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


METHODS
In vivo study.


METHODS
Animal laboratory in a university teaching hospital.


METHODS
Adult age-matched male WKY, SHR, and SHR-SP.


METHODS
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.


RESULTS
Infarction volume in the striatum of SHR-SP (42+/-4 mm3) was greater than in SHR (29+/-6 mm3) or WKY (1+/-1 mm3) (n = 9 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, 69%+/-22% [n = 8]). However, in this cohort, cortical infarction volume was less in SHR (30%+/-4% of ipsilateral cortex) than in SHR-SP (49%+/-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.
Harukuni
I
I
Department of Anesthesiology/Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Takahashi
H
H
Traystman
R J
RJ
Bhardwaj
A
A
Kirsch
J R
JR
D000818:Animals; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D002544:Cerebral Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D004396:Coloring Agents; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D006973:Hypertension / Q000150:complications*; D017078:Laser-Doppler Flowmetry; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III; D010095:Oxotremorine / Q000494:pharmacology*; D011237:Predictive Value of Tests; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D014463:Ultrasonography
D004396:Coloring Agents; D018721:Muscarinic Agonists; D010095:Oxotremorine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat