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Department of Surgery, Veterans Affairs Medical Center, Minneapolis 55417; and Department of Surgery, University of Minnesota, Minneapolis, Minnesota 55455
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Intimal hyperplasia, common at the deployment site of an intra-arterial stent, may be caused by artery wall hypoxia. The purpose of this study was to determine the effect of an intra-arterial stent on artery wall oxygen concentrations. Transarterial wall oxygen gradients were measured by microelectrode at stent deployment sites in New Zealand White rabbits. Thinned artery walls and decreased oxygen tensions were noted throughout the artery wall immediately following stent deployment with a return toward control values at 28 days. Angioplasty alone had no acute effect on artery wall oxygen concentrations. Larger stent deployment diameters yielded acutely lower artery wall oxygen tensions. Using a linear one-dimensional model for the oxygen profile, we noted that stent deployment resulted in acute changes in oxygen consumption in the inner artery wall that rapidly returned to control values. Changes were noted without differences in blood pressure or arterial blood oxygen concentrations. Oxygen delivery to and consumption within the artery wall are altered by intra-arterial stent deployment. A role for artery wall hypoxia in artery wall pathology at the deployment site of an intra-arterial stent is supported by these findings.
artery wall hypoxia; oxygen delivery; oxygen consumption
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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ENDOVASCULAR TREATMENT of arterial occlusive disease began with the pioneering work of Dotter and Judkins who, in 1964, mechanically dilated femoral arteries with a coaxial double catheter system (17, 18). Following the early results of angioplasty, other work led to the development of intra-arterial stents (16, 17), which were initially used to treat complications that developed during angioplasty, such as dissections or intimal flaps. However, intra-arterial stents were eventually utilized as primary intervention with the hope of preventing recurrent occlusive disease, which was commonly identified pathologically as intimal hyperplasia (IH) (19-23). The use of intravascular stents has been shown to improve short-term and long-term primary target artery patency, but IH remains a leading cause of intra-arterial stent failure (2, 35-37). Clinically, IH results in 1) repeat adverse clinical events (myocardial infarction, recurrent claudication, limb loss, and death), 2) repeat intervention, and 3) increased medical costs.
The available data reveal most patients who develop IH following deployment of an intra-arterial stent do so within the first 3 mo following stent placement. This suggests that an intervention directed at the early period after stent deployment would have the greatest impact on preventing IH.
Despite past and ongoing research, the complete etiology of IH remains unknown, and there is no effective method to control this pathological process. Artery wall hypoxia has been associated with arterial pathological processes including atherosclerosis (10, 11, 29, 31, 39-43), IH (1-3, 10, 11, 16, 17, 19, 20, 22, 23, 29a, 31, 33, 35-37, 39-43, 49), and fibromuscular dysplasia (46). The function of vascular smooth muscle cells is known to be altered by hypoxia (6, 32, 47) . Hypoxic smooth muscle cells function in a manner similar to those recovered from lesions of IH (5, 7-9). We hypothesize that the delivery of oxygen to the artery wall is decreased at the deployment site of an intra-arterial stent and that this artery wall hypoxia contributes to a change in cellular function leading to IH.
A review of the literature reveals that artery wall oxygen tensions have not been reported following deployment of an intra-arterial stent. Deployment of an intra-arterial stent might alter artery wall oxygen concentrations through either reduced oxygen diffusion or increased oxygen consumption. In this study we investigated the transarterial wall oxygen gradients at the deployment site of an intra-arterial stent in a rabbit model (20). We examined 1) the transarterial wall oxygen gradient at the deployment site of an intra-arterial stent in the rabbit infrarenal aorta, 2) the temporal sequence of oxygen recovery following deployment of an intra-arterial stent, and 3) the effect of varying intra-arterial stent deployment diameters on artery wall oxygen concentrations.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Animal Models
Female New Zealand White Rabbits (2-3 kg; 9-12 mo of age) from a single vendor were used for study. All animals were fed standard chow and water ad libitum and were housed according to University of Minnesota institutional guidelines. These studies were approved by the University of Minnesota Institutional Animal Care and Use Committee and complied with the "Principles of Laboratory Animal Care" and the Guide for the Care and Use of Laboratory Animals.Construction of the Oxygen Microelectrode
Transarterial wall oxygen gradient measurements were performed using an oxygen microelectrode constructed following the technique of I. A. Silver (45). Briefly, a 30-gauge 80% platinum-20% iridium wire (California Fine Wire, Grover City, CA) was electropolished to a 1- to 5-µm tip in a saturated alkaline NaCN solution using an alternating current of 0.5-2 A at 5-10 V. The wire was evenly tapered from the 1- to 5-µm tip to a diameter of ~100 µm at a distance of 200-300 µm from the tip. The electropolished wire was then coated with leaded glass, leaving the wire tip exposed. The glass near the tip was sufficiently thin so as to not add to the overall diameter of the electrode. The performance of the electrode was assessed in an oxygenated saline bath, and the size of the exposed tip was determined by assessing the amount of current per unit (mmHg) of oxygen tension. A current-voltage polarogram was constructed to look for a plateau between
