[The structure of the internal carotid artery wall in pathological tortuosity].

OBJECTIVE: to study a change in the content of main components of the internal carotid artery (ICA) wall in pathological tortuosity (PT) resulting from fibromuscular dysplasia, using immunohistochemistry and confocal laser scanning microscopy. MATERIAL AND METHODS: Immunohistochemical (IHC) analysis using antibodies to elastin, collagen types I and III, and smooth muscle actin was made. The levels of elastin and matrix metalloproteinase 9 (MMP-9) were determined by confocal laser scanning microscopy. The relative area of expression and the area of co-location of these markers were measured. RESULTS: IHC examination of the expression of elastin revealed that the patients with PT of ICA had its higher content than the controls, but they were observed to have fiber fragmentation. Comparison of collagen types I and III expressions showed no significant differences between the groups. The found significantly lower smooth muscle actin expression in the patients with PT of ICA than in the controls was suggestive of the decreased levels of smooth muscle cells. Confocal microscopy analysis showed high elastin and low MMP-9 expressions in the control group and, on the contrary, low elastin and high proteinase levels in the PT group (р<0.05). CONCLUSION: One of the causes of PT is impairment in vascular elastic properties due to the destruction of elastic fibers and to their fragmentation, as well as to the decreased count of smooth muscle cells, which in turn causes enhanced MMP-9 activity and tissue matrix degradation.

The influence of carotid endarterectomy on cerebral blood flow in significant carotid stenosis-perfusion computed tomography study.

AIM: Carotid endarterectomy (CEA) is well recognized procedure in the treatment of patients with significant symptomatic internal carotid artery (ICA) stenosis. Operation reconstitutes physiologic blood flow in the ICA. The influence of CEA on cerebral perfusion (CP) is not well established. Some data suggest increased CP after stenosis correction however evidence in post-endarterectomy patients is scarce. Our aim was to investigate the influence of CEA in patients with symptomatic carotid stenosis on CP parameters by means of perfusion computed tomography (PCT). METHODS: Thirty-four patients with symptomatic severe carotid stenosis qualified for CEA were included. The baseline PCT of the brain according to standardized protocol was performed within 3 weeks prior to surgical procedure. The follow-up PCT was performed between 30-60th day postop. The following perfusion parameters were analyzed: cerebral blood flow (CBF), cerebral blood volume (CBV), peak enhancement intensity (PEI) and time to peak (TTP). Pre- and postoperative average values of these parameters were compared. RESULTS: No death/stroke occurred in the investigated group. Mean preoperative total CBF was 66.2 mL/100 g/min and was not dependent on the degree of the carotid stenosis or the presence of contralateral carotid artery stenosis. Mean postoperative total CBF was significantly lower (61.8 mL/100g/min, P<0.05). No significant changes in PEI, TTP and CBV were observed CONCLUSION: PCT of the brain reveals that CEA in patients with symptomatic carotid stenosis decreased total CBF especially in the contralateral hemisphere.

Predictors and timing of recanalization in intracranial carotid artery and siphon dissection: an ultrasound follow-up study.

