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 MWCNT would exacerbate cardiac ischemia/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 conclude that instillation of MWCNT promoted cardiac injury by depressing coronary flow, invoking vasoconstrictive mechanisms involving ET-1, cyclooxygenase, thromboxane, and Rho-kinase.

Monocyte adhesion induced by multi-walled carbon nanotubes and palmitic acid in endothelial cells and alveolar–endothelial co-cultures

“…Oxidative stress is considered to be an important mechanism of action for carbon nanotube-mediated health effects (Shvedova et al, 2012). Airway exposure to MWCNTs in animals have shown impairment of endothelium-dependent vasodilation in coronary arteries (Stapleton et al, 2012), accelerated plaque progression in aorta (Cao et al, 2014), and exacerbated myocardial infarction after ischemia/reperfusion injury (Thompson et al, 2014;Urankar et al, 2012). In vitro model systems have shown that MWCNT exposure can induce the production of reactive oxygen species (ROS) and the expression of adhesion molecules in cultured endothelial cells (Cao et al, 2014;Pacurari et al, 2011;Vidanapathirana et al, 2012).…”

Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver

“…A relaxation response of >50% loss of the serotonin stress was considered acceptable endothelial integrity. Segments were washed every 10 minutes with fresh PSS for 30 minutes and subject to pharmacologic assessments [19]. Paired LAD segments were subjected to cumulative concentrations of serotonin (10 nM–3.0 μM).…”

New and revisited approaches to preserving the reperfused myocardium

“…Nanoparticles have also been developed to reduce cardiac mitochondrial injury 146,147 , although the nanoparticle vector might be more important for enhancing cellular uptake in damaged cells than for mitochondrial localization per se . However, cardiac toxicity has been observed with several types of nanoparticles 148,149 , indicating that more research is needed to develop these agents. Continued investigation into the safety and efficacy of vectors that deliver cargo to mitochondria is an exciting area for cardioprotective therapies.…”