Biomedical subjects

Peter Conzen

Publications and source records attributed to Peter Conzen.

8 recordsLinked to original sources

PubMed2006

The endothelial glycocalyx affords compatibility of Starling's principle and high cardiac interstitial albumin levels.

OBJECTIVE: To test the role of an oncotic pressure gradient across the endothelial glycocalyx with respect to extravasation of fluid and colloids and development of tissue edema in a whole organ setting. METHODS: We measured filtration in the intact coronary system of isolated guinea pig hearts, comparing colloid-free perfusion and perfusion with 1.67% albumin or 2% hydroxyethylstarch (oncotic pressures 5.30 vs. 11.10 mm Hg, respectively). Heparinase was used to alter the endothelial glycocalyx. RESULTS: Extremely high net organ hydraulic conductivity was obtained with colloid-free perfusion (9.14 microl/min/g tissue). Supplementing perfusate with albumin caused a significant decrease, also vs. hydroxyethylstarch (1.04 vs. 2.67 microl/min/g, p < 0.05). Albumin also lowered edema formation vs. the other perfusion modes (p < 0.05). Stripping the glycocalyx of heparan sulfate reduced the effect of colloids, especially that of albumin. The steady-state concentrations of hydroxyethylstarch and albumin in the mixed interstitial fluid leaving the intact coronary bed averaged about 95% of the intravascular level. Electron and light microscopy indicated that colloid extravasated mainly in the venular sections. CONCLUSION: We propose a low-filtration model for the coronary system with different barrier properties in arteriolar/capillary and venular sections. Arteriolar/capillary: very little fluid and colloid extravasation due to the endothelial surface layer formed by the glycocalyx and albumin plus the endothelial strand barrier; venular: little net extravsation of fluid and colloids despite large pores, because of low hydrostatic and oncotic pressure differences between intra- and extravascular spaces. The latter sites provide physiological access of large solutes (colloids) to the tissue.

Albumins↗

PubMed2006

Technical and physiological background of plasma volume measurement with indocyanine green: a clarification of misunderstandings.

The indocyanine green (ICG) dilution technique (DT) is frequently used for plasma volume (PV) measurement. However, because of inadequate knowledge about the properties of this dye, lack of accuracy has been attributed to the method. The aim of this report is to provide physiological background information about the ICG-DT to avoid some profound misunderstandings. When performing tracer dilution, one has to consider the tracer's distribution space before interpreting the result. For ICG, the distribution space is the total PV, i.e., circulating + noncirculating PV, fixed within the endothelial glycocalyx. The distribution space of red blood cells and large molecules, in contrast, is only the circulating part of PV. Therefore, it is erroneous to compare directly PV derived from different tracer dilution methods. The transcapillary escape rate of ICG should not relevantly influence measured PV if the method is performed properly, i.e., if a short time window of measurement is subjected to monoexponential extrapolation. A major problem of PV measurement in general is that the target itself is very inconstant. Thus, checking for constancy of ICG-DT with two consecutive measurements is unreliable. Nevertheless, the ICG-DT is a useful tool for determining PV, provided it is well understood by the investigator to enable correct interpretation of the results.

Blood Volume Determination↗

PubMed2006

Contrasting effects of colloid and crystalloid resuscitation fluids on cardiac vascular permeability.

BACKGROUND: Fluid extravasation may lead to myocardial edema and consequent reduction in ventricular function. Albumin is presumed to interact with the endothelial glycocalyx. The authors' objective was to compare the impact of different resuscitation fluids (human albumin, hydroxyethyl starch, saline) on vascular integrity. METHODS: In an isolated perfused heart model (guinea pig), Krebs-Henseleit buffer was augmented with colloids (one third volume 5% albumin or 6% hydroxyethyl starch 130/0.4) or crystalloid (0.9% saline). Perfusion pressure and vascular fluid filtration (epicardial transudate formation) were assessed at different flow rates. After global, stopped-flow ischemia (37 degrees C, 20 min), hearts were reperfused with the same resuscitation fluid additives. In a second series, the authors applied the respective perfusates after enzymatic digestion of the endothelial glycocalyx (heparinase, 10 U over 15 min). RESULTS: Both 5% albumin and 6% hydroxyethyl starch decreased fluid extravasation versus saline (68.4 +/- 5.9, 134.8 +/- 20.5, and 436.8 +/- 14.7 microl/min, respectively, at 60 cm H(2)O perfusion pressure; P < 0.05), the corresponding colloid osmotic pressures being 2.95, 5.45, and 0.00 mmHg. Digestion of the endothelial glycocalyx decreased coronary integrity in both colloid groups. After ischemia, a transient increase in vascular leak occurred with Krebs-Henseleit buffer containing hydroxyethyl starch and saline, but not with albumin. The authors observed no difference between intravascular and bulk interstitial colloid concentration in the steady state. Notwithstanding, electron microscopy revealed an intact endothelial glycocalyx and no interstitial edema in the albumin group. CONCLUSION: Ex vivo, albumin more effectively prevented fluid extravasation in the heart than crystalloid or artificial colloid. This effect was partly independent of colloid osmotic pressure and may be attributable to an interaction of albumin with the endothelial glycocalyx.

