Natriuretic Peptides as a Prognostic Marker for Delirium in Cardiac Surgery-A Pilot Study.

Background and Objectives: Delirium is a common and major complication subsequent to cardiac surgery. Despite scientific efforts, there are no parameters which reliably predict postoperative delirium. In delirium pathology, natriuretic peptides (NPs) interfere with the blood-brain barrier and thus promote delirium. Therefore, we aimed to assess whether NPs may predict postoperative delirium and long-term outcomes. Materials and Methods: To evaluate the predictive value of NPs for delirium we retrospectively analyzed data from a prospective, randomized study for serum levels of atrial natriuretic peptide (ANP) and the precursor of C-type natriuretic peptide (NT-proCNP) in patients undergoing coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass (off-pump coronary bypass grafting; OPCAB). Delirium was assessed by a validated chart-based method. Long-term outcomes were assessed 10 years after surgery by a telephone interview. Results: The overall incidence of delirium in the total cohort was 48% regardless of the surgical approach (CABG vs. OPCAB). Serum ANP levels >64.6 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 100% (75.3-100) and specificity of 42.9% (17.7-71.1). Serum NT-proCNP levels >1.7 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 92.3% (64.0-99.8) and specificity of 42.9% (17.7-71.1). Both NPs could not predict postoperative survival or long-term cognitive decline. Conclusions: We found a positive correlation between delirium and preoperative plasma levels of ANP and NT-proCNP. A well-powered and prospective study might identify NPs as biomarkers indicating the risk of delirium and postoperative cognitive decline in patients at risk for postoperative delirium.

Vascular Endothelial Dysfunction during Cardiac Surgery: On-Pump versus Off-Pump Coronary Surgery.

BACKGROUND: Cardiac surgery often causes ischemia and development of a systemic inflammatory response syndrome, which impairs vascular barrier function, normally maintained by the endothelial cell line and the endothelial glycocalyx (EG). The EG normally covers and protects healthy endothelial cells throughout the vasculature. The aim of the present study was to assess the disruption of the cellular part of the microvascular barrier by determining parameters of endothelial cell activation known to influence and reflect cell-cell junctional integrity. Particular attention was placed on angiopoietins and their important effects on endothelial gap junctions. Furthermore, comparative measurements were undertaken in patients undergoing on- and off-pump cardiac surgery, the latter group presumably experiencing less ischemic stress. METHODS: 30 patients undergoing elective coronary artery bypass surgery were assigned to the conventional coronary artery bypass (CCAB) group (n = 15) or the off-pump coronary artery bypass grafting (OPCAB) group (n = 15). Blood samples were obtained for measuring angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial (VE)-cadherin, and endocan at various time points. RESULTS: There were significant increases in all measured parameters in both study groups versus the respective basal values. Maximal increases were as follows: Ang-1: CCAB +220%, OPCAB +166%, p < 0.05 each; Ang-2: CCAB +150%, OPCAB +20%, p < 0.05 each; VE-cadherin: CCAB +87%, OPCAB +66%, p < 0.05 each; endocan: CCAB +323%, OPCAB +72%, p < 0.05 each. CONCLUSION: The present study demonstrates the activation of endothelial cells, shedding of cell-cell contacts and a potential intrinsic counterregulation by Ang-1 and endocan in patients undergoing major cardiac surgery. Quantitatively greater deviations of parameters in the CCAB than in the OPCAB group suggest a relation between the occurrence of ischemia/reperfusion and the extent of endothelial activation.

Acute degradation of the endothelial glycocalyx in infants undergoing cardiac surgical procedures.

