PubMed Health⌕ Search

Biomedical subjects

Can Ince

Publications and source records attributed to Can Ince.

35 records · Page 2Linked to original sources
PubMed2004

Bench-to-bedside review: sepsis is a disease of the microcirculation.

Microcirculatory perfusion is disturbed in sepsis. Recent research has shown that maintaining systemic blood pressure is associated with inadequate perfusion of the microcirculation in sepsis. Microcirculatory perfusion is regulated by an intricate interplay of many neuroendocrine and paracrine pathways, which makes blood flow though this microvascular network a heterogeneous process. Owing to an increased microcirculatory resistance, a maldistribution of blood flow occurs with a decreased systemic vascular resistance due to shunting phenomena. Therapy in shock is aimed at the optimization of cardiac function, arterial hemoglobin saturation and tissue perfusion. This will mean the correction of hypovolemia and the restoration of an evenly distributed microcirculatory flow and adequate oxygen transport. A practical clinical score for the definition of shock is proposed and a novel technique for bedside visualization of the capillary network is discussed, including its possible implications for the treatment of septic shock patients with vasodilators to open the microcirculation.

Critical Illness↗
PubMed2004

Direct observation of the human cerebral microcirculation during aneurysm surgery reveals increased arteriolar contractility.

BACKGROUND AND PURPOSE: The effects of aneurysmal subarachnoid hemorrhage on morphology and function of the cerebral microcirculation are poorly defined, partly due to the lack of suitable techniques to visualize the microvessels in vivo. We used orthogonal polarization spectral (OPS) imaging on the brain cortex during aneurysm surgery to directly observe the small cortical blood vessels and quantify their responses to hypocapnia. METHODS: In 16 patients undergoing aneurysm surgery, the diameter changes of small cortical vessels (15 to 180 microm) were observed using OPS imaging. Ten patients were operated on early (within 48 hours after bleeding) and 6 underwent late surgery. Immediately after dura opening, the response to hyperventilation of arterioles and venules was observed with OPS imaging under sevoflurane anesthesia. RESULTS: In patients operated on early, layers of subarachnoid blood were clearly visible. In this group, hyperventilation resulted in a 39+/-15% decrease in arteriolar diameter with a "bead-string" constriction pattern occurring in 60% of patients. In late surgery and in controls, no subarachnoid blood was seen. The arteriolar diameter decrease with hyperventilation was 17+/-20% in patients undergoing late surgery and 7+/-7% in controls. Venules were not affected by hyperventilation in any of the groups studied. CONCLUSIONS: OPS imaging allows direct in vivo observation of the cerebral microcirculation enabling us, for the first time, to visually observe and quantify microvascular reactivity in the human brain. The present study demonstrates increased contractile responses of the cerebral arterioles in the presence of subarachnoid blood, suggesting increased microvascular tonus with possibly greater susceptibility to ischemia.

Adult↗
PubMed2003

Functional thrombomodulin deficiency causes enhanced thrombus growth in a murine model of carotid artery thrombosis.

Thrombomodulin (TM) bound thrombin initiates the protein C anticoagulant pathway and defects in TM result in enhanced coagulation. Recent studies suggest a role for TM in arterial vascular disease. In order to corroborate this association we studied arterial thrombus formation in mice with a functional TM defect. We used mice homozygous for a (404)Glu-to-Pro mutation in the TM gene (TM(pro/pro)) and compared these with wildtype littermates in a model of FeCl(3) induced carotid artery thrombosis. Time-to-occlusion (TTO) was assessed by arterial blood flow measurement, using a Doppler flow probe. Complete occlusion occurred in 8/10 (80%) TM(pro/pro) mice and in 3/11 (27%) littermate controls. Mean time to occlusion (TTO) [+/- SE] was 767 +/- 196 s in the F2-TM(pro/pro) mice, versus 1507 +/- 159 s in controls (p = 0.007, Mann Whitney U test). Histology and immunostaining for tissue factor did not reveal any differences in thrombus morphology or thrombogenicity between the two groups. These data confirm and extend the finding that a functional deficiency in TM results in enhanced thrombus formation in a murine model of carotid artery thrombosis and support a role for TM defects in arterial thrombotic disease.