BACKGROUND: Intra- and extracranial internal carotid artery dissections (ICD) are two different pathological conditions. Extracranial dissection is considered to be among the most frequent causes of stroke in the young and the segment generally reopens in 2 out of 3 cases, completely or partially, within 6 months. Intracranial ICD (IICD) is considered a rare occurrence in stroke and, accordingly, there are few systematic published data. However, it is a clinically significant condition that may cause severely disabling ischemic stroke or subarachnoid hemorrhage. In the past, sole availability of invasive imaging methods for its detection may have induced an underreporting. The aim of the study was to analyze ultrasound findings, timing and predictors of recanalization in patients with IICD. METHODS: IICD acute patients admitted to our Stroke Unit were submitted to carotid sonographic seriated monitoring, daily for the 1st week after symptom onset, at day 14, at month 1 and every 3 months thereafter up to a follow-up of 4 years. Contrast carotid ultrasound was performed in patients with persistent occlusion after month 1. RESULTS: Fourteen acute patients with IICD were enrolled. Extracranial internal carotid patency was observed in 8 patients at first ultrasound scans; all of these showed complete intracranial recanalization within the 1st week and oral anticoagulants were withdrawn after 6 months. Conversely, in 6 patients retrograde extracranial internal carotid thrombosis was immediately observed, since the first ultrasound scans. In 4 of these the occlusion persisted after 4 years while 2 of them had only a partial recanalization, with evidence at contrast ultrasound of still late remodeling processes in the extracranial thrombus up to 2 years after the first observation; for this reason, in these 2 patients anticoagulation was not discontinued, while in the 4 patients with persistent, stable, occlusion, therapy was suspended 1 year after the diagnosis. CONCLUSIONS: Identification of the site of dissection - i.e. extra- versus intracranial - is fundamental in clinical studies for outcome and prognosis evaluation. Carotid ultrasound strict surveillance is important to monitor eventual recanalization in patients with ICD, even in a late phase. Retrograde internal carotid thrombosis seems to be correlated with persistent occlusion and partial recanalization. Remodeling of thrombotic material in the internal carotid artery may, however, continue for up to 2 years. In these cases, contrast ultrasound evidence of thrombus morphological changes may support the decision to continue anticoagulation.

Aneurisma da artéria carótida interna / Aneurysm of the internal carotid artery

Os aneurismas de artéria carótida interna (ACI) extracraniana são raros. Há poucos relatos na literatura médica quanto à sua etiologia, relacionando-os à doença aterosclerótica, às arterites e alterações decorrentes do trauma ou após procedimento cirúrgico. A história natural da doença ainda não está bem estabelecida. Entretanto, o potencial risco de embolia originário do aneurisma ou mesmo de sua ruptura indica necessidade de intervenção. Apresentamos o relato de caso de uma mulher de 71 anos diagnosticada com aneurisma de 3 cm de diâmetro da ACI extracraniana direita com queixas de cefaleia pulsátil. Após tentativa sem sucesso de tratamento endovascular, optou-se pelo tratamento cirúrgico com aneurismectomia e anastomose primária término-terminal próximo à base do crânio.

Aneurysms of the extracranial internalcarotid artery are rare. There are few reports in the medical literature about the etiology of this disease, relating it to atherosclerosis, arteritis and alterations due to trauma or after a surgical procedure. The natural history of this disease has not been defined. However, the potential risk of embolism or rupture creates a need for intervention. We will present the case of a 71 year old woman with pulsatile headaches who was diagnosed a 3 cm aneurysm of the right extracranial internal carotid artery. After an unsuccessful attempt at endovascular treatment, we performed an aneurysmectomy and primary arterial anastomosis near the cranium base.

Histomorphometric study of intracranial internal carotid artery in man

The incidence of cerebrovascular diseases in man is on an increase. Atherosclerotic lesions in intracranial vessels are the usual cause. The normal parameters and histological changes in the intracranial internal carotid arteries, one of the feeder vessels to the brain, were studied in apparently healthy young adults of the Indian population. Gross and histomorphometric features of the intracavernous part of the internal carotid artery (ICA) were studied in the Indian population, in order to determine normal parameters, and observe structural changes in healthy young individuals. Length and outer diameter of ICA were taken in 100 autopsy cases. Cases were grouped according to age – Group I: <20 years, Group II: 20-40 years, and Group III: >40 years. Thirty pairs of vessels were processed for paraffin sectioning (young adults: 20-40 years). Seven-micrometers-thick transverse sections were stained with Hematoxylin and Eosin, Masson’s Trichrome and Verhoeff’s Stains. The length was found to be significantly greater on the left side in Groups II and III. The outer diameter was found to be significantly longer in the left side Group III. The mean thickness of tunica intima was found to be greater on the right side. Preatherosclerotic ageing changes were observed in the third decade of life in apparently healthy young individuals (AU)

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Segment-specific genetic effects on carotid intima-media thickness: the Northern Manhattan study.

BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT) is a surrogate marker of subclinical atherosclerosis and a strong predictor of stroke and myocardial infarction. The object of this study was to determine the association between carotid IMT and 702 single nucleotide polymorphisms in 145 genes. METHODS: B-mode carotid ultrasound was performed among 408 Hispanics from the Northern Manhattan Study. The common carotid artery IMT and bifurcation IMT were phenotypes of interest. Genetic effects were evaluated by the multivariate regression model adjusting for traditional vascular risk factors. For each individual, we calculated a gene risk score (GRS) defined as the total number of the significant single nucleotide polymorphisms in different genes. Subjects were then divided into 3 GRS categories using the 2 cutoff points: mean GRS +/-1 SD. RESULTS: We identified 6 significant single nucleotide polymorphisms in 6 genes for common carotid artery IMT and 7 single nucleotide polymorphisms in 7 genes for bifurcation IMT using the probability value of 0.005 as the significant level. There were no common significant genes for both phenotypes. The most significant genes were the tissue plasminogen activator (P=0.0005 for common carotid artery IMT) and matrix metallopeptidase-12 genes (P=0.0004 for bifurcation IMT). Haplotype analysis did not yield a more significant result. Subjects with GRS >or=9 had significantly increased IMT than those with GRS

Electron microscopic study of the arterial wall in the cerebral aneurysms.

The ultrastructural modifications were observed in electron microscopy of the congenital aneurysm of the internal carotid artery with subarachnoid hemorrhage. The tunica intima very enlarged contains in the endothelial cells numerous microvesicles of pinocytosis, and rare cell organelles. The internal elastic lamina presented ruptured or absence zones. The luminal face of the cells appeared irregular with large evaginations and deep and narrow invaginations. Under the endothelial lining, large masses of extracellular matrix with different degrees of edema, and fragmented collagen fibrils realize a metabolic barrier between the tunica intima and media. The muscle fibers of the tunica media and the myofilaments in each myocyte are in reduced number.

Simvastatin attenuates cerebral vasospasm and improves outcomes by upregulation of PI3K/Akt pathway in a rat model of subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm is a common sequelae of subarachonoid hemorrhage (SAH), however, the mechanism of cerebral vasospasm is still unclear. Recently, statins have been shown to have efficacy in ameliorating cerebral vasospasm. The present study investigates whether simvastatin attenuates cerebral vasospasm after subarachnoid hemorrhage (SAH) via upregulation of the PI3K/Akt pathway. METHODS: 47 adult male Sprague-Dawley rats were divided into 6 groups: sham-operated, SAH treated with vehicle, SAH treated with low dose simvastatin (1 mg/kg), high dose simvastatin (20 mg/kg), SAH treated with simvastatin plus the PI3K inhibitor (wortmannin), and sham-operated plus wortmannin. Simvastatin was administered intraperitoneally 30 minutes after SAH created by the standard endovascular perforation model. Histological parameters of the ipsilateral internal carotid artery (ICA-diameter, perimeter, and wall thickness) and neurological score were assessed at 24 hours. FINDINGS: Mortality was reduced to zero in both the treated groups as compared to 20% in the vehicle-treated and 36% in the simvastatin plus wortmannin-treated groups. The decrease in ICA diameter and perimeter observed in vehicle-treated group (203.2 +/- 10.3 microm, 652.7 +/- 29.0 microm) as compared to sham (259.7 +/- 10.6, 865.4 +/- 39.5) were significantly attenuated by high-dose simvastatin (267.4 +/- 8.0, 882.4 +/- 30.0). The increase in wall thickness (vehicle 29.50 +/- 2.42 microm v/s sham 9.52 +/- 0.56 microm) was significantly attenuated by both high and low dose simvastatin (11.87 +/- 1.56, 19.75 +/- 1.40). These effects of simvastatin were blocked with the addition of wortmannin (162.7 +/- 20.6, 528.9 +/- 65.9, 29.19 +/- 1.97). High dose simvastatin improved the neurological deficits after SAH, but this was also blocked by wortmannin. CONCLUSIONS: The beneficial effects of high dose simvastatin in ameliorating cerebral vasospasm are likely mediated by upregulation of the PI3K/Akt pathway.

