Cardiac functional and structural alterations induced by endotoxin in rats: Importance of platelet-activating factor

Mitsunori Iwase, Mitsuhiro Yokota, Kiyoyuki Kitaichi, Li Wang, Kenji Takagi, Tetsuro Nagasaka, Hideo Izawa, Takaaki Hasegawa

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Objective: In this study, we evaluated the time course of the alterations in left ventricular (LV) dimensions, LV wall thickness, and LV systolic function in rats with endotoxemia by using echocardiography as well as myocardial histopathologic assessments. Our second goal was to examine whether pretreatment with a platelet-activating factor (PAF) antagonist would ameliorate the lipopolysaccharide (LPS)-induced cardiovascular collapse during the early phase. Design: A prospective, controlled, in vivo animal laboratory study. Setting: Research laboratory at a university. Subjects: Male, Wistar rats (8-9 wks old; n = 83). Interventions: In pentobarbital-anesthetized rats, the right carotid artery was cannulated to measure the arterial blood pressure and to sample blood. The right jugular vein also was catheterized for the administration of drugs. LPS (2 mg/kg) derived from Klebsiella pneumoniae or physiologic saline was administered in the presence or absence of pretreatment with TCV-309, a specific potent PAF antagonist. Echocardiographic studies were performed with an 8- to 13-MHz transducer. Measurements and Main Results: LPS administration immediately induced progressive hypotension. The maximal hypotensive response was observed at 10 mins after LPS infusion with mean arterial pressure decreasing from 119 ± 2 to 56 ± 3 mm Hg (p < .001). LV end-diastolic internal dimensions decreased from 6.4 ± 0.1 to 3.1 ± 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced compared with control rats. LV end-systolic dimensions also decreased dramatically from 3.5 ± 0.2 to 0.5 ± 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced throughout the experiment. LV fractional shortening increased from 45 ± 1% to 84 ± 2% (p < .001) at 30 mins after LPS and remained elevated compared with control rats. LV wall thickness increased strikingly from 15 mins until 2 hrs after LPS infusion. Pathologic studies demonstrated marked congestion of capillaries and mild edema in the LV myocardium. The hematocrit increased after the administration of LPS. LPS markedly increased sympathetic tone as demonstrated by the elevation of plasma concentrations of epinephrine and norepinephrine. There was no elevation of concentrations of nitrite and nitrate. Pretreatment with TCV-309, a specific potent PAF antagonist, reduced LPS-induced hypotension and attenuated LV functional and structural changes. TCV-309 administration reduced the LPS-induced adrenergic activation and hemoconcentration. Conclusions: The hypotension that occurred during the initial phase of LPS-induced shock was accompanied by LV 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. Pretreatment with a PAF antagonist reduced LPS-induced alterations. PAF may play a pivotal role during the initial phase of LPS-induced cardiovascular responses.

Original languageEnglish
Pages (from-to)609-617
Number of pages9
JournalCritical Care Medicine
Volume29
Issue number3
DOIs
Publication statusPublished - 01-01-2001
Externally publishedYes

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Platelet Activating Factor
Endotoxins
Lipopolysaccharides
Controlled Hypotension
Edema
Myocardium
Arterial Pressure
Endotoxemia
Jugular Veins
Laboratory Animals
Klebsiella pneumoniae
Pentobarbital
Nitrites
Transducers
Hematocrit
Left Ventricular Function
Carotid Arteries
Nitrates
Adrenergic Agents
Hypotension

