Effects of delayed preconditioning on myocardial regional contractility during repeated episodes of low-flow ischaemia in anaesthetized dogs

Possible role of nitric oxide

Zsolt Szigeti, Kornél Simon, J. Parratt, A. Végh

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The effect of cardiac pacing on repeated low-flow ischaemia-induced changes in regional myocardial segmental contractility, and the role in these changes of nitric oxide, were investigated in anaesthetized dogs. Dogs were instrumented for cardiac pacing (pacing electrode in the right ventricle). Dogs were paced (four times for 5 min; pacing rate 220 beats·min -1) 24 h prior to the repeated ischaemic insults. Controls were instrumented, but not paced. After 24 h, the dogs were re-anaesthetized with pentobarbitone and subjected to four 20 min low-flow ischaemia and reperfusion cycles, by constricting the left anterior descending coronary artery (LAD) to achieve an approx. 50 % reduction in resting coronary blood flow. In some dogs (both control and paced), NG-nitro-L-arginine methyl ester (L-NAME; a non-selective inhibitor of nitric oxide synthase) was infused into a side-branch of the LAD 10 min prior to the first ischaemia/reperfusion cycle. Regional contractile function was measured by ultrasonic microcrystals in the ischaemic and normal regions of the left ventricular wall supplied from the LAD and left circumflex coronary artery respectively, and expressed as percentage changes in segmental shortening (%SS). In some dogs, myocardial tissue blood flow (coloured microspheres) and lactate production (local coronary venous sampling) were measured; samples were also taken for histological analysis. In control dogs, the regional %SS was progressively reduced within the ischaemic segment during the four repeated occlusions (by 40 ± 6, 59 ± 6, 68 ± 6, 70 ± 6 % during occlusions 1-4 respectively). These reductions were more pronounced, especially during the first two cycles (68 ± 6, 68 ± 6, 67 ± 6, 67 ± 6 %, respectively), when the dogs had been previously subjected to cardiac pacing. In both paced and control dogs, these changes in contractile function were L-NAME-sensitive. Thus, in the presence of L-NAME, changes in regional segmental shortening in control dogs were 37 ± 8, 40 ± 8, 37 ± 8, 42 ± 11 % and in the paced dogs 46 ± 6, 45 ± 7, 45 ± 8, 45 ± 7 % respectively, during the four consecutive occlusions. There were no significant differences in tissue blood flow or in lactate production between the groups, and no structural changes indicative of infarction. These results show that the myocardium rapidly adapts to re-occurring acute ischaemia by reducing contractility within the ischaemic segment and, thereby, metabolic demand. Furthermore, cardiac pacing 24 h prior to these ischaemic challenges induces a similar adaptive response, a form of 'delayed preconditioning'. Since both the acute and delayed adaptation were L-NAME-sensitive, we suggest that this adaptation involves nitric oxide.

Original languageEnglish
Pages (from-to)201-213
Number of pages13
JournalClinical Science
Volume106
Issue number2
DOIs
Publication statusPublished - Feb 2004

Fingerprint

Myocardial Ischemic Preconditioning
Nitric Oxide
Ischemia
Dogs
NG-Nitroarginine Methyl Ester
Reperfusion
Lactic Acid
Coronary Vessels
Pentobarbital
Microspheres
Ultrasonics
Nitric Oxide Synthase
Infarction
Heart Ventricles

Keywords

  • Cardiac pacing
  • Low-flow ischaemia
  • Myocardial ischaemia
  • Nitric oxide (NO) synthase
  • Preconditioning
  • Regional contractility

