongly indicate the long-term benefit of bone marrow mononuclear cell transplantation, either as one or several injections, for retrieval from critical limb ischemia. Repeated cell injections have shown increased improvement of pain-free walking distance in patients. These findings warrant further exploration in later-phase clinical trials with repeated injections.

Anterior spinal cord infarction in a 77-year-old male after a right hemicolectomy: A case report

A 77-year-old man underwent an exploratory laparotomy and right hemicolectomy for bowel ischemia. An etiology that has been investigated was hypotension leading to hypoperfusion. Intraoperatively, the patient experienced hypotension with a decline in mean arterial pressure from 150 mmHg to 30 mmHg for a duration of 20 minutes. Postoperatively the patient had another episode of hypotension with a decline in mean arterial pressure from 80 mmHg to 55 mmHg for a-15-minute period. On post-operative day three the patient was paraplegic with spinal cord infarction seen on magnetic resonance imaging from T10 to the conus medullaris. The blood supply to this region appeared unobstructed on imaging and therefore it is likely that intermittent hypotension was associated with insufficient blood flow to this region.

Usefulness and Problems of Intraoperative Monitoring for Unruptured Aneurysm Surgery with the Motor Evoked Potential

It has been pointed out that the motor evoked potential(MEP)with a subdural electrode is useful in the intraoperative monitoring for unruptured aneurysm surgery. However, in some cases, we experienced postoperative ischemic complications despite evaluating the motor function via MEP monitoring. Herein, we have reported the usefulness and problems of intraoperative monitoring with MEP to evaluate brain dysfunction caused by insufficiency of cerebral blood flow. Out of 279 aneurysm surgery procedures, we performed MEP monitoring in 142 cases and successfully recorded in 126 cases. We compared the ischemic complication rate of the group for which MEP was monitored with that of the group for which MEP was not monitored. The whole ischemic complication rate was decreased in the group that underwent MEP monitoring. Thus, it was suggested that MEP monitoring was useful for avoiding ischemic complications. In internal carotid artery aneurysms, the amplitude of MEP changed and recovered in 2 cases and disappeared in one case. In anterior cerebral artery aneurysms, the amplitude of MEP changed and recovered in 2 cases. In middle cerebral artery aneurysms, the amplitude of MEP changed and recovered in 5 cases. We could avoid ischemic complications by intraoperative MEP monitoring in many cases. However, in some cases, we found ischemic complications that were not detected by MEP monitoring with a subdural electrode. In these cases, transcranial stimulation in combination with subdural electrode might be effective in avoiding ischemic complications that might occur after dural closure.

Fetal growth restriction but not preterm birth is a risk factor for severe hypospadias.

Hypospadias has multifactorial causes and occurs at a high frequency among very low-birthweight infants. Placental insufficiency is hypothesized to be one cause of hypospadias; that is, decreased human chorionic gonadotropin (hCG) secretion caused by placental insufficiency is suspected to result in abnormal male external genitalia, but there is little direct evidence to support this. The aim of this study was therefore to identify the features of hypospadias and to clarify the male genital abnormalities caused by fetal growth restriction (FGR). We reviewed the clinical data of boys who underwent hypospadias repair between 2005 and 2011 at Kyoto University Hospital. Twenty boys were included in this study. Fifteen (75%) of the subjects were preterm or low-birthweight infants. Thirteen (65%) had FGR, 60% of whom had severe hypospadias regardless of gestational age. In addition, 92% of the FGR infants also had other genital anomalies, such as cryptorchidism, bifid scrotum, or micropenis. In contrast, only 14% and 43% of the non-FGR infants had severe hypospadias or genital anomalies other than hypospadias, respectively. Placental histopathology was available in eight FGR infants, in seven of whom it was suggestive of blood flow deficiency such as infarction and single umbilical artery. Infants with FGR have a high incidence of hypospadias. FGR caused by placental dysfunction, but not low birthweight, is a risk factor for severe hypospadias associated with multiple genital anomalies.

A simple bracing technique to correct kinking of arterial branches to avoid ischemic sequelae during neurovascular surgery.

