The effect of graft caliber upon wall shear within in vivo distal vascular anastomoses.

Wall shear has been widely implicated as a contributing factor in the development of intimal hyperplasia in the anastomoses of chronic arterial bypass grafts. Earlier studies have been restricted to either: (1) in vitro or computer simulation models detailing the complex hemodynamics within an anastomosis without corresponding biological responses, or (2) in vivo models that document biological effects with only approximate wall shear information. Recently, a specially designed pulse ultrasonic Doppler wall shear rate (PUDWSR) measuring device has made it possible to obtain three near-wall velocity measurements nonintrusively within 1.05 mm of the vessel luminal surface from which wall shear rates (WSRs) were derived. It was the purpose of this study to evaluate the effect of graft caliber, a surgically controllable variable, upon local hemodynamics, which, in turn, play an important role in the eventual development of anastomotic hyperplasia. Tapered (4-7 mm I.D.) 6-cm-long grafts were implanted bilaterally in an end-to-side fashion with 30 deg proximal and distal anastomoses to bypass occluded common carotid arteries of 16 canines. The bypass grafts were randomly paired in contralateral vessels and placed such that the graft-to-artery diameter ratio, DR, at the distal anastomosis was either 1.0 or 1.5. For all grafts, the average Re was 432 +/- 112 and the average Womersley parameter, alpha, was 3.59 +/- 0.39 based on artery diameter. There was a sharp skewing of flow toward the artery floor with the development of a stagnation point whose position varied with time (up to two artery diameters) and DR (generally more downstream for DR = 1.0). Mean WSRs along the artery floor for DR = 1.0 and 1.5 were found to range sharply from moderate to high retrograde values (589 s-1 and 1558 s-1, respectively) upstream to high antegrade values (2704 s-1 and 2302 s-1, respectively) immediately downstream of the stagnation point. Although there were no overall differences in mean and peak WSRs between groups, there were significant differences (p < 0.05) in oscillatory WSRs as well as in the absolute normalized mean and peak WSRs between groups. There were also significant differences (p < 0.05) in mean and peak WSRs with respect to axial position along the artery floor for both DR cases. In conclusion, WSR varies widely (1558 s-1 retrograde to 2704 s-1 antegrade) within end-to-side distal graft anastomoses, particularly along the artery floor, and may play a role in the development of intimal hyperplasia through local alteration of mass transport and mechano-signal transduction within the endothelium.

In vitro evaluation of electrostatic endothelial cell transplantation onto 4 mm interior diameter expanded polytetrafluoroethylene grafts.

PURPOSE: To perform an in vitro evaluation of electrostatic endothelial cell transplantation of human umbilical vein endothelial cells (HUVEC) onto segments of 4 mm internal diameter expanded polytetrafluoroethylene (ePTFE) vascular prostheses. METHODS: This evaluation consisted of exposing vascular graft segments that had been subjected to either electrostatic or gravitation transplantation with HUVEC to a physiologic shear stress (15 dynes/cm2) under steady flow conditions within a flow loop system. Biochemical assays were performed on freshly transplanted grafts by means of radioimmunoassay for prostacyclin and thromboxane A2. RESULTS: There was a 30% loss of HUVEC after 30 minutes of shear stress exposure from the grafts subjected to gravitational transplantation with no additional significant (alpha = 0.05) loss after 120 minutes. Grafts subjected to electrostatic transplantation had no significant (alpha = 0.05) loss of HUVEC during exposure to physiologic shear stress. Furthermore, after 120 minutes of shear-stress exposure, the grafts subjected to electrostatic transplantation (78,420 +/- 6274 HUVEC/cm2) retained 2.3 times more HUVEC than the counterparts subjected to gravitational transplantation (34,427 +/- 4637 HUVEC/cm2). The biochemical assay results indicated no significant (alpha = 0.05) production of prostacyclin or thromboxane A2 regardless of the method of cell transplantation. CONCLUSIONS: (1) The electrostatic transplantation technique was superior to the gravitational transplantation technique in terms of cellular retention when the ePTFE grafts were exposed to physiologic shear stress. (2) Production of prostacyclin and thromboxane A2 did not differ between transplanted HUVEC subjected to gravitational or electrostatic procedures.

Doppler color-flow images from a stenosed arterial model: interpretation of flow patterns.

The capability of the recently introduced Doppler color-flow mapping devices to accurately detect flow patterns in the region of an arterial stenosis was evaluated by use of an in vitro flow model. Pulsatile flow simulating that in a low-resistance vessel was induced through a straight acrylic tube, which alternatively contained axisymmetric stenoses of 0%, 20%, 40%, 60%, and 80% diameter reduction. Doppler color-flow mapper images were taken in realtime along the tube midplane from 0 to 8 diameters downstream of each stenosis. Comparison of the Doppler color-flow mapping results with similarly recorded flow visualization (hydrogen bubble) images showed a close correspondence of key features of the flow, including detection of a high-velocity, centerline jet and near-wall separated flow zones. Distinctive flow patterns exist with each stenotic case, and these should be of considerable value in diagnosing clinical disease conditions.

