Prevention of early myocardial depression in hyperdynamic endotoxemia in dogs

Antal Wolfárd, József Kaszaki, Csaba Szabo, László Szalay, Sándor Nagy, Mihály Boros

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In our study the pathomechanism of sepsis-induced early myocardial depression was investigated. We determined the effects of the inducible nitric oxide synthase inhibitor and free radical scavenger mercaptoethylguanidine (MEG) on the myocardial contractility, the endothelial and inducible nitric oxide synthase (eNOS and iNOS) activities, and the activation and tissue accumulation of polymorphonuclear leukocytes in hyperdynamic endotoxemia in dogs. Group 1 served as endotoxemic control. Mean arterial pressure and cardiac output were measured, myocardial contractility was estimated from the end-systolic pressure-diameter relationship. The eNOS, iNOS and myeloperoxidase activities were determined on myocardial biopsy samples, and the free radical-producing capacity of granulocytes was measured from separated cells. The effect of MEG on the in vitro free radical production of isolated granulocytes was measured by chemiluminometry. Endotoxin induced a hyperdynamic circulatory reaction and significant myocardial depression. The myocardial eNOS activity was significantly increased 4 h after induction of endotoxemia and remained elevated, the iNOS activity was increased only 8 h after endotoxemia induction. The free radical-producing capacity and the myocardial accumulation of the granulocytes were significantly increased. In group 2, MEG treatment selectively inhibited the iNOS activity, prolonged the hyperdynamic circulatory reaction, prevented myocardial depression and decreased the activation and tissue accumulation of granulocytes. The compound dose-dependently decreased the in vitro activation of previously resting granulocytes. Our study demonstrates that iNOS do not contribute to the early cardiac failure in endotoxemia. MEG selectively inhibits iNOS in vivo, but its beneficial effects are rather related to the decreases in leukocyte and free radical-mediated myocardial dysfunction during early endotoxemia.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalShock
Volume13
Issue number1
StatePublished - Jan 2000
Externally publishedYes

Fingerprint

Endotoxemia
Granulocytes
Free Radicals
Dogs
Nitric Oxide Synthase Type II
Free Radical Scavengers
Nitric Oxide Synthase Type III
Endotoxins
Cardiac Output
Peroxidase
Sepsis
Arterial Pressure
Neutrophils
Leukocytes
Heart Failure
Blood Pressure
Biopsy
2-mercaptoethylguanidine

Keywords

  • Mercaptoethylguanidine
  • Myocardial contractility
  • Nitric oxide synthase activity
  • Oxygen free radicals
  • Polymorphonuclear leukocytes

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Wolfárd, A., Kaszaki, J., Szabo, C., Szalay, L., Nagy, S., & Boros, M. (2000). Prevention of early myocardial depression in hyperdynamic endotoxemia in dogs. Shock, 13(1), 46-51.

Prevention of early myocardial depression in hyperdynamic endotoxemia in dogs. / Wolfárd, Antal; Kaszaki, József; Szabo, Csaba; Szalay, László; Nagy, Sándor; Boros, Mihály.

In: Shock, Vol. 13, No. 1, 01.2000, p. 46-51.

Research output: Contribution to journalArticle

Wolfárd, A, Kaszaki, J, Szabo, C, Szalay, L, Nagy, S & Boros, M 2000, 'Prevention of early myocardial depression in hyperdynamic endotoxemia in dogs', Shock, vol. 13, no. 1, pp. 46-51.
Wolfárd A, Kaszaki J, Szabo C, Szalay L, Nagy S, Boros M. Prevention of early myocardial depression in hyperdynamic endotoxemia in dogs. Shock. 2000 Jan;13(1):46-51.
Wolfárd, Antal ; Kaszaki, József ; Szabo, Csaba ; Szalay, László ; Nagy, Sándor ; Boros, Mihály. / Prevention of early myocardial depression in hyperdynamic endotoxemia in dogs. In: Shock. 2000 ; Vol. 13, No. 1. pp. 46-51.
@article{07a50cee7e2f4308ab66f3ae840ec30a,
title = "Prevention of early myocardial depression in hyperdynamic endotoxemia in dogs",
abstract = "In our study the pathomechanism of sepsis-induced early myocardial depression was investigated. We determined the effects of the inducible nitric oxide synthase inhibitor and free radical scavenger mercaptoethylguanidine (MEG) on the myocardial contractility, the endothelial and inducible nitric oxide synthase (eNOS and iNOS) activities, and the activation and tissue accumulation of polymorphonuclear leukocytes in hyperdynamic endotoxemia in dogs. Group 1 served as endotoxemic control. Mean arterial pressure and cardiac output were measured, myocardial contractility was estimated from the end-systolic pressure-diameter relationship. The eNOS, iNOS and myeloperoxidase activities were determined on myocardial biopsy samples, and the free radical-producing capacity of granulocytes was measured from separated cells. The effect of MEG on the in vitro free radical production of isolated granulocytes was measured by chemiluminometry. Endotoxin induced a hyperdynamic circulatory reaction and significant myocardial depression. The myocardial eNOS activity was significantly increased 4 h after induction of endotoxemia and remained elevated, the iNOS activity was increased only 8 h after endotoxemia induction. The free radical-producing capacity and the myocardial accumulation of the granulocytes were significantly increased. In group 2, MEG treatment selectively inhibited the iNOS activity, prolonged the hyperdynamic circulatory reaction, prevented myocardial depression and decreased the activation and tissue accumulation of granulocytes. The compound dose-dependently decreased the in vitro activation of previously resting granulocytes. Our study demonstrates that iNOS do not contribute to the early cardiac failure in endotoxemia. MEG selectively inhibits iNOS in vivo, but its beneficial effects are rather related to the decreases in leukocyte and free radical-mediated myocardial dysfunction during early endotoxemia.",
keywords = "Mercaptoethylguanidine, Myocardial contractility, Nitric oxide synthase activity, Oxygen free radicals, Polymorphonuclear leukocytes",
author = "Antal Wolf{\'a}rd and J{\'o}zsef Kaszaki and Csaba Szabo and L{\'a}szl{\'o} Szalay and S{\'a}ndor Nagy and Mih{\'a}ly Boros",
year = "2000",
month = "1",
language = "English (US)",
volume = "13",
pages = "46--51",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Prevention of early myocardial depression in hyperdynamic endotoxemia in dogs

