Common Carotid Artery Injury Research Articles

Reduction in the response to coronary and iliac artery injury with photodynamic therapy using 5-aminolaevulinic acid.

Photodynamic therapy (PDT) uses red light (non-thermal, non-ionising) to activate a previously administered photosensitizing drug. This inhibits neointimal hyperplasia in injured arteries in small animals where it appears safe and well tolerated. Our aim was to develop a method for percutaneous application of PDT to iliac and coronary arteries in a large animal model and investigate its influence on the remodeling and intimal hyperplastic response to balloon injury. Studies were undertaken on 13 juvenile Large White-Landrace crossbred pigs (15-20 kg). After intravenous administration of the photosensitizing agent 5-amino laevulinic acid (ALA), the arterial tree was accessed via the left common carotid artery and balloon injuries made by over-distension in both common iliacs (thirteen animals) and one or two main coronary arteries (eight animals). Half the injured sites were then illuminated with red laser light transmitted via the catheter. Animals were culled 28 days later and tissue harvested for histomorphometry. Compared with control injured vessels, PDT treated, balloon injured coronary arteries had a larger lumen (1.4 vs. 0.8 mm2, P = 0.002), larger area within the external elastic lamina (2.8 vs. 2.2 mm2, P = 0.006) and smaller area of neointimal hyperplasia (0.4 vs. 0.7 mm2, P = 0.06), 28 days after intervention. Less neointimal hyperplasia and the absence of negative remodeling resulted in the lumen of PDT-treated, injured segments being the same as that of adjacent reference segments (1.5 vs. 1.6 mm2). Similar trends, but with smaller differences, were seen in the iliac vessels. Intra-arterial, trans-catheter PDT favourably influences the arterial response to balloon injury in both the coronary and peripheral circulations. This technique offers a promising new approach to restenosis after endovascular procedures.

Estrogen attenuates the adventitial contribution to neointima formation in injured rat carotid arteries.

This study tested, in ovariectomized rats, whether (1) adventitial activation plays a role in the vascular injury response, and (2) inhibition of adventitial activation and the subsequent wave of cell proliferation moving from adventitia to neointima contributes to the estrogen-induced attenuation of neointima formation in balloon injured carotid arteries. Ovariectomized Sprague-Dawley rats were treated with either 17 beta-estradiol or vehicle beginning 72 h prior to balloon injury of the right common carotid artery and were sacrificed at 0, 3, 7, 14 and 28 days after injury. BrdU was administered 18 h and 12 h prior to sacrifice in order to quantitate mitotic activity in adventitia, media and neointima of the damaged vessel at specified times post injury. Adventitial activation, evidenced by positive BrdU staining, was evident on the day of injury, peaked on day 3 and was resolved by day 7, thus preceding neointima formation. Numbers of BrdU labeled cells in adventitia on day 3 were significantly reduced in estrogen treated rats compared to controls. BrdU labeled cells were undetectable in media on the day of injury, appeared at day 3 and disappeared by day 14. Neointima appeared at day 7 and increased in area throughout the period of observation. Neointimal area and numbers of BrdU labeled cells in neointima were significantly reduced in estrogen treated rats compared to controls. These findings suggest that there is a wave of cell proliferation moving in an adventitia-to-lumen direction following endoluminal injury of the rat carotid artery and that estrogen modulates this proliferative response to injury. These results support the hypothesis that adventitial activation contributes to the vascular injury response and that estrogen reduces this contribution.

Extracellular matrix accumulation on the thickened neointima in a rat double-balloon injury model

