Cardiopulmonary bypass (CPB) surgeries cause an increase in plasma inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) along with whole-body inflammatory responses. The inflammatory responses during a CPB treatment are reduced when using a heparin-coated extracorporeal circuit. Because many cytokines, growth factors, and complements are known to interact with heparin, the reduction of inflammatory responses by a heparin-coated circuit is likely to depend on this heparin-binding nature of the inflammatory cytokines. In this study, the inflammatory cytokines, TNF-alpha and IL-6, in fetal bovine serum (FBS) bound to a heparin-agarose beads (heparin beads)-column and the adsorptions were competitively inhibited on addition of heparin in a concentration-dependent manner. TNF-alpha in FBS required a higher concentration of heparin (50% concentration inhibition [IC50] > 20microg/ml) to inhibit adsorption to the heparin beads-column compared with IL-6, probably because of a stronger interaction between TNF-alpha and heparin-beads. TNF-alpha and IL-6 concentrations in human heparinized blood significantly increased after a CPB treatment. Although the adsorbed amount of IL-6 onto the heparin-coated circuit was low (less than 6% of free circulating IL-6), a significant amount of TNF-alpha adsorbed onto the circuit (23.9-755% of free circulating TNF-alpha). Therefore, the adsorption of inflammatory cytokines, especially TNF-alpha, onto the inner heparin-coated surface of an extracorporeal circuit may partly account for a reduction in inflammatory responses.
The purpose of this study is to examine the efficiency of venous air removal with a new cardiopulmonary bypass (CPB) circuit design for conventional open-heart surgeries. A main concern with a closed circuit for open-heart surgeries is air entrainment into the venous line. A venous filter was placed proximal to the centrifugal pump. The circuit proximal to the centrifugal pump was divided into two lines; one line was attached to the venous reservoir outlet. By clamping the line to the reservoir, this circuit becomes closed. Negative pressure was applied to the purge line connected to the venous reservoir for venous air removal. Micro bubbles were measured at two locations, both distal to the venous and arterial filters. When the injection rate reached 100 ml/min, with the air-injection over 30 s, micro bubbles greater than 40 micro were observed at the outlet of venous filter. However, there was no micro bubble greater than 40 micro detected at the outlet of arterial filter. Although micro bubbles greater than 40 micro were not detected at the outlet of the arterial filter up to the injection rate of 300 ml/min, when the injection rate reached 400 ml/min, micro bubbles greater than 50 microm were detected distal to the arterial filter. From this examination, we determined that air entrained in the venous line up to approximately 300 ml/min is automatically removed by this method with the pressure-balanced condition. This pressure balance means that resistance of venous return, gravity siphon, negative pressure by centrifugal pump, and negative pressure applied to the air-purge line of the filter are balanced; that is, the venous return is sufficient, and the venous reservoir volume is kept stable. From this study we determined that this circuit design efficiently removes the entrained air in the venous line.
In a closed circuit with a centrifugal blood pump, one of the serious obstacles to clinical application is sucking of air bubbles into the drainage circuit. The goal of this study was to investigate the efficiency of an air filter at the drainage site. We used whole bovine blood and the experimental circuit consisted of a drainage circuit, two air filters, a centrifugal blood pump, a membrane oxygenator, a return circuit, and a reservoir. Air was injected into the drainage circuit with a roller pump, and the number and size of air bubbles were measured. The air filter at the drainage site could remove the air bubbles (>40 microm) by itself, but adding a vacuum removed more bubbles (>40 microm) than without vacuum. Our results suggest that an air filter at the drainage site could effectively remove air bubbles, and that adding the filter in a closed circuit with a centrifugal blood pump would be safer.
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