0.6 and
0.8 V. If the electrode performed satisfactorily, then it was coated with polymethylmethacrylate (Polysciences, Warrington, PA), leaving the
tip exposed. The electrode was then tested prior to use using the
criteria described by Silver (45). The six criteria for a
competent electrode were as follows: 1) the current
reading in the fluid bath was not affected by fluid movement,
2) the current per unit (mmHg) oxygen tension was
<1 × 10
10 A, 3) there was a linear
relationship between oxygen tension and current measurement,
4) there was a negligible current measurement at an oxygen
tension of zero, 5) the response of the electrode to changes
in oxygen tension was rapid (stabilization within 5 s), and
6) the electrode tip surface was noted to be smooth without contour irregularities when examined microscopically. The electrode was
soaked in fresh rabbit serum (prepared in our laboratory using standard
techniques) for 30 min to allow for surface coating with plasma
proteins. Immediately prior to and following measurement of the
transarterial wall oxygen gradient, the electrode was calibrated in an
oxygenated saline bath at 39.0°C (the average core temperature of the
rabbits while undergoing a laparotomy and general anesthesia) at oxygen
tensions of 0 and 89 mmHg.
Control Animals
After a 1-wk acclimatization period, female New Zealand White rabbits were anesthetized with ketamine hydrochloride (40 mg/kg), acepromazine (1 mg/kg), and xylazine (5 mg/kg) administered intramuscularly. They were intubated, and anesthesia was maintained with isofluorane. Prior to the start of the operation, penicillin (150,000 U) was administered intramuscularly, and a 24-gauge intravenous catheter was placed in a marginal ear vein to allow for the administration of intravenous fluids and medications. Under sterile conditions, the infrarenal aorta was exposed through a midline incision, and lumbar branches were ligated as needed, to completely dissect the distal 3 cm of infrarenal aorta. After the administration of 200 U/kg of intravenous heparin, the distal aorta was clamped proximally and distally, and a transverse aortotomy was created 0.5 cm above the aortic bifurcation.Experimental Animals
Placement of the intra-arterial stent/angioplasty. Animals were acclimated, and an aortotomy was created, as described above.
An angioplasty group was included to determine the relative contributions of angioplasty vs. stent deployment to changes in artery wall oxygen concentrations. STENT. A 3-mm intra-arterial stent (Cordis of Johnson and Johnson, Warren, NJ) was loaded on a 3-mm outer diameter (OD) by 2-cm long symmetry balloon dilation catheter (Meditech of Boston Scientific, Watertown, MA) and inserted proximally through the aortotomy into the distal aorta. The stent was positioned 1 cm proximal to the aortotomy and deployed by inflating the balloon to 3 atm for 30 s. The balloon catheter was withdrawn, and the aortotomy was closed with 7-0 polypropylene suture. For larger stent diameter groups, larger balloon dilation catheters were deployed using the same pressure and time. ANGIOPLASTY. Angioplasty was performed by placing a 3-mm OD by 2-cm symmetry balloon dilation catheter (Meditech of Boston Scientific) in the aorta through a transverse aortotomy 0.5 cm above the aortic bifurcation. The angioplasty balloon was inflated at 3 atm, 2 cm above the aortotomy, and withdrawn 1.5 cm three times to denude the endothelium as previously described by others (26, 28, 38). The aortotomy was closed as described above. Perioperative blood loss was replaced in all groups with intravenous normal saline, and postoperative analgesia (buprenorphine, 0.05 mg/kg im) was administered for 48 h.Transarterial Wall Oxygen Gradient Measurements
After the electrodes were calibrated the transarterial wall oxygen gradients were measured in a control group and 1 day following angioplasty in the angioplasty group, as well as at various time points (days 1, 7, and 28) following deployment of an intra-arterial stent.The abdomen was reopened through the previous midline incision, and the infrarenal aorta was exposed, taking care not to disrupt the vasa vasorum. The aorta was first covered topically with a solution of 2% xylocaine to prevent vasospasm, and the area in which measurements were made (either at 1.5 cm proximal to the aortotomy in the control and angioplasty groups or in the midstent region in the stented groups) was gently blotted dry. The oxygen microelectrode was brought into contact with the aortic adventitia under direct vision with an operating microscope at a 90° angle using a micromanipulator (model MO-11; Narishige, Tokyo, Japan). A drop of light mineral oil was applied to the body of the electrode and allowed to run to the tip (which was in contact with the aortic wall adventitia) to prevent electrical noise from nearby movement or air currents during the experiment. Oxygen tension measurements were recorded at 10-µm intervals using a chemical microsensor (model 1201; Diamond General, Ann Arbor, MI), and the transarterial wall oxygen profile was recorded with a chart recorder. The oxygen tension measurements were allowed to equilibrate before the electrode was advanced. A sudden rise in current coupled with a pulsatile recording signified entry into the aortic lumen. As the electrode approached the lumen (>140 µm through the artery wall toward the lumen), the speed of electrode advancement was decreased to permit recording of an oxygen tension value immediately prior to lumen entry. This value was recorded as 99% of the distance through the artery wall toward the lumen. Blood noted to exit the electrode tract following microelectrode withdrawal confirmed entry into the aortic lumen.
