High Shear Thrombus Formation under Pulsatile and Steady Flow

Abstract

Most previous studies have investigated in vitro thrombus formation under steady flow conditions at physiological shear rates, though occlusive thrombosis leading to myocardial infarction and stroke forms under elevated shear rates and pulsatile flow. Two reports of pulsatile flow on thrombosis have yielded conflicting results. In the present study, we quantify the effect of very high shear, reversing pulsatile flow relevant to coronary thrombosis on platelet deposition leading to occlusive thrombus formation. Whole porcine blood was perfused in a collagen-coated, tubular, stenotic test section under pulsatile or steady flow. Pulsatile flow was generated with a frequency of 60 beats per minute and large magnitude excursions similar to a coronary artery waveform. Alternatively, steady flow conditions from a pressure driven system created shear rates matched to the maximum (16000 s−1), mean (3800 s−1), and an intermediate (6500 s−1) shear rates corresponding to the pulsatile system. Thrombus growth in thickness was recorded using a high-resolution CCD attached to a microscope. Steady flow recreated pulsatile flow thrombus formation in most cases. Lag time, t lag, thrombus growth rate, dV/dt, and time to occlusion, t occ, did not show statistically significant differences between pulsatile flow and steady flow with matched mean shear rate. Pulsatile flow conditions yielded t occ = 5.5 ± 2.8 min, which was not significantly different compared to a steady mean shear rate condition with t occ = 6.2 ± 1.7 min. Similarly, occlusion times for steady intermediate and steady maximum shear rate conditions were not significantly difference from pulsatile flow conditions yielding t occ of 4.6 ± 2.9 and 4.6 ± 1.8 min, respectively. In contrast, lag time for steady flow at maximum shear rate of 16000 s−1 was decreased to 26.1 s compared to pulsatile flow (t lag = 42.7 s, p = 0.03), steady mean flow (t lag = 60.9 s, p = 0.02), and steady intermediate flow (t lag = 39.9 s, p = 0.01). Occlusive thrombus formation under high shear, pulsatile conditions may be modeled in vitro using steady flow with matched mean shear rate with respect to occlusion time, lag time, and growth rate. Our results indicate that the magnitude of shear rate more strongly affects thrombus growth characteristics than flow pulsatility for an arterial frequency.