Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors

AbstractPurpose: Pathologic remodeling of the extracellular matrix is a critical mechanism in the development and progression of abdominal aortic aneurysms (AAAs). Although angiotensin-converting enzyme (ACE) inhibitors are known to alter vascular wall remodeling in other conditions, their effects on AAAs are unknown. In this study we assessed the effect of ACE inhibitors in a rodent model of aneurysm development. Methods: Male Wistar rats underwent transient aortic perfusion with porcine pancreatic elastase, followed by treatment with one of three ACE inhibitors (captopril [CP], lisinopril [LP], or enalapril [EP]), an angiotensin (AT)1 receptor antagonist (losartan [LOS]), or water alone (9 rats in each group). Blood pressure and aortic diameter (AD) were measured before elastase perfusion and on day 14, with an AAA defined as an increase in AD (ΔAD) of more than 100%. The structural features of the aortic wall were examined by means of light microscopy. Results: Aneurysmal dilatation consistently developed within 14 days of elastase perfusion in untreated rats, coinciding with the development of a transmural inflammatory response and destruction of the elastic media (mean ΔAD, 223% ± 28%). All three ACE inhibitors prevented AAA development (mean ΔAD: CP, 67% ± 4%; LP, 18% ± 12%; and EP, 14% ± 3%; each P <.05 vs controls). ACE inhibitors also attenuated the degradation of medial elastin without diminishing the inflammatory response. Surprisingly, the aneurysm-suppressing effects of ACE inhibitors were dissociated from their effects on systemic hemodynamics, and LOS had no significant effect on aneurysm development compared with untreated controls (mean ΔAD, 186% ± 19%). Conclusion: Treatment with ACE inhibitors suppresses the development of elastase-induced AAAs in the rat. Although this is associated with the preservation of medial elastin, the mechanisms underlying these effects appear to be distinct from hemodynamic alterations alone or events mediated solely by AT1 receptors. Further studies are needed to elucidate how ACE inhibitors influence aortic wall matrix remodeling during aneurysmal degeneration. (J Vasc Surg 2001;33:1057-64.

Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors

AbstractPurpose: Pathologic remodeling of the extracellular matrix is a critical mechanism in the development and progression of abdominal aortic aneurysms (AAAs). Although angiotensin-converting enzyme (ACE) inhibitors are known to alter vascular wall remodeling in other conditions, their effects on AAAs are unknown. In this study we assessed the effect of ACE inhibitors in a rodent model of aneurysm development. Methods: Male Wistar rats underwent transient aortic perfusion with porcine pancreatic elastase, followed by treatment with one of three ACE inhibitors (captopril [CP], lisinopril [LP], or enalapril [EP]), an angiotensin (AT)1 receptor antagonist (losartan [LOS]), or water alone (9 rats in each group). Blood pressure and aortic diameter (AD) were measured before elastase perfusion and on day 14, with an AAA defined as an increase in AD (ΔAD) of more than 100%. The structural features of the aortic wall were examined by means of light microscopy. Results: Aneurysmal dilatation consistently developed within 14 days of elastase perfusion in untreated rats, coinciding with the development of a transmural inflammatory response and destruction of the elastic media (mean ΔAD, 223% ± 28%). All three ACE inhibitors prevented AAA development (mean ΔAD: CP, 67% ± 4%; LP, 18% ± 12%; and EP, 14% ± 3%; each P <.05 vs controls). ACE inhibitors also attenuated the degradation of medial elastin without diminishing the inflammatory response. Surprisingly, the aneurysm-suppressing effects of ACE inhibitors were dissociated from their effects on systemic hemodynamics, and LOS had no significant effect on aneurysm development compared with untreated controls (mean ΔAD, 186% ± 19%). Conclusion: Treatment with ACE inhibitors suppresses the development of elastase-induced AAAs in the rat. Although this is associated with the preservation of medial elastin, the mechanisms underlying these effects appear to be distinct from hemodynamic alterations alone or events mediated solely by AT1 receptors. Further studies are needed to elucidate how ACE inhibitors influence aortic wall matrix remodeling during aneurysmal degeneration. (J Vasc Surg 2001;33:1057-64.

