The effect of combined arterial hemodynamics on saphenous venous endothelial nitric oxide production

Introduction: Evidence exists that an ideal bypass conduit should have a fu nctional endothelial cell surface combined with mechanical properties simil ar to those of native arteries. We hypothesized that the effect of combined arterial levels of pulsatile shear stress, flow, and cyclic strain would e nhance saphenous venous endothelial cell nitric oxide (NO) production, and that variations in these "ideal" conditions could impair this function. We studied NO production as a measure of endothelial function in response to d ifferent hemodynamic conditions. Methods: Human adult saphenous venous endothelial cells were cultured in 10 -cm silicone tubes, similar in diameter (5 mm) and compliance (6%) to a med ium-caliber peripheral artery (eg, popliteal). Tube cultures were exposed t o arterial conditions: a combined pressure (120/80 mm/Hg; mean, 100 mm/Hg), flow (mean, 115 mL/min) and cyclic strain (2%), with a resultant pulsatile shear stress of 4.8 to 9.4 dyne/cm(2) (mean, 7.1). Identical tube cultures were used to study variations in these conditions. Modifications of the sy stem included a noncompliant system, a model with non-pulsatile flow, and a final group exposed to pulsatile pressure with no flow NO levels were meas ured with, fluorometric nitrite assay of conditioned media collected at 0, 0.25, 0.5, 1, 2, and 4 hours. Experimental groups were compared with cells exposed to nonpulsatile, nonpressurized low flow (shear stress 0.1 dyne/cm( 2)) and static cultures. Results: Ah experimental groups had greater rates of NO production than cel ls under static conditions (P < .05). Cells exposed to ideal conditions pro duced the greatest levels of NO. Independent decreases in compliance, flow, and pulsatility resulted in significantly lower rates of NO production tha n those in the group with these conditions intact (vs noncompliant P < .05, vs nonflow P < .05, and vs nonpulsatile P < .05). Conclusions: Our results show that in the absence of physiologically normal pulsatility, cyclic strain, and Volume flow endothelial NO production does not reach the levels seen under ideal conditions. Pulsatile flow and compl iance (producing flow with cyclic stretch) play a key role in NO production by vascular endothelium in a three-dimensional hemodynamically active mode l. This correlates biologically with clinical experience linking graft infl ow and runoff and the mechanical properties of the conduit to long-term pat ency.