Citations

Abstract Purpose: The purpose of this study was to investigate the difference in contact geometry at the undersurface of acromion in shoulders with and without a rotator cuff (RC) tear. Type of Study: Case‐control study. Methods: Forty fresh cadaveric shoulders (average age at death, 61 years) without gross osteoarthritic changes were divided into the intact RC group (n = 20) and the RC tear group (n = 20). Clinical impingement was simulated by compressing the humeral head and the intact portion of the RC against the coracoacromial arch with an axial compressive force of 25 kg while the humerus was held abducted 20° in the scapular plane. The contact pattern between the acromion and the RC was measured with Fuji Prescale super low‐pressure–sensitive film (Fuji Photo Film Co, Ltd, Tokyo, Japan). The imprint image was analyzed using Global Lab image software (Automatix, Marlboro, MA). Results: The percentage of the maximum anteroposterior dimension of the imprint on Fuji film to the anteroposterior diameter of the acromial undersurface was 29% ± 9% in intact RC shoulders, and 39% ± 13% in shoulders with an RC tear ( P >.05). The percentage of the maximum mediolateral dimension of the imprint to the mediolateral diameter of the corresponding part of the acromial undersurface was 27% ± 12% in intact RC shoulders, and 48% ± 11% in shoulders with an RC tear. This difference was statistically significant ( P <.005). Conclusions: The contact geometry of the acromial undersurface with the underlying RC in the anteroposterior dimension, which might be related to the appearance in supraspinatus outlet view, was not significantly different between shoulders with and without an RC tear. These findings suggest that factors other than acromial shape play a significant role in the pathogenesis of RC tears. The implication regarding the role of acromioplasty remains to be clarified.

The physiological mechanisms mediating the variability and diurnal rhythm of blood pressure are unclear. We tested the hypothesis that resting sympathetic activity is linked to the variability characteristics and 24-hour profile of ambulatory blood pressure measurements. We evaluated the relationship between muscle sympathetic nerve activity (MSNA) and the level, variability, and nocturnal fall of ambulatory blood pressure in 69 normal men. Subjects were subdivided according to the tertiles of MSNA distributions. Mean 24-hour blood pressure was not significantly different across the 3 groups. Compared with subjects in the first tertile (lowest MSNA, <18 bursts/min), subjects in the third tertile (highest MSNA, >25 bursts/min) had significantly greater daytime blood pressure variability, whether expressed as absolute values (10.2±0.5 versus 8.1±0.4 mm Hg for systolic blood pressure and 9.4±0.4 versus 7.2±0.4 mm Hg for diastolic blood pressure; P <0.01 for both comparisons) or as variation coefficients (8.1±0.4% versus 6.6±0.3% for systolic blood pressure and 12.7±0.7% versus 10.1±0.6% for diastolic blood pressure; P <0.01 for both comparisons). Subjects in the third tertile also had a more striking absolute and percentage fall in systolic blood pressure from daytime to nighttime than subjects in the first tertile (17±2 versus 10±2 mm Hg, P =0.02, or 13±1% versus 8.2±1.4%, P =0.02). In conclusion, higher resting measurements of sympathetic traffic are associated with greater daytime blood pressure variability and a more marked nocturnal decline in blood pressure in normal subjects. These findings suggest that sympathetic neural mechanisms may contribute importantly to the regulation of blood pressure over the 24-hour period.

Background and Purpose — Bovine endothelial nitric oxide synthase (eNOS) is phosphorylated directly by the protein kinase Akt at serine 1179. Mutation of this residue to the negatively charged aspartate (S1179DeNOS) increases nitric oxide (NO) production constitutively in the absence of agonist stimulus. The present study was designed to determine the effect of mutant S1179DeNOS gene expression on vasomotor function of canine cerebral arteries. Methods — Isolated basilar and middle cerebral arteries were exposed ex vivo (30 minutes at 37°C) to an adenoviral vector (10 10 plaque-forming units per milliliter) encoding the S1179DeNOS gene (AdCMVS1179DeNOS), the wild-type eNOS gene (AdCMVeNOS), or the green fluorescent protein (GFP) reporter gene (AdCMVGFP). Twenty-four hours after transduction, arteries were suspended in an organ chamber for isometric force recording, and levels of cGMP were measured by radioimmunoassay. Results — Transgene protein expression was detected mainly in the vascular adventitia. In AdCMVS1179DeNOS-transduced arteries, basal levels of cGMP were significantly elevated compared with those in control (nontransduced), AdCMVGFP-, or AdCMVeNOS-transduced vessels (n=8; P <0.01). The elevation of cGMP was abolished by a NOS inhibitor, N G -nitro- l -arginine methyl ester (L-NAME), or by incubation in the calcium-free medium in the presence of calcium chelators. In AdCMVS1179DeNOS-transduced arteries, contractions to endothelin-1 (10 −10 to 10 −8 mol/L) were significantly reduced compared with those in control and AdCMVGFP-transduced arteries (n=7; P <0.05). The vasoconstrictor effect of endothelin-1 was restored in the presence of the NOS inhibitor L-NAME. Conclusions — Our results suggest that in cerebral arteries, expression of recombinant S1179DeNOS increases basal production of NO and inhibits the vasoconstrictor effect of endothelin-1. This effect may have therapeutic application in prevention and treatment of cerebrovascular diseases.

