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Can Ince

Publications and source records attributed to Can Ince.

At least 19 recordsLinked to original sources

Influence of the application of platelet-enriched plasma in oral mucosal wound healing.

PURPOSE: The aim of this study was to describe and quantify the therapeutic value of platelet concentrate on the capillary density in oral mucosal wound healing. MATERIAL AND METHODS: The subjects included 10 healthy edentulous patients who underwent bilaterally a sinus floor elevation procedure and a buccal onlay graft with autologous iliac crest bone for maxillary reconstruction. During surgery, platelet-rich plasma (PRP) was prepared from a blood sample taken from the patient. After randomization in a split-mouth design, at one side PRP was administered in the wound and at the contralateral side a placebo. At baseline, microvascular capillary density was scored with the orthogonal polarization spectral (OPS) imaging technique and repeated measurements were performed postoperatively on a daily basis until the tenth day, after which measurements were continued weekly until the fifth postoperative week. RESULTS: Ten patients, five males and five females, were included in the study with a mean age of 54.2+/-9.1 years for females and 57.6+/-6.9 years for males. Donor platelet counts from whole blood had a mean value of 248.5+/-13.5 x 10(9)/l, while the value of platelet counts in the PRP had a mean of 975.9+/-97.9 x 10(9)/l. Wound healing was significantly accelerated in the PRP-treated mucosal wounds during the first 10 postoperative days. After the second week, no obvious differences between the PRP or placebo side could be noted. CONCLUSION: PRP has a strong stimulant effect on capillary regeneration in wound healing. These effects are mainly noticeable during the early stages of wound healing.

Alveolar Ridge Augmentation↗

Acute decrease in renal microvascular PO2 during acute normovolemic hemodilution.

Large differences in the tolerance of organ systems to conditions of decreased O(2) delivery such as hemodilution exist. The kidney receives approximately 25% of the cardiac output and O(2) delivery is in excess of the oxygen demand under normal circumstances. In a rat model of acute normovolemic hemodilution (ANH), we studied the effect of reduced hematocrit on renal regional and microvascular oxygenation. Experiments were performed in 12 anesthetized male Wistar rats. Six animals underwent four steps of ANH (hematocrit 25, 15, 10, and <10%). Six animals served as time-matched controls. Systemic and renal hemodynamic and oxygenation parameters were monitored. Renal cortical (c) and outer medullary (m) microvascular PO(2) (microPO(2)) and the renal venous PO(2) (P(rv)O(2)) were continuously measured by oxygen-dependent quenching of phosphorescence. Despite a significant increase in renal blood flow in the first two steps of ANH, cmicroPO(2) and mmicroPO(2) dropped immediately. From the first step onward oxygen consumption (VO(2(ren))) became dependent on oxygen delivery (DO(2(ren))). With a progressive decrease in hematocrit, a significant correlation between microPO(2) and VO(2(ren)) could be observed, as well as a PO(2) gap between microPO(2) and P(rv)O(2). Furthermore, there was a high correlation between VO(2(ren)) and RBF over a wide range of flows. In conclusion, the oxygen supply to the renal tissue is becoming critical already in an early stage of ANH due to the combination of increased VO(2(ren)), decreased DO(2(ren)), and intrarenal O(2) shunt. This has clinical relevance as recent publications reporting that hemodilution during surgery forms a risk factor for postoperative renal dysfunction.

Animals↗

Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia.

INTRODUCTION: Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO2 (microPO2) and oxygen consumption (VO2,ren), that endotoxemia is associated with a diminished kidney function, that fluid resuscitation can restore microPO2, VO2,ren and kidney function, and that colloids are more effective than crystalloids. METHODS: Male Wistar rats received a one-hour intravenous infusion of lipopolysaccharide, followed by resuscitation with HES130/0.4 (Voluven), HES200/0.5 (HES-STERIL 6%) or Ringer's lactate. The renal microPO2 in the cortex and medulla and the renal venous PO2 were measured by a recently published phosphorescence lifetime technique. RESULTS: Endotoxemia induced a reduction in renal blood flow and anuria, while the renal microPO2 and VO2,ren remained relatively unchanged. Resuscitation restored renal blood flow, renal oxygen delivery and kidney function to baseline values, and was associated with oxygen redistribution showing different patterns for the different compounds used. HES200/0.5 and Ringer's lactate increased the VO2,ren, in contrast to HES130/0.4. CONCLUSION: The loss of kidney function during endotoxemia could not be explained by an oxygen deficiency. Renal oxygen redistribution could for the first time be demonstrated during fluid resuscitation. HES130/0.4 had no influence on the VO2,ren and restored renal function with the least increase in the amount of renal work.

Animals↗

Orthogonal polarization spectral (OPS) imaging and topographical characteristics of oral squamous cell carcinoma.

Tumor microcirculatory characteristics until now have only been assessed by histological examination of biopsies or invasive imaging technique. The recent introduction of orthogonal polarization spectral (OPS) imaging as a new tool for in vivo visualization of human microcirculation makes it possible to acquire high resolution images of the oral mucosa. In this study we report the microcirculatory changes in ten patients with oral squamous cell carcinoma of the tongue and compared the images to the normal contralateral side as the control. All carcinomas were T2 tumors without evidence for lymph node metastasis. The carcinomas were characterized by chaotic and dilated vessels accompanied by numerous areas of haemorrhage. The OPS technique seems very promising in the assessment of oral squamous cell carcinoma microcirculatory characteristics and may possibly play a future role in both the detection of early oral mucosal vascular aberrations and the effect of anti-tumor agents on the tumor microvasculature.

Aged↗

Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX.

Molecular oxygen is the primary oxidant in biological systems. The ultimate destination of oxygen in vivo is the mitochondria where it is used in oxidative phosphorylation. The ability of this process to produce an amount of high-energy phosphates adequate to sustain life highly depends on the available amount of oxygen. Despite a vast array of techniques to measure oxygen, major (patho)physiological questions remain unanswered because of the unavailability of quantitative techniques to measure mitochondrial oxygen in situ. Here we demonstrate that mitochondrial PO(2) can be directly measured in living cells by harnessing the delayed fluorescence of endogenous protoporphyrin IX (PpIX), thereby providing a technique with the potential for a wide variety of applications. We applied this technique to different cell lines (V-79 Chinese hamster lung fibroblasts, HeLa cells and IMR 32-K1 neuroblastoma cells) and present the first direct measurements of the oxygen gradient between the mitochondria and the extracellular volume.

Animals↗

Mechanisms of critical illness--classifying microcirculatory flow abnormalities in distributive shock.

Over 30 years ago Weil and Shubin proposed a re-classification of shock states and identified hypovolemic, cardiogenic, obstructive and distributive shock. The first three categories have in common that they are associated with a fall in cardiac output. Distributive shock, such as occurs during sepsis and septic shock, however, is associated with an abnormal distribution of microvascular blood flow and metabolic distress in the presence of normal or even supranormal levels of cardiac output. This Bench-to-bedside review looks at the recent insights that have been gained into the nature of distributive shock. Its pathophysiology can best be described as a microcirculatory and mitochondrial distress syndrome, where time and therapy form an integral part of the definition. The clinical introduction of new microcirculatory imaging techniques, such as orthogonal polarization spectral and side-stream dark-field imaging, have allowed direct observation of the microcirculation at the bedside. Images of the sublingual microcirculation during septic shock and resuscitation have revealed that the distributive defect of blood flow occurs at the capillary level. In this paper, we classify the different types of heterogeneous flow patterns of microcirculatory abnormalities found during different types of distributive shock. Analysis of these patterns gave a five class classification system to define the types of microcirculatory abnormalities found in different types of distributive shock and indicated that distributive shock occurs in many other clinical conditions than just sepsis and septic shock. It is likely that different mechanisms defined by pathology and treatment underlie these abnormalities observed in the different classes. Functionally, however, they all cause a distributive defect resulting in microcirculatory shunting and regional dysoxia. It is hoped that this classification system will help in the identification of mechanisms underlying these abnormalities and indicate optimal therapies for resuscitating septic and other types of distributive shock.