On the atrophy of the internal carotid artery in capybara.

Capybara might be a useful model for studying changes in cerebral circulation as the natural atrophy of the internal carotid artery (ICA) occurs in this animal at maturation. In this study, confocal and electron microscopy combined with immunohistochemical techniques were applied in order to reveal the changes in morphology and innervation to the proximal part of ICA in young (6-month-old) and mature (12-month-old) capybaras. Some features of the basilar artery (BA) were also revealed. The ICA of young animals degenerated to a ligamentous cord in mature animals. Immunolabelling positive for pan-neuronal marker protein gene product 9.5 but negative for tyrosine hydroxylase was observed in the proximal part of ICA at both ages examined. Axon varicosities positive for synaptophysin were present in the adventitia of ICA of young animals but were absent in the ligamentous cord of mature animals. In the ICA of young animals, adventitial connective tissue invaded the media suggesting that the process of regression of this artery began within the first 6 months of life. An increase in size of the BA was found in mature animals indicating increased blood flow in the vertebro-basilar system, possibly making capybara susceptible to cerebrovascular pathology (e.g. stroke). Capybara may therefore provide a natural model for studying adaptive responses to ICA regression/occlusion.

Atherogenic region and diet diminish glycocalyx dimension and increase intima-to-media ratios at murine carotid artery bifurcation.

It was hypothesized that endothelial glycocalyx perturbation contributes to increased vulnerability of the arterial wall exposed to atherogenic risk factors. Glycocalyx and intima-to-media ratios (IMR) were studied at a low- and a high-risk region within the murine carotid artery (common region) and internal carotid branch (sinus region) in control C57BL/6J (C57BL6) and age-matched C57BL/6J/apoE*3-Leiden (apoE*3; on an atherogenic diet) mice. Electron micrographs revealed significantly thinner glycocalyces [73 (SD 36) vs. 399 (SD 174) nm, P < 0.05] and greater IMR [0.096 (SD 0.045) vs. 0.044 (SD 0.023), P < 0.05] at the sinus region of C57BL6 mice than in the common region. Thinner glycocalyces [100 (SD 27) vs. 399 (SD 174) nm, P < 0.05] and greater IMR [0.071 (SD 0.024) vs. 0.044 (SD 0.023), P < 0.05] were also observed in the common region of age-matched apoE*3 mice on an atherogenic diet for 6 wk vs. C57BL6 mice on a normal diet. Greater IMR were due to greater intima layers, without significant changes in media layer dimension. In addition, atherogenic diet resulted in increased endothelial cell thickness at the sinus region [0.85 (SD 0.49) vs. 0.53 (SD 0.28) microm, P < 0.05] but not at the common region [0.66 (SD 0.37) vs. 0.62 (SD 0.32) microm]. It is concluded that both regional and diet-induced increases in atherogenic risk are associated with smaller glycocalyx dimensions and greater IMR and that vascular sites with diminished glycocalyx are more vulnerable to proinflammatory and atherosclerotic sequelae.

