Chronic Nicotine Exposure Induces Murine Aortic Remodeling and Stiffness Segmentation-Implications for Abdominal Aortic Aneurysm Susceptibility.
Frontiers in physiology
2018; 9: 1459
Prolonged veno-arterial extracorporeal life support for cardiac failure.
The International journal of artificial organs
Aim: Arterial stiffness is a significant risk factor for many cardiovascular diseases, including abdominal aortic aneurysms (AAA). Nicotine, the major active ingredient of e-cigarettes and tobacco smoke, induces acute vasomotor effects that may temporarily increase arterial stiffness. Here, we investigated the effects of long-term nicotine exposure on structural aortic stiffness. Methods: Mice (C57BL/6) were infused with nicotine for 40 days (20 mg/kg/day). Arterial stiffness of the thoracic (TS) and abdominal (AS) aortic segments was analyzed using ultrasound (PWV, pulse wave velocity) and ex vivo pressure myograph measurements. For mechanistic studies, aortic matrix-metalloproteinase (MMP) expression and activity as well as medial elastin architecture were analyzed. Results: Global aortic stiffness increased with nicotine. In particular, local stiffening of the abdominal segment occurred after 10 days, while thoracic aortic stiffness was only increased after 40 days, resulting in aortic stiffness segmentation. Mechanistically, nicotine exposure enhanced expression of MMP-2/-9 and elastolytic activity in both aortic segments. Elastin degradation occurred in both segments; however, basal elastin levels were higher in the thoracic aorta. Finally, MMP-inhibition significantly reduced nicotine-induced MMP activity, elastin destruction, and aortic stiffening. Conclusion: Chronic nicotine exposure induces aortic MMP expression and structural aortic damage (elastin fragmentation), irreversibly increasing aortic stiffness. This process predominantly affects the abdominal aortic segment, presumably due in part to a lower basal elastin content. This novel phenomenon may help to explain the role of nicotine as a major risk factor for AAA formation and has health implications for ECIGs and other modes of nicotine delivery.
View details for PubMedID 30429794
In intractable cardiogenic shock, extracorporeal life support frequently is the last treatment option. Outcomes of prolonged veno-arterial extracorporeal life support for cardiac failure are poorly defined.We retrospectively analyzed 10 patients (4 females, age?=?36?±?16?years) who underwent prolonged extracorporeal life support (?7?days) from December 2015 to March 2017 for cardiogenic shock. The primary endpoint was survival to hospital discharge.Etiologies included ischemic cardiomyopathy with non ST-segment elevation myocardial infarction (n?=?1), dilated (n?=?3), hypertrophic (n?=?1), postpartum cardiomyopathy (n?=?1), and others (n?=?4). Heart failure was left or biventricular in 80.0% (left ventricular ejection fraction?=?15.6?±?5.5%). Among the 10 patients, 80.0% underwent femoral and 20.0% central cannulation, 40.0% required changes in the cannulation strategy, and 80.0% underwent left ventricular venting. No technical malfunctions occurred, but 50.0% required circuit exchanges for thrombus formation. 80.0% suffered from infections. 60.0% could be decannulated after 717?±?830 (168-2301)?h of support, and survival to hospital discharge was 40.0%. Longest follow-up available is 160?±?175 (12-409)?days after discharge, with 30.0% alive and in satisfying functional condition.Prolonged veno-arterial extracorporeal life support for cardiac failure is feasible with low technical complication rates. Survival rates are acceptable, yet inferior to short-term support. We observed a shift from initial shock-related complications to infections during prolonged support. Since recovery and thus weaning is rather unlikely after a prolonged need for extracorporeal life support, this form of support should be limited to centers offering the full spectrum of interdisciplinary cardiac care including ventricular assist device implantation and transplantation.
View details for PubMedID 29896993