We developed a rat double-balloon injury model and studied the thickened neointima using immunohistochemical and RT-PCR methods. Fourteen days after the first balloon injury of the rat left common carotid artery, a second balloon injury was inflicted in the same place. Histochemical sections taken 14 days after the single- and double-balloon injuries were used for calculating intimal/medial (I/M) area ratios, as an indicator of neointimal formation, and were subjected to immunohistochemical staining. Total RNA was also purified from some arteries and mRNA expression of some extracellular matrices (ECM) and cytokine receptors related to ECM metabolism was estimated using the RT-PCR method. The I/M ratio in the rat double-balloon injury model (II) (1.84+/-0.62 (mean+/-SE, n=5)) was significantly (p<0.05) higher than that in the single-balloon injury model (I) (1.30+/-0.19, n=10). The cell number per neointimal area was less in II than in I. As for the phenotype of smooth muscle cells, alpha-actin staining showed that the neointima of II consisted of more contractile form than synthetic, whereas that of I consisted of more synthetic form than contractile. The neointima of II was strongly stained with laminin and fibronectin, but that of I was stained only weakly. Consistent with these data, laminin and fibronectin mRNAs were markedly expressed in the neointima of II. Neointimas of both I and II were also stained positively with PDGF (alpha and beta) and TGF-beta (types I and II) receptors to the same extent. These results show: that ECM accumulation, particularly of laminin and fibronectin, characterizes the double-balloon injury model; that the marked accumulation of ECM in this model is due to a mechanism other than the PDGF or TGF-beta signalling pathway; and that this model resembles the lesion of post-PTCA re-stenosis, and therefore provides the key for its investigation.

All-Trans-retinoic acid reduces neointimal formation and promotes favorable geometric remodeling of the rat carotid artery after balloon withdrawal injury.

The multifactorial and unpredictable nature of human restenosis will probably necessitate interventional strategies that target multiple processes involved in acute vascular narrowing. Retinoids (eg, all-trans-retinoic acid, atRA) represent a growing class of pleiotropic biological response modifiers with demonstrable efficacy in managing several pathological conditions. In this report, we have initiated studies to examine the hypothesis that atRA limits neointimal formation after experimental vascular injury. Rats were predosed with atRA (30 mg . kg-1 . d-1 PO) or corn oil 4 days before balloon withdrawal injury (BWI) of the left common carotid artery and continued on this drug regimen for an additional 14 days. High-performance liquid chromatographic analysis documented therapeutic levels of atRA in serum and vascular tissue. atRA depressed peak DNA synthesis in the tunica media of BWI vessels (P<0.05). Histomorphometry revealed atRA-mediated reductions in neointimal area, neointimal cell number, and intimal/medial area ratio as well as significant increases in vessel wall perimeter (P<0. 05). Such changes in vascular architecture contributed to a 35% to 37% increase in the luminal area of BWI vessels exposed to atRA (P<0. 005 compared with controls). atRA reduces neointimal mass and elicits favorable geometric remodeling of the injured rat carotid artery.

Influence of local delivery of the protein tyrosine kinase receptor inhibitor tyrphostin-47 on smooth-muscle cell proliferation in a rat carotid balloon-injury model

Smooth-muscle cell proliferation in response to arterial injury represents an important etiologic factor in restenosis after angioplasty. Tyrphostin-47, a protein tyrosine kinase inhibitor, inhibits smooth-muscle cell proliferation in vitro. In this study tyrphostin-47 was incorporated into matrixes to determine whether prolonged local delivery would result in a reduction of neointimal proliferation after arterial injury in a rat carotid balloon-injury model. A polymer matrix (polylactic polyglycolic acid copolymer and pluronic gel F-127, mean matrix weight 7.83 ± 0.39 mg) was loaded with tyrphostin-47 (25% w/w). Release studies demonstrated delivery of 11% of the incorporated drug over a 21-day release period. In cell culture, tyrphostin-47 released from the polymer matrix produced a reduction in smooth-muscle cell proliferation ( p < 0.0007). Balloon denudation injury of the left common carotid artery of 34 animals was performed. In 12 animals, polymer matrixes containing tyrphostin-47 were wrapped around the injured arteries to provide prolonged drug delivery (estimated dosage 28 μg/kg/24 hr); in 10 animals a polymer matrix without tyrphostin-47 was implanted; and in 12 animals only balloon injury was performed. The mean neointimal cross-sectional areas, luminal areas, and intima/media ratios were not significantly different among animals receiving local treatment with tyrphostin-47, sham polymer after injury, or balloon injury without polymer implantation. We conclude that despite inhibition of smooth-muscle cell proliferation by tyrphostin-47 in vitro, sustained local delivery of this tyrosine kinase inhibitor does not result in a reduction of neointimal proliferation in the rat carotid injury model. (Am Heart J 1997;133:329-34.)

Neurocompensatory responses to balloon-catheter-induced injury of the rat carotid artery.

