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

Intratracheal DEP instillation increased apoptotic cell death and reduced cardiomyocyte viability. (a) Representative images of left ventricle from rats 6 h after instillation of DEP (0.5 mg, lower panel) or saline (0.5 ml, upper panel) showing blue staining of TUNEL-positive apoptotic cells. DEP instillations (black columns, b) increased the number of apoptotic cells in the heart and (c) decreased the area of viable myocardium (% of left ventricle (LV)), compared to hearts from non-instilled (grey columns) and saline instilled (open columns) rats. Results are expressed as mean ± SEM (n = 3-4) **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 3: Intratracheal DEP instillation increased apoptotic cell death and reduced cardiomyocyte viability. (a) Representative images of left ventricle from rats 6 h after instillation of DEP (0.5 mg, lower panel) or saline (0.5 ml, upper panel) showing blue staining of TUNEL-positive apoptotic cells. DEP instillations (black columns, b) increased the number of apoptotic cells in the heart and (c) decreased the area of viable myocardium (% of left ventricle (LV)), compared to hearts from non-instilled (grey columns) and saline instilled (open columns) rats. Results are expressed as mean ± SEM (n = 3-4) **P < 0.01, **P < 0.001, saline versus DEP; one-way ANOVA followed by Bonferroni post-hoc test.

Mentions: Oxidant stress, determined by electron paramagnetic resonance (EPR) of the heart perfusate before induction of ischemia and reperfusion, was higher in hearts from DEP-instilled rats (P < 0.01; Figure 2b & c). All hearts showed a small burst of oxidant stress on reperfusion but this did not differ between treatment groups (data not shown). In separate hearts, fixed 6 h after DEP instillation and prior to I/R, detection of TUNEL-labelled apoptotic cells was increased relative to hearts from non-instilled or saline instilled hearts (P < 0.01; Figure 3a & b), while assessment of tetrazolium chloride staining showed a corresponding loss in myocardial cardiac cell viability (P < 0.01, Figure 3c).


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)

Intratracheal DEP instillation increased apoptotic cell death and reduced cardiomyocyte viability. (a) Representative images of left ventricle from rats 6 h after instillation of DEP (0.5 mg, lower panel) or saline (0.5 ml, upper panel) showing blue staining of TUNEL-positive apoptotic cells. DEP instillations (black columns, b) increased the number of apoptotic cells in the heart and (c) decreased the area of viable myocardium (% of left ventricle (LV)), compared to hearts from non-instilled (grey columns) and saline instilled (open columns) rats. Results are expressed as mean ± SEM (n = 3-4) **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 3: Intratracheal DEP instillation increased apoptotic cell death and reduced cardiomyocyte viability. (a) Representative images of left ventricle from rats 6 h after instillation of DEP (0.5 mg, lower panel) or saline (0.5 ml, upper panel) showing blue staining of TUNEL-positive apoptotic cells. DEP instillations (black columns, b) increased the number of apoptotic cells in the heart and (c) decreased the area of viable myocardium (% of left ventricle (LV)), compared to hearts from non-instilled (grey columns) and saline instilled (open columns) rats. Results are expressed as mean ± SEM (n = 3-4) **P < 0.01, **P < 0.001, saline versus DEP; one-way ANOVA followed by Bonferroni post-hoc test.
Mentions: Oxidant stress, determined by electron paramagnetic resonance (EPR) of the heart perfusate before induction of ischemia and reperfusion, was higher in hearts from DEP-instilled rats (P < 0.01; Figure 2b & c). All hearts showed a small burst of oxidant stress on reperfusion but this did not differ between treatment groups (data not shown). In separate hearts, fixed 6 h after DEP instillation and prior to I/R, detection of TUNEL-labelled apoptotic cells was increased relative to hearts from non-instilled or saline instilled hearts (P < 0.01; Figure 3a & b), while assessment of tetrazolium chloride staining showed a corresponding loss in myocardial cardiac cell viability (P < 0.01, Figure 3c).

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