A 59-year-old woman presented with advanced, symptomatic carotid artery stenosis in the setting of severe medical comorbidities including coronary artery disease, congestive heart failure with recent ...admission for exacerbation, and diabetes mellitus. She underwent awake transcarotid artery revascularization because of her medically high-risk status. Postoperatively, she was noted to have developed pneumothorax, pneumomediastinum, and dysphonia, thought to be secondary to entrained air during the course of low neck dissection for carotid artery exposure in the setting of partial airway obstruction and high negative intrathoracic pressures during the procedure. After conservative treatment, she ultimately enjoyed complete clinical resolution. This case demonstrates an unusual complication of awake transcarotid artery revascularization.
Evaluate the mechanical and matrix effects on abdominal aortic aneurysms (AAA) during the initial aortic dilation and after prolonged exposure to beta-aminopropionitrile (BAPN) in a topical elastase ...AAA model.
Abdominal aortae of C57/BL6 mice were exposed to topical elastase with or without BAPN in the drinking water starting 4 days before elastase exposure. For the standard AAA model, animals were harvested at 2 weeks after active elastase (STD2) or heat-inactivated elastase (SHAM2). For the enhanced elastase model, BAPN treatment continued for either 4 days (ENH2b) or until harvest (ENH2) at 2 weeks; BAPN was continued until harvest at 8 weeks in one group (ENH8). Each group underwent assessment of aortic diameter, mechanical testing (tangent modulus and ultimate tensile strength UTS), and quantification of insoluble elastin and bulk collagen in both the elastase exposed aorta as well as the descending thoracic aorta.
BAPN treatment did not increase aortic dilation compared with the standard model after 2 weeks (ENH2, 1.65 ± 0.23 mm; ENH2b, 1.49 ± 0.39 mm; STD2, 1.67 ± 0.29 mm; and SHAM2, 0.73 ± 0.10 mm), but did result in increased dilation after 8 weeks (4.3 ± 2.0 mm; P = .005). After 2 weeks, compared with the standard model, continuous therapy with BAPN did not have an effect on UTS (24.84 ± 7.62 N/cm2; 18.05 ± 4.95 N/cm2), tangent modulus (32.60 ± 9.83 N/cm2; 26.13 ± 9.10 N/cm2), elastin (7.41 ± 2.43%; 7.37 ± 4.00%), or collagen (4.25 ± 0.79%; 5.86 ± 1.19%) content. The brief treatment, EHN2b, resulted in increased aortic collagen content compared with STD2 (7.55 ± 2.48%; P = .006) and an increase in UTS compared with ENH2 (35.18 ± 18.60 N/cm2; P = .03). The ENH8 group had the lowest tangent modulus (3.71 ± 3.10 N/cm2; P = .005) compared with all aortas harvested at 2 weeks and a lower UTS (2.18 ± 2.18 N/cm2) compared with both the STD2 (24.84 ± 7.62 N/cm2; P = .008) and ENH2b (35.18 ± 18.60 N/cm2; P = .001) groups. No differences in the mechanical properties or matrix protein concentrations were associated with abdominal elastase exposure or BAPN treatment for the thoracic aorta. The tangent modulus was higher in the STD2 group (32.60 ± 9.83 N/cm2; P = .0456) vs the SHAM2 group (17.99 ± 5.76 N/cm2), and the UTS was lower in the ENH2 group (18.05 ± 4.95 N/cm2; P = .0292) compared with the ENH2b group (35.18 ± 18.60 N/cm2). The ENH8 group had the lowest tangent modulus (3.71 ± 3.10 N/cm2; P = .005) compared with all aortas harvested at 2 weeks and a lower UTS (2.18 ± 2.18 N/cm2) compared with both the STD2 (24.84 ± 7.62 N/cm2; P = .008) and ENH2b (35.18 ± 18.60 N/cm2; P = .001) groups. Abdominal aortic elastin in the STD2 group (7.41 ± 2.43%; P = .035) was lower compared with the SHAM2 group (15.29 ± 7.66%). Aortic collagen was lower in the STD2 group (4.25 ± 0.79%; P = .007) compared with the SHAM2 group (12.44 ± 6.02%) and higher for the ENH2b (7.55 ± 2.48%; P = .006) compared with the STD2 group.
