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1.
A mathematic model of unilateral iliac vein obstruction was used to establish the theoretic basis for selecting saphenous vein or a larger diameter prosthetic cross-femoral venous bypass graft for relief of obstructive venous hypertension. Common femoral vein resting and postexercise peak flows, and common femoral vein and saphenous vein diameters were measured in 18 healthy individuals and used to estimate the pressure gradient (dP) across 20 cm long cross-femoral venous bypass grafts of saphenous vein or 4, 6, 8, 10, and 12 mm prosthetic conduits, in the presence of a transpelvic venous collateral network of varied cross section. The upper limits of normal for the gradients in our model (dPstd) were set at 4 mm Hg for resting flows and 6 mm Hg after exercise. Mean saphenous vein diameter was 4.3 +/- 0.22 mm, which was 36.5% +/- 1.73% of common femoral vein diameter. When the saphenous veins of two thirds of the individuals in our study were used as theoretic cross-femoral venous bypass conduits, greater than 80% of postobstruction peak cross-femoral venous bypass graft flow had to be carried by collaterals to maintain a gradient less than or equal to dPstd. We demonstrated that 4.5 to 6.0 mm diameter saphenous cross-femoral venous bypass grafts would be hemodynamically efficacious in relieving venous hypertension, but only when implanted in parallel with an existing venous collateral network that limited the preoperative dP to 4.5 to 7.5 mm Hg at resting flows and 7.0 to 11.5 mm Hg after exercise; only 44% of saphenous veins were adequate for cross-femoral venous bypass grafts by these criteria.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

2.
A canine model of occlusive hindlimb venous hypertension was used to determine which of two different, clinically applicable, adjunctive arteriovenous fistulas (AVFs), sequential or peripheral, would augment flow in autogenous cross-femoral venous bypass grafts (CFBs) with the least alteration of hindlimb hemodynamics. Unilateral venous hypertension was produced by iliofemoral venous ligation in three groups of five dogs: group I, venous ligation only (controls); group II, venous ligation followed by CFB with a sequential AVF; and group III, venous ligation with CFB and peripheral AVF. Bilateral hindlimb venous and arterial pressures and flows, and graft flows, were measured preoperatively and for 4 h postoperatively. Insertion of a CFB eliminated the venous hypertension in all 10 bypass dogs. Graft flow was augmented by addition of the sequential AVF (to 1167 +/- 309 mL/min from 92 +/- 12.3 mL/min: p less than .0001). However, this was accompanied, both in the limb ipsilateral to the AVF and in the contralateral limb, by the return of significant venous hypertension (p less than .001) and significant reduction (even reversal) of femoral vein flow caudad to the CFB (p less than .005). In contrast, adding the peripheral AVF augmented graft flow (to 200 +/- 62 mL/min from 65 +/- 43.7 mL/min; p less than .0001), but did not elevate venous pressure or impair venous flow in either hindlimb. The data from this short-term canine model suggest that a peripheral adjunctive AVF may effectively augment CFB graft flow without the potential for detrimental effects on venous hemodynamics characteristic of the sequential AVF.  相似文献   

3.
A short-term canine model of lower extremity venous hypertension was created to study the hemodynamics of crossfemoral venous bypass grafts (CFB). Specifically, the hemodynamic effects of bypass conduit diameter and adjunctive arteriovenous fistulas (AVFs) were investigated. Unilateral hind limb venous hypertension was produced by iliofemoral venous ligation in six groups of five greyhounds each. Group I had venous ligation alone. CFBs were constructed in the remaining five groups: group II, 3 mm bypass conduit alone; group III, 3 mm bypass plus sequential AVF; group IV, 3 mm bypass plus caudad AVF; group V, 3 mm bypass plus cephalad AVF; group VI, 6 mm bypass conduit alone. Venous hypertension was significantly reduced by CFB (group II, p less than 0.025; group VI, p less than 0.001); increasing the diameter of the bypass conduit from 3 to 6 mm produced significantly greater graft flow (p less than 0.05), while completely relieving venous hypertension. Addition of adjunctive AVFs significantly augmented graft flow (p less than 0.001) but tended to aggravate ipsilateral venous hypertension (group III, p less than 0.01; group IV increase, NSS; group V, p less than 0.001). During the 4 hours of pressure monitoring, venous hypertension diminished significantly (p less than 0.05) with the sequential AVF but not with the other AVF. We conclude that (1) AVFs may be required for adequate graft flow if a small-diameter (3 mm) bypass conduit is used to relieve venous hypertension; (2) adjunctive AVFs aggravate venous hypertension; (3) sequential AVFs seem to be the most hemodynamically efficacious; (4) AVFs may not be necessary if a large, isodiametric (6 mm) conduit is used.  相似文献   

