Endothelial Dysfunction in Patients with Severe Acute Pancreatitis: Improved by Continuous Blood Purification Therapy

Abstract

Objectives.

Endothelium dysfunction is one of the critical pathophysiologic disorders in patients with severe acute pancreatitis (SAP). To investigate the effect of continuous blood purification (CBP) on endothelial function, we conducted a prospective study of 20 patients with SAP, 9 of whom had evidence of sepsis.

Methods.

All patients underwent CVVH for 72 h. Soluble E-selectin (sE-selectin), soluble thrombomodulin, permeability of the endothelial monolayer, and endothelial intracellular calcium ([Ca²⁺]i) levels were used as the markers for the assessment of endothelial function and the effect of CBP therapy in patients with SAP. Blood samples were taken from the patients at 0, 2, 12, 24, 48, and 72 h during CVVH therapy. sE-selectin and thrombomoduiln were measured by ELISA. The endothelial permeability and activation were evaluated using cultured endothelial monolayer and intracellular Ca²+ concentration.

Results.

The results showed that during CVVH treatment, the hemodynamics and mean arterial pressure (MAP) were stable. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was improved significantly after CVVH. Endothelial dysfunction was evident in patients with SAP as compared to normal controls. Patients with SAP had increased levels of sE-selectin, endothelial permeability and intracellular [Ca²⁺]_i, which was higher in patients with sepsis than in those without sepsis. The level of thrombomodulin showed a tendency to increase; however, these changes were not significant between SAP patients and controls. After CBP treatment, sE-selectin levels substantially decreased in all patients. CBP treatment also significantly diminished the endothelial permeability and decreased the intracellular [Ca²+] concentration.

Conclusions.

These data demonstrate that endothelial dysfunction is present in patients with SAP and the degree of endothelial damage may be correlated with the disease severity. CBP therapy can not only improve the general conditions, as measured by the APACHE II score, but also effectively improve endothelial dysfunction.

Keywords

Severe acute pancreatitis Continuous veno-venous hemofiltration E-selectin Thrombomodulin Endothelial permeability Intracellular calcium

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References

Vallet

Bench-to-bedside review: endothelial cell dysfunction in severe sepsis: a role in organ dysfunction?

Crit Care Med 2003; 7: 130–8.

Gando

, Kameue

, Matsuda

, Hayakawa

, Hoshino

, Kato

Serial changes in neutrophil-endothelial activation markers during the course of sepsis associated with disseminated intravascular coagulation.

Thromb Res 2005; 116: 91–100.

Kurosawa

, Galvin

J.B.

, Esmon

N.L.

Proteolytic formation and properties of functional domains of thrombomodulin.

J Biol Chem 1987; 262: 2206–12.

Gando

, Kameue

, Nanzaki

, Nakanishi

Cytokines, soluble thrombomodulin and sisseminated intravascular coagulation in patients with systemic inflammatory response syndrome.

Tromb Res 1996; 80: 519–26.

Paul

, Joseph

, Hamid

: Continuous dialysis as systemic therapy in the critically ill patient? Crit Care Med 2003; 31: 988–89.

Chen

, Liu

, Chen

, Ji

, Li

Restoration of immune homeostasis in patients with SIRS/sepsis receiving continuous blood purification therapy.

Am J Soc Nephrol 2003; 14: 789A.

Cruz

, Hollenberg

S.M.

: Modifying leukocyte endothelial interactions in acute inflammatory models. Crit Care Med 2002; 30: 1924–25.

Bradley

E.L.

A clinically based classification system for acute pancreatitis.

Arch Surg 1993; 128: 586–90.

Bone

R.C.

, Balk

R.A.

, Cerra

F.B.

, Dellinger

R.P.

, Fein

A.M.

, Knaus

W.A.

. Definitions for sepsis and organ failure and guidelines for the use of innovatiove therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. Chest 1992; 101: 1644–55.

10.

Murphy

J.T.

, Duffy

S.L.

, Hybki

D.L.

, Kamm

Thrombin-mediated permeability of human microvascular pulmonary endothelia cells is calcium dependent.

J Trauma 2001; 50: 213–22.

11.

Vandenberghe

P.A.

, Ceuppens

J.L.

Flow cytometric measurement of cytoplasmic free calcium in human peripheral blood T lymphocytes with fluo-3, a new fluorescent calcium indicator.

J Immunol Methods 1990; 127: 197–205.

12.

Hernandez-Cruz

, Sala

, Adams

P.R.

Subcellular calcium transients visualized by confocal microscopy in a voltage-clamped vertebrate neuron.

Science 1990; 247: 858–62.

13.

Carnovale

, Rabitti

P.G.

, Manes

, Esposito

, Pacelli

, Uomo

Mortality in acute pancreatitis: is it an early or a late event?

JOP 2005; 6: 438–44.

14.

Ronco

, Bellomo

, Ricci

Continuous renal replacement therapy in critically ill patients.

Nephrol Dial Transplant 2001; 16(suppl 5): S67–72.

15.

Goldstein

S.L.

, Somers

M.J.

, Baum

M.A.

, Symons

J.M.

, Brophy

P.D.

, Blowey

. Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int 2005; 67: 653–8.

16.

Kayal

, Jais

J.P.

, Aguini

, Chaudiere

, Labrousse

Elevated circulating E-selectin, intercellular adhesion molecule 1, and von Willebrand factor in patients with severe infection.

Am J Respir Crit Care Med 1998; 157: 776–84.

17.

Cowley

H.C.

, Heney

, Gearing

A.J.

, Hemingway

, Webster

N.R.

Increased circulating adhesion molecule concentrations in patients with the systemic inflammatory response syndrome: A prospective cohort study.

Crit Care Med 1994; 22: 651–7.

18.

Rustom

, Leggat

, Tomura

H.R.

, Hay

C.R.

, Bone

J.M.

Plasma thrombomodulin in renal disease: effects of renal function and proteinuria.

Clin Nephrol 1998; 50: 337–41.

19.

Garcia-Fernandez

, Montes

, Purroy

, Rocha

Hemostatic disturbances in patients with systemic inflammatory response syndrome (SIRS) and associated acute renal failure (ARF).

Thromb Res 2000; 100: 19–25.

20.

Nooteboom

, Van Der Linden

C.J.

, Hendriks

Tumor necrosis factor-alpha and interleukin-1beta mediate endothelial permeability induced by lipopolysaccharide-stimulated whole blood.

Crit Care Med 2002; 30: 2063–8.