Background and Purpose — Post-subarachnoid hemorrhage (SAH) cerebral vasospasm is a potentially devastating condition whose pathogenesis involves impaired nitric oxide (NO) bioavailability. We aimed to determine whether recombinant endothelial NO synthase (eNOS) gene expression may protect vasomotor function and prevent vasospasm in a canine experimental SAH model. Methods — Recombinant adenoviral vectors (5×10 9 plaque-forming units/animal) encoding genes for eNOS (AdeNOS) and β-galactosidase (AdLacZ) or vehicle were injected into the cerebrospinal fluid (CSF) of dogs on day −1 (ie, 24 hours before the first intra-CSF injection of blood on day 0). Cerebral angiography was performed at day 0 (baseline) and day 7 (immediately before death), and tissues were harvested for additional studies. Results — Western analysis and immunohistochemistry detected recombinant eNOS exclusively in cerebral arteries isolated from AdeNOS-transduced dogs, and in this group of animals CSF NO concentrations were significantly elevated by day 2. Analysis of day 7 versus day 0 cerebral angiograms for each group revealed significant spasm at the basilar artery midpoint in AdLacZ-transduced and nontransduced dogs but not in AdeNOS-transduced dogs. Isometric force recording of basilar arteries isolated from AdeNOS-transduced dogs showed significantly augmented relaxations to bradykinin and reduced contractions to endothelin-1. Conclusions — Our results suggest that expression of recombinant eNOS in the adventitia of cerebral arteries may contribute toward protection against post-SAH vasospasm.

Background and Purpose — The aim of the study was to evaluate the relationship between daily aspirin use and urinary excretion of a stable thromboxane metabolite, 11-dehydrothromboxane B 2 (11-DTB2), in African American stroke patients. Methods — Subjects were a subgroup of those screened for the African American Antiplatelet Stroke Prevention Study. Subjects were within 4 months of noncardioembolic ischemic stroke and were not being treated with anticoagulants. Antithrombotic therapy at the time of urine collection varied according to the practice patterns of various attending physicians who treated the patients during their acute strokes. 11-DTB2 was measured by enzyme immunoassay in random urine samples 1 to 4 months after the stroke. Results — Eighty-seven of 92 patients enrolled were able to give a urine sample at the time of enrollment. There were 51 men and 36 women aged 36 to 87 (mean 62) years. On the basis of antithrombotic treatment before the sample collection, we divided patients into 4 groups: (1) 16 patients treated with no aspirin (no antithrombotic drugs [n=4] or ticlopidine [n=12]), (2) 21 patients treated with 81 to 325 mg aspirin per day (81 mg/d [n=2], 325 mg/d [n=19]), (3) 20 patients treated with 650 mg aspirin per day, and (4) 30 patients treated with 975 to 1300 mg aspirin per day (975 mg/d [n=2] and 1300 mg/d [n=28]). In patients taking daily aspirin at any dose, the median urinary 11-DTB2 was 783 pg/mg creatinine compared with 1386 pg/mg creatinine in patients not taking daily aspirin ( P =0.01 by Wilcoxon rank sum test). In multivariate regression analysis, aspirin use remained significantly associated with lower urinary 11-DTB2 ( P =0.008). There was no dose-response effect between the 3 aspirin dose groups and urinary 11-DTB2 ( P =0.70). Conclusions — In African American stroke patients, aspirin use is associated with significantly lower urinary 11-DTB2 independent of other vascular factors, and there does not appear to be a dose-response effect for aspirin doses of 325 to 1300 mg daily. The clinical significance of these finding remains to be determined.

Abstract— Coronary artery disease (CAD) is the leading cause of mortality in the developed world. Although several CAD risk factors, including measures of lipid metabolism, obesity, and blood pressure, have a genetic basis, many genes for CAD susceptibility have yet to be identified. Coronary atherosclerosis is the major cause of CAD, but many with coronary atherosclerosis lack symptoms. Thus, a major limitation of using symptomatic CAD endpoints (eg, sudden coronary death, myocardial infarction) as a study outcome is substantial disease misclassification. Coronary artery calcification (CAC) is part of the atherosclerotic process and is an independent predictor of CAD endpoints. In the present study, CAC was noninvasively quantified by electron beam computed tomography. We performed genome-wide multipoint mode-of-inheritance-free linkage analysis on affected sib pairs, defined as being ≥ the 70th sex- and age-specific percentile for CAC quantity, in a sample of 29 families enriched for hypertension. Almost 95% of participants were asymptomatic for CAD. Our LOD score (log 10 odds in favor of linkage) results provide evidence that chromosomal regions 6p21.3 (maximum LOD score=2.22, P =0.00070) and 10q21.3 (maximum LOD score=3.24, P =0.000057) may harbor genes associated with subclinical coronary atherosclerosis.