Percutaneous transluminal angioplasty relieves discrete arterial stenosis but causes extensive vascular injury. There is denudation of the endothelium and variable medial disruption, but the effect on adventitial structures has not been studied in detail. We have investigated the innervation of the left and right carotid arteries after unilateral balloon-catheter-induced injury. Immunohistochemical examination of the arteries 1 day after Fogarty-catheter-induced injury of the left common carotid artery revealed a reduction in the density of protein gene product 9.5 (PGP)-, substance P (SP)- and calcitonin-gene-related peptide (CGRP)-containing nerves close to the medial smooth muscle of the injured vessel. At the same time, on the side contralateral to the injury, there was a substantial increase in the density of PGP-, SP- and CGRP-containing nerves innervating the carotid artery and vasa vasorum compared to controls. Immunoassay data from these vessels showed a selective increase in SP and CGRP contents of the contralateral carotid artery (SP, controls 0.02 +/- 0.01, operated 0.59 +/- 0.32 pmol/cm; CGRP, controls 0.03 +/- 0.01, operated 0.14 +/- 0.03 pmol/cm, n = 6, p < 0.05). Neuropeptide Y levels were unchanged. Twenty-eight days after surgery, at which time a neointima was present, peptide levels were no different from controls, and the innervation of both the left and right carotid arteries and vasa vasorum was indistinguishable from the controls. In conclusion, balloon-catheter-induced injury includes damage to the perivascular nerves and induces a transient increase in the density of sensory neuropeptide-containing nerves innervating the contralateral, uninjured side. This novel observation may reflect neurocompensatory responses to vascular injury.

Medroxyprogesterone attenuates estrogen-mediated inhibition of neointima formation after balloon injury of the rat carotid artery.

Estrogen blunts the neointimal proliferative response to balloon injury of the carotid artery in intact female rats and gonadectomized rats of both sexes. This study tested whether, in gonadectomized rats of both sexes. (1) progestin (medroxyprogesterone acetate, MPA) alters neointima formation in injured carotid arteries, (2) addition of MPA alters the antiproliferative effects of estrogen, and (3) an interaction between MPA and estrogen can be accounted for by MPA-induced alterations in serum 17 beta-estradiol levels. Male and female Sprague-Dawley rats were subjected to gonadectomy, then were randomly divided into four subgroups and treated with either (1) 17 beta-estradiol, (2) MPA, (3) 17 beta-estradiol + MPA, or (4) vehicle, and balloon injury of the right common carotid artery was carried out. Two weeks later, rats were killed by overdose of pentobarbital, and the carotid arteries were subjected to morphometric analysis for evaluation of myointimal thickening. Estradiol inhibited myointimal proliferation after vascular injury in gonadectomized rats of both sexes (P < .05). MPA alone did not alter neointima formation, but addition of MPA to estradiol completely blocked the antiproliferative effects of estrogen without altering serum 17 beta-estradiol levels. These data indicate that exogenous progestin given alone does not alter the vascular injury response in the rat carotid injury model but that addition of a progestin blocks the antiproliferative effects of estrogen in this model. These effects are seen in gonadectomized rats of both sexes. These findings have direct implications for postmenopausal hormone replacement therapy in humans.

PENETRATING THORACIC VASCULAR INJURIES

1. Known injuries to the ascending aorta and arch are exposed by median sternotomy. Known injuries to the descending thoracic aorta can be exposed through a posterolateral thoracotomy. These injuries are more commonly diagnosed through emergent exploration by means of anterolateral thoracotomies. 2. Preoperative arteriography is extremely useful in managing penetrating injuries to the thoracic outlet, as it allows the choice of appropriate incisions for exposure and control. 3. Innominate artery, right common carotid or subclavian artery, as well as left intrathoracic common carotid artery injuries are best managed via median sternotomy with appropriate extension. 4. Left subclavian arteries are managed with high left anterolateral thoracotomy for proximal control combined with supraclavicular incision. 5. Distal subclavian arteries are managed with proximal control by a supraclavicular incision and distal control by an infraclavicular incision. 6. The bypass principle is useful for managing innominate or left carotid artery injuries. Ligation with brachiocephalic bypass can be a simple solution to a complex problem. 7. Soft grafts, fine sutures, and minimal mobilization are the techniques of choice. 8. Adjuncts such as Fogarty balloon catheters, Foley catheters, autotransfusion, shunts, and pulmonary tractotomy can be useful in managing these injuries. 9. Documentation of the preoperative neurovascular status of the patient should be performed, as well as discussion with the patient and the family, if available, of the potential outcome with appropriate documentation in the chart. 10. Rehabilitation services should be involved as appropriate to care for these patients. 11. Ligation is always an option to save the patient's life.

