Attenuation of cerebral vasospasm by systemic administration of an endothelin-A receptor antagonist, TBC 11251, in a rabbit model of subarachnoid hemorrhage

1997 ◽  
Vol 3 (4) ◽  
pp. E8 ◽  
Author(s):  
John E. Wanebo ◽  
Hunter G. Louis ◽  
Adam S. Arthur ◽  
Jie Zhou ◽  
Neal F. Kassell ◽  
...  

Cerebral vasospasm is a major complication of subarachnoid hemorrhage (SAH) after the rupture of an intracranial aneurysm. Although the cause of cerebral vasospasm has not been fully established, several lines of evidence suggest that the vasoconstrictor peptide endothelin (ET) may play a crucial role. In the present study the potential of TBC 11251 (TBC), a newly developed ETA receptor antagonist, to prevent and/or reverse cerebral vasospasm was examined in a well-established rabbit model of SAH. Sixty-five New Zealand White rabbits were assigned to one of six groups. Experimental SAH was induced in rabbits comprising five of the groups by injecting autologous arterial blood into the cisterna magna. The treatment groups were as follows: 1) control (no SAH); 2) SAH only; 3) SAH + placebo at 24 and 36 hours (24/36); 4) SAH + TBC (24/36); 5) SAH + placebo twice daily (BID); and 6) SAH + TBC BID. All drug-treated animals received an intravenous dosage of 5 mg/kg TBC. After 48 hours, the animals were killed by intracardiac perfusion with fixative. The brainstems were removed and the basilar arteries (BAs) were prepared for histological examination. The cross-sectional area of each BA was measured using computer-assisted videomicroscopy by an investigator blind to the group from which it came. A one-way analysis of variance and paired group mean comparisons with the post-hoc Fisher least significant difference test were used for analysis of BA diameters and physiological parameters. The model provided reliable vasospasm, with the mean BA cross-sectional area constricting from 0.388 mm2 in the control group to 0.106 mm2 (27.4% of control) in the SAH only group. Treatment with TBC (24/36) after SAH (reversal protocol) produced a mean BA area of 0.175 mm2 (44.2% of control) which, although larger than the placebo group value of 0.135 mm2 (39.9% of control), was not statistically significant. However, treatment with TBC BID (prevention protocol) produced a mean BA area of 0.303 mm2 (78.1% of control) compared with the placebo BID value of 0.134 mm2 (34.6% of control); this effect was statistically significant (p < 0.01). There were no side effects noted and no differences in the mean arterial pressures between drug and placebo groups. These findings demonstrate that systemic administration of the ETA receptor antagonist TBC significantly attenuates cerebral vasospasm after SAH when given as a preventative therapy, and they provide additional support for the role of ET in the establishment of vasospasm.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gernot Seppel ◽  
Andreas Voss ◽  
Daniel J. H. Henderson ◽  
Simone Waldt ◽  
Bernhard Haller ◽  
...  

Abstract Background While supraspinatus atrophy can be described according to the system of Zanetti or Thomazeau there is still a lack of characterization of isolated subscapularis muscle atrophy. The aim of this study was to describe patterns of muscle atrophy following repair of isolated subscapularis (SSC) tendon. Methods Forty-nine control shoulder MRI scans, without rotator cuff pathology, atrophy or fatty infiltration, were prospectively evaluated and subscapularis diameters as well as cross sectional areas (complete and upper half) were assessed in a standardized oblique sagittal plane. Calculation of the ratio between the upper half of the cross sectional area (CSA) and the total CSA was performed. Eleven MRI scans of patients with subscapularis atrophy following isolated subscapularis tendon tears were analysed and cross sectional area ratio (upper half /total) determined. To guarantee reliable measurement of the CSA and its ratio, bony landmarks were also defined. All parameters were statistically compared for inter-rater reliability, reproducibility and capacity to quantify subscapularis atrophy. Results The mean age in the control group was 49.7 years (± 15.0). The mean cross sectional area (CSA) was 2367.0 mm2 (± 741.4) for the complete subscapularis muscle and 1048.2 mm2 (± 313.3) for the upper half, giving a mean ratio of 0.446 (± 0.046). In the subscapularis repair group the mean age was 56.7 years (± 9.3). With a mean cross sectional area of 1554.7 mm2 (± 419.9) for the complete and of 422.9 mm2 (± 173.6) for the upper half of the subscapularis muscle, giving a mean CSA ratio of 0.269 (± 0.065) which was seen to be significantly lower than that of the control group (p < 0.05). Conclusion Analysis of typical atrophy patterns of the subscapularis muscle demonstrates that the CSA ratio represents a reliable and reproducible assessment tool in quantifying subscapularis atrophy. We propose the classification of subscapularis atrophy as Stage I (mild atrophy) in case of reduction of the cross sectional area ratio < 0.4, Stage II (moderate atrophy) in case of < 0.35 and Stage III (severe atrophy) if < 0.3.


