Efficacy versus Complications in Arterial Thrombolysis.

BACKGROUND: Acute peripheral arterial occlusions threaten life and limb. Thrombolysis is an established, minimally invasive alternative treatment for surgical thromboembolectomy. Yet, there is no consensus regarding an optimal thrombolysis protocol, and current knowledge is largely based on studies from the 1990s. This study reviews a contemporary cohort of patients treated with thrombolysis and aims to evaluate the treatment results and to identify possible predictors for outcome and (bleeding) complications. METHODS: The electronic health record data of all consecutive patients who underwent thrombolysis for acute limb ischemia due to thromboembolic lower extremity arterial occlusions between April 2006 and June 2012 were analyzed. End points were change in clinical stage of ischemia, incidence of bleeding complications, duration of thrombolysis, predictors of outcome and complications, and mortality and amputation-free rates after 30-day and 6-months follow-up. RESULTS: In total, 109 cases were included. Clinical improvement was observed in 79%. Amputation-free rates at 30 days and 6 months were 94% and 90%, respectively. The incidence of major bleeding complications was 13%. Median duration of thrombolysis was 27 (4-68) hr. Mortality rates at 30 days and 6 months were 7% and 16%, respectively; none bleeding related. In addition to age, popliteal artery occlusions and a progressed chronic vascular stage are predictive for a worse outcome. Age, female sex, and cardiac history were risk factors for bleeding. CONCLUSIONS: Treatment of peripheral arterial occlusions with high-dose thrombolysis on an intensive-care unit yields high clinical success rates, but major bleeding complications are often observed. Strict clinical observation remains essential since intensive monitoring of hemostatic parameters during thrombolysis does not predict bleeding complications.

Activation of extracellular signal-related kinase in abdominal aortic aneurysm.

BACKGROUND: Extracellular matrix degeneration, caused by matrix metalloproteinase-2, facilitates smooth muscle cell migration leading to medial layer decline and, ultimately, abdominal aortic aneurysm. It remains unclear what exactly causes aneurysms to rupture, which leads to death in most patients. The extracellular signal-related kinase may be linked to the latter process. We aimed to clarify the role of extracellular signal-related kinase in aortic aneurysm development and rupture in patients. DESIGN: Aortic fragments were harvested during open repair of nonruptured (n = 20) and ruptured (n = 8) aneurysms. As control, nondilated aortas (n = 6) were obtained during autopsy. We determined levels of phosphorylated and total extracellular signal-related kinase by Western blot, matrix metalloproteinase-2 by immunohistochemistry and medial layer thickness by conventional microscopy. RESULTS: Nonruptured aneurysms had 1·8 times higher activation of extracellular signal-related kinase (ratio: phosphorylated/total) than controls (P = 0·011). However, the ruptured aneurysms had only 0·9 times the activation of controls (ns). Both nonruptured and ruptured aneurysms showed significantly higher matrix metalloproteinase-2 than controls (3·8 and 4·0-times, respectively; P < 0·005). Of the medial layer thickness in controls, the median was 1·5 mm, in nonruptured 1·0 mm and in ruptured aneurysms 0·7 mm. Activation of extracellular signal-related kinase correlated positively to medial layer thickness (Rs  = 0·48; P = 0·014), but not to matrix metalloproteinase-2 (Rs  = -0·36; P = 0·10). CONCLUSIONS: In this study, nonruptured aneurysms are associated with increased extracellular signal-related kinase activation while ruptured aneurysms are not. Extracellular signal-related kinase was not related to total matrix metalloproteinase-2 expression. We therefore speculate that increased extracellular signal-related kinase, in response to medial layer decline, could be protective against aneurysm rupture.