AU - Wolfárd, Antal

AU - Kaszaki, József

AU - Szabo, Csaba

AU - Szalay, László

AU - Nagy, Sándor

AU - Boros, Mihály

PY - 2000/1

Y1 - 2000/1

N2 - In our study the pathomechanism of sepsis-induced early myocardial depression was investigated. We determined the effects of the inducible nitric oxide synthase inhibitor and free radical scavenger mercaptoethylguanidine (MEG) on the myocardial contractility, the endothelial and inducible nitric oxide synthase (eNOS and iNOS) activities, and the activation and tissue accumulation of polymorphonuclear leukocytes in hyperdynamic endotoxemia in dogs. Group 1 served as endotoxemic control. Mean arterial pressure and cardiac output were measured, myocardial contractility was estimated from the end-systolic pressure-diameter relationship. The eNOS, iNOS and myeloperoxidase activities were determined on myocardial biopsy samples, and the free radical-producing capacity of granulocytes was measured from separated cells. The effect of MEG on the in vitro free radical production of isolated granulocytes was measured by chemiluminometry. Endotoxin induced a hyperdynamic circulatory reaction and significant myocardial depression. The myocardial eNOS activity was significantly increased 4 h after induction of endotoxemia and remained elevated, the iNOS activity was increased only 8 h after endotoxemia induction. The free radical-producing capacity and the myocardial accumulation of the granulocytes were significantly increased. In group 2, MEG treatment selectively inhibited the iNOS activity, prolonged the hyperdynamic circulatory reaction, prevented myocardial depression and decreased the activation and tissue accumulation of granulocytes. The compound dose-dependently decreased the in vitro activation of previously resting granulocytes. Our study demonstrates that iNOS do not contribute to the early cardiac failure in endotoxemia. MEG selectively inhibits iNOS in vivo, but its beneficial effects are rather related to the decreases in leukocyte and free radical-mediated myocardial dysfunction during early endotoxemia.

AB - In our study the pathomechanism of sepsis-induced early myocardial depression was investigated. We determined the effects of the inducible nitric oxide synthase inhibitor and free radical scavenger mercaptoethylguanidine (MEG) on the myocardial contractility, the endothelial and inducible nitric oxide synthase (eNOS and iNOS) activities, and the activation and tissue accumulation of polymorphonuclear leukocytes in hyperdynamic endotoxemia in dogs. Group 1 served as endotoxemic control. Mean arterial pressure and cardiac output were measured, myocardial contractility was estimated from the end-systolic pressure-diameter relationship. The eNOS, iNOS and myeloperoxidase activities were determined on myocardial biopsy samples, and the free radical-producing capacity of granulocytes was measured from separated cells. The effect of MEG on the in vitro free radical production of isolated granulocytes was measured by chemiluminometry. Endotoxin induced a hyperdynamic circulatory reaction and significant myocardial depression. The myocardial eNOS activity was significantly increased 4 h after induction of endotoxemia and remained elevated, the iNOS activity was increased only 8 h after endotoxemia induction. The free radical-producing capacity and the myocardial accumulation of the granulocytes were significantly increased. In group 2, MEG treatment selectively inhibited the iNOS activity, prolonged the hyperdynamic circulatory reaction, prevented myocardial depression and decreased the activation and tissue accumulation of granulocytes. The compound dose-dependently decreased the in vitro activation of previously resting granulocytes. Our study demonstrates that iNOS do not contribute to the early cardiac failure in endotoxemia. MEG selectively inhibits iNOS in vivo, but its beneficial effects are rather related to the decreases in leukocyte and free radical-mediated myocardial dysfunction during early endotoxemia.

KW - Mercaptoethylguanidine

KW - Myocardial contractility

KW - Nitric oxide synthase activity

KW - Oxygen free radicals

KW - Polymorphonuclear leukocytes

UR - http://www.scopus.com/inward/record.url?scp=0033629690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033629690&partnerID=8YFLogxK

M3 - Article

VL - 13

SP - 46

EP - 51

JO - Shock

JF - Shock

SN - 1073-2322

IS - 1

ER -