Human neutrophil degranulation during extracorporeal circulation

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 324-330 ◽  
Author(s):  
YT Wachtfogel ◽  
U Kucich ◽  
J Greenplate ◽  
P Gluszko ◽  
W Abrams ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Extracorporeal Circulation ◽  
Neutrophil Elastase ◽  
Membrane Oxygenator ◽  
Protein Marker ◽  
Extracorporeal Membrane Oxygenator ◽  
Bubble Oxygenator ◽  
Neutrophil Degranulation ◽  
Specific Proteins

Cardiopulmonary bypass, especially when prolonged, may result in hemostatic failure and pulmonary dysfunction, which has been attributed to changes in platelets and leukocytes, respectively. It has been well documented that contact of blood with synthetic surfaces causes platelet activation. In this report, we explore mechanisms of the activation of neutrophils during simulated in vitro extracorporeal circulation and document the release of neutrophil lactoferrin and elastase during clinical cardiopulmonary bypass (CCB). Inhibition in the simulated circuit by prostaglandin E1 (PGE1) and lidocaine suggests different mechanisms for release of neutrophil-specific proteins. During CCB with a bubble oxygenator it was observed that platelet counts fell to 42% +/- 2% of baseline. In addition, beta- thromboglobulin antigen (beta TG), a platelet-specific, alpha-granule protein marker reflecting the release reaction, increased from 0.15 +/- 0.05 to 0.84 +/- 0.11 microgram/mL. Neutrophil counts decreased to 67% +/- 7% of prebypass levels but then gradually rose as bypass continued. Both lactoferrin, a neutrophil-specific granule marker, and neutrophil elastase, an azurophilic granule marker, increased in plasma threefold to 1.66 +/- 0.33 micrograms/mL and 1.65 +/- 0.68 microgram/mL, respectively, just before bypass was stopped. When fresh heparinized human blood was recirculated within an extracorporeal membrane oxygenator bypass circuit for 120 minutes, plasma beta-TG rose to 5.13 micrograms/mL, lactoferrin increased from 0.13 +/- 0.04 to 1.62 +/- 0.22 micrograms/mL, and neutrophil elastase rose from 0.05 +/- 0.02 to 1.86 +/- 0.41 micrograms/mL. At 120 minutes, lidocaine (100 mumol/L), which inhibits neutrophil activation, delayed release of lactoferrin (1.33 +/- 0.26 micrograms/mL) and markedly inhibited release of elastase (0.24 +/- 0.05 microgram/mL) but did not inhibit release of beta-TG antigen (5.66 micrograms/mL at 120 minutes). PGE1 (0.3 mumol/L) inhibited significantly the release of beta-TG (0.31 microgram/mL) and elastase (0.52 +/- 0.11 microgram/mL) and attenuated the release of lactoferrin (1.57 +/- 0.45 micrograms/mL).

scholarly journals Human neutrophil degranulation during extracorporeal circulation

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 324-330 ◽  
Author(s):  
YT Wachtfogel ◽  
U Kucich ◽  
J Greenplate ◽  
P Gluszko ◽  
W Abrams ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Extracorporeal Circulation ◽  
Neutrophil Elastase ◽  
Membrane Oxygenator ◽  
Protein Marker ◽  
Extracorporeal Membrane Oxygenator ◽  
Bubble Oxygenator ◽  
Neutrophil Degranulation ◽  
Specific Proteins