Animals↗
PubMed2003

Laser-assisted optical rotational cell analyzer measurements reveal early changes in human RBC deformability induced by photodynamic treatment.

BACKGROUND: The ability to deform is important for circulating RBCs in vivo, and earlier studies showed that this property can objectively be measured in vitro by the LORCA. In this study it was investigated whether photodynamic treatment of human RBCs (meant to inactivate contaminating pathogens) affects deformability. STUDY DESIGN AND METHODS: WBC-reduced RBC suspensions (30% Hct) were treated with 1,9-dimethylmethylene blue (DMMB) and red light. Changes in deformability were analyzed by LORCA measurements, in which elongation of the cells is measured at increasing shear stress. The effect of DMMB concentration and light dose was determined as well as the interfering effect of two scavengers of reactive oxygen species, that is, dipyridamole and Trolox. RESULTS: Photodynamic treatment with DMMB resulted in clear changes in RBC deformability. Deformability changes occurred before onset of hemolysis. Under relatively mild treatment conditions, especially deformability at low shear stress was decreased, whereas deformability changes at high shear stress only occurred under harsher treatment conditions. Inclusion of dipyridamole and/or Trolox primarily prevented deformability changes at high shear stress. CONCLUSION: LORCA measurements can effectively be used to detect changes in deformability that are induced by photodynamic treatment of human RBCs. A change in deformability represents an early marker of RBC damage under these conditions.

Antioxidants↗
PubMed2003

Commonly used numbers of microspheres affect cardiac vascular resistance.

The main goal of the study was to examine how the microsphere technique affects the hemodynamics and mitochondrial energy status of the Langendorff-perfused rat heart. The hearts were perfused at a constant flow with Tyrode solution. NADH videofluorometry of the surface of the left ventricle was used to record the mitochondrial energy status as indication of regional ischemia. The effects of seven successive (separated by 10 min) injections of 0.1 ml of saline or (0.05% Tween 20; polysorbate 20, Sigma-Aldrich, St. Louis, MO, U.S.A.) or (0.05% Tween 20 + microspheres) were studied. The number of microspheres per injection were: #1 (2,500), #2 (5,000), #3 (10,000), #4 (20,000), #5 (40,000), #6 (40000), and #7 (80000). The anti-aggregation agent Tween always caused a biphasic response in perfusion pressure. Compared with the Tween effect, the injection of microspheres caused an initial change (mm Hg) in perfusion pressure of #1 (-10), #2 (NS), #3 (NS), #4 (+7.5), #5 (+12.3), #6 (+14.4), #7 (+18.3), and a delayed change (10 min after injection) of #1 (-22.2), #2 (-6.0), #3 (-4.1), #4 (-4.5), #5 (NS), #6 (NS), and #7 (+5.9). The microspheres caused a significant delayed increase in NADH only for injection #6 and #7. Similar results were found for different durations of the input function or when hearts were perfused at constant perfusion pressure. In hearts without flow reserve (10 microM adenosine), Tween injections were without effect, whereas three successive injections of 60,000 microspheres each only caused increases in perfusion pressure and NADH. The data demonstrate that in hearts with flow reserve present, even very low numbers of microspheres (2,000/g heart) cause large decreases in perfusion pressure without obvious signs of ischemia. When flow reserve was exhausted by either microsphere loading or adenosine addition, microspheres only caused increases in perfusion pressure and resulted in detectable ischemia (NADH). It is concluded that microspheres affect the vascular resistance of the heart and that these effects are flow reserve dependent.

Animals↗
PubMed2003

Hemoglobin-based oxygen carrier provides heterogeneous microvascular oxygenation in heart and gut after hemorrhage in pigs.