Anatomia microscópica do canal carótico e suas relações com a cóclea e a cavidade timpânica / Microscopic anatomy of the carotid canal and its relations with cochlea and middle ear

As relações entre as diversas estruturas nobres e vitais que se apresentam na intimidade do osso temporal constituem ainda hoje um grande desafio para o cirurgião otológico. Os estudos micro-anatômicos do mesmo se encontram entre as grandes armas na busca deste entendimento. OBJETIVO: Estudar as correlações anatômicas entre o canal carótico e a cóclea, e a ocorrência de deiscências do mesmo junto à cavidade timpânica. MATERIAL E MÉTODO: Estudo microscópico de 122 ossos temporais humanos. RESULTADOS As distâncias médias entre o canal carótico e os giros cocleares foram: no local de menor distância 1,05mm; no giro basal, 2,04mm; no giro médio, 2,32mm; e no giro apical, 5,7mm. A ocorrência de deiscências do canal carótico na cavidade timpânica foi de 35,2 por cento. CONCLUSÃO: A pequena distância entre estruturas cocleares e o canal carótico, e a alta prevalência de deiscências do mesmo na cavidade timpânica nos relembram o desafio com o qual o cirurgião otológico se depara ao atuar sobre o osso temporal.

A pilot study into measurements of markers of atherosclerosis in periodontitis.

BACKGROUND: Periodontitis may be a possible risk factor for atherosclerosis. The current pilot study explored arterial wall thickness and other variables associated with atherosclerosis in healthy subjects with and without periodontitis. METHODS: Patients with moderate (N = 34) and severe periodontitis (N = 15) and controls (N = 14) were recruited. Intima media thickness (IMT) of the common carotid arteries (CCA), internal carotid arteries (ICA), and bifurcations of carotid arteries (BCA) was estimated bilaterally using B-mode ultrasound. An overall IMT was calculated as the mean of these six measurements. C reactive protein (CRP), fibrinogen, and von Willebrand factor (vWf) were measured in plasma as indicators of systemic inflammation and atherosclerotic disease. Microalbuminuria was determined as a marker of endothelial cell dysfunction. RESULTS: IMT for CCA were 0.64, 0.68, and 0.69 mm for control, moderate, and severe periodontitis, respectively (not significant). IMT for BCA did not vary among groups. IMT of ICA was largest for severe periodontitis (0.81 mm); corresponding values for controls and moderate periodontitis were 0.58 and 0.55 mm, respectively (P= 0.023). Severe periodontitis patients had an overall IMT of 0.76 mm, while moderate periodontitis patients and controls had lower values (0.64 and 0.65 mm, respectively; P= 0.153). After adjusting for potential confounding factors, the increased IMT for ICA in severe periodontitis was also significant (Padj = 0.040). CRP (P= 0.020, Padj = 0.050) and vWf (P= 0.019, Padj = 0.013) were higher in periodontitis than controls; microalbuminuria was not different between groups. Power calculations suggest that a 4-fold expansion of the severe patient and control groups will result in a high chance (power level 80%) that a clinically significant association between the overall IMT and periodontitis will be observed. CONCLUSION: The present pilot study indicates that a full study investigating the relationship between periodontitis and atherosclerosis is warranted.

Microscopic anatomy of the carotid canal and its relations with cochlea and middle ear.

UNLABELLED: The knowledge of the relations between the noble and vital structures of temporal bone is still a great challenge for the otologic surgeon. The microscopic anatomic studies of the temporal bone are one of the greatest help to prevent lesions during surgical intervention. AIM: To study the anatomic correlations between the carotid canal and the cochlea, and the occurrence of dehiscence of the carotid canal in the middle ear tympanic cavity. MATERIAL AND METHODS: Microscopic study of 122 human temporal bones. RESULTS: The average distance between the carotid canal and the cochlea were: the shortest distance, 1.05 mm; basal turn, 2.04 mm; middle turn, 2.32 mm; and apical turn, 5.70 mm. The occurrence of dehiscence of the carotid canal inside the tympanic cavity was 35.2%. CONCLUSION: The small distances between the cochlea and carotid canal, and the high incidence of dehiscence in the tympanic cavity remind us that anatomical knowledge of the temporal bone is required for the best qualification of otologists.