4.
Saphenous vein resistance influences graft flow rates and may affect graft patency in lower limb revascularization. To quantitate specifically the contribution of saphenous vein valves to this resistance, 10 human saphenous veins (mean length 68 cm, diameter 0.42 mm, and 5.2 valves per vein) were perfused with water under carefully controlled pressure gradients designed to simulate different peripheral resistances in the outflow bed. The Reynolds number was maintained at 350 to 600, within the physiologic range for in vivo grafts. Veins were perfused under both venous (10 mm Hg) and arterial (100 mm Hg) mean pressures to determine the effects of distension on the overall resistance of the conduit. The valves were bisected according to Leather's techniques and flow was measured in both directions, antegrade (simulating "reversed" grafts) and retrograde (simulating "in situ" grafts). Data (mean +/- standard error) were normalized to the baseline flow for each vein with intact valves and expressed as a percentage change. Data were analyzed by means of Student's t test (p less than 0.05). Baseline antegrade flow with intact valves averaged 71.0 +/- 3.0 ml/min at pressure gradients (delta P) of 10 mm Hg and 95.0 +/- 2.6 ml/min for delta P = 20 mm Hg. After valve incision, antegrade flow (reversed) increased an average of 29% at both pressure gradients. Retrograde flow (in situ) through the bisected valves was only 19% greater than baseline antegrade flow and was significantly less than antegrade flow through bisected valves. The difference is explained by theoretic considerations of stenosis area and orifice shape. The increases in flow did not correlate with vein length or diameter, nor did flow change with different distension pressures.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

5.
We performed intraoperative pressure monitoring in a clinical setting and demonstrated that the average venous distention pressure observed during preparation of autogenous vein grafts for arterial implantation was 300 to 500 mm Hg and often exceeded 500 mm Hg. Similar data on venous distention pressures were obtained by Ramos et al [4] and by Abbott et al [1]. Although the exact relation between venous distention pressure, venous endothelial fibrinolytic activity and long-term autogenous vein graft patency is unknown, our data suggest that autogenous vein graft distention pressure should be kept under 500 mm Hg during graft procurement and static pressure testing before venous autograft implantation. Ideally, either venous distention pressure should be monitored during vein graft harvesting and preparation, and kept as low as possible, or procured autogenous vein grafts should not be statically distended but rather allowed to gradually enlarge due to pulsatile arterial flow after implantation.  相似文献   

6.
The relative effects of distention, intraluminal pressure, and wall tension on venous smooth muscle and endothelial cell function were examined in 40 external jugular veins from New Zealand white rabbits. Vein grafts (n = 5) were interposed in the common carotid artery and explanted after 10 minutes. Distended veins were inflated in vitro with modified Krebs' solution at 37 degrees C for 10 minutes at pressures of either 20 mm Hg (D-20; n = 5) or 80 mm Hg (D-80; n = 5). Externally supported veins (ES-80; n = 5) were inflated at 80 mm Hg pressure, but distention was prevented by covering with a 3 mm internal diameter polytetrafluoroethylene sleeve. Bradykinin-induced in vitro maximal tension was attenuated significantly in vein grafts (0.13 +/- 0.04 g) and D-80 rings (0.27 +/- 0.07 g) compared with D-20 rings (1.20 +/- 0.14 g), ES-80 rings (0.99 +/- 0.13 g), or nondistended control rings (n = 40; 1.19 +/- 0.10 g; p less than 0.001). The attenuation in contraction in the vein graft and D-80 groups was nonspecific (i.e., similar results were obtained with respect to other smooth muscle agonists). Contractile function was inversely associated with wall tension, the product of pressure and radius (r2 = 0.7438; p = 0.06). In contrast, there were no differences in endothelium-dependent or endothelium-independent relaxation among the five groups. It is concluded that, in this experimental system, (1) venous smooth muscle function is significantly attenuated after short-term in vitro distention or grafting although endothelial function is largely preserved, and (2) the decrement in contraction is due to elevated wall tension.  相似文献   

