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

Izumi Harukuni, Hiroshi Takahashi, Richard J. Traystman, Anish Bhardwaj, Jeffrey Kirsch

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)190-195
Number of pages6
JournalCritical Care Medicine
Volume28
Issue number1
StatePublished - 2000
Externally publishedYes

Fingerprint

Oxotremorine
Hyperemia
Infarction
Inbred SHR Rats
Stroke
Cerebrovascular Circulation
Inbred WKY Rats
Arterial Pressure
Nitric Oxide Synthase Type III
Suture Techniques
Muscarinic Agonists
Endovascular Procedures
Laser-Doppler Flowmetry
Transient Ischemic Attack
Laboratory Animals
Halothane
Teaching Hospitals
Brain Injuries
Reperfusion
Endothelium

Keywords

  • Cerebral blood flow
  • Endothelium
  • Focal
  • Hypertensive
  • Ischemia
  • Laser Doppler flowmetry
  • Nitric oxide
  • Oxotremorine
  • Stroke

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Oxotremorine-induced cerebral hyperemia does not predict infarction volume in spontaneously hypertensive or stroke-prone rats. / Harukuni, Izumi; Takahashi, Hiroshi; Traystman, Richard J.; Bhardwaj, Anish; Kirsch, Jeffrey.

In: Critical Care Medicine, Vol. 28, No. 1, 2000, p. 190-195.

Research output: Contribution to journalArticle

@article{37aa02a4885443bf98165fbe219c4b85,
title = "Oxotremorine-induced cerebral hyperemia does not predict infarction volume in spontaneously hypertensive or stroke-prone rats",
abstract = "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.",
keywords = "Cerebral blood flow, Endothelium, Focal, Hypertensive, Ischemia, Laser Doppler flowmetry, Nitric oxide, Oxotremorine, Stroke",
author = "Izumi Harukuni and Hiroshi Takahashi and Traystman, {Richard J.} and Anish Bhardwaj and Jeffrey Kirsch",
year = "2000",
language = "English (US)",
volume = "28",
pages = "190--195",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Oxotremorine-induced cerebral hyperemia does not predict infarction volume in spontaneously hypertensive or stroke-prone rats

AU - Harukuni, Izumi

AU - Takahashi, Hiroshi

AU - Traystman, Richard J.

AU - Bhardwaj, Anish

AU - Kirsch, Jeffrey

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Cerebral blood flow

KW - Endothelium

KW - Focal

KW - Hypertensive

KW - Ischemia

KW - Laser Doppler flowmetry

KW - Nitric oxide

KW - Oxotremorine

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=0033953621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033953621&partnerID=8YFLogxK

M3 - Article

C2 - 10667521

AN - SCOPUS:0033953621

VL - 28

SP - 190

EP - 195

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 1

ER -