Tortuosity of the internal carotid artery cervicalcourse: case reports and literature review

Variations in the course of the internal carotid arteries (ICA) are reported in the literature as coiling, looping,kinking or tortuosities of the vessels. Nevertheless, the definitions between these variants are confusing. Also, the clinical relevance of morphological anomalies of extracranial ICA is a matter of debate because of up to date the natural history of kinking, coiling and tortuosities of this artery is not well known. However, some authors consider that these conditions are burdened with disabling, even fatal neurological complications.Also, variations of the ICA cervical course may lead to direct contact of the artery with the pharyngeal wall, being of great clinical relevance due to the large number of routine procedures performed in this region. In the present study, we describe two cases of ICA tortuosities and review the current literature regarding the causes, symptoms and clinical significances of the variations of the cervical ICA course. Tortuosity of the cervical ICA is not a rare condition and they can easily be mistaken clinically for an aneurysm, a tumor or an abscess and subsequently injured during an attempted biopsy or excision. Thus, regardless the controversy of its causes (congenital or acquired) it should be included in the differential diagnosis of cervical soft tissue widening. Also, they should be taken into consideration on the diagnostic procedures for ischemic transitory attacks and/or stroke.

Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy.

In young men and women, melatonin influences vascular reactivity and reduces blood pressure and norepinephrine levels. Herein, we investigated whether these effects are conserved in postmenopausal women without and with hormone replacement therapy (HRT). Oral melatonin (1 mg) or placebo was randomly and in double blind fashion administered to 18 untreated and 13 postmenopausal women who were treated continuously with transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). Internal carotid artery pulsatility index (PI), an index of downstream resistance to blood flow, blood pressure and catecholamine levels were evaluated. In untreated postmenopausal women, melatonin was ineffective, while in HRT-treated women, studied during the only estrogenic phase, melatonin reduced, within 90 min, systolic (-8.1 +/- 9.9 mmHg; P = 0.054), diastolic (-5.0 +/- 7.0 mmHg; P = 0.049) and mean (- 6.0 +/- 6.6 mmHg; P = 0.037) blood pressure. Norepinephrine (-50.1 +/- 66.7 pg/mL; P = 0.019), but not epinephrine levels, were also significantly reduced. Similarly, resistance to blood flow in the internal carotid artery, as evaluated by the PI, decreased (-0.190 +/- 0.15; P = 0.0006) in a way that was linearly related to pre-existing PI values (r2 = 0.5; P = 0.0059). These data show that the circulatory response to melatonin is conserved in postmenopausal women on HRT but not in untreated postmenopausal women. Possible physiological and pharmacological implications of these data on the cardiovascular risk of postmenopausal women can be envisioned.

Carotid stenting with cerebral protection: first clinical experience using the PercuSurge GuardWire system.

PURPOSE: To study the feasibility and safety of carotid angioplasty and stenting using a new cerebral protection device that temporarily occludes the distal internal carotid artery (ICA). METHODS: Forty-eight high-risk patients (39 men, mean age 69.1 +/- 8 years, range 54 to 86) with 53 ICA stenoses underwent percutaneous angioplasty and stenting via the femoral approach under cerebral protection afforded by a 0.014-inch GuardWire balloon occlusion device. Mean stenosis was 82.1% +/- 9.65% (range 70 to 96) and mean lesion length was 16.0 +/- 7.5 mm (range 6 to 50). Thirty-three (62%) lesions were calcified, and 38 (72%) were ulcerated. Thirty-two (60%) of the lesions were asymptomatic. With the occlusion balloon inflated in the distal ICA, the lesion was dilated and stented. The area was cleaned by aspiration and flushed via an aspiration catheter advanced over the wire. Blood samples were collected from the external carotid artery (ECA) and analyzed to measure the size and number of particles collected. Computed tomography and neurological examinations were performed the day after the procedure. RESULTS: Immediate technical success was achieved in all patients with the implantation of 38 Palmaz stents, 8 Expander stents, and 11 Wallstents. Carotid occlusion was well tolerated in all patients but 1 who had multiple, severe carotid lesions and poor collateralization. Mean cerebral flow occlusion time was 346 +/- 153 seconds during predilation and 303 +/- 143 seconds during stent placement. Total mean flow occlusion time was 542 +/- 243 seconds. One immediate neurological complication (transient amaurosis) occurred in a patient who had an anastomosis between the external carotid (EC) and ICA territories. Debris was removed in all patients with a mean 0.8-mm diameter catheter. CONCLUSION: Cerebral protection with the GuardWire device is easy, safe, and effective in protecting the brain from cerebral embolism. Larger studies are warranted.