Albumins↗

PubMed2005

Changes in acid-base balance following bolus infusion of 20% albumin solution in humans.

OBJECTIVE: To evaluate changes in acid-base balance following bolus infusions of a 20% albumin solution. DESIGN AND SETTING: Randomized prospective study in a university hospital. PATIENTS AND PARTICIPANTS: Two groups of eight patients each undergoing gynecological surgery. INTERVENTIONS: Patients were randomly assigned to receive either 0.9% saline or lactated Ringer's solution. At the end of surgery two boluses of 0.5 g/kg body weight of a 20% albumin solution were administered. Arterial blood gases, electrolytes, and total protein were measured. The strong ion difference and the amount of weak plasma acid were calculated. pH and titratable acidity of the 20% albumin solution were determined. MEASUREMENTS AND RESULTS: The infusion of a 20% albumin solution resulted in a significant decrease in pH from 7.284 to 7.262 in the saline group and from 7.422 to 7.394 in the Ringer's group. In both groups the 20% albumin solution caused an increase in strong ion difference and an increase in the amount of weak plasma acid. The observed changes in serum bicarbonate concentration were in good agreement with the changes in strong ion difference and the amount of weak plasma acid. The 20% albumin solution possessed a pH of 6.95 and a titratable acidity of 8.5 [corrected] mEq/l. CONCLUSIONS: According to the Stewart approach, the observed changes in acid-base balance are the net result of the two opposing effects of the strong ion difference and the amount of weak plasma acid. Alternatively, the acidifying effect of the 20% albumin solution may stem from the titratable acid content of the solution.

Acid-Base Equilibrium↗

PubMed2005

Atrial natriuretic peptide induces shedding of endothelial glycocalyx in coronary vascular bed of guinea pig hearts.

Atrial natriuretic peptide (ANP) is reported to enhance vascular permeability in vivo. Our aim was to evaluate the impact of ANP on coronary extravasation of fluids and macromolecules and on the integrity of the endothelial glycocalyx. Isolated guinea pig hearts (n = 6/group) were perfused with Krebs-Henseleit buffer in a Langendorff mode. A 6% hydroxyethyl starch (HES) solution was infused into the coronary system for 20 min without (Control group) and simultaneously with (ANP group) ANP at 10(-9) M. In two further series, the glycocalyx was enzymatically degraded by means of heparinase (Hep) application (10 IU over 15 min), followed again by the infusion of HES in the absence (Hep group) and presence (ANP+Hep group) of ANP. Net fluid filtration, extravasation of HES, electron microscopic visualization of the glycocalyx, and quantification of shedding of syndecan-1, a component of the glycocalyx, were determined. An increase in fluid leak was observed in ANP, ANP+Hep, and Hep hearts [+29%, +31%, +14%, respectively; a decrease was observed in Control hearts (-13%)]. Similarly, an accelerated extravasation of colloid was observed in these three groups. Coronary release of syndecan-1 increased 9- to 18-fold during infusion of ANP. Electron microscopy revealed a dramatic degradation of the glycocalyx after ANP. These results indicate that the endothelial glycocalyx serves as a barrier to transmural exchange of fluid and colloid in the coronary vascular system. ANP causes rapid shedding of individual components of the glycocalyx and histologically detectable degradation. Thus the permeability-increasing effect of ANP may be at least partially related to changes in the integrity of the endothelial glycocalyx.

Animals↗

PubMed2005

Development and validation of a mathematical algorithm for quantifying preoperative blood volume by means of the decrease in hematocrit resulting from acute normovolemic hemodilution.

BACKGROUND: The interindividual variability of blood volume (BV) is high. The aim of this work was to use the decrease in large-vessel hematocrit (HK(LV)) during acute normovolemic hemodilution (ANH) as an instrument for estimating preoperative BV. STUDY DESIGN AND METHODS: In 39 patients, (Group 1) preoperative ANH was performed. Plasma volume, red cell volume, and HK(LV) were measured before and 30 minutes after ANH, respectively. In a retrospective analysis, a mathematical algorithm was developed for estimating BV before ANH by means of the measured changes in HK(LV) and the amount of blood removed during ANH. To validate the method prospectively, ANH was performed in an additional 10 patients (Group 2). Preoperative BV was estimated and measured in the same way as in Group 1. RESULTS: In Group 1, the mean difference between estimated and measured BV before ANH was 200 +/- 403 mL (5.14 +/- 10.12%; p > 0.05; r = 0.8). In Group 2, the estimated BV before ANH was 41 +/- 348 mL (-0.53 +/- 7.84%) lower than the measured BV (p > 0.05; r = 0.94). In this group, however, two patients with an extraordinarily small (2691 mL) and large (6172 mL) preoperative BV, respectively, were identified correctly by means of the algorithm. CONCLUSIONS: The changes in HK(LV) determined during ANH provide a good "bedside" estimation of preoperative BV.

