title: Pulmonary instillation of multi-walled carbon nanotubes promotes coronary vasoconstriction and exacerbates injury in isolated hearts.
abstract: The growing use of multi-walled carbon nanotubes (MWCNTs) across industry has increased human exposures. We tested the hypothesis that pulmonary instillation of MWCNTs would exacerbate cardiac ischaemia/reperfusion (I/R) injury. One day following intratracheal instillation of 1, 10 or 100 μg MWCNT in Sprague-Dawley rats, we used a Langendorff isolated heart model to examine cardiac I/R injury. In the 100 μg MWCNT group we report increased premature ventricular contractions at baseline and increased myocardial infarction. This was associated with increased endothelin-1 (ET-1) release and depression of coronary flow during early reperfusion. We also tested if isolated coronary vascular responses were affected by MWCNT instillation and found trends for enhanced coronary tone, which were dependent on ET-1, cyclooxygenase, thromboxane and Rho-kinase. We concluded that instillation of MWCNTs promoted cardiac injury and depressed coronary flow by invoking vasoconstrictive mechanisms involving ET-1, cyclooxygenase, thromboxane and Rho-kinase.
authors.affiliation: Department of Physiology, Brody School of Medicine at East Carolina University , Greenville, NC , USA.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Thompson
authors.forename: Chad R
authors.initials: CR
authors.lastname: Frasier
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Sloan
authors.forename: Erin E
authors.initials: EE
authors.lastname: Mann
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Harrison
authors.forename: Jared M
authors.initials: JM
authors.lastname: Brown
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wingard
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003326:Coronary Circulation / Q000187:drug effects; D019332:Endothelin-1 / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D037742:Nanotubes, Carbon / Q000633:toxicity*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000633:toxicity*; D017725:Ventricular Pressure / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D037742:Nanotubes, Carbon; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D011451:Prostaglandin-Endoperoxide Synthases; D054460:rho-Associated Kinases