2000 Fiscal Year Final Research Report Summary
THE IMPORTANT ROLES OF MEDIATORS IN ENDOTOXIN-INDUCED CARDIOVASCULAR ALTERATIONS
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants |
Circulatory organs internal medicine
|Research Institution||NAGOYA UNIVERSITY |
IWASE Mitsunori SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (20303646)
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
|Keywords||ENDOTOXIN SHOCK / ECHOCARDIOGRAPHY / PLATELET-ACTIVATING FACTOR (PAF) / CARDIAC FUNCTION / PATHOLOGY|
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
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
Research Products (4 results)