BACKGROUND: There is no doubt today about the existence of the endothelial glycocalyx (EG) and its decisive role in maintaining vascular homeostasis in adult humans. Shedding of the EG has been demonstrated in adults with sepsis or trauma, in patients undergoing major operations, and after ischemia/reperfusion. The aim of the present study was to demonstrate whether shedding of the EG also occurs in infants undergoing heart operations. METHODS: Two major constituents of the EG (syndecan-1 and hyaluronan) were measured in the arterial serum of 42 infants during cardiac operations in a prospective observational study. The groups were defined according to the ischemic impact: cardiac operations with cardiopulmonary bypass under beating heart conditions (CPB group, regional ischemia of lungs, n = 10), operations with cardiopulmonary bypass and aortic clamping (CPB+AC group, regional ischemia of heart and lungs, n = 24), and cardiac operations with deep hypothermic circulatory arrest (CPB+AC+DHCA group, whole-body ischemia, n = 8). RESULTS: Syndecan-1 and hyaluronan were detected in all infants, providing an indication for the presence of a glycocalyx. During the operations, no significant difference in syndecan-1 concentration was observed in the CPB group, but levels increased significantly in both other groups (maximum increases: CPB+AC 3.0-fold, CPB+AC+DHCA 3.7-fold, p < 0.05). Hyaluronan increased significantly in the course of the operation in all groups (maximum increases: CPB 1.2-fold, CPB+AC 1.4-fold, CPB+AC+DHCA 1.7-fold, p < 0.05). CONCLUSIONS: The present data provides the first evidence for basal turnover of vascular EG in infants. Similarly to the process in adults, the shedding of this structure increases with ischemia/reperfusion, the extent being dependent on the degree of ischemic challenge.

Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx.

INTRODUCTION: Acute normovolemic hemodilution (ANH) and volume loading (VL) are standard blood-sparing procedures. However, VL is associated with hypervolemia, which may cause tissue edema, cardiopulmonary complications and a prolonged hospital stay. The body reacts to hypervolemia with release of atrial natriuretic peptide (ANP) from the heart. ANP has been shown to deteriorate the endothelial glycocalyx, a vital part of the vascular permeability barrier. The aim of the present study was to evaluate and compare ANP release and damage to the glycocalyx during ANH and VL. METHODS: ANH or VL with 6% hydroxyethyl starch 130/0.4 was administered prior to elective surgery in patients of good cardiopulmonary health (n =9 in each group). We measured concentrations of ANP in plasma and of three main constituent parts of the glycocalyx (hyaluronan, heparan sulfate and syndecan 1) in serum before and after ANH or VL. Heparan sulfate and syndecan 1 levels in urine were also determined. RESULTS: In contrast to ANH, VL (20 ml/kg) induced a significant release of ANP (approximately +100%, P <0.05) and increased the serum concentration of two glycocalyx constituents, hyaluronan and syndecan 1 (both by about 80%, P <0.05). Elevation of syndecan 1 was also detected in the urine of patients undergoing VL, but no increase was found in patients undergoing ANH. Heparan sulfate levels were not influenced by either procedure. CONCLUSION: These data suggest that hypervolemia increases the release of ANP and causes enhanced shedding of the endothelial glycocalyx. This perturbation must be expected to impair the vascular barrier, implying that VL may not be as safe as generally assumed and that it should be critically evaluated.

Protection of glycocalyx decreases platelet adhesion after ischaemia/reperfusion: an animal study.

BACKGROUND: Strategies targeting the protection of the vascular barrier, in particular the endothelial glycocalyx, are subjects of current research. Antithrombin III and hydrocortisone have been shown to reduce shedding of the glycocalyx following ischaemia/reperfusion. Platelet adhesion to endothelial cells is one consequence of ischaemia/reperfusion. OBJECTIVE: Our goal was to evaluate the effect of pharmacological protection of the glycocalyx on platelet adhesion. DESIGN: An experimental interventional animal study. SETTING: The study was carried out in a basic science laboratory at the University of Munich. ANIMALS: Eighty male guinea pigs (250 to 300 g) were used for the experiment. MAIN OUTCOME MEASURES: The effect of preischaemic treatment with hydrocortisone 10 µg ml(-1) or antithrombin 1 IU ml on adherence of platelets was evaluated in isolated, beating guinea pig hearts (Langendorff model). Hearts were subjected to warm ischaemia (20 min at 37 °C) and consecutive reperfusion. Platelets were injected at the beginning of reperfusion via the aortic cannula and platelet concentration was measured in the effluent (after passing through the coronary vascular system). RESULTS: Ischaemia and reperfusion led to significant shedding of the endothelial glycocalyx. Coronary venous release of syndecan-1 increased nine-fold, and heparan sulphate showed a 20.3-fold increase after ischaemia/reperfusion (both P < 0.01). Pretreatment with hydrocortisone or antithrombin III reduced endothelial glycocalyx shedding significantly (P < 0.05). Adherence of platelets to the coronary vascular bed increased more than 2.5-fold when they were injected during reperfusion. About 40% of this increase was blocked by pretreatment of hearts with hydrocortisone or antithrombin. CONCLUSION: Pretreatment with hydrocortisone or antithrombin III can reduce platelet adhesion during reperfusion after warm ischaemia by protection of the endothelial glycocalyx.