2016 ◽  
Vol 52 (1) ◽  
pp. 12-23 ◽  
Author(s):  
Ran S Sopher ◽  
Andrew A Amis ◽  
D Ceri Davies ◽  
Jonathan RT Jeffers

Data about a muscle’s fibre pennation angle and physiological cross-sectional area are used in musculoskeletal modelling to estimate muscle forces, which are used to calculate joint contact forces. For the leg, muscle architecture data are derived from studies that measured pennation angle at the muscle surface, but not deep within it. Musculoskeletal models developed to estimate joint contact loads have usually been based on the mean values of pennation angle and physiological cross-sectional area. Therefore, the first aim of this study was to investigate differences between superficial and deep pennation angles within each muscle acting over the ankle and predict how differences may influence muscle forces calculated in musculoskeletal modelling. The second aim was to investigate how inter-subject variability in physiological cross-sectional area and pennation angle affects calculated ankle contact forces. Eight cadaveric legs were dissected to excise the muscles acting over the ankle. The mean surface and deep pennation angles, fibre length and physiological cross-sectional area were measured. Cluster analysis was applied to group the muscles according to their architectural characteristics. A previously validated OpenSim model was used to estimate ankle muscle forces and contact loads using architecture data from all eight limbs. The mean surface pennation angle for soleus was significantly greater (54%) than the mean deep pennation angle. Cluster analysis revealed three groups of muscles with similar architecture and function: deep plantarflexors and peroneals, superficial plantarflexors and dorsiflexors. Peak ankle contact force was predicted to occur before toe-off, with magnitude greater than five times bodyweight. Inter-specimen variability in contact force was smallest at peak force. These findings will help improve the development of experimental and computational musculoskeletal models by providing data to estimate force based on both surface and deep pennation angles. Inter-subject variability in muscle architecture affected ankle muscle and contact loads only slightly. The link between muscle architecture and function contributes to the understanding of the relationship between muscle structure and function.


2004 ◽  
Vol 96 (2) ◽  
pp. 463-468 ◽  
Author(s):  
Eric Laffon ◽  
Christophe Vallet ◽  
Virginie Bernard ◽  
Michel Montaudon ◽  
Dominique Ducassou ◽  
...  

The present method enables the noninvasive assessment of mean pulmonary arterial pressure from magnetic resonance phase mapping by computing both physical and biophysical parameters. The physical parameters include the mean blood flow velocity over the cross-sectional area of the main pulmonary artery (MPA) at the systolic peak and the maximal systolic MPA cross-sectional area value, whereas the biophysical parameters are related to each patient, such as height, weight, and heart rate. These parameters have been measured in a series of 31 patients undergoing right-side heart catheterization, and the computed mean pulmonary arterial pressure value (PpaComp) has been compared with the mean pressure value obtained from catheterization (PpaCat) in each patient. A significant correlation was found that did not differ from the identity line PpaComp = PpaCat ( r = 0.92). The mean and maximal absolute differences between PpaComp and PpaCat were 5.4 and 11.9 mmHg, respectively. The method was also applied to compute the MPA systolic and diastolic pressures in the same patient series. We conclude that this computed method, which combines physical (whoever the patient) and biophysical parameters (related to each patient), improves the accuracy of MRI to noninvasively estimate pulmonary arterial pressures.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Qianru Li ◽  
Qi Zhang ◽  
Yehua Cai ◽  
Yinghui Hua