7.
While it is generally thought that collateral back pressure (CBP) is a reliable predictor of graft patency, this correlation has not yet been validated. We have used a new, simple technique to measure CBP without direct puncture of the recipient artery. After the distal anastomosis is completed, the graft is filled with saline and clamped proximally. A transducer connected needle is then inserted into the distal portion of the graft for CBP measurements (mm Hg). These were obtained in 84 grafts (43 femoropopliteals [FP] and 41 femorodistals [FD]). Outflow resistance (OR) measurements (mm Hg/ml/min) were also obtained in 70 (36 FP; 34 FD) of these grafts by a previously described technique. The mean CBP for FP and FD bypasses was 41 +/- 17 and 26 +/- 19 mm Hg, respectively (P less than 0.001). Although early graft patency (3 months) (13 occluded, 71 patent) did not correlate with angiographic findings of popliteal runoff or integrity of pedal arch, it did significantly relate to CBP. Mean CBP for occluded grafts was 22 +/- 17 mm Hg and for patent grafts it was 36 +/- 19 mm Hg (P less than 0.01). Similarly, mean OR was significantly related to patency, 1.29 +/- 0.23 mm Hg/ml/min for occluded grafts and 0.36 +/- 0.23 mm Hg/ml/min for patent grafts (P less than 0.0001). Moreover, only OR was a significant predictor of infrapopliteal graft patency (P less than 0.01). OR was found to be a better predictor of graft patency than CBP by stepwise logistic regression analysis (P less than 0.0001). We conclude that CBP is a more reliable predictor of graft outcome than angiographic criteria.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

8.
To evaluate the effect of dipyridamole on coronary bypass graft flow, 10 mg of dipyridamole was injected intravenously, during the measurement of graft flow, at the time of surgery. Its concentration in serum was measured and compared with that after oral administration. In 50 individual vein grafts performed on 35 patients, graft flow increased from 65 +/- 37 to 96 +/- 55 ml/min (p less than 0.001) after the dipyridamole injection and the arterial pressure decreased slightly. In 40 grafts whose graft flow was increased by more than 10 ml/min by dipyridamole, the patency rate (at 5 weeks) was 98 per cent, whereas that of the 10 other grafts, which responded poorly, was only 50 per cent (p less than 0.01). The serum concentration of dipyridamole, 3 minutes after intravenous injection, was 1.46 +/- 0.68 micrograms/ml, while the level of orally administered dipyridamole, in 3 groups of patients who were given 50 mg, 75 mg and 100 mg, three times a day, respectively, was steady, being 0.68 +/- 0.20 micrograms/ml, 1.43 +/- 0.41 micrograms/ml and 1.73 +/- 0.50 micrograms/ml, 2 hours following ingestion. We concluded that intravenous dipyridamole increases the graft flow and that a better patency is obtained in those grafts in which the graft flow is increased by more than 10 ml/min. It is also expected that routine doses of oral dipyridamole possibly increase the graft flow after coronary bypass surgery.  相似文献   

9.
A canine model was designed to evaluate the changes in abdominal aortic aneurysm (AAA) pressure and wall stress after endovascular repair. Eight canines underwent laparotomy and creation of an AAA. The aneurysm was then excluded with a transluminally placed endovascular graft (TPEG) inserted through the right femoral artery and deployed across the AAA to exclude the infrarenal aortic branches from aortic perfusion. Blood pressure and flow data were recorded for 6 hours. The AAA blood pressure decreased from 135 ± 9.3 mm Hg before exclusion to 45 ± 17.6 mm Hg at 10 minutes after exclusion (p < 0.001). At 6 hours, AAA blood pressure had declined further to 26 ± 12.5 mm Hg. Blood flow in the excluded iliac artery decreased from a baseline of 242 ± 58 ml/min to 41 ± 29 ml/min 10 minutes after TPEG placement (p < 0.001). At 6 hours, flow was reduced to 12 ± 3.5 ml/min (p < 0.05 compared with that at 10 minutes). Aortic wall stress was significantly reduced by TPEG placement but was only slightly lower than baseline aortic wall stress before AAA creation. The lumbar arteries were patent with retrograde flow in all cases and were found to be the major contributors to postexclusion aneurysm pressure. Endovascular AAA exclusion results in an immediate decrease in blood pressure and wall stress within the excluded aneurysm, but the aneurysm remains perfused by retrograde flow through the lumbar arteries, which resulted in near-baseline levels of aneurysm wall stress in this canine model. Embolization of patent lumbar vessels at prosthesis placement may further reduce the risk of late rupture.Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995.  相似文献   

