A Heparin-Coated Circuit Reduces Complement Activation and the Release of Leukocyte Inflammatory Mediators During Extracorporeal Circulation in a Rabbit

Heparin coating modifies complement activation during extracorporeal circulation much more effcclively than systemically administered heparin. This rabbit study was undertaken to address possible mechanisms responsible for this difference. We evaluated the effect of heparin coating on complement activation and subsequently the release of leukocyte inflammatory mediators during extracorporeal circulation through a simplified circuit. We found in the heparin-coated group a significantly reduced complement hemolytic activity (CH 50 ), remaining higher leukocyte numbers, significantly decreased release of -glucuronidase, and most strikingly a complete prevention of tumor necrosis factor (TNF) formation. The significantly reduced CH 50 activity in the heparin-coated groups indicates the reduction of one or more native classical complement products. This could be explained by the absorption of complement components by the circuit, which results in reduced activity of the complement cascade. We conclude therefore that heparin coating reduces complement activation and consequently reduces the release of leukocyte inflammatory mediators.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73454/1/j.1525-1594.1992.tb00533.x.pd

Platelet consumption during neonatal extracorporeal life support (ECLS)

This paper reports the results of a retrospective study of blood use and blood loss in 40 neonates during extracorporeal life support (ECLS). Immediately after onset of bypass 39±2.5ml platelets, 59.4±6.5ml packed red blood cells (PRBC) and 15.0±5.4ml fresh frozen plasma (FFP) per patient were needed. The average daily amount given per patient was 49.0±3.0ml of platelets and 48.0±3.4ml and 9.6±3.9ml of PRBC and FFP respectively. The 10 patients who had bleeding complications received 50.0±6.3ml/day of platelets compared to 49.0±3.4ml in the other patients. The majority of blood loss during the entire period of ECLS was from samples, averaging 43.0 ± 1.5ml/day. Neck wound drainage, 6.7±2.5ml/day per patient, lasted for the entire period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68887/2/10.1177_026765919200700106.pd

Pressure-diameter relationship in the human greater saphenous vein

BACKGROUND: Compliance of artificial and autologous vascular grafts is related to future patency. We investigated whether differences in compliance exist between saphenous vein grafts derived from the upper or lower leg, which might indicate upper or lower leg saphenous vein preference in coronary artery bypass surgery. Furthermore, the effect of perivenous application of fibrin glue on mechanical vein wall properties was studied to evaluate its possible use as perivenous graft support. METHODS: Vein segments (N = 10) from upper or lower leg saphenous vein grafts were collected for histopathologic examination and smooth muscle cell/extracellular matrix (SMC/ECM) ratio was calculated. This ratio is suggested to be related with vascular elastic compliance. In a second group vein graft segments (N = 6) from upper and lower leg were placed in an in vitro model generating stepwise increasing static pressure up to 150 cm H(2)O. Outer diameter was measured continuously with a video micrometer system. Distensibility was calculated from the pressure-diameter curves. A third group of vein graft segments (N = 7) was pressurized after fibrin glue application to prevent overdistension, and studied in the same setup. RESULTS: Vein segments from the lower leg demonstrated a consistent higher relative response compared with the upper leg saphenous vein graft (0.9176 +/- 0.03993 vs 0.5245 +/- 0.02512). Both reach a plateau in the high-pressure range (> 100 cm H(2)O). A significant difference in in vitro distensibility between upper and lower leg saphenous vein was only found at a pressure of 50 cm H(2)O (p < 0.05). With fibrin glue, support overdistension is prevented as revealed by the maximum relative response between fibrin glue supported upper and lower leg saphenous vein segments (0.4080 +/- 0.02464 vs 0.582 +/- 0.051), and no plateau is reached in the pressure range up to 150 cm H(2)O. CONCLUSIONS: No upper or lower leg saphenous vein preference could be deduced from the differences in pressure-diameter response due to loss of distensibility (and thus of compliance) in the high-pressure range. Fibrin glue effectively prevents overdistension and preserves some distensibility in the high-pressure range in both the upper and lower leg saphenous vein. This might provide a basis for clinical application of perivenous support

Reduced complement activation and improved postoperative performance after cardiopulmonary bypass with heparin-coated circuits

A randomized controlled trial that involved 30 patients undergoing elective coronary artery bypass grafting was done to determine the effect of heparin-coated circuits and full heparinization on complement activation, neutrophil-mediated inflammatory response, and postoperative clinical recovery. Peak concentrations of terminal complement complex were 38% lower (p = 0.004) in 15 patients treated with heparin-coated circuits (median 775 μg/L, interquartile range 600 to 996) compared with those in 15 patients treated with uncoated circuits (median 1249 μg/L, interquartile range 988 to 1443). Although no significant intergroup differences in concentrations of polymorphonuclear neutrophil elastase were found, a positive correlation (r s = 0.74, p < 0.0007) was calculated between peak concentrations of terminal complement complex and polymorphonuclear neutrophil elastase. Differences in patient recovery were analyzed with use of a score composed of fluid balance, postoperative intubation time, and the difference between rectal temperature and skin temperature. The score was significantly lower in patients treated with heparin-coated circuits (p = 0.03), whereas its components showed no intergroup significance. We conclude that the use of heparin-coated circuits with full systemic heparinization results in improved biocompatibility, as assessed by complement activation, and leads to an improved postoperative recovery of the patient. (J THORAC CARDIOVASC SURG 1995;110: 829-34)

The impact of heparin coated circuits upon metabolism in vital organs: effect upon cerebral and renal function during and after cardiopulmonary bypass

During cardiopulmonary bypass (CPB), the brain and the kidneys may be damaged because of microemboli, ischemia, and inflammation. The latter has been reduced by the use of heparin coated circuits. We questioned whether heparin coated circuits could also reduce cerebral and renal damage and whether inflammatory markers correlate with damage to the brain and the kidneys. Fifty-one patients scheduled for coronary artery bypass grafting were perfused with either a heparin coated or an uncoated circuit. To compare the effect of a heparin coated circuit with an uncoated circuit upon cerebral and renal function in relation to inflammation, we assessed markers of cerebral (S100beta) and renal (N-acetyl-beta-D-glucosaminidase [NAG], creatinine, and urea) function, inflammation, and oxygen metabolism. S100beta levels and NAG levels increased during CPB in both groups as compared with baseline levels (p <0.01), without differences between the groups. After 15 minutes on CPB, C4b/c levels were significantly higher in the coated group compared with the uncoated group (p <0.02). C4b/c correlated with S100beta (p <0.01). Total body oxygen delivery (DO2) and consumption (VO2) decreased significantly in both groups during CPB (p <0.01), but recovery was better in the coated group. After protamine infusion, total body oxygen delivery and consumption correlated negatively with S100beta levels (both p <0.05) and with NAG levels (both p <0.01). This study suggests that, if adequate tissue perfusion is not maintained, the use of a heparin coated circuit gives no additional benefit beyond that of the uncoated circuit. The inverse relationship of both cerebral and renal markers with DO2 and VO2 suggests that increased levels of S100beta and NAG during CPB may primarily be caused by an oxygen deficit and secondary to the inflammatory respons