BACKGROUND: In this study, the hypothesis was tested that resuscitation with hemoglobin-based oxygen carriers (HBOCs) affects the oxygenation of the microcirculation differently between and within organs. To this end, we tested the influence of the volume of an HBOC on the microcirculatory oxygenation of the heart and the gut serosa and mucosa in a porcine model of hemorrhage. METHODS: In anesthetized open-chested pigs (n = 24), a controlled hemorrhage (30 mL/kg over 1 hour) was followed by resuscitation with 10, 20, or 30 mL/kg diaspirin-crosslinked hemoglobin (DCLHb) or isovolemic resuscitation with 30 mL/kg of a 6% hydroxyethyl starch solution (HAES). Measurements included systemic and regional hemodynamic and oxygenation parameters. Microvascular oxygen pressures (microPO2) of the epicardium and the serosa and mucosa of the ileum were measured simultaneously by the palladium-porphyrin phosphorescence technique. Measurements were obtained up to 120 minutes after resuscitation. RESULTS: After hemorrhage, a low volume of DCLHb restored both cardiac and intestinal microPO2. Resuscitation of gut microPO2 with a low volume of DCLHb was as effective as isovolemic resuscitation with HAES. Higher volumes of DCLHb did not restore cardiac microPO2, as did isovolemic resuscitation with HAES, but increased gut microPO2 to hyperoxic values, dose-dependently. Effects were similar for the serosal and mucosal microPo2. In contrast to a sustained hypertensive effect after resuscitation with DCLHb, effects of DCLHb on regional oxygenation and hemodynamics were transient. CONCLUSION: This study showed that a low volume of DCLHb was effective in resuscitation of the microcirculatory oxygenation of the heart and gut back to control levels. Increasing the volume of DCLHb did not cause an additional increase in heart microPO2, but caused hyperoxic microvascular values in the gut to be attained. It is concluded that microcirculatory monitoring in this way elucidates the regional behavior of oxygen transport to the tissue by HBOCs, whereas systemic variables were ineffective in describing their response.

Analysis of Variance↗
PubMed2002

Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia.

OBJECTIVE: To determine the mechanisms of improved gut mucosal acidosis associated with selective inducible nitric oxide synthase (iNOS) inhibition. DESIGN: Prospective, controlled experimental study. SETTING: Animal research laboratory. ANIMALS: Fourteen domestic pigs. INTERVENTIONS: Anesthetized and mechanically ventilated pigs received continuous i.v. endotoxin for 24 h. A selective iNOS-inhibitor (1400 W, n=8) or vehicle (control, n=6) was started at 12 h of endotoxin and infused until the end of the experiment. MEASUREMENTS AND RESULTS: Before as well as at 12 and 24 h of endotoxin, portal venous flow (ultrasound probe), intestinal oxygen (O(2)) extraction, portal venous-arterial carbon dioxide (CO(2)) content difference and ileal mucosal-arterial PCO(2) gap (fiberoptic sensor) were assessed together with video recordings of the villous microcirculation (number of perfused/unperfused villi) using orthogonal polarization spectral imaging via an ileostomy. The gut wall microvascular blood flow (units) and hemoglobin O(2) saturation ( micro Hb-O(2)) were assessed with a combined laser Doppler flow and remission spectrophotometry probe. 1400 W blunted the otherwise progressive rise in the PCO(2) gap without affecting portal venous flow, regional O(2) and CO(2) exchange or the number of unperfused villi. While endotoxin markedly aggravated the heterogeneity of the microvascular blood flow and oxygenation, 1400 W had no further effect. CONCLUSIONS: Given the uninfluenced parameters of the ileal mucosal microcirculation in our model of long-term porcine endotoxemia, selective iNOS inhibition probably improved the PCO(2) gap due to a redistribution of the microvascular perfusion within the gut wall and/or an amelioration of the cellular respiration.

Acidosis↗
PubMed2002

Nitroglycerin in septic shock after intravascular volume resuscitation.