10.
There is controversy regarding the flow reserve and capacity of arterial conduits to meet the needs of the myocardium. This study compared flow in 22 free arterial bypasses to 15 saphenous vein grafts in procedures involving twenty patients. To assess the maximal flow possible, (flow capacity) graft flow was measured using a calibrated pump while perfusing blood cardioplegia through the conduit and distal anastomosis during cardiac arrest (no competitive flow). This assessment was subsequently confirmed with whole blood during myocardial contraction while on cardiopulmonary bypass. Twenty-two free arterial grafts were used; 15 right internal mammary artery grafts, 4 right gastroepiploic grafts, 3 inferior epigastric artery grafts, and 3 sequential bypasses. Free arterial conduit flow ranged from 50 to 180cc/ml, with an average flow of 102.5+/-28.5ml/min as compared to saphenous vein graft flow, 102+/-28 ml/min. No correlation of flow with the conduit size was found. Arterial graft flow demonstrated a mild correlation with the size of the native coronary artery bypassed (R=0.47, P相似文献   

11.
OBJECTIVE: Internal diameter is a strong predictor of patency of infrainguinal vein grafts. However, most vein grafts are tapered, with variable diameter along their length. It is unknown which diameter is most important in determining graft resistive properties, that is, its mean diameter, minimum diameter, or some geometric combination thereof. The purpose of this analysis was to examine the hydraulic consequences of vein graft tapering, with longitudinal impedance (Z(L)), a conduit-specific measure of pulsatile resistance along straight rigid tubes. METHODS: Proximal and distal graft pressure, pressure gradient (DeltaP), and blood flow (Q) were measured intraoperatively in a 100 cm bypass graft and digitally recorded for 10 seconds at 200 Hz. With the Womersley solution for fully developed fluid flow in a rigid tube, a series of DeltaP waveforms were generated for graft diameters ranging from 1.2 to 8.2 mm. With an axisymmetric form of the Navier-Stokes equations, a second series of DeltaP waveforms were computed for grafts with long smooth symmetric tapers ranging from 0% to 90%, with geometric mean diameter of 3.2, 4.2, and 5.2 mm (%Taper = 100 x [proximal diameter - distal diameter]/proximal diameter). For each set of DeltaP and Q, Z(L) was calculated as DeltaP/Q, plotted over a range of 8 Hz, and integrated over 4 Hz to yield integral Z(L). RESULTS: The architecture of the calculated DeltaP and Z(L) waveforms closely approximated their measured counterparts, validating the method. As expected, Z(L) was highly diameter-dependent in a nonlinear fashion. With a clinically relevant boundary of less than 50 x 10(3) dyne/cm(5) as "acceptable," the minimum acceptable diameter of nontapered 100 cm bypass conduits was 4.3 mm. Analysis of graft taper revealed that small amounts of taper in large conduits were well-tolerated. For example, introduction of 32% taper in a 5.2 mm graft (6.2 mm --> 4.2 mm) caused only an 8% increase in integral Z(L) (from 32 to 35 x 10(3) dyne/cm(5)). More pronounced taper in smaller conduits rendered them unacceptable. For example, 53% taper of a 4.2 mm graft (5.7 mm --> 2.7 mm) created a conduit with integral Z(L) of 70 x 10(3) dyne/cm(5), well above the acceptable limit. The relationship between Z(L) and percent taper was nonlinear and strongly dependent on mean diameter. CONCLUSIONS: The relationship between Z(L) and diameter in vein grafts is nonlinear; thus Z(L) increases rapidly in conduits smaller than 4 mm. Tapered vein grafts behave hydraulically like nontapered grafts, provided their geometric mean is greater than 4 mm and their degree of taper is less than 40%. Tapered veins are satisfactory conduits for long-segment bypass grafts, provided their mean diameter is acceptable.  相似文献   