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{c47ff90ac89e4e61be610c74024256da,
title = "Effects of delayed preconditioning on myocardial regional contractility during repeated episodes of low-flow ischaemia in anaesthetized dogs: Possible role of nitric oxide",
abstract = "The effect of cardiac pacing on repeated low-flow ischaemia-induced changes in regional myocardial segmental contractility, and the role in these changes of nitric oxide, were investigated in anaesthetized dogs. Dogs were instrumented for cardiac pacing (pacing electrode in the right ventricle). Dogs were paced (four times for 5 min; pacing rate 220 beats·min -1) 24 h prior to the repeated ischaemic insults. Controls were instrumented, but not paced. After 24 h, the dogs were re-anaesthetized with pentobarbitone and subjected to four 20 min low-flow ischaemia and reperfusion cycles, by constricting the left anterior descending coronary artery (LAD) to achieve an approx. 50 {\%} reduction in resting coronary blood flow. In some dogs (both control and paced), NG-nitro-L-arginine methyl ester (L-NAME; a non-selective inhibitor of nitric oxide synthase) was infused into a side-branch of the LAD 10 min prior to the first ischaemia/reperfusion cycle. Regional contractile function was measured by ultrasonic microcrystals in the ischaemic and normal regions of the left ventricular wall supplied from the LAD and left circumflex coronary artery respectively, and expressed as percentage changes in segmental shortening ({\%}SS). In some dogs, myocardial tissue blood flow (coloured microspheres) and lactate production (local coronary venous sampling) were measured; samples were also taken for histological analysis. In control dogs, the regional {\%}SS was progressively reduced within the ischaemic segment during the four repeated occlusions (by 40 ± 6, 59 ± 6, 68 ± 6, 70 ± 6 {\%} during occlusions 1-4 respectively). These reductions were more pronounced, especially during the first two cycles (68 ± 6, 68 ± 6, 67 ± 6, 67 ± 6 {\%}, respectively), when the dogs had been previously subjected to cardiac pacing. In both paced and control dogs, these changes in contractile function were L-NAME-sensitive. Thus, in the presence of L-NAME, changes in regional segmental shortening in control dogs were 37 ± 8, 40 ± 8, 37 ± 8, 42 ± 11 {\%} and in the paced dogs 46 ± 6, 45 ± 7, 45 ± 8, 45 ± 7 {\%} respectively, during the four consecutive occlusions. There were no significant differences in tissue blood flow or in lactate production between the groups, and no structural changes indicative of infarction. These results show that the myocardium rapidly adapts to re-occurring acute ischaemia by reducing contractility within the ischaemic segment and, thereby, metabolic demand. Furthermore, cardiac pacing 24 h prior to these ischaemic challenges induces a similar adaptive response, a form of 'delayed preconditioning'. Since both the acute and delayed adaptation were L-NAME-sensitive, we suggest that this adaptation involves nitric oxide.",
keywords = "Cardiac pacing, Low-flow ischaemia, Myocardial ischaemia, Nitric oxide (NO) synthase, Preconditioning, Regional contractility",
author = "Zsolt Szigeti and Korn{\'e}l Simon and J. Parratt and A. V{\'e}gh",
year = "2004",
month = "2",
doi = "10.1042/CS20030290",
language = "English",
volume = "106",
pages = "201--213",
journal = "Clinical Science",
issn = "0143-5221",
publisher = "Portland Press Ltd.",
number = "2",

}

TY - JOUR

T1 - Effects of delayed preconditioning on myocardial regional contractility during repeated episodes of low-flow ischaemia in anaesthetized dogs

T2 - Possible role of nitric oxide

AU - Szigeti, Zsolt

AU - Simon, Kornél

AU - Parratt, J.

AU - Végh, A.

PY - 2004/2

Y1 - 2004/2

N2 - The effect of cardiac pacing on repeated low-flow ischaemia-induced changes in regional myocardial segmental contractility, and the role in these changes of nitric oxide, were investigated in anaesthetized dogs. Dogs were instrumented for cardiac pacing (pacing electrode in the right ventricle). Dogs were paced (four times for 5 min; pacing rate 220 beats·min -1) 24 h prior to the repeated ischaemic insults. Controls were instrumented, but not paced. After 24 h, the dogs were re-anaesthetized with pentobarbitone and subjected to four 20 min low-flow ischaemia and reperfusion cycles, by constricting the left anterior descending coronary artery (LAD) to achieve an approx. 50 % reduction in resting coronary blood flow. In some dogs (both control and paced), NG-nitro-L-arginine methyl ester (L-NAME; a non-selective inhibitor of nitric oxide synthase) was infused into a side-branch of the LAD 10 min prior to the first ischaemia/reperfusion cycle. Regional contractile function was measured by ultrasonic microcrystals in the ischaemic and normal regions of the left ventricular wall supplied from the LAD and left circumflex coronary artery respectively, and expressed as percentage changes in segmental shortening (%SS). In some dogs, myocardial tissue blood flow (coloured microspheres) and lactate production (local coronary venous sampling) were measured; samples were also taken for histological analysis. In control dogs, the regional %SS was progressively reduced within the ischaemic segment during the four repeated occlusions (by 40 ± 6, 59 ± 6, 68 ± 6, 70 ± 6 % during occlusions 1-4 respectively). These reductions were more pronounced, especially during the first two cycles (68 ± 6, 68 ± 6, 67 ± 6, 67 ± 6 %, respectively), when the dogs had been previously subjected to cardiac pacing. In both paced and control dogs, these changes in contractile function were L-NAME-sensitive. Thus, in the presence of L-NAME, changes in regional segmental shortening in control dogs were 37 ± 8, 40 ± 8, 37 ± 8, 42 ± 11 % and in the paced dogs 46 ± 6, 45 ± 7, 45 ± 8, 45 ± 7 % respectively, during the four consecutive occlusions. There were no significant differences in tissue blood flow or in lactate production between the groups, and no structural changes indicative of infarction. These results show that the myocardium rapidly adapts to re-occurring acute ischaemia by reducing contractility within the ischaemic segment and, thereby, metabolic demand. Furthermore, cardiac pacing 24 h prior to these ischaemic challenges induces a similar adaptive response, a form of 'delayed preconditioning'. Since both the acute and delayed adaptation were L-NAME-sensitive, we suggest that this adaptation involves nitric oxide.