After measurement of the transarterial wall oxygen gradient was completed, the electrode was again placed in an oxygenated saline bath and recalibrated at 0 and 89 mmHg oxygen tensions to confirm that no significant drift occurred during the experiment. If this recalibration revealed greater than a 7% drift in oxygen tension readings, then the transarterial wall oxygen profile was discarded, and the electrode was tested for a mechanical flaw.
Two measurements were attempted at similar locations on each rabbit. Because of mechanical malfunctions, electrode breakage, electrode calibration drift, or unstable physiological conditions, two recordings could not be obtained on all rabbits. Therefore, varying numbers of rabbits were required in each group to complete the experiments (as noted in RESULTS).
Arterial Blood Pressure Measurements
Arterial blood pressure was continuously monitored during measurement of the transarterial wall oxygen gradient with an indwelling femoral artery catheter and standard pressure transducer system.Arterial Blood Gas Analysis
Immediately following measurement of the transarterial wall oxygen gradient, blood was withdrawn through the previously placed indwelling femoral artery catheter and sent to the clinical laboratory at the Veterans Affairs Medical Center, Minneapolis, MN, for arterial blood gas analysis.Artery Wall Thickness
Artery wall thickness was measured in vivo by recording the distance from the adventitia to lumen entry using the micromanipulator.Statistics
Values are means ± SE. Data were analyzed using ANOVA for a repeated measures design. An F test statistic was first calculated to determine the overall P value. If the overall P < 0.05, then Dunnett's post hoc test was used for multiple comparisons.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Transarterial Wall Oxygen Measurements
Control group vs. the 3.0-mm stent group at day 1.
For the control group (n = 4), the oxygen tension at
the adventitia was 60.8 ± 3.7 mmHg, fell to a nadir of 24.8 ± 2.3 mmHg at 70% of the distance through the artery wall, and then
rose to 41.8 ± 2.0 mmHg before lumen entry (Fig.
1).
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Control group vs. the 3.0-mm stent group at day 7. The control group (n = 4) is described above.
For the day 7, 3.0-mm stent group (n = 5), the oxygen tension at the adventitia was 45.4 ± 2.6 mmHg, fell to a nadir of 18.2 ± 2 mmHg at 60% of the distance through the artery wall, and then rose to 41.4 ± 1.7 mmHg before lumen entry (Fig. 1). Oxygen tensions were significantly decreased in the outer 60% of the artery wall in the 3.0-mm stent group at day 7 compared with the control group.Control group vs. the 3.0-mm stent group at day 28. The control group (n = 4) is described above.
For the day 28, 3.0-mm stent group (n = 5), the oxygen tension at the adventitia was 50 ± 3.4 mmHg, fell to a nadir of 24.6 ± 2.9 mmHg at 70% of the distance through the artery wall, and then rose to 39.2 ± 2.0 mmHg before lumen entry. Oxygen tensions were significantly decreased in the outer 20% of the artery wall in the 3.0-mm stent group at day 28 compared with the control group.Control group vs. the angioplasty group. The control group (n = 4) is described above.