Use of methylene blue in the treatment of refractory vasodilatory shock after cardiac assist device implantation: report of four consecutive cases.

Vasodilatory shock frequently occurs after cardiac surgery, particularly after cardiac assist device implantation. This complication is often associated with high mortality, especially if refractory to conventional vasoconstrictor treatment. Methylene blue, a guanylate cyclase inhibitor, has been successfully used in the management of vasodilatory shock associated with cardiopulmonary bypass. We present four successive cases after implantation of cardiac assist devices suffering from norepinephrine and vasopressin refractory severe vasodilatory shock. In all patients, administration of a single dose of methylene blue (2 mg/kg body weight) resulted in an immediate and persistent decrease in vasoconstrictor dosages and serum lactate concentrations. Despite of this benefit, all patients deceased during hospital stay, however, this was not related to the methylene blue treatment. Methylene blue seems to be a promising therapeutical option in patients with otherwise resistant vasodilatory shock after cardiac assist device implantation. However, controlled clinical trials are necessary to substantiate safety and efficacy.

Ischemia-reperfusion-induced unmeasured anion generation and glycocalyx shedding: sevoflurane versus propofol anesthesia.

INTRODUCTION: Vascular leakage after ischemia-reperfusion (IR) is largely attributed to the destruction of the endothelial barrier and its associated negatively charged glycocalyx. In vitro, sevoflurane attenuates these changes. Therefore, we compared sevoflurane with propofol with regard to the protection of the glycocalyx and the release of negatively charged substances in vivo. METHODS: After surgical preparation under midazolam-fentanyl, nine pigs each received either propofol or sevoflurane. Ischemia of 90 min was induced by a balloon catheter in the thoracic aorta. After 120 min of reperfusion, the anesthetics were changed back to midazolam-fentanyl. Five animals, each without aortic occlusion, served as time controls. Blood electrolyte parameters were measured, from which the strong ion gap (SIG) was calculated. Serum heparan sulfate concentrations and immunohistology served as a marker of glycocalyx destruction. RESULTS: Immediately after reperfusion, SIG increased significantly only in the propofol group (+6.7 mEq/l versus baseline; p < .05), remaining stable in sevoflurane and both time-controlled groups. Initially, heparan sulfate concentration increased comparably in both experimental groups, but after 120 min, it became stable in sevoflurane-anesthetized animals, while increasing further in the propofol group (p < .05). CONCLUSIONS: Unmeasured anions, predictive of negative outcome in previous studies, did not increase significantly in sevoflurane-anesthetized animals. Additionally, there was less heparan sulfate shedding over time, signaling less destruction of the glycocalyx. Therefore, in this in-vivo situation, sevoflurane proves to be superior to propofol in protecting the endothelium from IR injury.

Delayed intracardial shunting and hypoxemia after massive pulmonary embolism in a patient with a biventricular assist device.

We describe the interdisciplinary management of a 34-year-old woman with dilated cardiomyopathy three months postpartum on a cardiac biventricular assist device (BVAD) as bridge to heart transplantation with delayed onset of intracardial shunting and subsequent hypoxemia due to massive pulmonary embolism. After emergency surgical embolectomy pulmonary function was highly compromised (PaO2/FiO2 54) requiring bifemoral veno-venous extracorporeal membrane oxygenation. Transesophageal echocardiography detected atrial level hypoxemic right-to-left shunting through a patent foramen ovale (PFO). Percutaneous closure of the PFO was achieved with a PFO occluder device. After placing the PFO occluder device oxygenation increased significantly (Δ paO2 119 Torr). The patient received heart transplantation 20 weeks after BVAD implantation and was discharged from ICU 3 weeks after transplantation.An increase in pulmonary vascular resistance in patients on BVAD can reopen a PFO resulting in atrial right-to-left shunting and subsequent hypoxemia. The case demonstrates the usefulness of transesophageal echocardiography examinations in the detection of this unexpected event. Percutaneous placement of a PFO occluder device is an appropriate strategy to stop intracardiac shunting through PFO in fixed elevation of pulmonary vascular resistance.