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

Iwase, Mitsunori ; Yokota, Mitsuhiro ; Kitaichi, Kiyoyuki ; Wang, Li ; Takagi, Kenji ; Nagasaka, Tetsuro ; Izawa, Hideo ; Hasegawa, Takaaki. / Cardiac functional and structural alterations induced by endotoxin in rats : Importance of platelet-activating factor. In: Critical Care Medicine. 2001 ; Vol. 29, No. 3. pp. 609-617.
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abstract = "Objective: In this study, we evaluated the time course of the alterations in left ventricular (LV) dimensions, LV wall thickness, and LV systolic function in rats with endotoxemia by using echocardiography as well as myocardial histopathologic assessments. Our second goal was to examine whether pretreatment with a platelet-activating factor (PAF) antagonist would ameliorate the lipopolysaccharide (LPS)-induced cardiovascular collapse during the early phase. Design: A prospective, controlled, in vivo animal laboratory study. Setting: Research laboratory at a university. Subjects: Male, Wistar rats (8-9 wks old; n = 83). Interventions: In pentobarbital-anesthetized rats, the right carotid artery was cannulated to measure the arterial blood pressure and to sample blood. The right jugular vein also was catheterized for the administration of drugs. LPS (2 mg/kg) derived from Klebsiella pneumoniae or physiologic saline was administered in the presence or absence of pretreatment with TCV-309, a specific potent PAF antagonist. Echocardiographic studies were performed with an 8- to 13-MHz transducer. Measurements and Main Results: LPS administration immediately induced progressive hypotension. The maximal hypotensive response was observed at 10 mins after LPS infusion with mean arterial pressure decreasing from 119 ± 2 to 56 ± 3 mm Hg (p < .001). LV end-diastolic internal dimensions decreased from 6.4 ± 0.1 to 3.1 ± 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced compared with control rats. LV end-systolic dimensions also decreased dramatically from 3.5 ± 0.2 to 0.5 ± 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced throughout the experiment. LV fractional shortening increased from 45 ± 1{\%} to 84 ± 2{\%} (p < .001) at 30 mins after LPS and remained elevated compared with control rats. LV wall thickness increased strikingly from 15 mins until 2 hrs after LPS infusion. Pathologic studies demonstrated marked congestion of capillaries and mild edema in the LV myocardium. The hematocrit increased after the administration of LPS. LPS markedly increased sympathetic tone as demonstrated by the elevation of plasma concentrations of epinephrine and norepinephrine. There was no elevation of concentrations of nitrite and nitrate. Pretreatment with TCV-309, a specific potent PAF antagonist, reduced LPS-induced hypotension and attenuated LV functional and structural changes. TCV-309 administration reduced the LPS-induced adrenergic activation and hemoconcentration. Conclusions: The hypotension that occurred during the initial phase of LPS-induced shock was accompanied by LV 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. Pretreatment with a PAF antagonist reduced LPS-induced alterations. PAF may play a pivotal role during the initial phase of LPS-induced cardiovascular responses.",
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Cardiac functional and structural alterations induced by endotoxin in rats : Importance of platelet-activating factor. / Iwase, Mitsunori; Yokota, Mitsuhiro; Kitaichi, Kiyoyuki; Wang, Li; Takagi, Kenji; Nagasaka, Tetsuro; Izawa, Hideo; Hasegawa, Takaaki.

In: Critical Care Medicine, Vol. 29, No. 3, 01.01.2001, p. 609-617.

Research output: Contribution to journalArticle

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T1 - Cardiac functional and structural alterations induced by endotoxin in rats