For the angioplasty group (n = 4), the oxygen tension at the adventitia was 58.5 ± 2.6 mmHg, fell to a nadir of 22.8 ± 1.9 mmHg at 70% of the distance through the artery wall, and then rose to 41.8 ± 2.1 mmHg before lumen entry (Fig. 2).
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Comparisons of control group, 3.0-mm stent group at day 1, the 3.5-mm stent group at day 1, and the 4.0-mm stent group at day 1. The control group (n = 4) is described above.
For the day 1, 3.0-mm stent group (n = 6), the oxygen tension at the adventitia was 40.8 ± 3.5 mmHg, fell to a nadir of 14.7 ± 2.4 mmHg at 60% of the distance through the artery wall, and then rose to 41.3 ± 3.7 mmHg before lumen entry (Fig. 3).
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Arterial Blood Pressure
Mean systolic blood pressure was 90.7 ± 8.2 mmHg, and mean diastolic blood pressure was 57.9 ± 6.6 mmHg. There was no significant variation in blood pressure during measurement of the transarterial wall oxygen gradients (blood pressure was continuously monitored) in any of the animals used for data analysis.Arterial Blood Gas Analysis
There was no difference in the partial pressure of oxygen in the arterial blood gas analysis among any of the animals in any group used for the study. Mean partial pressure of oxygen was 87.3 ± 4.35 mmHg.Artery Wall Thickness
Artery wall thickness as recorded from the adventitia to the lumen was 195 ± 3.4 µm in the control group, 163.3 ± 6.1 µm in the day 1, 3.0-mm stent group, 170 ± 6.1 µm in the day 7, 3.0-mm stent group, 166 ± 7.7 µm in the day 28, 3.0-mm stent group, 196.5 ± 5.4 µm in the angioplasty group, 162.5 ± 2.9 µm in the day 1, 3.5-mm stent group, and 142.5 ± 3.9 µm in the day 1, 4.0-mm stent group. Artery wall thickness was significantly decreased in all stent groups compared with both the control and angioplasty groups. There was no difference in artery wall thickness when comparing the control and angioplasty groups.Histology
Vasa vasorum were identified in the periadventitial tissue with no evidence of penetration of the vasa vasorum into the media in any specimen by light microscopy. Light microscopic examination revealed persistence of peri-adventitial vasa vasorum in all groups following either deployment of an intra-arterial stent or angioplasty.| |
DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We believe that we have the first in vivo evidence that deployment of an intra-arterial stent alters the transarterial wall oxygen gradient. Our experiments demonstrate 1) deployment of an intra-arterial stent acutely reduces oxygen tensions throughout the artery wall, 2) artery wall oxygen tensions return to near control values 28 days following stent deployment, 3) angioplasty alone has no acute effect on artery wall oxygen concentrations, and 4) larger stent diameters have an inverse relationship to artery wall oxygen concentrations.
Niinikoski et al. (34) demonstrated that a transarterial wall oxygen gradient is present in normal rabbit aortas with oxygen tensions falling from the adventitia, reaching a nadir at the junction of the inner one-third and outer two-thirds of the vessel wall. Oxygen tensions then slowly rise until the lumen is entered. It is proposed that the vasa vasorum supply oxygen to the outer two-thirds of the artery wall, whereas the inner one-third is supplied by luminal diffusion of oxygen (32a). Our results correlate quite well with the transarterial wall oxygen gradients measured by Niinikoski et al. (34). Wolinsky and Glagov (49) have previously shown that arteries with the diameter and wall thickness of the rabbit aorta do not have medial vasa vasorum. Our control oxygen profiles show steadily falling oxygen tensions away from the adventitial or luminal surfaces of the artery, suggesting that the rabbit aortic wall is not supplied by any penetrating vessels from the peri-adventitial vasa vasorum. This fact is supported by light microscopic examinations, which revealed vasa vasorum to be present only in the peri-adventitial tissue of the specimens with no penetrating vessels.
This study demonstrates that immediately following deployment of an
intra-arterial stent, oxygen tensions are decreased throughout the
artery wall (associated with no loss of vasa vasorum on light microscopy) and increasing stent diameters are associated with lower
artery wall oxygen tensions. We propose stent-associated increases in
both circumferential and radial wall stresses as one possible mechanism
for the change in artery wall oxygen tensions. Pressurized arteries
undergo deformation in three directions: 1) increased
circumference, 2) increased length, and 3)
increased radial deformation (decreased wall thickness). The artery
wall generates stresses to oppose these deformations: 1)
increased circumferential stress, 2) increased longitudinal
stress, and 3) increased radial stress. Circumferential and
longitudinal stresses are tensile (stretch), whereas radial stress is
compressive (13-15, 32a). Circumferential and radial
stresses may play a role in intra-arterial stent-induced artery wall
hypoxia. Circumferential stress is related to vessel diameter. As a
vessel dilates, circumferential stress initially remains low, because
the initial increase in diameter is related to the gradual stretching
of the retracted elastic lamellae. This distention continues at low
circumferential stress until the elastic fibers reach their maximum
stretch. At this point, circumferential stress begins to increase
exponentially. Also, it is at this point that collagen begins to
contribute to the circumferential stress. Collagen is several 100 to
1,000 times stiffer than elastin and, with the recruitment of collagen
circumferential stress, rises dramatically (13).