Background:During microscopic procedures for neurovascular disease, we sometimes encounter kinking of arterial branches resulting in ischemic sequelae. A simple and useful technique that involves inserting a small, ball-like prosthesis made of oxidized cellulose or shredded Teflon with fibrin glue that corrects the arterial branch kinking and avoids subsequent compromise is reported.Methods:Between January and December 2014, three patients developed arterial kinking during microscopic procedures, including two in the caudal loop of the posterior inferior cerebellar artery during microvascular decompression for glossopharyngeal neuralgia and one in a branch of the middle cerebral artery (MCA) during clipping for an unruptured MCA aneurysm. Blood flow insufficiency was confirmed by microvascular Doppler ultrasonography (MDU) and indocyanine green (ICG) videoangiography. The prosthesis, which was made of shredded Teflon in two cases and oxidized cellulose in one case, was inserted into the crotch of the kinked arteries to correct the kinking of the arteries and restore the proper vascular shape and normal blood flow.Results:The small, ball-shaped prosthesis corrected the kinked arteries and maintained the proper shape, which was confirmed by ICG videoangiography and MDU during the operation and three-dimensional computerized tomography angiography postoperatively. Postoperatively, the patients did not manifest any ischemic sequelae related to the kinked arteries.Conclusion:The insertion of prostheses with fibrin glue into the crotch of a kinked artery for repair is considered a simple and useful method for correcting a kinked artery that avoids ischemic sequelae.

Surgical Unroofing for Anomalous Aortic Origin of Coronary Arteries

Anomalous aortic origin of a coronary artery (AAOCA) from an opposite sinus of Valsalva is an uncommon congenital defect that is typically only discovered on cardiac catheterization or on autopsy following sudden cardiac death. Conjectured mechanisms for the ischemia are generally believed to relate to the unique and easily obstructed geometry of the coronary ostium and the stenotic intramural coronary segment. Given the potentially devastating consequences of not repairing an AAOCA—that is, sudden cardiac death—these patients should undergo repair of the anomaly when it is discovered. Multiple options for surgically correcting the AAOCA have been developed, and the most used approaches include coronary artery bypass grafting, coronary reimplantation, and unroofing of the intramural segment. Here we present the technique for surgical unroofing of the intramural segment of an anomalous coronary artery of aortic origin.

Патогенетические и патофизиологические механизмы формирования острой и хронической недостаточности мозгового кровообращения в артериях вертебрально-базилярной системы у больных с мальформацией Киари

Патогенетические и патофизиологические механизмы формирования острой и хронической недостаточности мозгового кровообращения в артериях вертебрально-базилярной системы у больных с мальформацией Киари

Consecutive flap transfer for repairing massive soft tissue defects in the opisthenar with improved donor site closure

ObjectiveTo explore a surgical model of utilizing consecutive free scapular flap and adjacent pedicled flap transfer for repairing massive soft tissue defects on the dorsum of the hand while minimizing the donor site morbidity. MethodsSix patients with massive soft tissue injuries on the opisthenar and forearm were treated with free scapular flaps. Afterwards, a pedicled flap adjacent to the donor site was transferred to cover the donor site defect by direct closure. ResultsAll six free scapular flaps survived without signs of infection. Three adjacent pedicled flaps presented minor signs of insufficient blood flow on the distal apex, which resolved after six weeks with only conservative therapy. All the incisions healed without other complications. At six-month follow-up, the patients regained full shoulder function. ConclusionWith the assistance of an adjacent pedicled flap, the scapular flap is a highly applicable approach in repairing massive soft tissue defects in the opisthenar. It can achieve positive outcomes in both reconstructive and aesthetic aspects.

Simultaneous Reconstruction of Forefoot and Hindfoot Defects with a Thoracodorsal-Axis Chimeric Flap.

Simultaneous Reconstruction of Forefoot and Hindfoot Defects with a Thoracodorsal-Axis Chimeric Flap.

Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease.