T2 - Importance of platelet-activating factor

AU - Iwase, Mitsunori

AU - Yokota, Mitsuhiro

AU - Kitaichi, Kiyoyuki

AU - Wang, Li

AU - Takagi, Kenji

AU - Nagasaka, Tetsuro

AU - Izawa, Hideo

AU - Hasegawa, Takaaki

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Objective: In this study, we evaluated the time course of the alterations in left ventricular (LV) dimensions, LV wall thickness, and LV systolic function in rats with endotoxemia by using echocardiography as well as myocardial histopathologic assessments. Our second goal was to examine whether pretreatment with a platelet-activating factor (PAF) antagonist would ameliorate the lipopolysaccharide (LPS)-induced cardiovascular collapse during the early phase. Design: A prospective, controlled, in vivo animal laboratory study. Setting: Research laboratory at a university. Subjects: Male, Wistar rats (8-9 wks old; n = 83). Interventions: In pentobarbital-anesthetized rats, the right carotid artery was cannulated to measure the arterial blood pressure and to sample blood. The right jugular vein also was catheterized for the administration of drugs. LPS (2 mg/kg) derived from Klebsiella pneumoniae or physiologic saline was administered in the presence or absence of pretreatment with TCV-309, a specific potent PAF antagonist. Echocardiographic studies were performed with an 8- to 13-MHz transducer. Measurements and Main Results: LPS administration immediately induced progressive hypotension. The maximal hypotensive response was observed at 10 mins after LPS infusion with mean arterial pressure decreasing from 119 ± 2 to 56 ± 3 mm Hg (p < .001). LV end-diastolic internal dimensions decreased from 6.4 ± 0.1 to 3.1 ± 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced compared with control rats. LV end-systolic dimensions also decreased dramatically from 3.5 ± 0.2 to 0.5 ± 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced throughout the experiment. LV fractional shortening increased from 45 ± 1% to 84 ± 2% (p < .001) at 30 mins after LPS and remained elevated compared with control rats. LV wall thickness increased strikingly from 15 mins until 2 hrs after LPS infusion. Pathologic studies demonstrated marked congestion of capillaries and mild edema in the LV myocardium. The hematocrit increased after the administration of LPS. LPS markedly increased sympathetic tone as demonstrated by the elevation of plasma concentrations of epinephrine and norepinephrine. There was no elevation of concentrations of nitrite and nitrate. Pretreatment with TCV-309, a specific potent PAF antagonist, reduced LPS-induced hypotension and attenuated LV functional and structural changes. TCV-309 administration reduced the LPS-induced adrenergic activation and hemoconcentration. Conclusions: The hypotension that occurred during the initial phase of LPS-induced shock was accompanied by LV 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. Pretreatment with a PAF antagonist reduced LPS-induced alterations. PAF may play a pivotal role during the initial phase of LPS-induced cardiovascular responses.

AB - Objective: In this study, we evaluated the time course of the alterations in left ventricular (LV) dimensions, LV wall thickness, and LV systolic function in rats with endotoxemia by using echocardiography as well as myocardial histopathologic assessments. Our second goal was to examine whether pretreatment with a platelet-activating factor (PAF) antagonist would ameliorate the lipopolysaccharide (LPS)-induced cardiovascular collapse during the early phase. Design: A prospective, controlled, in vivo animal laboratory study. Setting: Research laboratory at a university. Subjects: Male, Wistar rats (8-9 wks old; n = 83). Interventions: In pentobarbital-anesthetized rats, the right carotid artery was cannulated to measure the arterial blood pressure and to sample blood. The right jugular vein also was catheterized for the administration of drugs. LPS (2 mg/kg) derived from Klebsiella pneumoniae or physiologic saline was administered in the presence or absence of pretreatment with TCV-309, a specific potent PAF antagonist. Echocardiographic studies were performed with an 8- to 13-MHz transducer. Measurements and Main Results: LPS administration immediately induced progressive hypotension. The maximal hypotensive response was observed at 10 mins after LPS infusion with mean arterial pressure decreasing from 119 ± 2 to 56 ± 3 mm Hg (p < .001). LV end-diastolic internal dimensions decreased from 6.4 ± 0.1 to 3.1 ± 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced compared with control rats. LV end-systolic dimensions also decreased dramatically from 3.5 ± 0.2 to 0.5 ± 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced throughout the experiment. LV fractional shortening increased from 45 ± 1% to 84 ± 2% (p < .001) at 30 mins after LPS and remained elevated compared with control rats. LV wall thickness increased strikingly from 15 mins until 2 hrs after LPS infusion. Pathologic studies demonstrated marked congestion of capillaries and mild edema in the LV myocardium. The hematocrit increased after the administration of LPS. LPS markedly increased sympathetic tone as demonstrated by the elevation of plasma concentrations of epinephrine and norepinephrine. There was no elevation of concentrations of nitrite and nitrate. Pretreatment with TCV-309, a specific potent PAF antagonist, reduced LPS-induced hypotension and attenuated LV functional and structural changes. TCV-309 administration reduced the LPS-induced adrenergic activation and hemoconcentration. Conclusions: The hypotension that occurred during the initial phase of LPS-induced shock was accompanied by LV 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. Pretreatment with a PAF antagonist reduced LPS-induced alterations. PAF may play a pivotal role during the initial phase of LPS-induced cardiovascular responses.

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