Circumferential stress can be expressed mathematically as
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Deployment of an intra-arterial stent will increase transmural
pressure, increase the internal radius, and decrease wall thickness. These changes all contribute to an increase in circumferential stress
being directly related to the size and force of stent deployment. Radial stress (13-15, 32a) results from increased
luminal pressure causing thinning of the artery wall. Radial stress is
compressive, squeezes all the structures in the artery wall, and can be
expressed mathematically as
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Again, deployment of an intra-arterial stent will increase transmural pressure, thereby increasing radial stress. A direct link may exist between increasing circumferential and radial stresses and artery wall hypoxia. In normal arteries, vasa vasorum are found only in the outer one-third to one-half of the artery wall, a distribution that may result from tissue distortion by the circumferential and radial stresses (13, 24). It is unlikely that the vasa vasorum could remain patent as circumferential and radial stresses increase, given that the vasa vasorum are perfused by pressures lower than mean arterial pressure (13, 24). Diminished flow through the vasa vasorum following deployment of an intra-arterial stent (as a result of increased circumferential and radial stresses) could contribute to artery wall hypoxia. These findings concur with data previously published by Buerk and Kahn (5) using a two-layer oxygen transport model. Their model predicts that impaired blood flow through the vasa vasorum will result in medial artery wall hypoxia. Schneiderman and Goldstick (44) further strengthened the role of the vasa vasorum in artery wall oxygen supply in a carbon monoxide exposure model of cigarette smoking. They also found that artery wall hypoxia is dependent on vascular wall properties and the ability of the vasa vasorum to vasodilate. Increasing circumferential and radial wall stresses could lead to a decrease in artery wall oxygen delivery and artery wall hypoxia following stent deployment. Currently, clinicians limit stent dilation to a ratio of 1.2:1 (stent diameter to normal artery diameter) to minimize the risk of artery rupture (12, 18). These data relating to circumferential and radial stresses to artery wall hypoxia may be another reason to limit the degree of artery dilation following stent deployment.
The changes we observed in artery wall concentrations could be due to various causes, including decreased oxygen delivery and increased oxygen consumption. Oxygen delivery to the outer artery wall is through the vasa vasorum. Increasing circumferential and radial wall stresses could compress the vasa vasorum, impairing delivery to the outer artery wall, which would explain our findings that the oxygen concentrations in the outer artery wall are significantly decreased following stent deployment.
Our finding of inner artery wall hypoxia cannot be explained by limited
oxygen delivery through the vasa vasorum. This finding may be related
to increased oxygen consumption. With the use of a linear
one-dimensional model for the oxygen profile, the Q/Dk (4) (oxygen consumption over the product of diffusion and
solubility coefficients) can be calculated for the inner artery wall as
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We found that angioplasty alone has no acute effect on artery wall oxygen tensions or oxygen consumption. This finding suggests that the injury of balloon dilatation alone is not the mechanism for artery wall hypoxia and increased Q/Dk. The presence of an intra-arterial stent results in a further alteration of oxygen concentrations (possibly through changes in artery wall stresses and a direct continuing cellular injury secondary to the presence of the stent) to account for this discrepancy.
Our results show that artery wall oxygen tensions return toward control values 28 days following stent deployment, which could be related to a decrease in cellular activity or a decrease in artery wall stresses.
In summary, artery wall oxygen tensions and oxygen consumption are altered after deployment of an intra-arterial stent, and the mechanism for this observation is an area for future study.