12.
The internal mammary artery is a dynamic coronary graft, whereas the saphenous vein graft is passive. Therefore, potential exists not only for beneficial vasodilation but also for catastrophic spasm of the artery. The purpose of this study was to examine blood flow in the internal mammary and saphenous vein grafts during infusion of drugs that are commonly used after cardiac operations. A canine right heart bypass preparation allowed precise control of cardiac output, blood pressure, and heart rate, which were maintained constant during drug infusion. Both the internal mammary and saphenous vein grafts were constructed so that they perfused the same coronary bed: They were anastomosed in a Y fashion to a ligated anterior descending coronary artery. Electromagnetic flow probes measured graft flow (with the other graft occluded) before and after 15 minutes of drug infusion. The order of drug infusion was randomized and changes were compared by tests for paired differences. Phenylephrine (2 micrograms/kg/min) decreased flow in both the internal mammary and saphenous vein grafts, whereas norepinephrine (0.1 microgram/kg/min) increased flow in both grafts. Epinephrine (0.05 microgram/kg/min) increased mammary artery flow 16% +/- 6% but decreased saphenous vein graft flow 9% +/- 7%. Nitroglycerin (1 microgram/kg/min) significantly increased internal mammary flow (36% +/- 13%), from 47 +/- 7 to 59 +/- 7 ml/min (p less than 0.01), whereas flow decreased significantly in the saphenous vein graft 14% +/- 3%, from 64 +/- 9 to 59 +/- 8 ml/min (p less than 0.01). Nitroprusside (1 microgram/kg/min) decreased mammary artery flow 12% +/- 2%, from 50 +/- 7 to 44 +/- 7 ml/min (p less than 0.01), but increased saphenous vein graft flow 25% +/- 8%, from 64 +/- 9 to 77 +/- 7 ml/min (p less than 0.01). All hemodynamic variables were unchanged, except for norepinephrine, which significantly increased the first derivative of left ventricular pressure. The results suggest that flow through the canine internal mammary artery is changed by the drugs commonly used in perioperative management. Epinephrine and nitroglycerin increased internal mammary artery flow and decreased saphenous vein graft flow, whereas nitroprusside had the opposite effect. The vascular reactivity of the internal mammary artery must be considered when these drugs are used after coronary revascularization.  相似文献   

13.
BACKGROUND: Hemodialysis patients require a vascular access to deliver sufficient blood flow to the artificial kidney. Of these vascular accesses, 30% are prosthetic (mainly polytetrafluorethylene [PTFE]) graft implants. These grafts are prone to the development of stenosis in the vein due to intimal hyperplasia, subsequently leading to thrombosis and graft failure. AIM: We investigated the hemodynamics in a straight and a tapered PTFE-graft and compare the hydrodynamical behavior of both grafts. MATERIALS AND METHODS: Two different vascular access geometry models were examined: a 6-mm diameter straight graft and a 4- to 7-mm tapered graft. The grafts were sutured to a compliant silicon model of an artery and vein in a loop configuration. Flow rate varied between 500 and 1500 mL/min. Two conditions were tested: 1). control: mean pressure is 100 mm Hg at the arterial inlet; and 2). low resistance condition: pressure is 20 mm Hg at the venous outlet. Pulse pressure is 60 mm Hg at the arterial inlet for both conditions. Pressure and flow velocity are measured continuously, while flow rate is measured volumetrically. RESULTS: The pressure drop at the arterial anastomosis of the tapered graft is three times higher compared to the straight graft model. Intragraft pressure drops are similar in both graft types. Mean pressure and pulse pressure in the graft and vein are decreased in the low resistance condition. Also, the difference between maximum and minimum velocity is smaller in this. CONCLUSIONS: No significant differences are noted between the graft geometries: pressure drop over the graft is almost equal. The major difference is the higher pressure drop at the arterial anastomosis of the tapered graft.  相似文献   

