SUMMARY Diastolic time (DT) is calculated as the cycle length (RR) minus electromechanical systole (QS2). The ratio of DT (RR-QS2) to RR interval times 100, or the percent diastole (%D), varies nonlinearly with heart rate (HR), increasing rapidly with decreasing HR. The effect of commonly used cardioactive agents on %D was studied in five groups of normal subjects.In group I (n = 12), propranolol (160 mg daily) increased %D from 55. DIASTOLIC TIME can be calculated as the cardiac cycle (RR) minus electromechanical systole (QS2). It has a curvilinear relationship with heart rate (HR), increasing rapidly as rates fall below 75 beats/min. Cardioactive drugs may affect diastolic time by altering HR, QS2 or both. Subendocardial perfusion and perfusion distal to a significant obstruction in patients with coronary artery disease is nearly all diastolic. As such, it is related not only to diastolic perfusion pressure and microcirculatory tone, but also to the diastolic time.'-'0 While the effect of cardioactive drugs on systolic time intervals (STIs) has been studied,'1-14 the effect of these agents on diastole has not been emphasized. In this study we investigated the effect of commonly used cardioactive drugs on diastolic time in normal subjects.Material and Methods

The observation of intimal hyperplasia at bypass graft anastomoses has suggested a potential interaction between local hemodynamics and vascular wall response. Wall shear has been particularly implicated because of its known effects upon the endothelium of normal vessels and, thus, was examined as to its possible role in the development of intimal hyperplasia in arterial bypass graft distal anastomoses. Tapered (4-7 mm I.D.) e-PTFE synthetic grafts 6 cm long were placed as bilateral carotid artery bypasses in six adult, mongrel dogs weighing between 25 and 30 kg with distal anastomotic graft-to-artery diameter ratios (DR) of either 1.0 or 1.5. Immediately following implantation, simultaneous axial velocity measurements were made in the toe and artery floor regions in the plane of the anastomosis at radial increments of 0.35 mm, 0.70 mm, and 1.05 mm using a specially designed 20 MHz triple crystal ultrasonic wall shear rate transducer Mean, peak, and pulse amplitude wall shear rates (WSRs), their absolute values, the spatial and temporal wall shear stress gradients (WSSG), and the oscillatory shear index (OSI) were computed from these velocity measurements. All grafts were harvested after 12 weeks implantation and measurements of the degree of intimal hyperplasia (IH) were made along the toe region and the artery floor of the host artery in 1 mm increments. While some IH occurred along the toe region (8.35+/-23.1 microm) and was significantly different between DR groups (p<0.003), the greatest amount occurred along the artery floor (81.6+/-106.5 microm, mean +/- S.D.) (p < 0.001) although no significant differences were found between DR groups. Linear regressions were performed on the paired IH and mean, peak, and pulse amplitude WSR data as well as the absolute mean, peak, and pulse amplitude WSR data from all grafts. The mean and absolute mean WSRs showed a modest correlation with IH (r = -0.406 and -0.370, respectively) with further improvements seen (r = -0.482 and -0.445, respectively) when using an exponential relationship. The overall best correlation was seen against an exponential function of the OSI (r = 0.600). Although these correlation coefficients were not high, they were found to be statistically significant as evidenced by the large F-statistic obtained. Finally, it was observed that over 75 percent of the IH occurred at or below a mean WSR value of 100 s(-1) while approximately 92 percent of the IH occurred at or below a mean WSR equal to one-half that of the native artery. Therefore, while not being the only factor involved, wall shear (and in particular, oscillators wall shear) appears to provide a stimulus for the development of anastomotic intimal hyperplasia.

Flow in distal end-to-side anastomoses of iliofemoral artery bypass grafts was simulated using a steady flow, three-dimensional numerical model. With the proximal artery occluded, anastomotic angles were varied over 20, 30, 40, 45, 50, 60 and 70 deg while the inlet Reynolds numbers were 100 and 205. Fully developed flow in the graft became somewhat skewed toward the inner wall with increasing angle for both Reynolds numbers. Separated flow regions were seen along the inner arterial wall (toe region) for angles > or = 60 deg at Re = 100 and for angles > or = 45 deg at Re = 205 while a stagnation point existed along the outer arterial wall (floor region) for all cases which moved downstream relative to the toe of the anastomosis with decreasing angles. Normalized shear rates (NSR) along the arterial wall varied widely throughout the anastomotic region with negative values seen in the separation zones and upstream of the stagnation points which increased in magnitude with angle. The NSR increased with distance downstream of the stagnation point and with magnitudes which increased with the angle. Compared with observations from chronic in vivo studies, these results appear to support the hypothesis of greater intimal hyperplasia occurring in regions of low fluid shear.

SUMMARY Autologous femoral veins grafted between the external iliac arteries in 18 dogs provided a model for studying the hemodynamics and histopathology of vein graft bypasses. The angle of proximal anastomosis was varied by groups (<90°, 90°, >90°) to produce a wide range of flow conditions within the grafts. Four months after implantation, point velocity measurements of blood flow and histological examination of the superior and inferior walls were made at proximal, middle, and distal locations in each graft. Hot-film velocity measurements revealed outwardly skewed velocity profiles in the proximal locations in all grafts, and flow visualization models showed secondary fluid motions and separation zones at those regions. Velocity profiles in the middle and distal regions of the grafts were more symmetrical and showed no flow separation. Histological examination of wall sections along the graft length showed that intimal proliferation occurred focally and ranged from 1 to 100 fita in thickness. No signficant correlation between graft angle and degree of intimal proliferation was found. However, there was a weak inverse correlation between the apparent fluid shear rate and the corresponding degree of intimal proliferation, with the greatest proliferation occurring in the regions experiencing the lowest shearing forces. Regions of low shear rate should be avoided by maintaining adequate flow rates through the grafts and thus minimising losses of patency due to both thrombus formation and intimal proliferation.