Abstract Cardiopulmonary bypass, especially when prolonged, may result in hemostatic failure and pulmonary dysfunction, which has been attributed to changes in platelets and leukocytes, respectively. It has been well documented that contact of blood with synthetic surfaces causes platelet activation. In this report, we explore mechanisms of the activation of neutrophils during simulated in vitro extracorporeal circulation and document the release of neutrophil lactoferrin and elastase during clinical cardiopulmonary bypass (CCB). Inhibition in the simulated circuit by prostaglandin E1 (PGE1) and lidocaine suggests different mechanisms for release of neutrophil-specific proteins. During CCB with a bubble oxygenator it was observed that platelet counts fell to 42% +/- 2% of baseline. In addition, beta- thromboglobulin antigen (beta TG), a platelet-specific, alpha-granule protein marker reflecting the release reaction, increased from 0.15 +/- 0.05 to 0.84 +/- 0.11 microgram/mL. Neutrophil counts decreased to 67% +/- 7% of prebypass levels but then gradually rose as bypass continued. Both lactoferrin, a neutrophil-specific granule marker, and neutrophil elastase, an azurophilic granule marker, increased in plasma threefold to 1.66 +/- 0.33 micrograms/mL and 1.65 +/- 0.68 microgram/mL, respectively, just before bypass was stopped. When fresh heparinized human blood was recirculated within an extracorporeal membrane oxygenator bypass circuit for 120 minutes, plasma beta-TG rose to 5.13 micrograms/mL, lactoferrin increased from 0.13 +/- 0.04 to 1.62 +/- 0.22 micrograms/mL, and neutrophil elastase rose from 0.05 +/- 0.02 to 1.86 +/- 0.41 micrograms/mL. At 120 minutes, lidocaine (100 mumol/L), which inhibits neutrophil activation, delayed release of lactoferrin (1.33 +/- 0.26 micrograms/mL) and markedly inhibited release of elastase (0.24 +/- 0.05 microgram/mL) but did not inhibit release of beta-TG antigen (5.66 micrograms/mL at 120 minutes). PGE1 (0.3 mumol/L) inhibited significantly the release of beta-TG (0.31 microgram/mL) and elastase (0.52 +/- 0.11 microgram/mL) and attenuated the release of lactoferrin (1.57 +/- 0.45 micrograms/mL).

Determination of significant differences in performance of the Bentley BOS-CM 40 hollow fibre membrane oxygenator and the Polystan VT5000 venotherm bubble oxygenator

Perfusion ◽  
1987 ◽  
Vol 2 (4) ◽  
pp. 289-295 ◽  
Author(s):  
Ludwig von Segesser
Keyword(s):  
Cardiopulmonary Bypass ◽  
Hollow Fibre ◽  
Membrane Oxygenator ◽  
Mean Flow ◽  
Hollow Fibre Membrane ◽  
Fibre Membrane ◽  
Bubble Oxygenator ◽  
Venous Oxygen Saturation ◽  
The Difference

Ten mongrel dogs were connected to cardiopulmonary bypass by cavoaortic cannulation, classic roller pump and either Bentley BOS-CM 40 hollow fibre membrane oxygenator or Polystan VT5000 Venotherm bubble oxygenator for eight hours, with mean flow rate of 100 ml/kg min. Platelet counts (all values corrected by prebypass haematocrit) were significantly lower in the bubble oxygenator group after two hours of cardiopulmonary bypass (p < 0·01). Plasma haemoglobin production was significantly higher after two hours of cardiopulmonary bypass in the bubble oxygenator group (p < 0·01). Venous oxygen saturation (SvO2) was above 65% during the eight hours perfusion in the membrane oxygenator group. In the bubble oxygenator group, however, SvO2 was below 60% after six hours of cardiopulmonary bypass. After eight hours perfusion the difference in SvO2 between the two groups was significant (p < 0·05). Thus membrane oxygenators such as the Bentley BOS-CM 40 appear to be indicated in cardiopulmonary bypass of more than two hours duration.