Results of endoluminal grafting in an experimental aortic aneurysm model

AbstractWe studied the impact of an endoluminally placed stented aortic graft on the geometry of a surgically created abdominal aortic dilation (AAD) in nonatherosclerotic mongrel dogs. Patulous iliac vein patch infrarenal aortoplasty produced a fusiform AAD, doubling the aorta diameter. Lumbar and mesenteric aortic tributaries were preserved and no mural thrombus formed. AADs created in 23 dogs were endoluminally excluded through transfemoral placement of a thin-wall Dacron graft 4 ± 2 months later. Balloon-expandable stents were used to anchor each end of the graft to the aorta. The graft was crimped radially in its body and longitudinally at its ends to provide longitudinal and radial expandability in these respective zones. Serial color duplex, angiography, and direct caliper measurements were made. Before graft placement, a 19% ± 11% diameter growth was observed. At graft placement, flow arrest immediately occurred in the space between the graft and the AAD intima in all cases. Although microscopic recanalization of the thrombus in this space was seen at sacrifice 6 and 12 months later, no macroscopic duplex flow was imaged. A 10% ± 11% reduction in AAD diameter was measured at 6 months (p < 0.001), with no further reduction at 12 months. Graft dimensions remained stable. No anastomotic leaks developed. AAD growth stopped during the first year after effective endoluminal exclusion in normotensive dogs despite patent side branches (<1.5 mm internal diameter) and no mural thrombus at the time of graft placement. Whether microscopic recanalization of the thrombus that forms outside the graft has an impact after 1 year remains to be seen. (J Vasc Surg 1996;23:819-31.

Brainwave profiles of efficient versus inefficient working memory retrievals inhealthy older adults

General slowing of mental processing speed is hallmark of brain and cognitive aging. Thus far it has been limited under-standing in neural mechanisms underlying mental states during fluctuations between efficient versus inefficient cognitiveperformance within individual older adults. Here we examined electrophysiological responses during visual working mem-ory retrieval trials that are fast versus slow reactions. Wireless EEG along with accuracy and reaction times were recordedduring a modified delayed match-to-sample task in 17 cognitively normal older adults (age 65-95) from North America.Compared to trials that are faster than averaged (mean 584 ms), the late positive potentials during trials that are slowerthan average (mean 747 ms) showed increased responses to memory nonmatch distractors than those to object matchingmemory targets in frontal sites, as previously reported in older brains. Interestingly, the brainwaves during efficient andaccurate memory retrievals resemble those typically seen in younger adults

Spin dynamics in semiconductors

This article reviews the current status of spin dynamics in semiconductors which has achieved a lot of progress in the past years due to the fast growing field of semiconductor spintronics. The primary focus is the theoretical and experimental developments of spin relaxation and dephasing in both spin precession in time domain and spin diffusion and transport in spacial domain. A fully microscopic many-body investigation on spin dynamics based on the kinetic spin Bloch equation approach is reviewed comprehensively.Comment: a review article with 193 pages and 1103 references. To be published in Physics Reports

Advancement of the German version of the moral distress scale for acute care nurses : a mixed methods study

Aim: Moral distress experienced by nurses in acute care hospitals can adversely impact the affected nurses, their patients and their hospitals; therefore, it is advisable for organizations to establish internal monitoring of moral distress. However, until now, no suitable questionnaire has been available for use in German‐speaking contexts. Hence, the aim of this study was to develop and psychometrically test a German‐language version of the Moral Distress Scale. Design: We chose a sequential explanatory mixed methods design, followed by a second quantitative cross‐sectional survey. Methods: An American moral distress scale was chosen, translated, culturally adapted, tested in a pilot study and subsequently used in 2011 to conduct an initial web‐based quantitative cross‐sectional survey of nurses in all inpatient units at five hospitals in Switzerland's German‐speaking region. Data were analysed descriptively and via a Rasch analysis. In 2012, four focus group interviews were conducted with 26 nurses and then evaluated using knowledge maps. The results were used to improve the questionnaire. In 2015, using the revised German‐language instrument, a second survey and Rasch analysis were conducted. Results: The descriptive results of the first survey's participants (n = 2153; response rate: 44%) indicated that moral distress is a salient phenomenon in Switzerland. The data from the focus group interviews and the Rasch analysis produced information valuable for the questionnaire's further development. Alongside the data from the second survey's participants (n = 1965; response rate: 40%), the Rasch analysis confirmed the elimination of previous deficiencies on its psychometrics. A Rasch‐scaled German version of the Moral Distress Scale is now available for use

Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries

Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20–37) versus 47 (IQR 32–58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11–40]) than in HICs (44/102 [43%, 95% CI 34–53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.</p

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19

Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28–54) vs 45 (28–56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28–79) vs 68 (30–125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19–62) vs 53 (20–92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.</p

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19

Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28–54) vs 45 (28–56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28–79) vs 68 (30–125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19–62) vs 53 (20–92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.</p