Noninvasive blood flow measurement in expanded polytetrafluoroethylene grafts for hemodialysis access.

Volume flow rates were measured in 31 expanded polytetrafluoroethylene grafts (6 mm) of 26 patients undergoing hemodialysis. Flow was calculated from the known access graft diameter and by measurement of the mean Doppler shift frequency waveform. Overall flow rates were 750 +/- 383 ml/min (range, 0 to 1921 ml/min). There was no difference in flow between grafts anastomosed to either antecubital or upper arm veins but there was a significant difference in flow rate between straight and loop grafts (652 and 914 ml/min) and between grafts anastomosed to the radial, distal brachial, and proximal brachial arteries (648, 876, and 1169 ml/min, respectively). Flow rates measured during a preocclusive 14-day period in five grafts were significantly lower than flow rates in grafts that remained patent for at least 2 weeks following examination (307 +/- 172 vs. 849 +/- 346 ml/min). This is a safe, repeatable noninvasive measure of access graft hemodynamics, which may be useful as a functional monitor and a warning of impending failure.

Detection of renal artery stenosis: experimental and clinical analysis of velocity waveforms.

Mass screening of hypertensive patients by a noninvasive method could uncover the 10% of those cases where renal artery stenosis is the primary etiology. Treatment by transluminal angioplasty or surgery could replace a long-term medical regimen. To investigate an ultrasonic technique, normal velocity waveforms were obtained from the abdominal aorta, celiac artery and renal arteries in seven mongrel dogs using a 5 MHz, continuous-wave Doppler detector. Renal artery pressure gradients, volume flow rates and velocity recordings were subsequently made during induced proximal renal artery stenoses. The ratio of peak renal artery frequency to peak aortic frequency was 88% sensitive to stenoses of greater than 20 mm Hg pressure gradient, while the renal artery systolic frequency window was 79% sensitive to the same obstructions. Ninety-five hypertensive and vascular surgical patients were examined using a 3 MHz duplex scanner with 175 of the 190 (92%) renal arteries adequately detected (clear signal with high diastolic component). Analysis of velocity waveforms based on peak frequency, proximal to distal peak frequency changes, evidence of flow disturbances and associated bruit were compared to contrast arteriograms in 84 vessels. Of the 76 (90%) arteries adequately examined by duplex scanning, 59 of 61 (97%) with 0-59% diameter reduction, 10 of 12 (83%) with 60-99% diameter reduction and 1 of 3 (33%) occlusions were correctly identified. Velocity waveform analysis can accurately detect renal artery stenosis and may prove effective in mass screening of hypertensive patients for renovascular disease.

Noninvasive evaluation of renal artery stenosis and renovascular resistance. Experimental and clinical studies.

Doppler ultrasound was used to detect experimental and clinical renal artery stenosis (RAS) and increased renovascular resistance (RVR). Parameters assessing RAS included elevated systolic frequency and spectral broadening, while diastolic/systolic frequency ratios predicted elevated RVR. In canine models these parameters detected graded RAS before reduction in renal blood flow. Index values were 88% sensitive and 100% specific in identifying RAS with gradients greater than or equal to 25 mm Hg. Diastolic/systolic frequency correlated well with increased RVR induced by microsphere injections (p less than 0.05). Duplex scanning noninvasively detected bilateral renal artery velocity in 113 of 120 patients. Index values were 83% sensitive and 97% specific in identifying greater than or equal to 60% RAS in 86 vessels visualized by angiography. Estimated RVR was significantly higher in age-matched hypertensive and atherosclerotic patients than in controls (p less than 0.01). Ultrasound may be useful to screen patients for RAS and increased RVR.

Evaluation of transplant renal artery blood flow by Doppler sound-spectrum analysis.

Doppler ultrasonography sound-spectrum analysis (SSA) was used to evaluate blood flow in the transplanted kidney and its renal artery. Seven patients with posttransplant hypertension and a bruit over the transplanted kidney were screened for renal artery stenosis (RAS). In five patients, RAS was diagnosed by SSA, and in two it was not. These findings were confirmed by subsequent angiography in all patients. Three patients studied after surgical correction of their RAS had improvement in their SSA patterns. Fourteen hypertensive patients with a cause other than RAS were evaluated by SSA. None of them had SSA findings suggestive of RAS. Doppler ultrasonography with SSA is an effective, noninvasive technique of monitoring transplant renal blood flow, especially in the screening of hypertensive transplant recipients for transplant RAS.

Real-time Doppler spectrum analysis: predictive value in defining operable carotid artery disease.