AB - The effect of cardiac pacing on repeated low-flow ischaemia-induced changes in regional myocardial segmental contractility, and the role in these changes of nitric oxide, were investigated in anaesthetized dogs. Dogs were instrumented for cardiac pacing (pacing electrode in the right ventricle). Dogs were paced (four times for 5 min; pacing rate 220 beats·min -1) 24 h prior to the repeated ischaemic insults. Controls were instrumented, but not paced. After 24 h, the dogs were re-anaesthetized with pentobarbitone and subjected to four 20 min low-flow ischaemia and reperfusion cycles, by constricting the left anterior descending coronary artery (LAD) to achieve an approx. 50 % reduction in resting coronary blood flow. In some dogs (both control and paced), NG-nitro-L-arginine methyl ester (L-NAME; a non-selective inhibitor of nitric oxide synthase) was infused into a side-branch of the LAD 10 min prior to the first ischaemia/reperfusion cycle. Regional contractile function was measured by ultrasonic microcrystals in the ischaemic and normal regions of the left ventricular wall supplied from the LAD and left circumflex coronary artery respectively, and expressed as percentage changes in segmental shortening (%SS). In some dogs, myocardial tissue blood flow (coloured microspheres) and lactate production (local coronary venous sampling) were measured; samples were also taken for histological analysis. In control dogs, the regional %SS was progressively reduced within the ischaemic segment during the four repeated occlusions (by 40 ± 6, 59 ± 6, 68 ± 6, 70 ± 6 % during occlusions 1-4 respectively). These reductions were more pronounced, especially during the first two cycles (68 ± 6, 68 ± 6, 67 ± 6, 67 ± 6 %, respectively), when the dogs had been previously subjected to cardiac pacing. In both paced and control dogs, these changes in contractile function were L-NAME-sensitive. Thus, in the presence of L-NAME, changes in regional segmental shortening in control dogs were 37 ± 8, 40 ± 8, 37 ± 8, 42 ± 11 % and in the paced dogs 46 ± 6, 45 ± 7, 45 ± 8, 45 ± 7 % respectively, during the four consecutive occlusions. There were no significant differences in tissue blood flow or in lactate production between the groups, and no structural changes indicative of infarction. These results show that the myocardium rapidly adapts to re-occurring acute ischaemia by reducing contractility within the ischaemic segment and, thereby, metabolic demand. Furthermore, cardiac pacing 24 h prior to these ischaemic challenges induces a similar adaptive response, a form of 'delayed preconditioning'. Since both the acute and delayed adaptation were L-NAME-sensitive, we suggest that this adaptation involves nitric oxide.

KW - Cardiac pacing

KW - Low-flow ischaemia

KW - Myocardial ischaemia

KW - Nitric oxide (NO) synthase

KW - Preconditioning

KW - Regional contractility

UR - http://www.scopus.com/inward/record.url?scp=1242284387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1242284387&partnerID=8YFLogxK

U2 - 10.1042/CS20030290

DO - 10.1042/CS20030290

M3 - Article

VL - 106

SP - 201

EP - 213

JO - Clinical Science

JF - Clinical Science

SN - 0143-5221

IS - 2

ER -