In patients with septic shock, oxygen consumption is increased, but oxygen delivery and extraction is impaired, partly because of microcirculatory shutdown and shunting. Orthogonal polarisation spectral (OPS) imaging allows visualisation of the microcirculation. We used this technique to assess microcirculatory flow in septic-shock patients who had a mean arterial blood pressure of more than 60 mm Hg and central venous pressure greater than 12 mm Hg. The infusion of 0.5 mg of nitroglycerin intravenously then resulted in a marked increase in microvascular flow on OPS imaging. Improved recruitment of the microcirculation could be a new resuscitation endpoint in septic shock.

APACHE↗
PubMed2002

Opening the microcirculation: can vasodilators be useful in sepsis?

OBJECTIVE: A prominent feature of sepsis is dysfunction of the microcirculation, with impaired perfusion and regional tissue oxygenation causing a deficit in oxygen extraction. If shunting of oxygen transport past closed hypoxic microcirculatory beds is responsible for this, vasodilator therapy, which raises the driving pressure of the microcirculation and thereby promotes flow, could recruit such shunted microcirculatory units and improve tissue oxygenation. DESIGN: A literature search was conducted in Medline for evidence of this expected benefit of vasodilators in sepsis. METHODS: Studies were searched using the keyword for vasodilating drugs in combination with "sepsis," "septic," "multiple organ failure," or "critically ill patients." The search included animal and clinical investigations but only where the effects of vasodilator therapy were demonstrated by regional measures of oxygen transport variables (e.g., oxygen extraction variables, regional ischemia, microcirculatory flow or tissue oxygenation measurements). The vasodilating drugs investigated included prostacyclin, pentoxifylline, N-acetyl-cysteine, and nitric oxide donors used in animal and human sepsis. RESULTS: Prostacyclin and nitric oxide donors are the best studied vasodilating agents in experimental sepsis and have shown improved tissue perfusion and oxygen extraction. In several clinical studies prostacyclin has also been shown to have such beneficial effects. Recent studies using orthogonal polarization spectral imaging have shown microcirculatory recruitment by nitric oxide donors in hemodynamically resuscitated septic patients. Whether such therapeutic modalities aimed at recruitment of the microcirculation improve outcome, however, still has to be determined.

Acetylcysteine↗
PubMed2002

Intestinal and cerebral oxygenation during severe isovolemic hemodilution and subsequent hyperoxic ventilation in a pig model.

BACKGROUND: During severe isovolemic hemodilution, determination of critical hematocrit levels for the microvascular oxygenation of different organs might provide more insight into the effect of the redistribution of blood flow and oxygen delivery on the oxygenation of different organs. The effect of an increased amount of dissolved oxygen on tissue oxygenation during severely decreased hematocrit levels is not clear. METHODS: Fifteen anesthetized pigs were randomized between an experimental group (n = 10), in which severe isovolemic hemodilution was performed with 6% hydroxyethylstarch (1:1), and a time-matched control group (n = 5). Systemic, intestinal, and cerebral hemodynamic and oxygenation parameters were monitored. Microvascular oxygen partial pressure (muPo(2) ) was measured in the cerebral cortex and the intestinal serosa and mucosa, using the oxygen-dependent quenching of Pd-porphyrin phosphorescence. In the final phase of the experiment, fraction of inspired oxygen was increased to 1.0. RESULTS: Hemodilution decreased hematocrit from 25.3 +/- 3.0 to 7.6 +/- 1.2% (mean +/- SD). Systemic and intestinal oxygen delivery fell with the onset of hemodilution; intestinal oxygen consumption deceased at a hematocrit of 9.9%, whereas the systemic oxygen consumption decreased at a hematocrit of 7.6%. During hemodilution, the intestinal and cerebral oxygen extraction ratios increased from baseline with 130 and 52%, respectively. Based on the intersection of the two best-fit regression lines, determined by a least sum of squares technique, similar critical hematocrit levels were found for systemic oxygen consumption and the cerebral and intestinal mucosa muPo(2); the intestinal serosa muPo(2) decreased at an earlier stage (P < 0.05). Hyperoxic ventilation improved the muPo(2) values but not systemic or intestinal oxygen consumption. CONCLUSIONS: During isovolemic hemodilution, the diminished oxygen supply was redistributed in favor of organs with a lower capacity to increase oxygen extraction. It is hypothesized that redirection of the oxygen supply within the intestines resulted in the preservation of oxygen consumption and mucosal muPo(2) compared with serosal muPo(2).