Angiotensin II-Induced Progression of Neointimal Thickening in the Balloon-Injured Rat Carotid Artery Is AT 1 Receptor Mediated

To investigate the relative importance of AT1 and AT2 receptors in angiotensin II (Ang II)-induced restimulation of neointimal smooth muscle cell (SMC) DNA synthesis and increased neointimal cross-sectional area (CSA), male Wistar rats were subcutaneously infused for 2 weeks with Ang II and losartan, an AT1 receptor antagonist, or Ang II and PD123319, an AT2 receptor antagonist, during the third and fourth week after balloon injury of the left common carotid artery. Concomitantly, all rats received 5-bromo-2'-deoxyuridine to label DNA-synthesizing SMCs. Neointimal CSAs and SMC DNA synthesis were compared with control groups that received Ang II, 0.9% NaCl, losartan, or PD123319. Systolic blood pressure (SBP) was measured at different times during the infusion. Ang II induced an increase in SBP that was significantly different from the SBP in the NaCl group. Infusion of Ang II together with losartan reduced the Ang II-induced increase in SBP to levels comparable with those obtained in the NaCl group. Infusion of Ang II+PD123319 caused an increase in SBP that was comparable with the increase in SBP of the Ang II group and significantly different from the SBP of the NaCl group. Infusion of losartan or PD123319 alone did not affect SBP. Ang II significantly enhanced neointimal CSA (47%, P < .05) compared with the control group infused with NaCl. Losartan significantly reduced Ang II-induced neointimal thickening (neointimal CSA, -37%, P < .05). Infusion of PD123319 together with Ang II did not affect Ang II-induced neointimal thickening. Losartan or PD123319 alone did not reduce neointimal thickening, since the neointimal CSAs in these groups did not differ from the neointimal CSA of the NaCl group. Comparable effects were found for SMC DNA synthesis in the neointima. Ang II infusion increased neointimal SMC DNA synthesis. Addition of losartan reduced the fraction of DNA-synthesizing neointimal SMCs from 23.7 +/- 2.1% in the Ang II group to 12.8 +/- 1.8% in the Ang II+losartan group, whereas the labeling fraction in the neointima remained 26.6 +/- 3.1% in the Ang II+PD123319 group. The labeling fractions in the neointimas of the groups that received losartan or PD123319 alone did not differ from the labeling fraction in the NaCl group. These data indicate that AT1 but not AT2 receptors mediate the progression of neointimal thickening induced by delayed application of Ang II in the injured left carotid artery in the rat. Furthermore, these data suggest that AT1 and AT2 receptors are not involved in the regulation of normal growth of a neointima in the third and fourth week after balloon injury.

Cigarette smoking increases the development of intimal hyperplasia after vascular injury

Our purpose was to determine whether exposure to cigarette smoke increases the development of intimal hyperplasia (IH) after vascular injury. Sixteen adult male Sprague-Dawley rats underwent standardized balloon catheter injury of the left common carotid artery. For 4 weeks before and 4 weeks after injury, animals in the experimental group (n=8) were exposed to cigarette smoke with an automated vacuum pump device. Animals in the control group (n=8) were restrained in the smoking device for an identical amount of time and underwent arterial injury at 4 vivo, prepared as histologic cross sections, and stained for elastin. IH was measured by planimetry and is reported both as the absolute area of IH and as the ratio (IH/IEL) of the absolute area of IH to the normalized area enclosed by the internal elastic lamina (expressed as a percent). The absolute area of IH was 2.09 +/- 0.34 for the experimental group compared with 0.94 +/- 0.25 for the control group; mean IH/IEL was 43% +/- 7.1% for the experimental group versus 17.7% +/- 4.7% for the control group (p < 0.05, two tailed unpaired t test. Inhalation of cigarette smoke increases the development of intimal hyperplasia in a rat model of a balloon catheter arterial injury.