Atherosclerosis manifests as a systemic disease with near global involvement of the named segments of the arterial tree. Acute thrombotic arterial occlusion, however, is not equally distributed. To evaluate intra-individual regional differences in arterial thrombogenicity, we compared 111 In-platelet deposition in porcine carotid and femoral arteries after a standardized crush injury. Within the unidirectional flow conditions of elastic carotid arteries, platelet deposition was more than 3-fold higher compared with predominantly muscular femoral arteries with triphasic arterial flow. To determine the influence of rheology on platelet deposition after crush injury, carotid arteries were transplanted into the femoral position and compared with the paired native carotid and femoral arteries. Similarly, femoral arteries transposed to the carotid position were compared with the paired native carotid artery. In each of these experiments, arterial transposition to a new anatomic location imparts a predilection for platelet deposition indigenous to the new location. In the controlled environment of two high-shear thrombin–independent and –dependent flow chambers, porcine carotid and femoral arterial substrates were indistinguishable from one another with respect to platelet deposition. Regional differences in arterial hemodynamics may account for substantial differences in thrombosis arising from deep arterial injury.

Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily, and endothelin-1 (ET-1) are potent hypertrophic factors in cardiomyocytes. Although CT-1 and ET-1 gene expression in the heart is upregulated in experimental heart failure, their role in the activation of the cardiac fibroblast is unknown. This study was designed to identify the presence and action of CT-1 and its receptor complex, glycoprotein130 (gp130) and leukemia inhibitory factor (LIF) receptor, on cardiac fibroblast growth in cultured adult canine cardiac fibroblasts. In addition, we investigated the interaction between CT-1/gp130/LIF receptor and ET-1/endothelin type A (ET A ) receptor axis. Immunohistochemistry was performed using the indirect immunoperoxidase method, while we assessed the cell cycle of cardiac fibroblasts by flow cytometry, DNA synthesis by [ 3 H]thymidine incorporation, and collagen synthesis by [ 3 H]proline incorporation, respectively. CT-1 and gp130/LIF receptor were widely present in the cytoplasm of the cardiac fibroblasts. Exogenous CT-1 markedly stimulated [ 3 H]thymidine and [ 3 H]proline incorporations ( P <0.01), with accumulation of cells in the S phase. Blockade of gp130 or LIF receptor inhibited basal growth as well as CT-1– or ET-1–stimulated cardiac fibroblast growth. The specific ET A receptor antagonist, BQ123, significantly inhibited CT-1–stimulated DNA synthesis. This study demonstrates that CT-1 and its receptors are present in cardiac fibroblasts. In addition, growth of these cells stimulated by endogenous and exogenous CT-1 requires gp130/LIF receptor as well as ET A receptor activation. We conclude that gp130/LIF receptor and ET A receptor activation are essential for cardiac fibroblast growth by CT-1 and that there is synergism with ET-1/ET A receptor axis.

Background — Left atrial (LA) thrombus is infrequently detected in the presence of sinus rhythm (SR) and, in these cases, is usually associated with additional cardiac pathologies. We sought to determine the clinical and echocardiographic characteristics of patients with LA thrombus and SR to define a high-risk group of patients prone to this uncommon clinical presentation. Methods and Results — The institution’s echocardiographic laboratory database was searched to identify patients with LA thrombus, diagnosed by transesophageal echocardiography (TEE), who were in SR during the TEE examination. Of 20 643 consecutive TEE examinations performed during an 11-year period, LA thrombus was detected in 314 patients in 380 TEE examinations. Of these, SR was present in 20 patients (age 69±13 years; 40% men) in 23 examinations (0.1% of all TEE examinations; 6.1% of TEE examinations with LA thrombus). High-risk structural heart disease (severe left ventricular dysfunction or significant left-sided valve disease [predominantly mitral valve disease]), previous documented episodes of atrial fibrillation, or both (structural heart disease and previous atrial fibrillation) were present in 10, 4, and 5 of the 20 patients, respectively. Only 1 patient with LA thrombus and SR did not have high-risk features. Conclusions — LA thrombus is very infrequently detected in the presence of SR. Patients with LA thrombus and SR constitute a high-risk group characterized by specific structural cardiac abnormalities or previous atrial fibrillation, abnormalities that are potentially detectable before TEE.