Purpose. To evaluate differences of Achilles tendon (AT) hardness and morphology between asymptomatic tendons in patients with acute AT ruptures on the contralateral side and asymptomatic tendons in healthy people by using computer-assisted quantification on axial-strain sonoelastography (ASE). Methods. The study consisted of 33 asymptomatic tendons in 33 patients (study group) and 34 tendons in 19 healthy volunteers (control group). All the tendons were examined by both ASE and conventional ultrasound. Computer-assisted quantification on ASE was applied to extract hardness variables, including the mean (Hmean), 20th percentile (H20), median (H50) and skewness (Hsk) of the hardness within tendon, and the ratio of the mean hardness within tendon to that outside tendon (Hratio) and three morphological variables: the thickness (THK), cross-sectional area, and eccentricity (ECC) of tendons. Results. The Hmean, Hsk, H20, H50, and Hratio in the proximal third of the tendon body in study group were significantly smaller than those in control group (Hmean: 0.43±0.09 vs 0.50±0.07, p=0.001; Hsk: -0.53±0.51 vs -1.09±0.51, p<0.001; H20: 0.31±0.10 vs 0.40±0.10, p=0.001; H50: 0.45±0.10 vs 0.53±0.08, p<0.001; Hratio: 1.01±0.25 vs 1.20±0.23, p=0.003). The THK and cross-sectional area of tendons in the study group were larger than those in the control group (p<0.05). Conclusions. As a quantitative objective method, the computer-assisted ASE reveals that the asymptomatic ATs contralateral to acute rupture are softer than those of healthy control group at the proximal third and the asymptomatic tendons in people with rupture history are thicker, larger, and rounder than those of normal volunteers especially at the middle and distal thirds of AT body.


2021 ◽  
Vol 20 (1) ◽  
pp. 50-54
Author(s):  
Thyago Guirelle Silva ◽  
Rodrigo Augusto do Amaral ◽  
Raphael Rezende Pratali ◽  
Luiz Pimenta

ABSTRACT Objective: To verify the effectiveness of indirect decompression after lateral access fusion in patients with high pelvic incidence. Methods: A retrospective, non-comparative, non-randomized analysis of 22 patients with high pelvic incidence who underwent lateral access fusion, 11 of whom were male and 11 female, with a mean age of 63 years (52-74), was conducted. Magnetic resonance exams were performed within one year after surgery. The cross-sectional area of the thecal sac, anterior and posterior disc heights, and bilateral foramen heights, measured pre- and postoperatively in axial and sagittal magnetic resonance images, were analyzed. The sagittal alignment parameters were measured using simple radiographs. The clinical results were evaluated using the ODI and VAS (back and lower limbs) questionnaires. Results: In all cases, the technique was performed successfully without neural complications. The mean cross-sectional area increased from 126.5 mm preoperatively to 174.3 mm postoperatively. The mean anterior disc height increased from 9.4 mm preoperatively to 12.8 mm postoperatively, while the posterior disc height increased from 6.3 mm preoperatively to 8.1 mm postoperatively. The mean height of the right foramen increased from 157.3 mm in the preoperative period to 171.2 mm in the postoperative period and that of the left foramen increased from 139.3 mm in the preoperative to 158.9 mm in the postoperative. Conclusions: This technique is capable of correcting misalignment in spinal deformity, achieving fusion and promoting the decompression of neural elements. Level of evidence III; Retrospective study.


