Delayed protection against ischaemia-induced ventricular arrhythmias and infarct size limitation by the prior administration of Escherichia coli endotoxin

Wu Song, Brian L. Furman, J. Parratt

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Abstract

1. Bacterial endotoxin (lipopolysaccharide derived from Escherichia call) was injected intraperitoneally in conscious rats in doses ranging from 0.5 to 2.5 mg kg-1. At various times afterwards the animals were anaesthetized and subjected to a 30 min period of left coronary artery occlusion. 2. Under these conditions the severity of ventricular arrhythmias was markedly suppressed, in comparison with saline-injected controls, but this was particularly marked with the higher doses (1.5 and 2.5 mg kg-1); the number of ventricular premature beats was reduced from 1687 ± 227 over the 0.5 h coronary artery occlusion period to 190 ± 46 in those rats administered 2.5 mg kg-1 endotoxin 8 h previously (P <0.05). The duration of ventricular tachycardia was also significantly reduced (138 ± 26 s to 8.9 ± 4.2 s; P <0.01) and there was a reduction in the incidence of ventricular fibrillation (from 56% to 10%). 3. The time course of this protection was studied following the administration of a single dose of 2.5 mg kg-1 of endotoxin by anaesthetizing rats 4, 8 or 24 h later. Protection was apparent at each time but was particularly marked at 8 h. 4. No rat given the highest dose of endotoxin (32 in all) died as a result of ventricular fibrillation, or from any other cause, during an occlusion, in contrast to a 26% mortality in the controls (P <0.01). 5. Infarct size, measured following a 30 min period of coronary artery occlusion followed by a 3 h reperfusion period, was reduced both 8 and 24 h after the administration of 2.5 mg kg-1 endotoxin (reductions of 24.3 and 23.1% respectively; P <0.05). Endotoxin had no significant effect on the area at risk. 6. The beneficial effects of endotoxin on infarct size and on ventricular arrhythmias were markedly attenuated by the prior administration of dexamethasone, 3 mg kg-1 given 1 h prior to endotoxin administration. Dexamethasone itself reduced infarct size (P <0.05) but had no direct effect on arrhythmia severity following coronary artery occlusion. 7. The mechanisms of this 'cross-tolerance' induced by bacterial endotoxin against ischaemia-reperfusion injury remain to be elucidated but the most likely mechanisms appear to be the induction of protective enzymes or proteins (e.g. nitric oxide synthase, cyclo-oxygenase (COX) 2) probably mediated by cytokine release.

Original languageEnglish
Pages (from-to)2157-2163
Number of pages7
JournalBritish Journal of Pharmacology
Volume118
Issue number8
Publication statusPublished - 1996

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Endotoxins
Cardiac Arrhythmias
Ischemia
Coronary Occlusion
Coronary Vessels
Ventricular Fibrillation
Dexamethasone
Escherichia coli endotoxin
Escherichia
Enzyme Induction
Ventricular Premature Complexes
Ventricular Tachycardia
Prostaglandin-Endoperoxide Synthases
Reperfusion Injury
Nitric Oxide Synthase
Reperfusion
Lipopolysaccharides
Cytokines
Mortality
Incidence

Keywords

  • Cardiac arrhythmias
  • Dexamethasone
  • Endotoxin
  • Infarct size limitation
  • Myocardial ischaemia

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Delayed protection against ischaemia-induced ventricular arrhythmias and infarct size limitation by the prior administration of Escherichia coli endotoxin",
abstract = "1. Bacterial endotoxin (lipopolysaccharide derived from Escherichia call) was injected intraperitoneally in conscious rats in doses ranging from 0.5 to 2.5 mg kg-1. At various times afterwards the animals were anaesthetized and subjected to a 30 min period of left coronary artery occlusion. 2. Under these conditions the severity of ventricular arrhythmias was markedly suppressed, in comparison with saline-injected controls, but this was particularly marked with the higher doses (1.5 and 2.5 mg kg-1); the number of ventricular premature beats was reduced from 1687 ± 227 over the 0.5 h coronary artery occlusion period to 190 ± 46 in those rats administered 2.5 mg kg-1 endotoxin 8 h previously (P <0.05). The duration of ventricular tachycardia was also significantly reduced (138 ± 26 s to 8.9 ± 4.2 s; P <0.01) and there was a reduction in the incidence of ventricular fibrillation (from 56{\%} to 10{\%}). 3. The time course of this protection was studied following the administration of a single dose of 2.5 mg kg-1 of endotoxin by anaesthetizing rats 4, 8 or 24 h later. Protection was apparent at each time but was particularly marked at 8 h. 4. No rat given the highest dose of endotoxin (32 in all) died as a result of ventricular fibrillation, or from any other cause, during an occlusion, in contrast to a 26{\%} mortality in the controls (P <0.01). 5. Infarct size, measured following a 30 min period of coronary artery occlusion followed by a 3 h reperfusion period, was reduced both 8 and 24 h after the administration of 2.5 mg kg-1 endotoxin (reductions of 24.3 and 23.1{\%} respectively; P <0.05). Endotoxin had no significant effect on the area at risk. 6. The beneficial effects of endotoxin on infarct size and on ventricular arrhythmias were markedly attenuated by the prior administration of dexamethasone, 3 mg kg-1 given 1 h prior to endotoxin administration. Dexamethasone itself reduced infarct size (P <0.05) but had no direct effect on arrhythmia severity following coronary artery occlusion. 7. The mechanisms of this 'cross-tolerance' induced by bacterial endotoxin against ischaemia-reperfusion injury remain to be elucidated but the most likely mechanisms appear to be the induction of protective enzymes or proteins (e.g. nitric oxide synthase, cyclo-oxygenase (COX) 2) probably mediated by cytokine release.",
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T1 - Delayed protection against ischaemia-induced ventricular arrhythmias and infarct size limitation by the prior administration of Escherichia coli endotoxin

AU - Song, Wu

AU - Furman, Brian L.