Doxazosin blocks the angiotensin II-induced smooth muscle cell DNA synthesis in the media, but not in the neointima of the rat carotid artery after balloon injury

Infusion of angiotensin II (AngII) during the third and fourth week after balloon injury of the left common carotid artery of the rat induces smooth muscle cell (SMC) DNA synthesis. In this study we wanted to investigate whether alpha 1-adrenoreceptors are involved in AngII-induced SMC DNA synthesis in the neointima. Adult male Wistar Kyoto rats were subcutaneously infused for 2 weeks with AngII and the alpha 1-adrenoreceptor antagonist doxazosin during the 3rd and the 4th week after balloon injury of the left common carotid artery. Control groups received AngII, 0.9% NaCl, AngII + 50% dimethylsulfoxide (DMSO, the solvent of doxazosin), doxazosin or 50% dimethylsulfoxide. Each rat received 5-bromo-2'-deoxyuridine in a separate osmotic minipump to label DNA-synthesizing SMC. Systolic blood pressures were measured in all groups. Angiotensin II caused an increase in systolic blood pressure, whereas addition of doxazosin did not affect the increase in SBP caused by AngII. In the media of the non-injured carotid artery, AngII increased SMC DNA synthesis, as the BrdUrd labeling fraction increased from 0.2 +/- 0.1% (mean +/- s.e.m.) in the NaCl group towards 3.4 +/- 0.6% in the AngII group. Coinfusion with doxazosin reduced the AngII-induced increase in BrdUrd labeling fraction from 3.2 +/- 0.8% in the AngII + DMSO group towards 0.6 +/- 0.2% in the AngII+doxazosin group. A similar effect of doxazosin was found in the media of the injured left carotid artery, in which coinfusion with doxazosin also reduced the BrdUrd labeling fraction from 2.6 +/- 0.8% in the AngII+DMSO group towards 0.3 +/- 0.1% in the AngII+doxazosin group. In the neointima of the injured left carotid artery, AngII increased the BrdUrd labeling fraction from 11.7 +/- 1.6% in the NaCl group towards 28.0 +/- 3.4% in the AngII group. Coinfusion with doxazosin did not influence the AngII-induced SMC DNA synthesis, since the BrdUrd labeling fraction in the neointima of the AngII+doxazosin group was 22.5 +/- 2.9%, whereas the neointimal BrdUrd labeling fraction in the AngII+DMSO group was 22.9 +/- 2.3%. Little effect was found on the medial cross-sectional area. The neointimal cross-sectional area was increased as a result of infusion of AngII (0.12 +/- 0.01 mm2 vs. 0.18 +/- 0.01 mm2), and coinfusion of doxazosin did not reduce the AngII-induced increase in neointimal cross-sectional area (0.18 +/- 0.03 mm2). These data suggest that alpha 1-adrenoreceptors are not involved in AngII-induced neointimal SMC DNA synthesis and cross-sectional area, but only play a role in the media of the carotid artery.

Photodynamic therapy. Cytotoxicity of aluminum phthalocyanine on intimal hyperplasia.

To study the cytotoxic effect of photodynamic therapy (PDT) on myointimal hyperplasia (MIH) in 120 New Zealand white rabbits using the chromophore chloroaluminum phthalocyanine tetrasulfonate (APtS). A common carotid artery (CCA) injury model was used to initiate MIH. Photodynamic therapy was administered 1 week after injury (inhibition arm) or 6 weeks after injury (treatment arm). The inhibition arm CCAs were harvested 6 weeks after therapy. The treatment arm CCAs were harvested 1 week or 6 weeks after therapy. Each evaluation included four subgroups (n = 10 each): control, drug only, laser only, and drug plus laser. An established CCA balloon injury model was used. Photodynamic therapy was administered by exposing CCAs to continuous external laser irradiation 30 minutes after treatment with a 2.5-mg/kg intravenous dose of APtS (fluence = 25 J/cm2, lambda = 672 nm). The control and drug-only subgroups received sham reoperations without laser exposure. Following harvest, the CCAs were evaluated for area of stenosis and cell density. In the inhibition arm, no PDT effect was seen on intimal cell density or area stenosis. In the treatment arm, intimal cell density was markedly diminished (P < .05) in the rabbits in the drug-laser group that were killed 1 week but not 6 weeks after PDT compared with rabbits in the control, drug-only, and laser-only groups. Area stenosis was not significantly affected by PDT. Marked acute cytotoxicity of PDT on MIH was verified in vivo in the treatment arm. No sustained benefit of PDT was seen in the inhibition or the treatment arms. Refinements in dosimetry will be necessary to achieve long-term benefit of PDT for MIH.