Nitric oxide synthase inhibition in humans reduces cerebral blood flow but not the hyperemic response to hypercapnia.

BACKGROUND AND PURPOSE: Animal studies suggest that nitric oxide (NO) is important in basal cerebral blood flow (CBF) regulation and that it may mediate the vasodilatory response to carbon dioxide. We investigated its role in the human circulation using the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). METHODS: L-NMMA was administered as an intravenous bolus at three doses (1, 3, and 10 mg/kg). CBF was assessed by color velocity ultrasonic imaging of internal and common carotid artery volume flow (ICA flow and CCA flow) and transcranial Doppler ultrasound measurement of middle cerebral artery flow velocity (MCAv). The pressor effect of L-NMMA was controlled for by comparison with noradrenaline titrated to effect an equivalent blood pressure elevation. RESULTS: L-NMMA produced a dose-dependent reduction in basal mean+/-SD CCA flow from 415.2+/-51.9 to 294+/-56.2 mL/min (at 10 mg/kg) and ICA flow from 268.8+/-59.4 to 226.2+/-72.6 mL/min (P<.005 and P<.05, respectively, comparing areas under the dose-response curve). This was reversed by L-arginine. Mean+/-SD systemic blood pressure rose from 85.2+/-6.4 to 100.8+/-9.6 mm Hg (P<.01). There was no significant reduction in MCAv. There was no significant change in the CBF response to either 6% or 8% carbon dioxide after L-NMMA. Noradrenaline produced a lesser fall in basal CCA flow (12.0%) but had a similar effect on the hypercapnic response. CONCLUSIONS: Basal NO release is important in controlling human CBF, but intravenously administered L-NMMA does not inhibit the hypercapnic hyperemic response in humans. The discrepancy between CBF and MCAv after L-NMMA administration is consistent with MCA vasoconstriction. Neuronal NO synthase inhibition may be protective in stroke. However, our results suggest that nonselective NO synthase inhibitors such as L-NMMA should be used with caution because they reduce CBF.

In vivo angioplasty prevents the development of vasospasm in canine carotid arteries. Pharmacological and morphological analyses.