A prospective study compared the sensitivity, specificity, and predictive value of indirect periorbital Doppler screening and direct carotid Doppler interrogation using real-time sound spectrum analysis to detect operable extracranial carotid occlusive disease. The results of noninvasive studies were compared with independently assessed contrast arteriograms of carotid arteries of patients studied for symptomatic cerebrovascular disease. Periorbital Doppler ultrasound was insensitive to carotid stenosis of less than 75% and did not distinguish operable stenosis from inoperable occlusion of the internal carotid artery. Carotid Doppler spectrum analysis was sensitive to 98% of hemodynamically significant disease and correctly discriminated 77% of carotid occlusions, 96% of stenoses larger than 50%, and 70% of stenoses of less than 50%. The predictive value for direct carotid interrogation in identifying carotid occlusion or operable stenosis was 94% and 86%, respectively. Real-time spectrum analysis of direct carotid Doppler signals substantially improves the diagnostic accuracy of noninvasive identification of operable carotid artery disease.

Audible interpretation of carotid Doppler signals. An improved technique to define carotid artery disease.

Direct interrogation of the common, internal, and external carotid arteries with a bidirectional Doppler detector was performed on 199 vessels in 101 patients. Audible interpretations of normal, disturbed (stenotic), or absent (occluded) flow signals were made by vascular technologists and the results were compared with independently assessed carotid arteriograms. The sensitivity in detecting severe (greater than or equal to 50%) stenosis or occlusion was 9.2%, with correct differentiation of these two conditions in 84% of vessels. Nonobstructive (less than 50%) stenoses were detected in 30% of cases. The specificity in identifying normal carotid arteries was 91%. The predictive values of normal, abnormal, and absent flow signals were 95%, 90%, and 90%, respectively. Direct carotid Doppler signal analysis is more accurate than indirect periorbital Doppler screening in defining carotid stenosis or occlusion.

Prediction of amputation wound healing. Roles of Doppler ultrasound and digit photoplethysmography.

Segmental limb blood pressures (BPs) measured by Doppler ultrasound and digit photoplethysmography were used to define hemodynamic correlates of wound healing in 122 lower-extremity amputations for ischemia. Healing of digit or transmetatarsal amputations were influenced by the presence of diabetes and correlated better with digit pulsation and BP than with ankle pressure. Healing of below-knee amputation did not correlate with segmental limb BPs. In the absence of an absolute threshold to predict wound healing or failure, caution is urged in using hemodynamic indices to select the level of amputation of arterial insufficiency.

Potential role of velocity and wall tension in vein graft failure.

The factors contributing to early thrombosis or late intimal proliferation in arterialized vein grafts were studied in seven dogs. Autologous jugular veins replaced a segment of the cervical carotid artery bilaterally. Thirty minutes after graft installation and six months later, graft and proximal artery diameter, arterial pressure and blood flow were measured and wall tension, vascular resistance, flow velocity and energy loss between proximal artery and graft were computed. The diameter ratio of proximal artery to graft increased by 37% (p less than 0.05). Velocity of flow within the graft averaged 87% less than that in the proximal artery (p less than 0.05) and decreased by 58% after six months (p less than 0.05). Graft wall tension at both experimental periods was significantly higher than that of the proximal artery (p less than 0.05), increasing over six months by 91% (p less than 0.05). These results support contentions that low flow velocity contributes to early thrombosis of the graft and, that increased wall tension is significant factor in the pathogenesis of intimal thickening.

Increased diastolic time: a possible important factor in the benefical effect of propranolol in patients with coronary artery disease.

Diastolic time (DT) calculated as the cycle length minus electromechanical systole (QS2) has a nonlinear relationship to heart rate (HR), increasing rapidly as rates fall below 75. The effect of propranolol on DT was studied in 150 patients with coronary artery disease. Patients were divided into three groups. Group I included patients with stable angina pectoris: propranolol (2.5 mg, i.v.) significantly increased DT from 411 +/- 18 to 527 +/- 22 msec (p less than 0.001) in 23 patients of group I; therapy with propranolol (mean daily dose 200 +/- 15 mg) increased DT from 446 +/- 29 to 766 +/- 26 msec (p less than 0.001) in 15 patients with stable angina. Group II was made up of patients with acute myocardial infarction: Propranolol (2.5 mg, i.v.) increased DT from 379 +/- 16 to 458 +/- 24 (p less than 0.001) in 18 of these patients. Group III included patients with recent coronary bypass surgery: propranolol (2.5 mg, i.v.) increased DT from 323 +/- 9 to 468 +/- 24 msec (p less than 0.001) in 14 patients 7 days after surgery. In addition, DT at 15 hr and 2 weeks after surgery was compared in 30 patients maintained on propranolol (mean daily dose, 155 +/- 11 mg preoperative and 68 +/- 9 mg postoperative) and 50 other patients who underwent coronary bypass surgery not on propranolol. DT was greater in propranolol patients (546 +/- 21 vs. 388 +/- 16 msec, p less than 0.001), preoperative and 396 +/- 15 vs. 320 +/- 12 msec, p less than 0.001, postoperative). Changes in DT after propranolol are mainly attributed to decreased HR. Changes in QS2 were much less profound and always less (p less than 0.01) than changes in DT. Thus propranolol significantly increased DT per beat in patients with coronary artery disease, which allowed more time for coronary perfusion; this effect of propranolol could well be as important as the reduction of myocardial oxygen consumption.