Mithramycin inhibits myointimal proliferation after balloon injury of the rat carotid artery in vivo.

Smooth muscle proliferation and extracellular matrix formation in the subintimal region of blood vessels that have been subjected to intimal injury are responsible for restenosis following balloon angioplasty of the coronary arteries and for accelerated atherosclerosis in a variety of other pathophysiological states. The immediate early-response gene c-myc is overexpressed in proliferating vascular smooth muscle cells in vitro, and c-myc antisense oligomers have been shown to reduce c-myc expression and to inhibit proliferation of vascular smooth muscle cells in culture. Mithramycin is a commercially available G-C-specific DNA binding drug that selectively inhibits transcription of genes, such as c-myc, that have G-C-rich promoter sequences. This study tested the hypothesis that mithramycin inhibits transcription of the c-myc proto-oncogene and prevents myointimal proliferation after balloon injury of the rat carotid artery in vivo. Ten-week-old male Sprague-Dawley rats received mithramycin (150 micrograms/kg IP) or distilled H2O 1 hour before and 1 hour after balloon injury of the right common carotid artery. After 2 weeks, the rats were killed by overdose of pentobarbital, and the injured right and uninjured control left arteries were pressure-fixed and subjected to morphological analysis for evaluation of the degree of myointimal thickening. Separate groups of rats were killed at 2 and 6 hours after vascular injury, and total RNA from injured and control vessels of mithramycin- and vehicle-treated rats was subjected to Northern analysis for assessment of steady-state c-myc mRNA levels. The areas of neointima and the ratios of neointimal to medial area were significantly less in mithramycin-treated than in control rats (0.6 +/- 0.1 versus 1.2 +/- 0.1 mm2, P < .01 and 95 +/- 16% versus 190 +/- 14%, P < .01). Lumen size was significantly greater in mithramycin-treated than in control rats (1.5 +/- 0.1 versus 0.8 +/- 0.1 mm2, P < .01). Steady-state c-myc mRNA levels were increased 10-fold and 2-fold (compared with undamaged carotid arteries) at 2 and 6 hours after balloon injury, respectively; mithramycin treatment reduced c-myc mRNA levels at 2 and 6 hours by 66% and 53%, respectively. These results support the hypothesis that systemic administration of mithramycin immediately (1 hour before and after intervention effectively inhibits transcription of the c-myc proto-oncogene and prevents myointimal proliferation after balloon injury of the rat carotid artery in vivo. Because mithramycin has been shown to be well tolerated by humans and to effectively inhibit transcription of c-myc in proliferating human cells, this agent may be useful in the prevention of coronary restenosis.

Suppression of Intimal Hyperplasia in a Rabbit Model of Arterial Balloon Injury by Enalaprilat But Not Dimethyl Sulfoxide

Intimal hyperplasia appears to result from the deposition of collagen and matrix by medial myofibroblasts, which are stimulated in response to vascular injury. We hypothesized that pharmacologic inhibitors of fibroblast proliferation would suppress the development of intimal hyperplasia. We evaluated the effect of two agents known to inhibit fibroblast proliferation in vitro: enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor, and dimethyl sulfoxide (DMSO), an organic solvent. Thirty-five New Zealand white rabbits underwent standardized balloon catheter injury of the left common carotid artery. Experimental groups received daily intramuscular injections of the following: group I (n = 15), saline solution; group II (n = 10), 0.07 mg/kg enalaprilat; and group III (n = 10), 2 ml/kg of a 25% by weight DMSO solution. Injections were started 1 day prior to injury and continued 5 days a week for 8 weeks. Carotid arteries were perfusion-fixed at 12 weeks and cross-sectioned for measurement by planimetry. Intimal hyperplasia was measured as the ratio of the absolute area of intimal hyperplasia to the normalized area enclosed by the internal elastic lamina (IH/IEL) and was expressed as a percent. Mean values for IH/IEL were as follows: group I (control), 20.6 +/- 2.3%; group II (enalaprilat), 9.5 +/- 0.7%; and group III (DMSO), 17.6 +/- 2.6%. Enalaprilat-treated animals demonstrated a statistically significant suppression of intimal hyperplasia compared with controls (p < 0.01, ANOVA, Student's t test), whereas the DMSO-treated group did not. We conclude that enalaprilat is effective in suppressing the development of intimal hyperplasia in this model of arterial injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow affects development of intimal hyperplasia after arterial injury in rats.