Critical Illness↗

Orthogonal polarization spectral imaging of the microcirculation during acute hypervolemic hemodilution and epidural lidocaine injection.

We used Orthogonal Polarization Spectral Imaging to examine the microcirculation of the vaginal mucosa in nine anesthetized patients during two consecutive anesthetic interventions: hypervolemic hemodilution using hydroxyethyl starch followed by thoracic epidural lidocaine. Images taken before and after each intervention were compared. During hypervolemic hemodilution, systolic blood pressures increased significantly, but functional capillary density remained unchanged. Epidural anesthesia decreased systolic and diastolic blood pressures, but there was no change in capillary density, venular diameter, or flow velocity. We concluded that when using Orthogonal Polarization Spectral imaging, no consistent effects on the microcirculation of the vaginal wall can be detected.

Adult↗

Continuous real-time visualization of the human cerebral microcirculation during arteriovenous malformation surgery using orthogonal polarization spectral imaging.

OBJECTIVE: After excision of an arteriovenous malformation (AVM), intracerebral hemorrhage or edema can develop, most probably resulting from hyperperfusion. Changes in the perinidal cerebral microvessels probably play a role in the development of this complication but have not been well studied so far. In this study, microvascular changes associated with resection of an AVM were observed and quantified intraoperatively using orthogonal polarization spectral imaging. METHODS: In two patients undergoing craniotomy for excision of an AVM, microvessel diameter, functional capillary index, and microvascular flow index were assessed during surgery using orthogonal polarization spectral imaging and compared with controls (n = 2). RESULTS: Before excision of the AVM, arterioles were characterized by the observation of individual erythrocytes caused by slowing of flow. In venules, microvascular flow index was 2.0 per image field (sludging flow), and functional capillary index was 1.4 +/- 1.3 cm/mm. After resection, flow velocity increased to a level that individual erythrocytes could not be traced any more in arterioles. Furthermore, both microvascular flow index and functional capillary index increased to 3.7 (high flow) and 2.1 +/- 0.8 cm/mm, respectively. CONCLUSION: With intraoperative orthogonal polarization spectral imaging, microcirculatory hemodynamic changes in the human brain can be readily observed and quantified. In AVM surgery, a dramatic increase in microvascular flow was observed in the perinidal brain tissue, which seems consistent with current hypotheses regarding normal perfusion pressure breakthrough.

Adult↗

Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes.

Chronic hyperglycemia underlies microvascular complications in patients with type 1 diabetes. The mechanisms leading to these vascular complications are not fully understood. Recently, we observed that acute hyperglycemia results in endothelial glycocalyx damage. To establish whether glycocalyx is associated with microvascular damage, we performed glycocalyx perturbation volume measurements in type 1 diabetic patients with microalbuminuria (DM1-MA group; n = 7), without microalbuminuria (DM1-NA group; n = 7), and in age-matched control subjects (CON; n = 7). Systemic glycocalyx volume was determined comparing intravascular distribution volume of a glycocalyx-permeable tracer (dextran 40) to that of a glycocalyx-impermeable tracer (labeled erythrocytes). Sublingual capillaries were visualized using orthogonal polarization spectral microscopy to estimate microvascular glycocalyx. Patients and control subjects were matched according to age and BMI. Glycocalyx volume decreased in a stepwise fashion from CON, DM1-NA, and finally DM1-MA subjects (1.5 +/- 0.1, 0.8 +/- 0.4, and 0.2 +/- 0.1 l, respectively, P < 0.05). Microvascular glycocalyx in sublingual capillaries was also decreased in type 1 diabetes versus the control group (0.5 +/- 0.1 vs. 0.9 +/- 0.1 microm, P < 0.05). Plasma hyaluronan, a principal glycocalyx constituent, and hyaluronidase were increased in type 1 diabetes. In conclusion, type 1 diabetic patients are characterized by endothelial glycocalyx damage, the severity of which is increased in presence of microalbuminuria.