2018 ◽  
Vol 127 (4) ◽  
pp. 275-281 ◽  
Author(s):  
Paul R. Wistermayer ◽  
Wesley R. McIlwain ◽  
Nicholas Ieronimakis ◽  
Derek J. Rogers

1971 ◽  
Vol 15 (03) ◽  
pp. 231-245 ◽  
Author(s):  
C. M. Lee ◽  
J. N. Newman

A neutrally buoyant slender body of arbitrary sectional form, submerged beneath a free surface, is free to respond to an incident plane progressive wave system. The fluid is assumed inviscid, incompressible, homogeneous and infinitely deep. The first-order oscillatory motion of the body and the second-order time-average vertical force and pitching moment acting on the body are obtained in terms of Kochin's function. By use of slender-body theory for a deeply submerged body, the final expressions for the mean force and the moment are shown to depend on the longitudinal distribution of sectional area and added mass and on the amplitude and the frequency of the ambient surface waves. The magnitude of the mean force for various simple geometric cylinders is compared with that of a circular cylinder of equal cross-sectional area. The mean force on a nonaxisymmetric body is often approximated by replacing the section with circular profiles of equivalent cross-sectional area. A better scheme of approximation is presented, based on a simple way of estimating the two-dimensional added mass. It is expected that the effect of the cross-sectional geometry on mean vertical force and moment will be more significant when the body is very close to the free surface.


2014 ◽  
Vol 121 (3) ◽  
pp. 621-630 ◽  
Author(s):  
Naoya Matsuda ◽  
Hiroki Ohkuma ◽  
Masato Naraoka ◽  
Akira Munakata ◽  
Norihito Shimamura ◽  
...  

Object Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a serious complication. Free radicals derived from subarachnoid clotting are recognized to play an important role. Oxidized low-density lipoprotein (ox-LDL) and lectin-like oxidized LDL receptor-1 (LOX-1) have been shown to be related to the pathogenesis of atherosclerosis and may increase in cerebral arteries after SAH, due to the action of free radicals derived from a subarachnoid clot. These molecules may also affect the pathogenesis of vasospasm, generating intracellular reactive oxygen species and downregulating the expression of endothelial NO synthase (eNOS). If so, apple polyphenol might be effective in the prevention of vasospasm due to an abundant content of procyanidins, which exhibit strong radical scavenging effects, and the ability to suppress ox-LDL and LOX-1. The purposes of this study were to investigate changes in levels of ox-LDL and LOX-1 after SAH and whether administering apple polyphenol can modify cerebral vasospasm. Methods Forty Japanese white rabbits were assigned randomly to 4 groups: an SAH group (n = 10); a shamoperation group (n = 10), which underwent intracisternal saline injection; a low-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 10 mg/kg per day from Day 0 to Day 3; and a high-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 50 mg/kg per day. At Day 4, the basilar artery and brain was excised from each rabbit. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar artery, and the expression of ox-LDL, LOX-1, and eNOS was examined for each basilar artery by immunohistochemical staining and reverse transcriptase polymerase chain reaction. In addition, neuronal apoptosis in the cerebral cortex was evaluated by TUNEL. Results Compared with the sham group, the expression of ox-LDL and LOX-1 in the basilar arterial wall was significantly increased in the SAH group, the expression of eNOS was significantly decreased, and the cross-sectional area of basilar artery was significantly decreased. Compared with the SAH group, the cross-sectional area of basilar artery was increased in the polyphenol groups, together with the decreased expression of ox-LDL and LOX-1 and the increased expression of eNOS. In the high-dose polyphenol group, those changes were statistically significant compared with the SAH group. In the low-dose polyphenol group, those changes were smaller than in the high-dose polyphenol group. No apoptosis and no changes were seen in the cerebral cortex in all groups. Conclusions This is the first study suggesting that ox-LDL and LOX-1 increase due to SAH and that they may play a role in the pathogenesis of vasospasm. It is assumed that procyanidins in apple polyphenol may inhibit a vicious cycle of ox-LDL, LOX-1, and ROS in a dose-dependent manner. Apple polyphenol is a candidate for preventive treatment of cerebral vasospasm.


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