14.
Vasoactive agents are commonly used in the postcardiopulmonary bypass period to elevate the mean arterial pressure of myocardial revascularization patients. Concern exists that administration of vasoactive agents in this setting may affect flow through saphenous vein and internal mammary artery grafts. Twenty-eight patients were randomly assigned to receive one of the six two-drug combinations of phenylephrine, norepinephrine, and epinephrine. After termination of cardiopulmonary bypass baseline, hemodynamic measurements and electromagnetic flow probe measurements of saphenous vein and internal mammary artery graft flow were made. The first agent was then infused to elevate mean arterial pressure 20 mm Hg. After 5 minutes of stability, hemodynamic and graft flow measurements were repeated. The infusion was terminated, 5 minutes of stability were obtained, and baseline measurements were repeated. The second agent was then infused, and measurements were repeated after a 5-minute stabilization period. Phenylephrine induced a nonsignificant increase in saphenous vein graft flow (68 +/- 31 versus 81 +/- 49 ml/min) and a significant decrease in internal mammary artery graft flow (40 +/- 16 versus 32 +/- 12 ml/min). Norepinephrine induced a significant increase in saphenous vein graft flow (80 +/- 39 versus 97 +/- 39 ml/min) and no significant change in internal mammary artery graft flow (44 +/- 20 versus 45 +/- 20 ml/min). Epinephrine induced a significant increase in both saphenous vein (82 +/- 38 versus 96 +/- 40 ml/min) and internal mammary artery (38 +/- 12 versus 55 +/- 24 ml/min) graft flows. We conclude that administration of vasoactive agents in the postcardiopulmonary bypass period may significantly affect saphenous vein and internal mammary artery graft flows.  相似文献   

15.
BACKGROUND: Stenosis is a major cause of vein graft failure in peripheral arterial surgery. Our goal is to determine whether vein valves play a role in this process by creating a "pressure trap". METHODS: Seventeen patients with femoro-popliteal reversed saphenous vein grafts were studied intraoperatively. Flow and pressure in the grafts were measured, while the graft outflow was gradually occluded and released for 2-4 seconds. In 3 patients the graft flow was reduced by compressing calf muscles. RESULTS: Patients heart rates were 54-84 BPM, blood pressures 170/80-110/55 mm Hg, and normal graft flow was 40-180 ml/min. In 12 patients with competent vein valves, at reduced flow (<30 m/min) the valves opened and closed in each cardiac cycle. At each closure the pressure was "trapped" distal to the valve producing diastolic hypertension. Also the flow was stagnant for a considerable portion of the cardiac cycle. Maximum diastolic pressure gradient across the valve ranged from 35 to 60 mm Hg and the level of pressure trapped was inversely proportional to the graft flow. CONCLUSIONS: In patients in whom reversed vein grafts with competent valves are placed in the femoro-popliteal positions a "pressure-trap" develops in the distal segment. This segmental hypertension combined with the flow stagnation could play an important role in the graft thickening and stenosis.  相似文献   

16.
目的 研究脾切除贲门周围血管离断术后肝脏血流动力学及肝功能储备的变化.方法 对2006年6月至2007年8月在四川大学华西医院行脾切除贲门周围血管离断术的连续30例乙肝后肝硬化患者通过感应器连续测定手术中的门静脉压力梯度;运用彩色多普勒分别测最术前和术后肝动脉血流量、门静脉血流量、肝动脉阻力指数,通过术前和术后吲哚青绿试验分别测得有效肝血流量及ICGR15.结果 本组30例患者的门静脉压力梯度在开腹后为(19±4)mm Hg,结扎脾动脉后为(14±4)mm Hg,脾切除后为(14±3)mm Hg,贲门周围血管离断术后为(12±4)mm Hg,有逐渐下降的趋势.术后门静脉血流餐由(42±14)ml/s降至(16±8)ml/s,而肝动脉血流量代偿性增加.术后有效肝血流量由(0.48±0.10)L/min增至(0.56±0.10)L/min,而ICGR15由22%±8%减至18%±4%.结论 脾切除贲门周围血管离断术后,尽管门静脉压力梯度及门静脉血流量减少,但肝功能储备至少在术后短期内是得到了改善的.  相似文献   