Adult↗

Dual-wavelength phosphorimetry for determination of cortical and subcortical microvascular oxygenation in rat kidney.

This study presents a dual-wavelength phosphorimeter developed to measure microvascular PO2 (microPO2) in different depths in tissue and demonstrates its use in rat kidney. The used phosphorescent dye is Oxyphor G2 with excitation bands at 440 and 632 nm. The broad spectral gap between the excitation bands combined with a relatively low light absorption of 632 nm light by tissue results in a marked difference in penetration depths of both excitation wavelengths. In rat kidney, we determine the catchments depth of the 440-nm excitation to be 700 microm, whereas the catchments depth of 632 nm is as much as 4 mm. Therefore, the measurements differentiate between cortex and outer medulla, respectively. In vitro, no difference in PO2 readings between both channels was found. On the rat kidney in vivo, the measured cortical microPO2 was on average 20 Torr higher than the medullary microPO2 over a wide PO2 range induced by variations in inspired oxygen fraction. Examples provided from endotoxemia and resuscitation show differences in responses of mean cortical and medullary PO2 readings as well as in the shape of the PO2 histograms. It can be concluded that oxygen-dependent quenching of phosphorescence of Oxyphor G2 allows quantitative measurement of microPO2 noninvasively in two different depths in vivo. Oxygen levels measured by this technique in the rat renal cortex and outer medulla are consistent with previously published values detected by Clark-type oxygen electrodes. Dual-wavelength phosphorimetry is excellently suited for monitoring microPO2 changes in two different anatomical layers under pathophysiological conditions with the characteristics of providing oxygen histograms from two depths and having a penetration depth of several millimeters.

Animals↗

Quantifying bedside-derived imaging of microcirculatory abnormalities in septic patients: a prospective validation study.

INTRODUCTION: The introduction of orthogonal polarization spectral (OPS) imaging in clinical research has elucidated new perspectives on the role of microcirculatory flow abnormalities in the pathogenesis of sepsis. Essential to the process of understanding and reproducing these abnormalities is the method of quantification of flow scores. METHODS: In a consensus meeting with collaboraters from six research centres in different fields of experience with microcirculatory OPS imaging, premeditated qualifications for a simple, translucent and reproducible way of flow scoring were defined. Consecutively, a single-centre prospective observational validation study was performed in a group of 12 patients with an abdominal sepsis and a new stoma. Flow images of the microcirculation in vascular beds of the sublingual and stoma region were obtained, processed and analysed in a standardised way. We validated intra-observer and inter-observer reproducibility with kappa cross-tables for both types of microvascular beds. RESULTS: Agreement and kappa coefficients were >85% and >0.75, respectively, for interrater and intrarater variability in quantification of flow abnormalities during sepsis, in different subsets of microvascular architecture. CONCLUSION: Semi-quantitative analysis of microcirculatory flow, as described, provides a reproducible and transparent tool in clinical research to monitor and evaluate the microcirculation during sepsis.

APACHE↗

The microcirculation is the motor of sepsis.