Algorithms↗
PubMed2002

Adenosine triphosphate-magnesium dichloride during hyperdynamic porcine endotoxemia: effects on hepatosplanchnic oxygen exchange and metabolism.

OBJECTIVE: To assess the effects of adenosine triphosphate-magnesium dichloride (ATP-MgCl2) on systemic and hepatosplanchnic hemodynamics, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic normotensive porcine endotoxemia. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Seventeen pigs were divided into two groups: eight animals receiving endotoxin served as a control group and nine animals received endotoxin (lipopolysaccharide) and ATP-MgCl2. INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented. Endotoxemia was achieved by continuous intravenous infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch targeted to maintain mean arterial pressure of >75 mm Hg. Twelve hours after the start of the endotoxin infusion, ATP-MgCl2, or its vehicle, were administered for 12 hrs. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure was maintained in the control group because of a sustained increase in cardiac output achieved by fluid resuscitation, whereas ATP-MgCl2 significantly decreased mean arterial pressure because of further systemic vasodilatation. ATP-MgCl2 markedly increased portal venous flow. In contrast to the controls, hepatic arterial flow remained unchanged until the end of the experiment, despite the further increase in cardiac output. The ileal mucosal-arterial PCO2 gap (Delta PCO2) progressively increased (p <.05) in control animals, whereas it was restored to prelipopolysaccharide levels during ATP-MgCl2 infusion. Changes in Delta PCO2 correlated with those of portal vein blood flow in these animals (r = -.68, p <.05). Moreover, ATP-MgCl2 blunted the lipopolysaccharide-induced decrease in hepatic lactate balance but did not affect portal venous pH, hepatosplanchnic oxygen exchange, splanchnic lactate/pyruvate ratios, isoprostane, NO2- + NO3-, cytokine concentrations, or tissue nucleotide content. CONCLUSION: During long-term hyperdynamic porcine endotoxemia, ATP-MgCl2 normalized the otherwise progressive rise of the ileal mucosal-arterial Delta PCO2. Furthermore, it allowed blunting of the continuous decrease in hepatic lactate clearance, thus preserving the metabolic coupling between lactate release from the intestine and lactate utilization by the liver.

Adenosine Triphosphate↗
PubMed2002

Hemodynamics of anesthetized ventilated mouse models: aspects of anesthetics, fluid support, and strain.