BACKGROUND AND PURPOSE: To study the effects of in vivo transluminal balloon angioplasty (TBA) on the structure and function of the arterial wall, a canine model of hemorrhagic cerebral vasospasm of the high cervical internal carotid artery (ICA) was used. This model was also used to determine whether TBA performed before clot placement could prevent the development of vasospasm. METHODS: Twelve dogs underwent surgical exposure of both distal-cervical ICAs, followed by baseline angiography. One randomly selected ICA in each dog was then subjected to in vivo TBA and repeated angiography. Both distal ICAs were then surrounded with blood clots held by silicone elastomer sheaths. Seven days later angiography was repeated, and all animals were killed. The ICAs in four animals were perfusion-fixed in situ for morphological analysis by electron microscopy, and the arteries in the remaining eight animals were removed and immediately immersed in oxygenated Krebs' solution. Contractile responses of isolated arterial rings from each ICA were recorded after treatment with KCl, noradrenaline, serotonin, and prostaglandin F2 alpha, while relaxations in response to the calcium ionophore A23187 and papaverine were recorded after tonic contraction to noradrenaline had been established. The morphology and pharmacological responses of ICAs that had been exposed to blood with or without prior TBA were compared with data obtained from control arterial segments of intact, more proximal regions of the ICAs from each animal. RESULTS: TBA resulted in immediate angiographic enlargement of the ICA lumen that was still evident 7 days later despite the placement of clotted blood around the artery. Scanning and transmission electron microscopy demonstrated flattening of the intima and internal elastic lamina in these dilated arteries, associated with patchy losses of endothelial cells. In contrast, ICAs that had been exposed to clotted blood but had not undergone prior TBA developed consistent angiographic and morphological vasospasm. In comparison with control vessels and nondilated vasospastic vessels, vessels dilated with TBA and then exposed to clotted blood showed significantly diminished responses to all compounds tested, with the exception of prostaglandin F2 alpha. CONCLUSIONS: These results indicate that in vivo TBA results in a degree of functional impairment of vascular smooth muscle that persists for at least 7 days. This result is consistent with previous observations of the acute effects of TBA in isolated arteries. Furthermore, these results support the hypothesis that normal smooth muscle function is required for the development of vasospasm. Finally, these results indicate that TBA performed before the onset of vasospasm prevents its development.

Fibronectin inhibition of platelet thrombus formation in an in vivo porcine model of vascular injury.

Platelets adhere and aggregate in response to exposed subendothelial matrix during vascular injury. The present study examines the effect of plasma fibronectin on platelet deposition at a site of vascular injury in an in vivo porcine model. The internal carotid arteries in anesthetized Yorkshire pigs were bilaterally exposed and the distal half of each vessel stripped of endothelium. Following stripping, one in situ carotid artery preparation was filled with 0.5 mg/ml porcine plasma fibronectin and the other artery filled with vehicle solution, to serve as a control. After five minutes, 6-7 x 10(9) 111Indium-labeled autologous platelets were infused via a femoral vein cannula, and carotid blood flow was re-established for 20 minutes. The vessel segments were excised and deposition of platelets determined. Vascular stripping increased platelet deposition 52-fold, as compared to unstripped vessel segments. Fibronectin pretreatment did not affect platelet deposition in control vessel segments but decreased platelet deposition by 77% in stripped vessel segments. Transmission and scanning electron microscopy indicated that reduced platelet deposition in the fibronectin treated group was due to decreased platelet aggregation rather than decreased adhesion.

Electron microscopic structure and innervation of the carotid baroreceptor region in the rock hyrax (Procavia capensis).

Semi-thin plastic sections reveal that the carotid baroreceptor region in the rock hyrax comprising the origin of the internal carotid artery has a preponderantly elastic structure and a thick tunica adventitia. In contrast, the common carotid artery has a musculoelastic structure, whereas the cranial segment of the internal carotid artery (immediately distal to the baroreceptor areas) shows the features of a muscular artery. Electron microscopy discloses the presence of sensory nerve endings within the parts of the tunica adventitia adjoining the preponderantly elastic zone of the internal carotid artery. These nerve endings are characterized by varicose regions containing a large quantity of mitochondria. Bundles of collagen fibers in the tunica adventitia form convolutions or whorls around the nerve terminals and often terminate on the surface of the elastic fibers or into the basement membranes of the neuronal profiles. The large content of elastic tissue in the tunica media of the baroreceptor region may render the vessel wall highly distensible to intraluminal pressure changes. This, in turn, would facilitate the transmission of the stimulus intensity to the sensory nerve terminals located in the tunica adventitia. It is suggested that the stretching of elastic fibers may form the main mechanical event leading to the distortion of the associated nerve terminals. However, a change in the geometrical configuration of the bundles of collagen under the influence of the elastic fibers may provide a better insight into the mechanisms of distortion of the baroreceptors related to and/or in contact with collagen fibers.