Regional tissue distress caused by microcirculatory dysfunction and mitochondrial depression underlies the condition in sepsis and shock where, despite correction of systemic oxygen delivery variables, regional hypoxia and oxygen extraction deficit persist. We have termed this condition microcirculatory and mitochondrial distress syndrome (MMDS). Orthogonal polarization spectral imaging allowed the first clinical observation of the microcirculation in human internal organs, and has identified the pivotal role of microcirculatory abnormalities in defining the severity of sepsis, a condition not revealed by systemic hemodynamic or oxygen-derived variables. Recently, sublingual sidestream dark-field (SDF) imaging has been introduced, allowing observation of the microcirculation in even greater detail. Microcirculatory recruitment is needed to ensure adequate microcirculatory perfusion and the oxygenation of tissue cells that follows. In sepsis, where inflammation-induced autoregulatory dysfunction persists and oxygen need is not matched by supply, the microcirculation can be recruited by reducing pathological shunting, promoting microcirculatory perfusion, supporting pump function, and controlling hemorheology and coagulation. Resuscitation following MMDS must include focused recruitment of hypoxic-shunted microcirculatory units and/or resuscitation of the mitochondria. A combination of agents is required for successful rescue of the microcirculation. Single compounds such as activated protein C, which acts on multiple pathways, can be expected to be beneficial in rescuing the microcirculation in sepsis.

Animals↗

Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells.

Hyperglycemia is becoming recognized as an important risk factor for microvascular dysfunction. We hypothesized that short-term hyperglycemia, either on the scale of hours or weeks, alters the barrier function and the volume of the endothelial glycocalyx and decreases functional capillary density and deformability of the red blood cells (RBCs). All experiments were performed in anesthetized, mechanically ventilated, C57BL/6 mice that were either normoglycemic, acutely hyperglycemic (25 mM) for 60 min due to infusion of glucose, or hyperglycemic (25 mM) for 2-4 wk (db/db mice). The glycocalyx was probed using 40-kDa Texas red dextran, which is known to permeate the glycocalyx, and 70-kDa FITC dextran, which has impaired access to the glycocalyx in healthy animals. Clearance of the dye from the blood was measured. An orthogonal polarization spectral imaging technique was used to visualize the number of capillaries with flowing RBCs of the dorsal flexor muscle. The data indicate that short-term hyperglycemia causes a rapid decrease of the ability of the glycocalyx to exclude 70-kDa dextran. No change in the vascular permeation of 40-kDa dextran was observed. Glycocalyx volume was not affected by short-term hyperglycemia. In addition, 1 h of hyperglycemia resulted in a 38% decrease of the lineal density of capillaries with flowing RBCs. This decreased lineal density was not observed in the 2- to 4-wk hyperglycemia model. Short-term hyperglycemia was without any effect on the deformablity of the RBCs. The data indicate that the described increased vascular permeability with hyperglycemia can be ascribed to an increased permeability of the glycocalyx, identifying the glycocalyx as a potential early target of hyperglycemia.

Animals↗

Inducible nitric oxide synthase inhibition improves intestinal microcirculatory oxygenation and CO2 balance during endotoxemia in pigs.

OBJECTIVE: We examined whether selective inhibition of inducible nitric oxide synthase (iNOS) promotes intestinal microvascular oxygenation (microPO2) and CO2 off-load after endotoxic shock. DESIGN AND SETTING: Prospective, controlled experimental study in a university animal research laboratory. SUBJECTS: 13 domestic pigs. INTERVENTIONS: After baseline measurements shock was induced by 1 microg kg-1 h-1 endotoxin until mean arterial pressure fell below 60 mmHg. After 30 min in shock the animals were resuscitated with either fluid alone (control, n=6) or fluid and the iNOS inhibitor N-[3-(aminomethyl)benzyl]acetamidine hydrochloride (1400W, n=7). As final experimental intervention all animals received the nonselective NOS inhibitor L-NAME. MEASUREMENTS AND RESULTS: Systemic and regional hemodynamic and oxygenation parameters were measured at baseline, during endotoxemia and shock, hourly for 3 h of 1400W therapy, and 30 min after the final L-NAME administration. microPO2 was assessed by the Pd-porphyrin phosphorescence technique, and the arterial to intestinal PCO2 gap was determined by air tonometry. Endotoxemia and shock resulted in a decrease in ileal mucosal and serosal microPO2 and a rise in PCO2 gap. The combination of 1400W and fluid resuscitation, but not fluid alone, normalized both the serosal microPO2 and the intestinal PCO2 gap. Administration of L-NAME decreased cardiac output and oxygen delivery and intestinal microPO2 and blood flow in both groups. CONCLUSIONS: Partial blockade of NO production by 1400W increased serosal microvascular oxygenation and decreased the intestinal CO2 gap. This findings are consistent with the idea that 1400W corrects pathological flow distribution and regional dysoxia within the intestinal wall following endotoxic shock.

