Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Abstract

Although chronic arterial hypertension (CAH) increases the risk of stroke and the severity of the resultant lesion, it is rarely integrated in preclinical studies. Here, we analyzed the impact of CAH on the acute spatiotemporal evolution of the ischemic penumbra as defined by the perfusion-weighted imaging/diffusion-weighted imaging mismatch. Sequential 7T-MRI examinations were performed from 30 minutes up to 4 hours after permanent cerebral ischemia in genetically hypertensive rats (spontaneously hypertensive rats, SHR), renovascular-hypertensive rats (RH-WKY), and their normotensive controls (Wistar-Kyoto rats, WKY). The apparent diffusion coefficient (ADC)-defined lesion was larger in hypertensive rats than in normotensive animals as early as 30 minutes after the ischemia. The ischemic penumbra was smaller in both genetically and renovascular-hypertensive rats (at 30 minutes; SHR=66±25 mm(3), RH-WKY=55±17 mm(3) versus WKY=117±14 mm(3); P<0.008) and there was no significant difference between the perfusion deficit and ADC lesion (mismatch definition of penumbra) as early as 90 minutes after the occlusion. Genetic hypertension and induced renovascular hypertension resulted in larger lesion and smaller penumbra that vanished rapidly. These data support the need to integrate CAH in preclinical studies relative to the treatment of stroke, as failure to do so may lead to preclinical results nonpredictive of clinical trials, which include hypertensive patients.