Factor VLEIDEN and cardiopulmonary bypass: investigation of haemostatic parameters and the effect of aprotinin using an ex vivo model

Perfusion ◽  
2001 ◽  
Vol 16 (6) ◽  
pp. 476-484 ◽  
Author(s):  
M D Linden ◽  
M Schneider ◽  
W N Erber
Keyword(s):  
Cardiopulmonary Bypass ◽  
Extracorporeal Circulation ◽  
Ex Vivo ◽  
Normal Blood ◽  
Factor V ◽  
Ex Vivo Model ◽  
Haemostatic Agents ◽  
Increased Risk

It has been suggested that aprotinin results in significantly increased risk for perioperative thrombotic complications in patients with Factor VLEIDEN (F5L) due to its ability to competitively inhibit activated protein C (APC) function in vitro. No clinical studies have been performed to assess the effect of aprotinin on APC function of F5L in vivo. We developed an ex vivo model to mimic the effects of cardiopulmonary bypass with the exclusion of the patient in order to assess APC function. Blood from normal ( n = 2) and F5L heterozygous donors ( n = 2) was treated with aprotinin or placebo (saline). The blood was heparinized, added to the prime and circulated at 2 l/min through a modified cardiopulmonary bypass circuit. After 60 min of circulation, the heparin was neutralized with protamine sulfate. Blood samples, drawn at specific time points, were analysed for APC ratio. Results showed a decrease in APC ratio for both F5L and normal bloods with the addition of aprotinin (18% and 40%, respectively). APC ratios also decreased with the commencement of extracorporeal circulation for all bloods, resulting in an APC ratio of 1.35 in normal placebo-treated blood and 0.67 in F5L placebo-treated blood. The combined effect of aprotinin and extracorporeal circulation resulted in APC ratios of 0.90 for normal blood and 0.63 for F5L blood, corresponding to a severe dysfunction of APC intraoperatively (reference range 1.9-4.0). The data from this model predict an increased risk of perioperative thrombosis due to inhibition of APC function in cardiac surgical patients heterozygous for the F5L mutation. Aprotinin further compounds the severity of APC dysfunction, though the effect is more severe in normal blood. The ex vivo model employed was an effective tool for the investigation of the haemostatic effect of aprotinin. This model may be exploited for other applications such as the investigation of novel or emerging haemostatic agents prior to clinical trial.

Testing neonate-infant membrane oxygenators with the University of Texas neonatal pulsatile cardiopulmonary bypass system in vitro

Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 346-352 ◽  
Author(s):  
Akif Ündar ◽  
Marian C Holland ◽  
Russel V Howelton ◽  
Cherie K Benson ◽  
Jose R Ybarra ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Pulsatile Flow ◽  
Hollow Fibre ◽  
Membrane Oxygenator ◽  
Ejection Time ◽  
Hollow Fibre Membrane ◽  
University Of Texas ◽  
Membrane Oxygenators ◽  
The University

Neurologic complications are already well documented after cardiopulmonary bypass (CPB) procedures in neonates and infants. Physiologic pulsatile flow CPB systems may be the alternative to the currently used steady-flow CPB circuits. In addition to the pulsatile pump, a membrane oxygenator should be chosen carefully, because only a few membrane oxygenators are suitable for physiologic pulsatile flow. We have tested four different types of neonate-infant membrane oxygenators for physiologic pulsatility with The University of Texas neonate-infant pulsatile CPB system in vitro. Evaluation criteria were based on mean ejection time, extracorporeal circuit (ECC) pressure, and upstroke of d p/d t. The results suggested that the Capiox 308 hollow-fibre membrane oxygenator produced the best physiologic pulsatile waveform according to the ejection time, ECC pressure, and the upstroke of d p/d t. The Minimax Plus and Masterflo Infant hollow-fibre membrane oxygenators also produced adequate pulsatile flow. Only the Variable Prime Cobe Membrane Lung (VPCML) Plus flat-sheet membrane oxygenator failed to reach the criteria for physiologic pulsatility. Depending on the oxygenator used, the lowest priming volume of the infant CPB circuit was 415 ml and the highest 520 ml.

