Impact of alcohol consumption on the outcome of ischemic stroke and thrombolysis: role of the hepatic clearance of tissue-type plasminogen activator
E Lemarchand, M Gauberti, S Martinez de Lizarrondo… - Stroke, 2015 - Am Heart Assoc
Stroke, 2015•Am Heart Assoc
Background and Purpose—Tissue-type plasminogen activator (tPA) is the only acute
treatment for ischemic stroke. Unfortunately, the benefit of tPA-driven thrombolysis is not
systematic, and understanding the reasons for this is mandatory. The balance between
beneficial and detrimental effects of tPA might explain the limited overall efficiency of
thrombolysis. Here, we investigated whether this balance could be influenced by excessive
alcohol intake. Methods—We used a murine model of thromboembolic stroke, coupled to an …
treatment for ischemic stroke. Unfortunately, the benefit of tPA-driven thrombolysis is not
systematic, and understanding the reasons for this is mandatory. The balance between
beneficial and detrimental effects of tPA might explain the limited overall efficiency of
thrombolysis. Here, we investigated whether this balance could be influenced by excessive
alcohol intake. Methods—We used a murine model of thromboembolic stroke, coupled to an …
Background and Purpose
Tissue-type plasminogen activator (tPA) is the only acute treatment for ischemic stroke. Unfortunately, the benefit of tPA-driven thrombolysis is not systematic, and understanding the reasons for this is mandatory. The balance between beneficial and detrimental effects of tPA might explain the limited overall efficiency of thrombolysis. Here, we investigated whether this balance could be influenced by excessive alcohol intake.
Methods
We used a murine model of thromboembolic stroke, coupled to an array of biochemical assays, near-infrared or magnetic resonance imaging scans, 2-photon microscopy, hydrodynamic transfections, and immunohistological techniques.
Results
We found that 6 weeks of alcohol consumption (10% in drinking water) worsens ischemic lesions and cancels the beneficial effects of tPA-induced thrombolysis. We accumulate in vivo and in vitro evidence showing that this aggravation is correlated with a decrease in lipoprotein receptor–related protein 1–mediated hepatic clearance of tPA in alcohol-exposed mice.
Conclusions
An efficient liver-driven clearance of tPA might influence the safety of thrombolysis after stroke.
Am Heart Assoc