17.
OBJECTIVE: Adenoviral-mediated gene transfer to arterial and venous grafts has potential in the treatment of a number of vascular diseases. Despite widespread use of these vectors to mediate gene transfer to blood vessel walls, the optimal transduction conditions for each type of vessel has yet to be determined. Our objective was to study the effect of adenoviral titer and instillation pressure on efficiency of gene transfer to arterial and venous grafts ex-vivo. METHODS: Jugular vein and carotid artery segments of 8 cm were harvested from Yorkshire Cross pigs. Tissue culture media or different titers of an adenoviral vector encoding human placental alkaline phosphatase (hpAP) were instilled into venous and arterial grafts at 0 mm Hg or 80 to 100 mm Hg of pressure and bathed externally in the same solution at 37 degrees C for 30 minutes. The grafts were rinsed, opened longitudinally, and incubated in culture media at 37 degrees C for 48 hours. Grafts were fixed and stained for hpAP transgene expression to quantitate percent luminal transduction or homogenized for alkaline phosphatase (AP) activity to determine total transmural transduction. RESULTS: For venous grafts, the percent luminal area stained for hpAP was greatest with 10(8) plaque-forming units/mL at 0 mm Hg (81% +/- 7%) and decreased with increasing titers (53% +/- 9% at 10(9) pfu/mL and 44% +/- 11% at 5 x 10(9) pfu/mL; n = 7; P <.05). No increase in percent luminal area stain was achieved with an instillation pressure of 80 to 100 mm Hg at any viral titer. The inverse finding was observed in arterial grafts. For arterial grafts, the greatest percent luminal area stained was achieved with 5 x 10(9) pfu/mL at 80 to 100 mm Hg (76% +/- 7%). An instillation pressure of 80 to 100 mm Hg increased the percent luminal area stained at 10(8) pfu/mL from 31% +/- 9% to 66% +/- 8% (n = 8; P =.01). For venous grafts, total AP activity peaked with 10(9) pfu/mL at 0 mm Hg and decreased with an instillation pressure of 80 to 100 mm Hg (30.6 +/- 9.7 U/mg versus 10.9 +/- 2.5 U/mg; n = 7; P <.01). However, for arterial grafts, total AP activity peaked with 5 x 10(9) pfu/mL (0 mm Hg) and increased with an instillation pressure of 80 to 100 mm Hg (32.8 +/- 9.9 U/mg versus 63.4 +/- 20.5 U/mg; n = 8; P <.05). CONCLUSION: High transduction efficiency can be achieved with adenoviral-mediated gene transfer of arterial and venous grafts. Gene transfer with the vascular graft's physiologic pressure conditions improved transduction efficiency for the artery (80 to 100 mm Hg) and vein (0 mm Hg). Comprehensive analysis of adenoviral transduction conditions is important to realize the full promise of adenoviral-mediated gene transfer.  相似文献   

18.
This study examines the relative contributions of intraluminal pressure, blood flow, wall tension, and shear stress to the development of myointimal thickening in experimental vein grafts. To study these different hemodynamic parameters, several experimental models were created in 30 New Zealand White rabbits separated into six groups: common carotid interposition vein grafts harvested at 4 weeks (VG-4) or 12 weeks (VG-12), common carotid-linguofacial vein arteriovenous fistulas harvested at 4 weeks (AVF-4) or 12 weeks (AVF-12), AVFs with partial outflow obstruction harvested at 4 weeks (AVFobs), and combination VG-AVFs in series harvested at 4 weeks (VGAVF). Blood pressure and flow in the graft or vein were measured by use of a transducer-tipped pressure catheter and electromagnetic flow meter. At harvest, veins were perfusion-fixed and proximal, middle, and distal sections were subjected to computerized morphometric analysis. Vein grafts were characterized by a high mean pressure (VG-4, 51 +/- 4; VG-12, 62 +/- 3 mm Hg), low mean flow (VG-4, 17 +/- 1; VG-12, 16 +/- 4 ml/min), large luminal area (VG-4, 19.7 +/- 2.4; VG-12, 19.3 +/- 3.9 mm2), high wall tension (VG-4, 17.0 +/- 1.5; VG-12, 19.5 +/- 2.4 x 10(3) dyne/cm), low shear stress (VG-4, 0.75 +/- 0.13; VG-12, 0.96 +/- 0.38 dyne/cm2), and a high degree of myointimal thickening (VG-4, 5.89 +/- 0.90; VG-12, 4.72 +/- 0.83 mm2). Arteriovenous fistulas were characterized by a low mean pressure (AVF-4, 5 +/- 1, AVF-12, 6 +/- 2 mm Hg), elevated blood flow (AVF-4, 82 +/- 16; AVF-12, 82 +/- 17 ml/min), small luminal area (AVF-4, 2.43 +/- 0.58; AVF-12, 7.14 +/- 2.68), low wall tension (AVF-4, 0.62 +/- 0.19; AVF-12, 0.89 +/- 0.24 x 10(3) dyne/cm), elevated shear stress (AVF-4, 108 +/- 32; AVF-12, 71 +/- 50 dyne/cm2), and decreased myointimal area (AVF-4, 1.18 +/- 0.26; AVF-12, 1.90 +/- 0.55 mm2). The addition of outflow obstruction to AVFs (AVFobs) resulted in elevated pressure (48 +/- 2 mm Hg), decreased flow (17 +/- 4 ml/min), larger luminal area (8.71 +/- 2.31 mm2), elevated wall tension (10.3 +/- 1.7 x 10(3) dyne/cm), and a degree of myointimal thickening approaching that of vein grafts (3.79 +/- 0.66 mm2).(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

