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.

Keywords::

• nanomaterials
• coronary resistance
• premature ventricular contractions
• endothelin-1
• cyclooxygenase

Acknowledgments

We would like to acknowledge Corrine Watson for help with isolated heart data collection and Alvin Tsang for help with isolated coronary data collection. We are thankful for the generous donation of Infasurf^™ surfactant from Dr. Walter Klein of ONY, Inc. and to Dr. Richard Czerw of NanoTechLabs, Inc. for furnishing the multi-walled carbon nanotubes used in this study. We thank Justin LaFavor and Achini Vidanapathirana for in-depth discussion of the results of isolated coronary experiments and critical review of early manuscript drafts. We would also like to thank Jillian Dawkins for reviewing the finalized version of this manuscript.