Oxotremorine-induced cerebral hyperemia does not predict infarction volume in spontaneously hypertensive or stroke-prone rats

Objectives: We tested the following hypotheses: a) spontaneously hypertensive stroke-prone rats (SHR-SP) have more brain injury than spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats [WKY]) when exposed to transient focal ischemia; b) infarction size is not correlated with baseline blood pressure; and c) infarction size is inversely related to the cerebral hyperemic response to oxotremorine, a muscarinic agonist that increases cerebral blood flow (CBF) by stimulating endothelial nitric oxide synthase. Design: In vivo study. Setting: Animal laboratory in a university teaching hospital. Subjects: Adult age-matched male WKY, SHR, and SHR-SP. Interventions: Rats were instrumented under halothane anesthesia. Transient focal cerebral ischemia was produced for 2 hrs with the intravascular suture technique. Cerebral perfusion, estimated with laser Doppler flowmetry (LD-CBF), in response to intravenous oxotremorine, was measured in one cohort of rats to estimate endothelial nitric oxide synthase function. Infarction volume was measured at 22 hrs of reperfusion with 2,3,5-triphenyltetrazolium chloride staining. Measurements and Main Results: Infarction volume in the striatum of SHR-SP (42 ± 4 mm³) was greater than in SHR (20 ± 6 mm³) or WKY (1 ± 1 mm³) (n = g rats/strain). Resting (unanesthetized) mean arterial blood pressure was similar in SHR-SP (177 ± 5 mm Hg) and SHR (170 ± 5 mm Hg) despite a greater infarction volume in SHR-SP (n = 4) compared with SHR (n = 5). The percentage increase in LD-CBF signal in response to oxotremorine was similar for both groups (SHR, 64% ± 22% [n = 10]; SHR-SP, 60% ± 22% [n = 8]). However, in this cohort, cortical infarction volume was less in SHR (30% ± 4% of ipsilateral cortex) than in SHR-SP (40% ± 2% of ipsilateral cortex). Conclusions: Although SHR-SP have greater infarction volume than SHR, the mechanism of injury does not appear to be related to a difference in unanesthetized baseline mean arterial blood pressure or to an alteration in endothelium-produced nitric oxide.