Release of atrial natriuretic peptide precedes shedding of the endothelial glycocalyx equally in patients undergoing on- and off-pump coronary artery bypass surgery.

The present study investigates why shedding of the endothelial glycocalyx occurs both in patients undergoing on- and off-pump coronary artery bypass surgery. Release of atrial natriuretic peptide (ANP) was of special interest, because ANP initiates shedding ex vivo. Three major constituents of the glycocalyx (syndecan-1, heparan sulfate and hyaluronan) were measured in arterial blood of patients undergoing coronary artery bypass surgery with (n = 15) and without (n = 15) cardiopulmonary bypass at various phases of the procedure. Additionally, the levels of the inflammatory cytokines interleukin (IL)-6, -8, and -10 and of ANP were evaluated. Elevations of all three components of the glycocalyx were detected in blood of patients undergoing on- (maximum increases: syndecan-1 15-fold, heparan sulfate ninefold, hyaluronan fivefold basal) and off-pump (maximum increases: syndecan-1 fourfold, heparan sulfate twofold, hyaluronan threefold basal) coronary artery surgery. Maximum ANP concentrations increased three- and fourfold basal in on- and off-pump coronary artery surgery, respectively (P < 0.05). There were significant increases in the three cytokine concentrations in both on- (maximum increases: IL-6 146-fold, IL-8 23-fold, IL-10 238-fold basal) and off-pump (maximum increases: IL-6 77-fold, IL-8 eightfold, IL-10 58-fold basal) coronary artery surgery. However, the elevations of ANP preceded those of the cytokines and coincided with or even preceded shedding of the human endothelial glycocalyx in both surgical procedures. These data suggest that release of ANP may lead to perturbation of the endothelial glycocalyx in both on- and off-pump coronary artery bypass surgery.

Conservative treatment of a left atrial intramural hematoma after left atrial thrombus resection and concomitant mitral valve replacement--case report.

Left atrial intramural hematoma is a seldom cause of left atrial mass. It has been described to occur spontaneously, after interventional procedures, after blunt chest trauma, or after aortocoronary bypass surgery. We present a case of mitral valve replacement together with the removal of a large intraatrial space-occupying lesion. Intraoperative transesophageal echocardiography confirmed a successful resection of this mass. Surprisingly, upon admission to ICU, transesophageal and transthoracic echocardiography revealed a recurrence of an intramural lesion, closest matching a hematoma, which was confirmed by contrast-enhanced computed tomography. Surgical intervention was thoroughly discussed but a conservative management was favoured. 3 months after surgery, a reassessed transthoracic echocardiography and computed tomography demonstrated an almost complete resolution of the pre-existing hematoma.

Perspectives in microvascular fluid handling: does the distribution of coagulation factors in human myocardium comply with plasma extravasation in venular coronary segments?

BACKGROUND: Heterogeneity of vascular permeability has been suggested for the coronary system. Whereas arteriolar and capillary segments are tight, plasma proteins pass readily into the interstitial space at venular sites. Fittingly, lymphatic fluid is able to coagulate. However, heart tissue contains high concentrations of tissue factor, presumably enabling bleeding to be stopped immediately in this vital organ. The distribution of pro- and anti-coagulatively active factors in human heart tissue has now been determined in relation to the types of microvessels. METHODS AND RESULTS: Samples of healthy explanted hearts and dilated cardiomyopathic hearts were immunohistochemically stained. Albumin was found throughout the interstitial space. Tissue factor was packed tightly around arterioles and capillaries, whereas the tissue surrounding venules and small veins was practically free of this starter of coagulation. Thrombomodulin was present at the luminal surface of all vessel segments and especially at venular endothelial cell junctions. Its product, the anticoagulant protein C, appeared only at discrete extravascular sites, mainly next to capillaries. These distribution patterns were basically identical in the healthy and diseased hearts, suggesting a general principle. CONCLUSIONS: Venular extravasation of plasma proteins probably would not bring prothrombin into intimate contact with tissue factor, avoiding interstitial coagulation in the absence of injury. Generation of activated protein C via thrombomodulin is favored in the vicinity of venular gaps, should thrombin occur inside coronary vessels. This regionalization of distribution supports the proposed physiological heterogeneity of the vascular barrier and complies with the passage of plasma proteins into the lymphatic system of the heart.

Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential.

Damage of the endothelial glycocalyx, which ranges from 200 to 2000 nm in thickness, decreases vascular barrier function and leads to protein extravasation and tissue oedema, loss of nutritional blood flow, and an increase in platelet and leucocyte adhesion. Thus, its protection or the restoration of an already damaged glycocalyx seems to be a promising therapeutic target both in an acute critical care setting and in the treatment of chronic vascular disease. Drugs that can specifically increase the synthesis of glycocalyx components, refurbish it, or selectively prevent its enzymatic degradation do not seem to be available. Pharmacological blockers of radical production may be useful to diminish the oxygen radical stress on the glycocalyx. Tenable options are the application of hydrocortisone (inhibiting mast-cell degranulation), use of antithrombin III (lowering susceptibility to enzymatic attack), direct inhibition of the cytokine tumour necrosis factor-alpha, and avoidance of the liberation of natriuretic peptides (as in volume loading and heart surgery). Infusion of human plasma albumin (to maintain mechanical and chemical stability of the endothelial surface layer) seems the easiest treatment to implement.

Heparin-induced thrombosis without thrombocytopenia causing fulminant pulmonary embolism after off-pump coronary artery bypass grafting.

Heparin-induced thrombocytopenia (HIT) is a rare immune-mediated complication of heparin administration. A potentially life-threatening complication, HIT is difficult to diagnose in patients in the intensive care unit after cardiac surgery because there can be multiple reasons for thrombocytopenia. Moreover, immune-mediated platelet consumption may be masked by reactive thrombocytosis, which is common in the typical postoperative course after cardiac surgery. We report the case of a 57-year-old male patient who developed fulminant pulmonary embolism following heparin-induced thrombosis without thrombocytopenia after off-pump coronary artery bypass surgery.

Extracorporeal support in a patient with cardiogenic shock due to Aerococcus urinae endocarditis.

Aerococcus urinae is a newly identified Gram-positive coccus that causes serious infections. To date, only 15 cases of A. urinae infective endocarditis have been reported, but with a very high mortality. The case is reported of a patient with A. urinae double valve endocarditis. Following aortic and mitral valve replacement, the patient suffered from refractory cardiogenic shock; extracorporeal membrane oxygenation was used successfully as a rescue mechanical support.

Huge intracardiac thrombosis in a patient on veno-arterial extracorporeal membrane oxygenation support.

A young woman suffering from congenital hypertrophic obstructive cardiomyopathy (HOCM) received a transcoronary ablation of the septal hypertrophy (TASH) and an automated Cardioverter/Defibrillator (AICD) for the relief of progressive symptoms of heart failure. She developed an acute heart failure in the perioperative period and had to be put on veno-arterial extracorporeal membrane oxygenation. Following this the patient developed a nearly complete thrombosis of the left-sided cardiac chambers, despite successful laboratory anticoagulation.

Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts.

INTRODUCTION: Postischemic injury to the coronary vascular endothelium, in particular to the endothelial glycocalyx, may provoke fluid extravasation. Shedding of the glycocalyx is triggered by redox stress encountered during reperfusion and should be alleviated by the radical scavenger nitric oxide (NO). The objective of this study was to investigate the effect of exogenous administration of NO during reperfusion on both coronary endothelial glycocalyx and vascular integrity. METHODS: Isolated guinea pig hearts were subjected to 15 minutes of warm global ischemia followed by 20 minutes of reperfusion in the absence (Control group) and presence (NO group) of 4 microM NO. In further experiments, the endothelial glycocalyx was enzymatically degraded by means of heparinase followed by reperfusion without (HEP group) and with NO (HEP+NO group). RESULTS: Ischemia and reperfusion severely damaged the endothelial glycocalyx. Shedding of heparan sulfate and damage assessed by electron microscopy were less in the presence of NO. Compared with baseline, coronary fluid extravasation increased after ischemia in the Control, HEP, and HEP+NO groups but remained almost unchanged in the NO group. Tissue edema was significantly attenuated in this group. Coronary vascular resistance rose by 25% to 30% during reperfusion, but not when NO was applied, irrespective of the state of the glycocalyx. Acute postischemic myocardial release of lactate was comparable in the four groups, whereas release of adenine nucleotide catabolites was reduced 42% by NO. The coronary venous level of uric acid, a potent antioxidant and scavenger of peroxynitrite, paradoxically decreased during postischemic infusion of NO. CONCLUSION: The cardioprotective effect of NO in postischemic reperfusion includes prevention of coronary vascular leak and interstitial edema and a tendency to forestall both no-reflow and degradation of the endothelial glycocalyx.

Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions.

INTRODUCTION: Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis. METHODS: Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured at baseline, in shock, and during 3 hours post-therapy. Strong ion difference and the amount of weak plasma acid were calculated. To detect the presence of unmeasured anions, anion gap and strong ion gap were determined. Capillary electrophoresis was used to identify potential contributors to unmeasured anions. RESULTS: During induction of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to explain the transient increases in anion gap (+11.0 mEq/L) and strong ion gap (+7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have been generated. Capillary electrophoresis revealed increases in serum concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), alpha-ketoglutarate (35.3 microEq/L), fumarate (6.2 microEq/L), sulfate (0.1 mEq/L), and urate (55.9 microEq/L) after shock induction. CONCLUSION: Large amounts of unmeasured anions were generated after hemorrhage in this highly standardized model of hemorrhagic shock. Capillary electrophoresis suggested that the hitherto unmeasured anions citrate and acetate, but not sulfate, contributed significantly to the changes in strong ion gap associated with induction of shock.

Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx.

BACKGROUND: Hydrocortisone protects against ischemia-reperfusion injury, reduces paracellular permeability for macromolecules, and is routinely applied in the prevention of interstitial edema. Healthy vascular endothelium is coated by the endothelial glycocalyx, diminution of which increases capillary permeability, suggesting that the glycocalyx is a target for hydrocortisone action. METHODS: Isolated guinea pig hearts were perfused with Krebs-Henseleit buffer. Hydrocortisone was applied in a stress dose (10 microg/ml) before inducing 20 min of ischemia (37 degrees C). Hearts were reperfused for 20 min at constant flow (baseline perfusion pressure, 70 cm H2O) with Krebs-Henseleit buffer or Krebs-Henseleit buffer plus 2 g% hydroxyethyl starch (130 kd). Coronary net fluid filtration was assessed directly by measuring transudate formation on the epicardial surface. Hearts were perfusion fixed to visualize the glycocalyx. RESULTS: Ischemia-induced degradation of the glycocalyx enhanced coronary perfusion pressure (118.8 +/- 17.3 cm H2O) and increased vascular permeability (8 +/- 0.2 microl x min(-1) x cm H2O(-1) at baseline vs. 34 +/- 3.3 microl x min(-1) x cm H2O(-1) after reperfusion). Enzymatic digestion of the glycocalyx (heparinase) elicited similar effects. Hydrocortisone reduced postischemic oxidative stress, perfusion pressure (86.3 +/- 6.4 cm H2O), and transudate formation (11 +/- 0.6 microl x min(-1) x cm H2O(-1)). Applying colloid augmented this (70.6 +/- 5.6 cm H2O and 9 +/- 0.5 microl x min(-1) x cm H2O(-1)). Postischemic shedding of syndecan-1, heparan sulfate, and hyaluronan was inhibited by hydrocortisone, as was release of histamine from resident mast cells. Electron microscopy revealed a mostly intact glycocalyx after hydrocortisone treatment, but not after heparinase treatment. CONCLUSIONS: Hydrocortisone preserves the endothelial glycocalyx, sustaining the vascular barrier and reducing interstitial edema. The effect of colloids suggests that prevention of postischemic rise in coronary resistance by hydrocortisone could also be based on alleviation of endothelial swelling. Stabilization of myocardial mast cells by hydrocortisone may account for the mitigated inflammatory affect of ischemia-reperfusion.