Sickle cell disease (SCD) is complicated by silent cerebral infarcts, visible as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). Both local vaso-occlusion, elicited by endothelial dysfunction, and insufficiency of cerebral blood flow (CBF) have been proposed to be involved in the aetiology. We performed an explorative study to investigate the associations between WMHs and markers of endothelial dysfunction and CBF by quantifying WMH volume on 3.0 Tesla MRI. We included 40 children with HbSS or HbSβ(0) thalassaemia, with a mean age of 12.1 ± 2.6 years. Boys demonstrated an increased risk for WMHs (odds ratio 4.5, 95% confidence interval 1.2-17.4), unrelated to glucose-6-phosphate dehydrogenase deficiency. In patients with WMHs, lower fetal haemoglobin (HbF) was associated with a larger WMH volume (regression coefficient = -0.62, R2 = 0.5, P = 0.04). Lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels were associated with lower CBF in the white matter (regression coefficient = 0.07, R2 = 0.15, P = 0.03), suggesting that endothelial dysfunction could potentially hamper CBF. The findings of our explorative study suggest that a high level of HbF may be protective for WMHs and that endothelial dysfunction may contribute to the development of WMHs by reducing CBF.

Retinal region-dependent susceptibility of capillaries to high-concentration oxygen exposure and vascular endothelial growth factor receptor inhibition in neonatal mice

Retinal blood flow insufficiency due to capillary loss induces hypoxia in the retina, leading to an abnormal angiogenesis, relating to ischemic retinopathy. To better understand the mechanism and process of retinal capillary regression, we examined the process of hyperoxia- and vascular endothelial growth factor receptor (VEGFR) inhibitor-induced retinal capillary regression in neonatal mice. We also investigated the effects of Ca2+ channel blockers, amlodipine and nicardipine, on hyperoxia-induced capillary regression. The regression of capillaries adjacent to arteries began immediately after the mice were exposed to 80% oxygen on postnatal day 7. An apparent avascular zone was established within 24 h after the initiation of oxygen exposure, whereas capillaries in the retinal vascular front were not affected. Axitinib, an inhibitor of VEGFR tyrosine kinase, induced capillary regression throughout the retinal vasculature. High-concentration oxygen exposure affected the capillaries on the arterial side of the retinal circulation more preferentially than axitinib. The Ca2+ channel blockers significantly delayed hyperoxia-induced capillary regression and changes in the capillaries on the arterial side. These results suggest that the decreased blood flow due to arterial constriction contributes to hyperoxia-induced capillary regression. Compounds that improve the retinal blood flow may prevent ischemia by preventing capillary loss.

Paralysis and Sexuality in Medical Literature and the Acts of Peter

This paper focuses on the story of Peter’s daughter that is found in the Berlin Coptic papyrus BG 8502.4, and is associated with the apocryphal Acts of Peter. Research on the story of Peter’s daughter has primarily focused on its interpretation of the theme of chastity, or whether the story was originally included in the Acts of Peter. In the course of these investigations, scholars have taken for granted the curious assumption of the text that paralysis renders Peter’s daughter unfit for marriage, and thus safe from Ptolemy’s unwanted advances. This paper explores the underlying understandings of paralysis and sexuality that would have enabled ancient Christian audiences to make this leap from paralysis to sexual inviolability. Using data from ancient medical texts, this work demonstrates that both paralysis and infertility were understood as symptoms of excessive cooling and insufficient blood flow. Thus, for the ancient audience a paralyzed female body was incapable of bearing children, and an undesirable candidate for marriage. When read in light of these findings, Peter’s daughter is not only a model of early Christian chastity, but of early Christian story telling—using common cultural assumptions about disability to redefine normativity.

The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease.