α1-Antitrypsin Pittsburgh (Met358 → Arg) Inhibits the Contact Pathway of Intrinsic Coagulation and Alters the Release of Human Neutrophil Elastase during Simulated Extracorporeal Circulation

1994 ◽  
Vol 72 (06) ◽  
pp. 843-847 ◽  
Author(s):  
Yanina T Wachtfogel ◽  
Rainer Bischoff ◽  
Ross Bauer ◽  
C Erik Hack ◽  
Jan H Nuijens ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Complex Formation ◽  
Platelet Activation ◽  
Extracorporeal Circulation ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Neutrophil Activation ◽  
Whole Body ◽  
Postoperative Blood Loss ◽  
Human Neutrophil Elastase

SummaryCardiopulmonary bypass prolongs bleeding time, increases postoperative blood loss, and triggers activation of plasma proteolytic enzyme systems and blood cells referred to as the “whole body inflammatory response”. Contact of blood with synthetic surfaces leads to qualitative and quantitative alterations in platelets, neutrophils, contact and complement systems. Contact and complement pathway proteins both induce neutrophil activation, a j-antitrypsin Pittsburgh (Met358 → Arg), a mutant of α1-antitrypsin, is a potent inhibitor of plasma kalli-krein and thrombin. We investigated whether this recombinant mutant protein inhibited platelet activation, as well as contact and/or complement-induced neutrophil activation during simulated extracorporeal circulation.Arg358 α1-antitrypsin did not prevent the 34% drop in platelet count at 5 min of recirculation, did not block the 50% decrease in ADP-induced platelet aggregation at 120 min of recirculation, nor inhibit the release of 6.06 α 1.07 µg/ml (3-thromboglobulin at 120 min of recirculation suggesting that the inhibitor had little effect on platelet activation. However, Arg358 α1 arantitrypsin totally blocked kallikrein-Cl-in-hibitor complex formation but not Cl-Cl-inhibitor complex formation. Most importantly, Arg358 α1-antitrypsin decreased the release of 1.11 α 0.16 µg/ml human neutrophil elastase by 43%. The attenuation of neutrophil activation in the absence of an effect on complement activation via the classical pathway, supports the concept that kallikrein is a major mediator of neutrophil degranulation during cardiopulmonary bypass.

Air removal capacity of two different minimal invasive ECC systems: an in vitro comparison

Perfusion ◽  
2019 ◽  
Vol 34 (7) ◽  
pp. 561-567
Author(s):  
Marco C Stehouwer ◽  
Roel de Vroege
Keyword(s):  
Cardiopulmonary Bypass ◽  
Minimally Invasive ◽  
Extracorporeal Circulation ◽  
In Vitro Study ◽  
Vitro Study ◽  
Circulation System ◽  
Arterial Line ◽  
Minimized Extracorporeal Circulation ◽  
Air Removal

Minimally invasive extracorporeal circulation systems are developed to decrease the deleterious effects of cardiopulmonary bypass. For instance, prime volume and foreign surface area are decreased in these systems. However, because of the lack of a venous reservoir in minimized systems, air handling properties of these minimally invasive extracorporeal circulation systems may be decreased as compared to conventional cardiopulmonary bypass systems. The aim of this in vitro study is to compare the air handling properties of two complete minimized cardiopulmonary bypass systems of two manufacturers, of which one system is provided with the air purge control. In an in vitro study, two minimally invasive extracorporeal circulation systems, Inspire Min.I manufactured by Sorin Group Italia, Mirandola, Italy (LivaNova, London, United Kingdom) and minimized extracorporeal circulation manufactured by Maquet, Rastatt, Germany (Getinge, Germany), were challenged with two types of air challenges; a bolus air challenge and a gaseous microemboli challenge. The air removal characteristics of the venous bubble traps and of the complete minimally invasive extracorporeal circulation systems were assessed by measuring the gaseous microemboli volume and number downstream of the venous bubble traps in the arterial line with a bubble counter. No significant differences were observed in air reduction between the venous bubble traps of Getinge (venous bubble traps) and LivaNova (Inspire venous bubble traps 8 in conjunction with the air purge control). Similarly, no significant differences were observed in volume and number of gaseous microemboli in the arterial line of both complete minimally invasive extracorporeal circulation systems. However, the gaseous microemboli load of the Inspire Min.I system was marginally lower after both the bolus air and the gaseous microemboli challenges. Both minimally invasive extracorporeal circulation systems assessed in this study, the LivaNova Inspire Min.I and the Getinge minimized extracorporeal circulation, showed comparable air removal properties, after both bolus and gaseous microemboli air challenges. Besides, air purge control automatic air removal system provided with the LivaNova Inspire Min.I. system may enhance patient’s safety with the use of a minimally invasive extracorporeal circulation system. We consider both systems equally safe for clinical use.