Enhancing an elastase AAA model with BAPN does not affect the initial (2-week) dilation phase substantially, either mechanically or by altering the matrix content. Late mechanical and matrix effects of prolonged BAPN treatment are limited to the elastase-exposed segment of the aorta.
This paper explores the use of short- and long-term exposure to beta-aminopropionitrile to create an enhanced topical elastase abdominal aortic aneurysm model in mice. Readouts of aneurysm severity included loss of mechanical stability and vascular extracellular matrix composition reminiscent of what is seen in the course of human disease. Additionally, we show that the thoracic aorta, unlike the findings below the renal arteries, is not damaged in our animal model.
Elastolytic matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAA), a disorder characterized by chronic aortic wall inflammation and destruction ...of medial elastin. The purpose of this study was to determine if human macrophage elastase (HME; MMP-12) might participate in this disease. By reverse transcription-polymerase chain reaction, HME mRNA was consistently demonstrated in AAA and atherosclerotic occlusive disease (AOD) tissues (six of six), but in only one of six normal aortas. Immunoreactive proteins corresponding to proHME and two products of extracellular processing were present in seven of seven AAA tissue extracts. Total HME recovered from AAA tissue was sevenfold greater than normal aorta (P < 0.001), and the extracted enzyme exhibited activity in vitro. Production of HME was demonstrated in the media of AAA tissues by in situ hybridization and immunohistochemistry, but HME was not detected within the media of normal or AOD specimens. Importantly, immunoreactive HME was specifically localized to residual elastin fragments within the media of AAA tissue, particularly areas adjacent to nondilated normal aorta. In vitro, the fraction of MMP-12 sequestered by insoluble elastin was two- to fivefold greater than other elastases found in AAA tissue. Therefore, HME is prominently expressed by aneurysm-infiltrating macrophages within the degenerating aortic media of AAA, where it is also bound to residual elastic fiber fragments. Because elastin represents a critical component of aortic wall structure and a matrix substrate for metalloelastases, HME may have a direct and singular role in the pathogenesis of aortic aneurysms.
Objective To assess alterations in the regional perfusion and oxygenation of the calf muscles in individuals with diabetes. Methods Age-matched individuals with (n = 5) and without diabetes (n = 6) ...were investigated. Skeletal muscle perfusion, oxygen extraction fraction, and oxygen consumption rate were measured by newly developed noncontrast magnetic resonance imaging (MRI) techniques. The subjects lay supine on the MRI table with their foot firmly strapped to a custom-built isometric exercise device. The measurements were performed at rest and during an isometric plantar flexion muscle contraction. Results Individuals without diabetes had up to a 10-fold increase in muscle perfusion, 25% elevation in muscle oxygen extraction fraction, and a 12-fold increase in oxygen consumption rate in the calf during the plantar flexion isometric contraction. In patients with diabetes, the increases in these parameters were only up to sixfold, 2%, and sixfold, respectively. Exercise oxygen consumption rate was inversely associated with blood HbA1c levels ( r2 = .91). Conclusions This is the first study to quantify regional skeletal muscle oxygenation in patients with diabetes using noncontrast MRI and warrants additional study. Attenuation of perfusion and oxygenation during exercise may have implications for understanding diabetic complications in the lower extremities.