AU - Parratt, J.

PY - 1996

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N2 - 1. Bacterial endotoxin (lipopolysaccharide derived from Escherichia call) was injected intraperitoneally in conscious rats in doses ranging from 0.5 to 2.5 mg kg-1. At various times afterwards the animals were anaesthetized and subjected to a 30 min period of left coronary artery occlusion. 2. Under these conditions the severity of ventricular arrhythmias was markedly suppressed, in comparison with saline-injected controls, but this was particularly marked with the higher doses (1.5 and 2.5 mg kg-1); the number of ventricular premature beats was reduced from 1687 ± 227 over the 0.5 h coronary artery occlusion period to 190 ± 46 in those rats administered 2.5 mg kg-1 endotoxin 8 h previously (P <0.05). The duration of ventricular tachycardia was also significantly reduced (138 ± 26 s to 8.9 ± 4.2 s; P <0.01) and there was a reduction in the incidence of ventricular fibrillation (from 56% to 10%). 3. The time course of this protection was studied following the administration of a single dose of 2.5 mg kg-1 of endotoxin by anaesthetizing rats 4, 8 or 24 h later. Protection was apparent at each time but was particularly marked at 8 h. 4. No rat given the highest dose of endotoxin (32 in all) died as a result of ventricular fibrillation, or from any other cause, during an occlusion, in contrast to a 26% mortality in the controls (P <0.01). 5. Infarct size, measured following a 30 min period of coronary artery occlusion followed by a 3 h reperfusion period, was reduced both 8 and 24 h after the administration of 2.5 mg kg-1 endotoxin (reductions of 24.3 and 23.1% respectively; P <0.05). Endotoxin had no significant effect on the area at risk. 6. The beneficial effects of endotoxin on infarct size and on ventricular arrhythmias were markedly attenuated by the prior administration of dexamethasone, 3 mg kg-1 given 1 h prior to endotoxin administration. Dexamethasone itself reduced infarct size (P <0.05) but had no direct effect on arrhythmia severity following coronary artery occlusion. 7. The mechanisms of this 'cross-tolerance' induced by bacterial endotoxin against ischaemia-reperfusion injury remain to be elucidated but the most likely mechanisms appear to be the induction of protective enzymes or proteins (e.g. nitric oxide synthase, cyclo-oxygenase (COX) 2) probably mediated by cytokine release.

AB - 1. Bacterial endotoxin (lipopolysaccharide derived from Escherichia call) was injected intraperitoneally in conscious rats in doses ranging from 0.5 to 2.5 mg kg-1. At various times afterwards the animals were anaesthetized and subjected to a 30 min period of left coronary artery occlusion. 2. Under these conditions the severity of ventricular arrhythmias was markedly suppressed, in comparison with saline-injected controls, but this was particularly marked with the higher doses (1.5 and 2.5 mg kg-1); the number of ventricular premature beats was reduced from 1687 ± 227 over the 0.5 h coronary artery occlusion period to 190 ± 46 in those rats administered 2.5 mg kg-1 endotoxin 8 h previously (P <0.05). The duration of ventricular tachycardia was also significantly reduced (138 ± 26 s to 8.9 ± 4.2 s; P <0.01) and there was a reduction in the incidence of ventricular fibrillation (from 56% to 10%). 3. The time course of this protection was studied following the administration of a single dose of 2.5 mg kg-1 of endotoxin by anaesthetizing rats 4, 8 or 24 h later. Protection was apparent at each time but was particularly marked at 8 h. 4. No rat given the highest dose of endotoxin (32 in all) died as a result of ventricular fibrillation, or from any other cause, during an occlusion, in contrast to a 26% mortality in the controls (P <0.01). 5. Infarct size, measured following a 30 min period of coronary artery occlusion followed by a 3 h reperfusion period, was reduced both 8 and 24 h after the administration of 2.5 mg kg-1 endotoxin (reductions of 24.3 and 23.1% respectively; P <0.05). Endotoxin had no significant effect on the area at risk. 6. The beneficial effects of endotoxin on infarct size and on ventricular arrhythmias were markedly attenuated by the prior administration of dexamethasone, 3 mg kg-1 given 1 h prior to endotoxin administration. Dexamethasone itself reduced infarct size (P <0.05) but had no direct effect on arrhythmia severity following coronary artery occlusion. 7. The mechanisms of this 'cross-tolerance' induced by bacterial endotoxin against ischaemia-reperfusion injury remain to be elucidated but the most likely mechanisms appear to be the induction of protective enzymes or proteins (e.g. nitric oxide synthase, cyclo-oxygenase (COX) 2) probably mediated by cytokine release.

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