Hemolysis caused by pumps in extracorporeal circulation (in vitro evaluation of pumps)

1959 ◽  
Vol 14 (6) ◽  
pp. 1039-1044 ◽  
Author(s):  
John J. Cahill ◽  
Willem J. Kolff
Keyword(s):  
Polyvinyl Chloride ◽  
Human Blood ◽  
Extracorporeal Circulation ◽  
Exchange Transfusion ◽  
Clinical Use ◽  
Membrane Oxygenator ◽  
Free Hemoglobin ◽  
System A ◽  
Rate Of Accumulation

To test in vitro the hemolytic properties of pumps used in extracorporeal circulation, a system was made of polyvinyl chloride tubing. Hemolysis was expressed as the rate of accumulation of free hemoglobin in the plasma determined colorphotometrically. Human blood was recirculated with a single pump in the system. Several pumps—the Sigmamotor, the Leonards occlusive roller, the Hercik nonocclusive roller, the MacNeill-Collins and three modifications of the Dale-Schuster were tested under similar conditions. Some pumps in general clinical use produced as much as 19 mg/100 ml of free hemoglobin/hr. A modified Dale-Schuster pump and a Clowes membrane oxygenator also were tested in the system recirculating 800 ml of blood. The hourly production of free hemoglobin was only 3.2 mg/100 ml/hr. The concentration of free hemoglobin was kept constant by exchange transfusion with a modified Dale-Schuster pump and Clowes membrane oxygenator in the system. A formula used to calculate the required amount of blood to be exchanged is presented. Submitted on May 11, 1959

Selective kallikrein inhibitors alter human neutrophil elastase release during extracorporeal circulation

1995 ◽  
Vol 268 (3) ◽  
pp. H1352-H1357 ◽  
Author(s):  
Y. T. Wachtfogel ◽  
C. E. Hack ◽  
J. H. Nuijens ◽  
C. Kettner ◽  
T. M. Reilly ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Complex Formation ◽  
Inflammatory Response ◽  
Extracorporeal Circulation ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Human Neutrophil Elastase ◽  
C1 Inhibitor ◽  
Selective Inhibitors ◽  
Inhibitor Complex

Cardiopulmonary bypass causes hemorrhagic complications and initiates a biochemical and cellular “whole body inflammatory response.” This study investigates whether a variety of selective inhibitors of the contact pathway of intrinsic coagulation modulate complement and neutrophil activation during simulated extracorporeal circulation. After 60 min of recirculation in the presence of the slow tight-binding boronic acid inhibitor, Bz-Pro-Phe-boroArg-OH (10.7 microM), complete inhibition of kallikrein-C1-inhibitor complex formation and marked inhibition of C1-C1-inhibitor complex formation and the release of human neutrophil elastase were observed. Arg15-aprotinin (3.1 microM), Ala357,Arg358 alpha 1-antitrypsin (2.6 microM), and soybean trypsin inhibitor (48.0 microM) either completely or partially inhibited the generation of kallikrein-C1-inhibitor complexes but were less effective inhibitors of human neutrophil elastase release. The second-order rate constants for the inhibition of kallikrein in purified systems are consistent with the order of effectiveness of the inhibitors in blocking human neutrophil elastase release in heparinized blood. Our results suggest that low-molecular-weight selective inhibitors of kallikrein may be effective agents in the attenuation of the contact-mediated inflammatory response in cardiopulmonary bypass.

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