19.
Impaired coronary flow during postischemic reperfusion may limit functional recovery. In the present studies we used the heterotopically transplanted rat heart and the isolated working rat heart to assess whether adenosine, given during reperfusion, could improve either the rate or the extent of postischemic recovery. Hearts were arrested (2 minutes at 4 degrees C) with the St. Thomas' Hospital cardioplegic solution and stored by immersion in the same solution for 8 hours at 4 degrees C. Hearts were then transplanted into the abdomen of homozygous recipients. Immediately before reperfusion, adenosine (0.5 ml of a 1 mumol/L solution, equivalent to 0.13 micrograms) was injected into the left ventricle (control rats received an equivalent amount of saline). Hearts were reperfused in vivo for 30 minutes or 24 hours, after which they were excised and perfused (Langendorff) for 20 minutes for the assessment of function. They were then freeze clamped and taken for metabolic analysis. After 50 minutes of reperfusion, left ventricular developed pressure was 75 +/- 5 mm Hg (4 mm Hg end-diastolic pressure) in the adenosine group versus 61 +/- 4 mm Hg in the control group (p less than 0.05); however, after 24 hours function was identical in the two groups (52 +/- 4 versus 52 +/- 3 mm Hg). After 50 minutes of reperfusion coronary flow was greater in the adenosine group (11.0 +/- 0.4 versus 9.7 +/- 0.4 ml/min in control rats; p less than 0.05), a difference that was sustained for 24 hours (12.8 +/- 0.3 versus 11.4 +/- 0.4 ml/min in control rats; p less than 0.05). Adenosine triphosphate and creatine phosphate contents recovered to similar extents in control and adenosine groups after both 50 minutes and 24 hours of reperfusion. In further studies with an identical storage protocol (8 hours at 4 degrees C), hearts were not transplanted but were reperfused with crystalloid medium in the Langendorff mode for 15 minutes (creatine kinase leakage measured) and in the working mode for 180 minutes. In an attempt to mimic the heterotopic transplant protocol, adenosine (1 mumol/L) was included in the perfusion fluid for the first 2 minutes of reperfusion. Similar results to those of the transplant studies were obtained, with coronary flow being consistently improved in the adenosine group; however, this benefit was lost after only 2 hours of reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

20.
The influence of pressure, flow, and pulsatility on the release of prostacyclin (measured as 6-keto-PGF1 alpha) and thromboxane (measured as TxB2) was assessed in canine jugular veins perfused ex vivo with Hanks' balanced salt solution for five consecutive 15-minute periods. Control segments were perfused at 7 mm Hg with nonpulsatile flow at a rate of 90 ml/min, whereas experimental segments were perfused with pulsatile flow as well as nonpulsatile flow at pressures of 50 or 100 mm Hg and flow rates of 60 or 130 ml/min. Prostacyclin release from control segments during the first 15-minute period was 49.5 +/- 7.4 pg/mm2/15 min, which declined to 13.9 +/- 2.5 pg/mm2/15 min after 60 minutes (p less than 0.002). Arachidonic acid stimulation during the last 15-minute perfusion period increased the release to 56.1 +/- 9.4 pg/mm2/15 min (p less than 0.002). Thromboxane release from control segments was initially 4.4 +/- 1.2 pg/mm2/15 min, which declined to 0.8 +/- 0.2 pg/mm2/15 min after 60 minutes (p less than 0.002), and subsequently increased with arachidonic acid stimulation to 1.3 +/- 0.1 pg/mm2/15 min (p less than 0.01). In contrast to control perfusion conditions, changes in nonpulsatile flow rates did not affect prostacyclin release, whereas thromboxane release was lower when perfused at 60 ml/min. Pressures of 50 and 100 mm Hg increased the initial release of prostacyclin. Similarly, pulsatile flow enhanced prostacyclin release at both low and high pressures, being more pronounced with the latter.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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