Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

Journal Article · Wed Apr 01 04:00:00 EDT 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.01.008· OSTI ID:21182769

Yamada, Shigeyuki; Xiuquan, Zhang; Kadono, Toshie; Matsuoka, Nobuhiro ^[1]; Rollins, Douglas ^[2]; Badger, Troy ^[1]; Rodesch, Christopher K ^[3]

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1. Cardiology Division, University of Utah, Health Sciences Center, 50 N Medical Dr, Salt Lake City, UT 84132 (United States)
2. Center for Human Toxicology, Department of Pharmacy and Toxicology, University of Utah, Salt Lake City, UT (United States)
3. Imaging Core Facility, University of Utah, Salt Lake City, UT (United States)

Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca{sup 2+}]{sub i} was measured by flow cytometry using fluo-3. Mitochondrial [Ca{sup 2+}] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca{sup 2+} uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca{sup 2+}]{sub i} in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca{sup 2+}]{sub i} during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca{sup 2+}]{sub i} during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold.

• OSTI ID: 21182769
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 236; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CALCIUM
CALCIUM IONS
CARBON NITRIDES
CYANIDES
FLUORESCENCE
GLUCOSE
HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY
ISCHEMIA
MICE
MITOCHONDRIA
NICOTINE
OXIDATION
RABBITS
TIRON
TOBACCO SMOKES
TOXICITY