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THE IMPORTANT ROLES OF MEDIATORS IN ENDOTOXIN-INDUCED CARDIOVASCULAR ALTERATIONS

Research Project

Project/Area Number 11670671
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNAGOYA UNIVERSITY

Principal Investigator

IWASE Mitsunori  SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (20303646)

Co-Investigator(Kenkyū-buntansha) HASEGAWA Takaaki  SCHOOL OF HEALTH SCIENCES, NAGOYA UNIVERSITY, PROFESSOR, 医学部, 教授 (80198720)
NAGASAKA Teturo  SCHOOL OF MEDICINE, NAGOYA UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (40262894)
YOKOYA Mitsuhiro  SCHOOL OF HEALTH SCIENCES, NAGOYA UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (50201851)
KITAICHI Kiyoyuki  SCHOOL OF HEALTH SCIENCES, NAGOYA UNIVERSITY, RESEACH ASSOCIATE, 医学部, 助手 (40301220)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsENDOTOXIN SHOCK / ECHOCARDIOGRAPHY / PLATELET-ACTIVATING FACTOR (PAF) / CARDIAC FUNCTION / PATHOLOGY / エンドトキシン / 循環器病学
Research Abstract

This study evaluates the time course of the alterations in LV dimensions, LV wall thickness and LV systolic function in rats with endotoxemia using echocardiography as well as the myocardial histopathological findings. Our second goal is to examine whether pretreatment with a platelet activating factor (PAF) antagonist would ameliorate the LPS-induced cadiov as cular collapse.
Subjects : and Interventions : Male, Wistar rats were used (8 to 9 weeks old, n=56). In pentobarbital-anesthetized rats, the right carotid artery was cannulated to measure the arterial blood pressure and to sample blood. The right jugular vein was also catheterized for the administration of drugs. LPS (2mg/kg) derived from Klebsiella pneumoniae or physiological saline was administered in the presence or absence of pretreatment with TCV-309, a specific potent PAF antagonist. Echocardiographic studies were performed with a 8-13MHz transducer.
Measurements and Main Results : LPS administration immediately produced pro … More gressive hypotension. The maximal hypotensive response was observed at 10 minutes after LPS infusion with mean arterial pressure (MAP) falling from 119±2 to 56±3mmHg (p<0.001). LV end-diastolic internal dimension decreased from 6.4±0.1 to 3.1±0.1 mm (p<0.001) at 30 minutes after LPS and remained significantly reduced as compared with control rats receiving saline. LV end-systolic dimension also decreased dramatically from3.5±0.2 to 0.5±0.1 mm (p<0.001) at 30 minutes after LPS, and remained significantly reduced throughout the experiment. LV fractional shortening increased from 45±1 to 84±2 % (p<0.001) at 30 minutes after LPS, and remained elevated as compared with control rats. LV wall thickness of the interventricular septum and the posterior wall increased strikingly from 15 minutes until 2 hours after LPS infusion. Pathological studies revealed marked congestion of capillaries and mild edema in the LV myocardium. LPS markedly increased sympathetic tone as demonstrated by the elevation of plasma levels of epinephrine and norepinephine. There was no elevation of concentrations of NOx (nitrite and nitrate) or adenosine.
Pretreatment with TCV-309, a specific potent PAF antagonist, reduced LPS-induced hypotension and attenuated changes in LV function. TCV-309 administration abolished the LPS-mediated elevation of the plasma level of norepinephrine and reduced the plasma level of epinephrine.
Conclusions The hypotension that occurred in the early phase of LPS-induced shock was accompanied by cardiac functional and structural alterations. The marked increase in LV wall thickness can be ascribed to the congestion of capillaries and edema in the LV myocardium. PAF plays an important role in the early phase of LPS-induced cardiov ascular responses. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Kiyoyuki Kitaichi: "Decreased antipyrine clearance following endotoxin administration : In vivo evidence of the role of nitric oxide"Antimicrobial Agents and Chemotherapy. 43.11. 2697-2701 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mitsunori Iwase: "cardiac functional and structural alterations induced by endotoxin in rats : Importance of platelet-activating factor"Critical Care Medicine. 29.3(印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kiyoyuki Kitaichi: "Decreased antipyrine clearance following endotoxin administration : In vivo evidence of the role of nitric oxide."Antimicrobial Agents and Chemotherapy. 43-44. 2697-2701 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mitsunori Iwase: "Cardiac functional and structural alterations induced by endotoxin in rats : Importance of platelet-activating factor"Critical Care Medicine. 29-3 (in print). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kiyoyuki Kitaichi: "Decreased antipyrine clearance following endotoxin administration : In vivo evidence of the role of nitric oxide"Antimicrobial Agents and Chemotherapy. 43.11. 2697-2701 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mitsunori lwase: "cardiac functional and structural alterations induced by endotoxin in rats : Importance of platelet-activating factor"Critical Care Medicine. 29.3(発表予定). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kiyoyuki Kitaichi: "Decreased antipyrine clearance following endotoxin administration : In vivo evidence of the role of nitric oxide"Antimicrob.Agents Chemother.. 43・11. 2697-2701 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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