Effect of nitric oxide upon gas transfer and structural integrity of a polypropylene membrane oxygenator.

Gaseous nitric oxide (NO) may act as a membrane passivator during cardiopulmonary bypass by inhibition of platelet and leukocyte adhesion, activation, and aggregation. However, NO and its by-product nitrogen dioxide (NO2) are potently reactive and may be capable of degradation of membrane oxygenator constituents in an oxygen-rich environment. To test these concepts, nine polypropylene hollow fiber membrane oxygenators received 224 +/- 10 ppm NO and 6.7 +/- 1.7 ppm NO2 in 73% oxygen (O2), and six oxygenators received 73% O2, while being perfused with heparinized thrombocytopenic bovine blood for 6 hours. Oxygenators were used for measurement of O2 and carbon dioxide (CO2) transfer rates, structural integrity by pulsing with 22 psi water at 0.5 Hz for 6 hours, and scanning electron microscopic (SEM) examination of structural integrity. Transfer rates between groups at 0, 1, 3, and 6 hours revealed no differences in O2 or CO2. No oxygenator failed hydraulic tests of structural integrity or exhibited "wet-out" during bypass. No evidence of material degradation was shown in the SEM appearance of oxygenators. There were no differences in hematologic values. These data support the safety of gaseous NO in polypropylene membrane oxygenators for limited-term cardiopulmonary bypass.

Hematologic evaluation of cardiopulmonary bypass circuits prepared with a novel block copolymer.

BACKGROUND: To decrease the complications associated with cardiopulmonary bypass, novel biomaterials have been introduced that may be less thrombogenic than standard synthetic surfaces. METHODS: Thirty-four patients undergoing coronary artery bypass grafting were randomized to bypass using either a control circuit or a circuit prepared "tip-to-tip" with a triblock-copolymer (polycaprolactone-polydimethylsiloxane-polycaprolactone). RESULTS: There was a progressive increase in thrombin generation in the control group during bypass, which was not seen in the test group. The test surface decreased the release of tissue plasminogen activator and plasmin-alpha2-antiplasmin complex formation (p<0.005). There was also an increased platelet count and a decreased platelet activation in the test group, as detected by GMP-140 expression and beta-thromboglobulin release (p = 0.017). There was also significantly more debris that accumulated on the arterial filter in the control group, as confirmed by scanning electron microscopy. CONCLUSIONS: This clinical trial has demonstrated a significant difference in the hematologic effects of the test circuits, with evidence of platelet preservation, decreased fibrinolysis, and decreased thrombin generation. A larger trial would be necessary to establish the clinical relevance of these differences.

Surface modifying additives for improved device-blood compatibility.

Copolymers composed of polar and nonpolar blocks, when blended with a base polymer in low concentrations, migrate to the base polymer surface during and after fabrication. Migration of these surface modifying additives (SMAs) dramatically changes the outermost surface molecular layers that comprise the region that determines biocompatibility. The blood compatibility of cardiopulmonary bypass and hemodialysis components have been improved by using SMA blended polymers or SMA coated surfaces. The particular SMAs used were a series of triblock copolymers with a general formulation of polycaprolactone-polydimethylsiloxane-polycaprolactone. X-ray fluorescence (XRF), fourier transform infrared (FTIR), refractive increments (RI), and gel permeation chromatography (GPC) were used to characterize the molecular weight of SMA and the bulk concentration of SMA after blending. Electron spectroscopy for chemical analysis (ESCA) proved that the surface of blended polymers was highly saturated with SMA. Results of in vitro experiments with human blood demonstrated that SMA blended polymers delay contact activation (kallikrein-like activity), reduce coagulation activity (thrombin-antithrombin [TAT] generation), and do not adversely affect complement activation (terminal complement complex [TCC] generation) or mononuclear cells activation (IL-1 beta production). Ex vivo canine AV shunt studies showed improvement of platelet compatibility of SMA blended polymers. Reduction of cellular and protein system activation by using components fabricated with SMA blood contacting surfaces can potentially result in reduced morbidity associated with extracorporeal circulation.

Evaluation of platelet damage in extracorporeal circuits using a visual platelet morphology method.

Platelet damage in extracorporeal circuits occurs as the result of contact with foreign surfaces, shear stress, gas interface, and other nonphysiologic conditions. A scoring method developed to determine platelet activation was modified for evaluating platelet damage in extracorporeal circuits. This method assigns a numerical score to platelet damage, as assessed by direct visualization with phase microscopy. Various commercially available blood oxygenators were tested by using a modified AAMI/ASAIO in vitro blood trauma protocol. Direct gas contact oxygenators showed a marked decrease in total platelet count and significant platelet damage. Platelet depletion and platelet damage were lower in membrane oxygenators than in direct gas contact oxygenators. Differences in platelet damage were observed between membrane oxygenators. The observed differences between devices demonstrate the influence of materials and hemodynamic design on platelet depletion and damage. The method developed allows quantitative evaluation of platelet damage caused by extracorporeal devices and is a sensitive indicator of lethal and sublethal trauma.