These findings may have significant clinical impact. Artery wall hypoxia leading to artery wall pathology (atherosclerosis, IH, and fibromuscular dysplasia) is a topic of past and current investigation. Hueper (29a) in 1945 first suggested artery wall hypoxia may have a role in the pathogenesis of atherosclerosis, whereas Martin et al. (31) reported that artery wall hypoxia due to thrombosis of the vasa vasorum is an initial lesion in atherosclerosis. Crawford and Kramsch (11) reported that hypertension causes artery wall hypoxia and could lead to atherosclerosis through oxyradicals (10), and Santilli et al. have shown that risk factors for atherosclerosis [diabetes (40), hypertension (41), cigarette smoking (42), an arterial bifurcation (43), and aging (39)] lead to artery wall hypoxia prior to the formation of an atherosclerotic lesion. Nakata and Shionoya (33) determined that artery wall hypoxia due to removal of the vasa vasorum resulted in intimal vascular lesions resembling IH, whereas Williams (48) demonstrated that freeing the femoral artery from its surrounding connective tissue (thereby disrupting the vasa vasorum) leads to fibroelastic intimal thickening. Brody et al. (3) demonstrated that interruption of the vasa vasorum leads to medial fibrosis from tissue hypoxia, and Barker et al. (1) reported that removal of the adventitia of the rabbit carotid artery induced the formation of IH (1). Finally, Stanley (46) has hypothesized that fibromuscular dysplasia is in part due to artery wall hypoxia. Artery wall hypoxia following intra-arterial stent deployment may be a contributor to IH and could lead to a simple, safe, and effective method to control IH, i.e., the short-term administration of supplemental oxygen.
The oxygen profiles recorded by our laboratory have demonstrated a steep rise in oxygen concentration within the last 1-2% of the distance through the artery wall approaching the lumen. This finding could be considered an artifact of tissue distortion secondary to use of a nonvibrating method of electrode advancement. We may also be criticized for our use of a non-recessed-tip metal oxygen microelectrode. However, we feel that the reliable in vivo measurement of artery wall oxygen tensions can be accomplished with a metal-tipped electrode. Our previous work (39-43) and that of others (34) consistently demonstrate this gradient, and we feel the abrupt rise in oxygen concentrations in the inner artery wall is in part an effect of laminar blood flow (which results in a stagnant layer of relatively hypoxic red blood cells at the endothelial cell/blood interface) as well as tissue distortion.
Tissue distortion may potentially be minimized by using a different measurement technique. Use of a glass-tipped electrode is reliable in vitro, but in vivo arterial use frequently results in electrode breakage. This has necessitated the development of a vibratory advancement system to decrease electrode breakage. A vibratory technique for electrode advancement has been proposed as a method to prevent tissue distortion and false oxygen readings (30). However, use of a vibratory electrode advancement system still results in tissue distortion (average tissue distortion 2.7 µm; see Ref. 30). Our technique of electrode construction (very fine, pointed metal tips) and electrode advancement (10-µm intervals with allowance for stabilization) results in minimal tissue distortion (when with observed with an operating microscope), and we consider our oxygen values reproducible and reliable.
The validity of the rabbit model of IH as it applies to the human condition may be questioned. However, this model has been used by other investigators successfully and does mimic the human condition both on gross and microscopic examination (1, 10, 11, 29a, 31).
This study demonstrates that there is an acute decrease in the delivery of oxygen to the artery wall at the deployment site of an intra-arterial stent in the rabbit infrarenal aorta. These low oxygen tensions return toward control values 28 days following stent deployment. Low artery wall oxygen tensions may contribute to IH at the deployment site of an intra-arterial stent.
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ACKNOWLEDGEMENTS |
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We thank Ian A. Silver (University of Bristol, UK) for instruction in the technique of oxygen microelectrode construction. We thank Connie Lindberg for editorial assistance in the preparation of this manuscript. We thank Cordis Corporation for providing the intra-arterial stents used in this series of experiments.
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FOOTNOTES |
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This work was supported by a Department of Veterans Affairs Merit Review Grant and by the National Heart, Lung, and Blood Institute National Research Service Award 5F32-HL-10076-02.
Address for reprint requests and other correspondence: S. M. Santilli, Surgery 112 K Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417 (E-mail: santi002{at}tc.umn.edu)
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 26 October 1999; accepted in final form 7 April 2000.
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TOP
ABSTRACT
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METHODS
RESULTS
DISCUSSION
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) and 3.0-mm stent groups at
days 1 (
), 7 (
),
and 28 (
) oxygen tension profiles.
P < 0.05 in the outer 70% of the artery wall for the
day 1, 3.0-mm stent group compared with control group.
P < 0.05 in the outer 50% of the artery wall for the
day 7, 3.0-mm stent group compared with control group.
P < 0.05 in the outer 20% of the artery wall for the
day 28, 3.0-mm stent group compared with control group.