Poor vascular homeostasis drives many clinical disorders including diabetes, arthritis, atherosclerosis, and peripheral artery disease. Local tissue ischemia resultant of insufficient blood flow is a potent stimulus for recruitment of endothelial progenitor cells (EPCs). This mobilization and homing is a multi-step process involving EPC detachment from their steady state bone marrow niches, entry into circulation, rolling along vessel endothelium, transmigration, and adhesion to denuded extracellular matrix (ECM) where they may participate in neovessel formation. However, these events are often interrupted in pathological conditions partly due to an imbalance in factor presentation at the tissue level. EPC number and function is impaired in patients with vascular diseases and this dysfunction has been proposed as a prominent contributor to disease pathogenesis. Research approaches aimed at providing therapeutic angiogenesis commonly involve the delivery of proangiogenic cells and/or soluble factors. Nevertheless, greater understanding of the mechanisms involved in EPC homing in both healthy and diseased states is critical for improving efficacy of such strategies. This review underscores the matrix-related signals necessary for enhancing EPC recruitment to ischemic tissue and provides an overview of the development of synthetic ECMs that aim to mimic functions of the local native microenvironment for use in therapeutic angiogenesis.

An experimental study of the effect of pre-operative administration of cilostazol on random skin flap survival in rats: double blinded randomized controlled trial.

BackgroundInsufficient arterial blood flow is the one cause of flap necrosis. Cilostazol is an inhibitor of phosphodiesterase III and increases cyclic AMP level in vascular smooth muscle cell causing vasodilation. Therefore, effect of cilostazol is expected to improve the viability of the flap.MethodsDouble blinded randomized controlled trial was conducted. The study was to compare the survival of dorsal rat flaps between preoperative cilostazol supplemented diet and regular diet. The flap survival area was measured using PixArea Image software on post operative day 1,3,5 and 7. Fluorescein injection was performed to evaluate the exactly area of flap survival on postoperative day 7 and morphology of arterioles and venules were examined by histopathologic examination.ResultsA statistical significance was found in the percentage of area of flap survival between cilostazol supplemented diet and control group on postoperative day 3, 5 and 7 (p < 0.05). Fluorescein injection showed the higher area of flap survival in cilostazol group than the control group (p < 0.05). Histopathologic examination showed dilation of vessels in the cilostazol group.ConclusionPreoperative cilostazol in rats can enhance skin flap survival.Electronic supplementary materialThe online version of this article (doi:10.1186/s13022-015-0011-4) contains supplementary material, which is available to authorized users.

Surgical sepsis

Sepsis represents a clinical syndrome following an infection and it is characterized by classical signs of systemic inflammatory response syndrome (SIRS): fever or ipothermia, tachycardia, tachipnea, leucocytosis or leucopenia. There may also be symptoms related to a specific infection such as a cough in pneumonia or burning with urination in a kidney infection, and abdominal pain in an intraabdominal sepsis. Common locations for the primary infection include lungs, brain, urinary tract, skin and soft tissues, and mainly abdominal organs. Patients who develop sepsis have an increased risk of complications and death and face higher healthcare costs and longer treatment. The infection is caused most commonly by bacteria, but can also be by fungi, viruses, or parasites. Severe sepsis is sepsis causing poor organ function or insufficient blood flow; septic shock is the situation with ipotension and/or need for high dosage of inotropes or vasopressors and multiple organ failure syndrome is when multiple organ dysfunction or failure is present. Outcomes depend on the severity of disease with the risk of death from sepsis being as high as 30%, severe sepsis as high as 50%, and septic shock as high as 80%. Prevention, early diagnosis, and treatment, both medical (antibiotics) and surgical (source control), together with the prompt intensive care and organ support are crucial to increase survival rate.

Erratum to: The hippo signaling pathway: implications for heart regeneration and disease.