Animals↗

Effects of recombinant-hemoglobin solutions rHb2.0 and rHb1.1 on blood pressure, intestinal blood flow, and gut oxygenation in a rat model of hemorrhagic shock.

The vasoconstriction induced by hemoglobin-based oxygen carriers (HBOCs), mainly a result of nitric oxide (NO) scavenging, until now has limited the application of HBOCs as resuscitation fluids. In this study, we tested the hypothesis that the new modified recombinant-hemoglobin solution rHb2.0, with a 20 to 30 times lesser NO-scavenging rate, would minimize vasoconstriction without adverse effects on microvascular oxygenation. Responses were compared with those to rHb1.1, a recombinant-hemoglobin solution with a wild-type NO-scavenging rate, as well as an oncotically matched albumin solution. In a fixed-pressure (40 mm Hg) rat model of hemorrhagic shock and resuscitation, rHb2.0 and albumin both restored mean arterial pressure (MAP) to baseline values, whereas rHb1.1 increased MAP to 27% above the baseline value. Mesenteric vascular resistance after resuscitation with rHb2.0 was 57% less than that with rHb1.1. rHb2.0 was found to have 55% greater intestinal oxygen delivery (Do2int ) and resulted in a 27% lower oxygen-extraction rate than did rHb1.1 after resuscitation. Intestinal microvascular Po2 , determined on the basis of oxygen-dependent quenching of palladium-porphyrin phosphorescence, revealed no difference between rHb2.0 and rHb1.1. The findings of this study confirm that the well-known pressure effect of HBOCs is caused by their effect on the NO-scavenging rate; recombinant modification of this rate did not increase MAP during resuscitation compared with baseline values. Although systemic vasoconstriction was absent, intestinal vasoconstriction almost negligible, and Do2int greater after resuscitation with rHb2.0, the effect of rHb2.0 on pH, base-excess and microvascular Po2 levels after resuscitation were comparable to those achieved with the use of the albumin solution.

Animals↗

The effect of nitroglycerin on microvascular perfusion and oxygenation during gastric tube reconstruction.

Esophagectomy followed by gastric tube reconstruction is the surgical treatment of choice for patients with esophageal cancer. Complications of the cervical anastomosis are associated with impaired microvascular blood flow (MBF) and ischemia in the gastric fundus. The aim of the present study was to differentiate whether the decrease in MBF is a result of arterial insufficiency or of venous congestion. To do this we assessed MBF, microvascular hemoglobin oxygen saturation (muHbSo(2)), and microvascular hemoglobin concentration (muHbcon) simultaneously during different stages of gastric tube reconstruction. In 14 patients, MBF was determined with laser Doppler flowmetry, and muHbSo(2) and muHbcon were determined with reflectance spectro- photometry. After completion of the anastomosis, nitroglycerin was applied at the fundus. Although MBF did not change significantly in the pylorus, MBF decreased progressively during surgery in the fundus from 210 +/- 18 Arbitrary Units at baseline (normal stomach) to 52 +/- 9 Arbitrary Units after completion of reconstruction (mean +/- sem; P < 0.05). There was no change in muHbSo(2) and muHbcon during the reconstruction. After application of nitroglycerin, MBF doubled. We conclude that MBF decreases during gastric tube reconstruction but that muHbSo(2) and muHbcon do not. This decrease might be the result of venous congestion, which can partly be counteracted by application of nitroglycerin.

Adult↗