Background. Abdominal aortic aneurysms (AAAs) involve an unfavorable balance between the destruction and the repair of connective tissue proteins. The purpose of this study was to assess the ...functional importance of connective tissue repair during experimental aneurysmal degeneration. Methods. Male Wistar rats (n = 70) underwent transient intraluminal perfusion of the abdominal aorta with porcine pancreatic elastase. In Study I, the aortic diameter was measured before elastase perfusion and at days 0, 2, 7, and 14 (n = 6 rats at each interval). Aortic wall concentrations of desmosine (Des) and hydroxyproline (OHP) were measured at each interval, and the expression of tropoelastin (TE), α1(I) procollagen (PC), and lysyl oxidase genes was evaluated by reverse transcription-polymerase chain reaction. In Study II, 22 rats were treated with β-aminopropionitrile (BAPN) to block connective tissue repair. In Study III (n = 30), rats were treated with doxycycline, a matrix metalloproteinase inhibitor, beginning 7 days after elastase perfusion. Results. AAAs consistently developed between 7 and 14 days after elastase perfusion. Aortic wall Des concentration decreased markedly during aneurysm development, reaching 3% of normal by day 14 (377 ± 22 pmol of Des/sample on day 0 vs 9 ± 1 pmol of Des/sample on day 14; P <.05). Aortic wall OHP decreased to only 68% of normal at the same interval (121 ± 10 nmol of OHP/sample on day 0 vs 82 ± 14 nmol of OHP/sample on day 14; P <.05). TE and PC expression was undetectable in healthy aorta, but they both increased by day 7 (P <.05); while TE expression decreased again by day 14, PC continued to rise. Lysyl oxidase expression progressively decreased at all intervals after elastase perfusion. Treatment with β-aminoproprionitrile resulted in acute aortic dissection in 81% of the rats (50% mortality). These early deaths occurred between days 3 and 6, coinciding with aortic infiltration by proteinase-secreting inflammatory cells. Delayed treatment with doxycycline suppressed the progression of aneurysmal dilatation between days 7 and 21 (P <.05 vs untreated controls). Conclusions. The development of elastase-induced AAAs is accompanied by an active process of connective tissue repair. While this reparative process is necessary to stabilize the developing aneurysm wall, it is insufficient to prevent aneurysm progression. In contrast, reducing the proteolytic destruction of connective tissue proteins promotes stabilization of the aneurysmal aorta. (Surgery 2000;128:429–38)
Objective Radial artery harvesting has been questioned because of purported long-term circulatory consequences. Previous midterm Doppler ultrasonographic results are inconsistent regarding ulnar ...arterial effects. Flow-mediated vasodilatation more sensitively measures response to shear stress as index of arterial reactivity and function. Methods We contacted 231 patients who had undergone radial artery harvesting at least 10 years previously (mean follow-up, 12.9 ± 0.8 years). Subcohort of 25 volunteers (mean age, 69.2 ± 8.4 years) underwent ultrasonographic evaluation of ipsilateral (harvest) and contralateral (control) ulnar arteries. Flow-mediated vasodilatation compared changes in ulnar arterial diameters before and after occlusion. Results In subcohort, peak systolic velocity of harvest ulnar artery was 0.82 ± 0.15 m/s, versus 0.63 ± 0.23 m/s on control side ( P < .001), with no differences in intimomedial thickness ( P = .763) or presence of atherosclerotic plaques ( P = .364). Baseline diameter of harvest ulnar artery was 3.0 ± 0.5 mm, versus 2.7 ± 0.6 mm on control side ( P = .007). Postocclusion diameter of harvest ulnar artery was 3.2 ± 0.5 mm, versus 2.9 ± 0.6 mm on control side ( P = .001). No differences were seen in preocclusion and postocclusion absolute and percentage changes in ulnar arterial diameter ( Table 1 ). Conclusions Despite increased shear stress, no deterioration in either ulnar arterial structure or functional reactivity was measured by flow-mediated vasodilatation more than 10 years after radial artery harvesting. With appropriate preoperative evaluation, radial arterial grafting for coronary artery bypass grafting is not associated with long-term donor limb vascular insufficiency.