This study evaluates the effects of anesthesia and fluid support on hemodynamic parameters of the mechanically ventilated mouse of four different strains. All experiments were performed at a similar surgical level of anesthesia, as indicated by the probing of the pedal withdrawal reflex. Three anesthetic regimens [fentanyl-fluanisone-midazolam (FFM), ketamine-medetomidine-atropine (KMA), and isoflurane (ISO)], four commonly used mouse strains (Swiss, CD-1, BalbC, and C57Bl6), and three different fluid support strategies (no fluid, 0.2 ml x h(-1) x 10 g(-1) of 6% polystarch solution, and 0.5 ml x h(-1) x 10 g(-1) saline) were studied. Mean arterial pressure (MAP) or heart rate (HR) was similar among the four strains of mice except a trend toward lower HR for the BalbC mice. In terms of MAP, KMA is the preferred anesthetic for the Swiss and CD-1 mice, whereas KMA or ISO are recommended for BalbC or C57Bl6 mice. In terms of HR, ISO is the preferred anesthetic for the Swiss, CD-1, and C57Bl6 strains. No differences in HR for the three anesthetics were observed for the BalbC strain. Compared with administration of no fluid, both saline and polystarch administration similarly increased MAP by 7 +/- 2, 10 +/- 2, and 11 +/- 2 mmHg at t = 1, 2, and 3 h, respectively, whereas fluid administration was without effect on HR. Saline supplementation resulted in an increased dry-to-wet ratio of the heart and both fluid regimens decreased total hemoglobin in the blood from 12.6 +/- 0.5 to 10.4 +/- 0.5 g/100 ml. Saline administration was associated with blood acidosis (pH 7.20 +/- 0.03) compared with the Haes (pH 7.29 +/- 0.02) or no-fluid group (pH 7.34 +/- 0.03), whereas PCO(2) was approximately 30 mmHg for all groups. We conclude that at similar surgical levels of anesthesia, the preferable type of anesthesia (ISO or KMA, but never FFM) depends on the strain used and whether MAP or HR is the focus of study. Additional fluid support is beneficial in terms of raising arterial blood pressure, although this is at the cost of changes in organ water content and increased anemia.

Anesthesia↗
PubMed2002

Excitation pulse deconvolution in luminescence lifetime analysis for oxygen measurements in vivo.

Oxygen-dependent quenching of phosphorescence has been proven to be a valuable tool for the measurement of oxygen concentrations both in vitro and in vivo. For biological measurements the relatively long lifetimes of phosphorescence have promoted time-domain-based devices using xenon arc flashlamps as the most common excitation light source. The resulting complex form of the excitation pulse leads to complications in the analysis of phosphorescence lifetimes and ultimately to errors in the recovered pO2 values. Although the problem has been recognized, the consequences on in vivo phosphorescence lifetime measurements have been neglected so far. In this study, the consequences of finite excitation flash duration are analyzed using computer simulations, and a method for the recovery of phosphorescence decay times from complex photometric signals is presented. The analysis provides an explanation as to why different calibration constants are reported in the literature and presents a unified explanation whereby calibration constants are not solely a property of the dye but also of the measuring device. It is concluded that complex excitation pulse patterns without appropriate analysis methods lead to device-specific calibration constants and nonlinearity and can be a potent source of errors when applied in vivo. The method of analysis presented in this article allows reliable phosphorescence lifetime measurements to be made for oxygen pressure measurements and can easily be applied to existing phosphorimeters.

Algorithms↗
PubMed2002

Fentanyl-fluanisone-midazolam combination results in more stable hemodynamics than does urethane alpha-chloralose and 2,2,2-tribromoethanol in mice.

Near-physiologic hemodynamic conditions for several hours were needed to study cardiovascular physiology in a murine model. We compared two commonly used anesthetic treatments, urethane alpha-chloralose (U-alphaCh; 968 mg U and 65 mg alphaCh/kg) and 2,2,2-tribromoethanol (TBE; 435 mg/kg) and fentanyl fluanisone midazolam (FFM; 3.313 mg fentanyl, 104.8 mg fluanisone, and 52.42 mg midazolam/kg) with respect to mean arterial blood pressure (MAP) and heart rate (HR) for 100 min at similar levels of surgical anesthesia. Assessed every 10 to 15 min, the U-alphaCh+TBE group maintained a significantly (P < 0.001) lower mean MAP (49 4 mmHg) than did the FFM group (78 5 mmHg). Mean HR in the U-alphaCh+TBE group significantly (P < 0.001) increased from 308 34 bpm at the beginning to 477 43 bpm at the end of the experiment. In comparison, the FFM group showed a stable HR of 431 37 bpm. The MAP and HR of the U-alphaCh+TBE group were extremely unstable, with sudden and unpredictable changes in MAP when examined at 1-min intervals. The results of our study show that U-alphaCh+TBE anesthesia should not be used in murine models in which stable, near-physiologic hemodynamics are needed for cardiovascular studies.

Anesthesia↗