Algorithms↗

PubMed2004

Selective inhibition of cyclooxygenase-2 enhances platelet adhesion in hamster arterioles in vivo.

BACKGROUND: Selective inhibitors of cyclooxygenase-2 (Cox-2) are reported to cause cardiovascular side effects in patients at risk. However, direct proof of prothrombotic effects of these drugs is lacking. We investigated in the microcirculation in vivo whether selective inhibition of Cox-2 induces platelet activation. METHODS AND RESULTS: The behavior of fluorescence-labeled human platelets was studied in hamster arterioles (dorsal skinfold chamber) by intravital microscopy. Transient platelet-vessel wall interactions (PVWIs), firm platelet adhesion to the vessel wall, and vessel occlusion after FeCl3-induced wall injury were analyzed as platelet activation parameters. In vitro experiments in human umbilical vein endothelial cells (HUVECs) were performed to assess specific effects of Cox-2 inhibition on platelet adhesion under shear stress (16 dyn/cm2) and on endothelial release of 6-ketoprostaglandin (PG) F(1alpha). Selective inhibition of Cox-2 (NS-398, 0.5 mg/kg) increased platelet adhesion to the vessel wall in vivo (11.9+/-3.9 platelets/mm2; controls, 1.4+/-1.4 platelets/mm2, P<0.05) and platelet adhesion after ADP stimulation in vitro. PVWIs were significantly enhanced in NS-398-treated animals, which were reduced by platelet pretreatment with aspirin (5 mg/kg) or iloprost (1 nmol/L). Inhibition of Cox-2 reduced levels of 6-keto-PGF1alpha in vivo and in HUVEC supernatants. Time to occlusion after vessel wall injury was significantly shortened by NS-398 (125.4+/-13.6 seconds in NS-398-treated animals versus 270.8+/-46 seconds in controls; P<0.01). CONCLUSIONS: Selective inhibition of Cox-2 reduces 6-keto-PGF(1alpha) endothelial release, increases PVWIs, and increases firm platelet adhesion in hamster arterioles. Moreover, it leads to faster occlusion of damaged microvessels. Thus, selective inhibition of Cox-2 may trigger thrombotic events by diminishing the antiplatelet properties of the endothelium.

6-Ketoprostaglandin F1 alpha↗

PubMed2004

Endothelial glycocalyx as an additional barrier determining extravasation of 6% hydroxyethyl starch or 5% albumin solutions in the coronary vascular bed.

BACKGROUND: The impact on the endothelial glycocalyx for the extravasation of colloidal infusion solutions has not been investigated sufficiently. METHODS: Isolated guinea pig hearts were perfused with Krebs-Henseleit buffer in a Langendorff mode. Solutions of 0.9% saline, 5% albumin (70 kd), or 6% hydroxyethyl starch (200 kd) were infused into the coronary system for 20 min at a rate of one third of the coronary flow, also during reperfusion after 15 min of ischemia, and after enzymatic digestion of the endothelial glycocalyx by heparinase. Net coronary fluid filtration was assessed directly by measuring the formation of transudate on the epicardial surface, and solute extravasation was assessed by measuring albumin and hydroxyethyl starch in the coronary effluent and transudate. Hearts were perfusion fixed to visualize the endothelial glycocalyx using transmission electron microscopy. RESULTS: Only infusion of hydroxyethyl starch, not infusion of albumin, significantly decreased net coronary fluid filtration. Heparinase application without ischemia increased coronary leak by 25% but did not accelerate the passage of colloids. Ischemia alone did not alter permeability. However, there was a large (approximately +200%), transient (approximately 4 min) increase in permeability for water, albumin, and hydroxyethyl starch after ischemia with heparinase application. Also, histamine (10 m) only increased permeability after pretreatment of the hearts with heparinase. The thickness of the glycocalyx after colloid administration was 0.2-0.3 microm. No glycocalyx could be detected after application of heparinase. CONCLUSION: The endothelial glycocalyx acts as a competent barrier for water and colloids. Only after its destruction do changes in endothelial morphology (postischemic reperfusion or histamine application) become effective determinants of coronary extravasation.

Animals↗