Limits...
Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors.

Robertson S, Thomson AL, Carter R, Stott HR, Shaw CA, Hadoke PW, Newby DE, Miller MR, Gray GA - Part Fibre Toxicol (2014)

Bottom Line: Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators.Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury.These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.

View Article: PubMed Central - HTML - PubMed

Affiliation: BHF/ University Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK. gillian.gray@ed.ac.uk.

ABSTRACT

Background: Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion.

Methods & results: 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury.

Conclusions: Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.

Show MeSH

Related in: MedlinePlus

Infarct size and oxidant stress generation was increased in hearts isolated from DEP instilled rats and perfused ex vivo. Myocardial infarct size (a, expressed as percentage of area at risk; AAR) and (b, c) oxygen free radicals (via quantification of CP˙ spin adducts by electron paramagnetic resonance; EPR) in coronary perfusate of hearts from non-instilled rats (non-instilled, grey column) and hearts isolated 6 h after instillation of saline (saline, 0.5 ml, open columns) or DEP (0.5 mg, black column). Results are expressed as mean ± SEM (n = 4-6) **P < 0.01, ***P < 0.001 saline versus DEP; one-way ANOVA followed by Bonferroni post-hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4016506&req=5

Figure 2: Infarct size and oxidant stress generation was increased in hearts isolated from DEP instilled rats and perfused ex vivo. Myocardial infarct size (a, expressed as percentage of area at risk; AAR) and (b, c) oxygen free radicals (via quantification of CP˙ spin adducts by electron paramagnetic resonance; EPR) in coronary perfusate of hearts from non-instilled rats (non-instilled, grey column) and hearts isolated 6 h after instillation of saline (saline, 0.5 ml, open columns) or DEP (0.5 mg, black column). Results are expressed as mean ± SEM (n = 4-6) **P < 0.01, ***P < 0.001 saline versus DEP; one-way ANOVA followed by Bonferroni post-hoc test.

Mentions: Neither baseline coronary perfusion pressure (CPP), nor AAR after induction of ischemia, was different between groups (Additional file 1: Table S3). Leakage of Evans Blue into the AAR did not occur in hearts from DEP instilled animals, in contrast to in vivo studies, allowing reperfusion injury to be calculated at % AAR. In agreement with in vivo observations, infarct size following ischemia and reperfusion ex vivo was increased in hearts from DEP-instilled rats relative to hearts isolated from saline-instilled or non-instilled rats (P < 0.001; Figure 2a).


Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors.

Robertson S, Thomson AL, Carter R, Stott HR, Shaw CA, Hadoke PW, Newby DE, Miller MR, Gray GA - Part Fibre Toxicol (2014)

Infarct size and oxidant stress generation was increased in hearts isolated from DEP instilled rats and perfused ex vivo. Myocardial infarct size (a, expressed as percentage of area at risk; AAR) and (b, c) oxygen free radicals (via quantification of CP˙ spin adducts by electron paramagnetic resonance; EPR) in coronary perfusate of hearts from non-instilled rats (non-instilled, grey column) and hearts isolated 6 h after instillation of saline (saline, 0.5 ml, open columns) or DEP (0.5 mg, black column). Results are expressed as mean ± SEM (n = 4-6) **P < 0.01, ***P < 0.001 saline versus DEP; one-way ANOVA followed by Bonferroni post-hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4016506&req=5

Figure 2: Infarct size and oxidant stress generation was increased in hearts isolated from DEP instilled rats and perfused ex vivo. Myocardial infarct size (a, expressed as percentage of area at risk; AAR) and (b, c) oxygen free radicals (via quantification of CP˙ spin adducts by electron paramagnetic resonance; EPR) in coronary perfusate of hearts from non-instilled rats (non-instilled, grey column) and hearts isolated 6 h after instillation of saline (saline, 0.5 ml, open columns) or DEP (0.5 mg, black column). Results are expressed as mean ± SEM (n = 4-6) **P < 0.01, ***P < 0.001 saline versus DEP; one-way ANOVA followed by Bonferroni post-hoc test.
Mentions: Neither baseline coronary perfusion pressure (CPP), nor AAR after induction of ischemia, was different between groups (Additional file 1: Table S3). Leakage of Evans Blue into the AAR did not occur in hearts from DEP instilled animals, in contrast to in vivo studies, allowing reperfusion injury to be calculated at % AAR. In agreement with in vivo observations, infarct size following ischemia and reperfusion ex vivo was increased in hearts from DEP-instilled rats relative to hearts isolated from saline-instilled or non-instilled rats (P < 0.001; Figure 2a).

Bottom Line: Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators.Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury.These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.

View Article: PubMed Central - HTML - PubMed

Affiliation: BHF/ University Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK. gillian.gray@ed.ac.uk.

ABSTRACT

Background: Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion.

Methods & results: 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury.

Conclusions: Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.

Show MeSH
Related in: MedlinePlus