After publication of this review [1] it emerged that the references in the Introduction section were incorrect. Several references were omitted and other references were numbered incorrectly. These errors were introduced during the final production process by the publisher and SpringerOpen apologises for any inconvenience caused. The relevant Introduction and references have been replaced with: Myocardial infarction (MI), or insufficient blood flow to the heart muscle, promotes the death and loss of cardiomyocytes resulting in heart damage and impaired cardiac function. While patient survival following MI has improved, the prognosis is typically poor and can eventually progress to heart failure, a leading cause of morbidity and mortality (one). Because mature cardiomyocytes have a limited capacity to re-enter the cell cycle and proliferate [116, 117], the ability of the adult heart to regenerate is similarly restricted and cannot adequately replace lost cardiomyocytes. The Hippo signaling pathway is evolutionarily conserved from flies to mammals and has emerged as an important regulator of both cell survival and proliferation (four) [20]. Importantly, this cascade also appears critical for proper mammalian heart development and the post-natal response to cardiac stress and injury [60, 123, 124]. It is therefore plausible to hypothesize that Hippo signaling could be targeted to promote heart regeneration after MI and heart injury. This review will provide an overview of the Hippo pathway and examine its role in cardiac development, disease and regeneration. The omitted references can be found below: Reference one Go, A. S., Mozaffarian, D., Roger, V. L., Benjamin, E. J., Berry, J. D., Blaha, M. J., Dai, S., Ford, E. S., Fox, C. S., Franco, S., Fullerton, H. J., Gillespie, C., Hailpern, S. M., Heit, J. A., Howard, V. J., Huffman, M. D., Judd, S. E., Kissela, B. M., Kittner, S. J., Lackland, D. T., Lichtman, J. H., Lisabeth, L. D., Mackey, R. H., Magid, D. J., Marcus, G. M., Marelli, A., Matchar, D. B., McGuire, D. K., Mohler, E. R., 3rd, Moy, C. S., Mussolino, M. E., Neumar, R. W., Nichol, G., Pandey, D. K., Paynter, N. P., Reeves, M. J., Sorlie, P. D., Stein, J., Towfighi, A., Turan, T. N., Virani, S. S., Wong, N. D., Woo, D., Turner, M. B., American Heart Association Statistics, C. and Stroke Statistics, S. (2014) Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 129, e28-e292 Reference four Staley, B. K. and Irvine, K. D. (2012) Hippo signaling in Drosophila: recent advances and insights. Developmental dynamics : an official publication of the American Association of Anatomists. 241, 3–15

Simulations reveal adverse hemodynamics in patients with multiple systemic to pulmonary shunts.

For newborns diagnosed with pulmonary atresia or severe pulmonary stenosis leading to insufficient pulmonary blood flow, cyanosis can be mitigated with placement of a modified Blalock-Taussig shunt (MBTS) between the innominate and pulmonary arteries. In some clinical scenarios, patients receive two systemic-to-pulmonary connections, either by leaving the patent ductus arteriosus (PDA) open or by adding an additional central shunt (CS) in conjunction with the MBTS. This practice has been motivated by the thinking that an additional source of pulmonary blood flow could beneficially increase pulmonary flow and provide the security of an alternate pathway in case of thrombosis. However, there have been clinical reports of premature shunt occlusion when more than one shunt is employed, leading to speculation that multiple shunts may in fact lead to unfavorable hemodynamics and increased mortality. In this study, we hypothesize that multiple shunts may lead to undesirable flow competition, resulting in increased residence time (RT) and elevated risk of thrombosis, as well as pulmonary overcirculation. Computational fluid dynamics-based multiscale simulations were performed to compare a range of shunt configurations and systematically quantify flow competition, pulmonary circulation, and other clinically relevant parameters. In total, 23 cases were evaluated by systematically changing the PDA/CS diameter, pulmonary vascular resistance (PVR), and MBTS position and compared by quantifying oxygen delivery (OD) to the systemic and coronary beds, wall shear stress (WSS), oscillatory shear index (OSI), WSS gradient (WSSG), and RT in the pulmonary artery (PA), and MBTS. Results showed that smaller PDA/CS diameters can lead to flow conditions consistent with increased thrombus formation due to flow competition in the PA, and larger PDA/CS diameters can lead to insufficient OD due to pulmonary hyperfusion. In the worst case scenario, it was found that multiple shunts can lead to a 160% increase in RT and a 10% decrease in OD. Based on the simulation results presented in this study, clinical outcomes for patients receiving multiple shunts should be critically investigated, as this practice appears to provide no benefit in terms of OD and may actually increase thrombotic risk.

Neuroprotective Effect of Resveratrol on Acute Brain Ischemia Reperfusion Injury by Measuring Annexin V, p53, Bcl-2 Levels in Rats

BackgroundCerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V.MethodsWe preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001.ResultsAfter administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups.ConclusionIn the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53.