This study examined the effects of blood flow on intimal hyperplasia after balloon catheter injury of the rat common carotid artery. Flow was altered by ligation of the opposite common carotid artery (increased flow) or of the ipsilateral internal carotid artery (decreased flow). Blood flow decreased by 35% in the low-flow group and increased by 29% in the high-flow group. Similar changes in mean velocity were observed. Cross-sectional intimal area was significantly greater in the low- than the high-flow group at 2 weeks (0.11 +/- 0.01 versus 0.06 +/- 0.01 mm2, p less than 0.01) and 4 weeks (0.17 +/- 0.02 versus 0.12 +/- 0.01 mm2, p = 0.01) but not at 1 or 8 weeks. Smooth muscle cell proliferation rates (thymidine labeling indexes) were not different in high- and low-flow groups at 2 days and at 1 and 4 weeks. Matrix accumulation at 2 and 4 weeks was the same in both groups. Mature neointima did not respond to changes in flow; when vessel ligation was delayed until 2 months after injury, there was no effect on neointimal area. These data indicate that early neointimal hyperplasia is increased when flow is reduced, possibly because of alteration of smooth muscle cell migration.

Role of basic fibroblast growth factor in proliferation of endothelium and smooth muscle after denuding injury in vivo.

Balloon catheter injury of the rat common carotid artery causes complete denudation of endothelium. Using this model, endothelial regrowth from the aortic arch and the carotid bifurcation is initially rapid but cessation of endothelial outgrowth occurs after approximately 6 weeks [1]. This leaves a central portion of the common carotid artery permanently denuded of endothelium. However, if a less traumatic technique (filament loop denudation) is used to remove the endothelium, proliferation of endothelium proceeds at a continuously high rate until complete coverage of the vessel is achieved within approximately 12 weeks. The difference in endothelial regrowth in these two models allowed us to investigate which factors might be involved in controlling the growth of these cells. With an antibody raised against human recombinant basic fibroblast growth factor (bFGF) immunocytochemistry was performed on en face (Häutchen) preparations of the leading edge of the regenerating endothelium. Strong staining with this antibody was found only in those endothelial cells that continued to proliferate, i.e. at early times after balloon catheter denudation and at all times after filament denudation [1]. The staining appeared to be predominantly nuclear. Endothelial cells that had stopped proliferating, i.e. at later times after balloon catheter injury or normal endothelium in uninjured vessels showed markedly less staining.KeywordsBasic Fibroblast Growth FactorEndothelial Cell ProliferationSmooth Muscle Cell ProliferationIntimal ThickeningNormal EndotheliumThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Common carotid artery injury from an airgun pellet

A Id-year-old boy was hit in the left side of the neck by an airgun pellet while playing. The missile was aimed directly at him from a distance of approximately 9m. He experienced a moderately sharp pain in the left side of the neck and complained of slight swelling. Blood loss was minimal and soon controlled by a first-aid dressing. On admission to hospital z h after the injury, he was well and fully alert with no evidence of blood loss. On the left side of the neck, just anterior to the stemocleidomastoid muscle exactly midway along the muscle belly, was a small entry wound measuring 0.5 an in diameter. This was surrounded by a soft nonpulsatile haematoma, measuring 4 x 3 cm. No bruit was audible. Both superficial temporal arteries were palpable with possibly some diminution on the left side. The pellet was not palpable but plain films confirmed the presence of a foreign body within the soft tissues, anterior to the U-C5 intervertebral disc space (Fig. 1). It was decided to observe his progress. Antitetanus toxoid was given and intravenous cefuroxime started. On review of his radiographs 12 h later, it was considered appropriate to explore the left side of the neck, mainly with a view to extracting the lead pellet.

Encefalopatia hemi-mioclônica pós anóxica: registro de um caso

É relatado o caso de um paciente jovem, do sexo masculino que após ferida da artéria carótida primitiva esquerda e choque séptico, apresentou abalos mioclônicos no dimidio corporal direito. O traçado eletrencefalográfico foi do tipo difuso, discordando da localização dimidiada. Os autores chamam a atenção para a originalidade do caso e acreditam que a origem dos abalos mioclônicos foi em decorrência da somação das duas causas de hipoxia, isto é, a lesão da artéria carótida primitiva esquerda e o choque séptico.