Efectos del CO, Pb++, y SO2 en el canal de calcio tipo L y potencial de acción en miocitos auriculares humanos. Estudio en silico
Resumen
La exposición a contaminantes atmosféricos, como el monóxido de carbono (CO), plomo (Pb++) y dióxido de azufre (SO2), promueve la aparición de enfermedades cardiovasculares. Estudios experimentales han demostrado que el CO, el Pb++ y el SO2 bloquean los canales de calcio tipo L, disminuyendo la corriente de calcio (ICaL) y la duración del potencial de acción (APD), favoreciendo el inicio de arritmias auriculares. El objetivo es estudiar los efectos del CO, Pb++ y SO2 a diferentes concentraciones, sobre ICaL y el potencial de acción auricular mediante simulación computacional. Para ello, se desarrollaron modelos matemáticos de los efectos de los contaminantes atmosféricos sobre el canal de calcio auricular tipo L y se incorporaron en un modelo matemático de células auriculares humanas. Los resultados sugieren que el CO, el Pb++ y el SO2, bloquean la corriente ICaL en una fracción que aumenta a medida que aumenta, la concentración, generando un acortamiento del APD. Estos resultados son consistentes con estudios experimentales. El efecto combinado de los tres contaminantes atmosféricos generó un acortamiento del APD, lo cual es considerado un efecto pro-arrítmico.
Referencias bibliográficas
OECD, The Cost of Air Pollution. OECD Publishing, 2014.
C. R. Henry, “Myocardial Injury and Long-term Mortality Following Moderate to Severe Carbon Monoxide Poisoning,” JAMA, vol. 295, no. 4, p. 398, Jan. 2006.
U.S. EPA, “Integrated Science Assessment (ISA) for Lead (Final Report, Jul 2013),” Washington, 2013.
W. H. Organization, “Lead poisoning and health,” 2016. [Online]. Available: http://www.who.int/mediacentre/factsheets/fs379/en/.
United States Environmental Protection Agency, “Air Quality Planning and Stand-ards.,” 2016. [Online]. Available: https://www3.epa.gov/airquality/.
A. Bhatnagar, “Cardiovascular pathophysiol-ogy of environmental pollutants,” Am. J. Physiol. Heart Circ. Physiol., vol. 286, no. 2, pp. H479--H485, 2004.
S. J. Kopp, J. C. Baker, L. S. D’Agrosa, and P. L. Hawley, “Simultaneous recording of his bundle electrogram, electrocardiogram, and systolic tension from intact modified Langen-dorff rat heart preparations I: Effects of per-fusion time, cadmium, and lead,” Toxicol. Appl. Pharmacol., vol. 46, no. 2, pp. 475–487, Nov. 1978.
R. C. Prentice and S. J. Kopp, “Cardiotoxicity of lead at various perfusate calcium concen-trations: Functional and metabolic responses of the perfused rat heart,” Toxicol. Appl. Pharmacol., vol. 81, pp. 491–501, 1985.
M. A. Ansari, Z. H. Maayah, S. A. Bakheet, A. O. El-Kadi, and H. Korashy, “The role of aryl hydrocarbon receptor signaling pathway in cardiotoxicity of acute lead intoxication in vi-vo and in vitro rat model,” Toxicology, vol. 306, pp. 40–49, 2013.
E. Samoli, G. Touloumi, J. Schwartz, H. R. Anderson, C. Schindler, B. Forsberg, M. A. Vigotti, J. Vonk, M. Kosnik, J. Skorkovsky, and K. Katsouyanni, “Short-Term Effects of Carbon Monoxide on Mortality: An Analysis within the APHEA Project,” Environ. Health Perspect., vol. 115, no. 11, pp. 1578–1583, Nov. 2007.
R. Dales, “Ambient Carbon Monoxide May Influence Heart Rate Variability in Subjects With Coronary Artery Disease,” J. Occup. Environ. Med., vol. 46, no. 12, pp. 1217–1221, 2004.
X. Qin, Z. Qian, M. G. Vaughn, E. Trevathan, B. Emo, G. Paul, W. Ren, Y. Hao, and G. Dong, “Gender-specific differences of interac-tion between obesity and air pollution on stroke and cardiovascular diseases in Chinese adults from a high pollution range area: A large population based cross sectional study,” Sci. Total Environ., vol. 529, pp. 243–248, Oct. 2015.
B. Z. Simkhovich, M. T. Kleinman, and R. A. Kloner, “Air Pollution and Cardiovascular In-jury. Epidemiology, Toxicology, and Mecha-nisms,” Journal of the American College of Cardiology, vol. 52, no. 9. pp. 719–726, 2008.
J. Bernal, J. H. Lee, L. L. Cribbs, and E. Perez-Reyes, “Full reversal of Pb++ block of L-type Ca++ channels requires treatment with heavy metal antidotes.,” J. Pharmacol. Exp. Ther., vol. 282, no. 1, pp. 172–80, Jul. 1997.
S. Dinanian, C. Boixel, C. Juin, J.-S. Hulot, A. Coulombe, C. Rücker-Martin, N. Bonnet, B. Le Grand, M. Slama, J.-J. Mercadier, and S. N. Hatem, “Downregulation of the calcium current in human right atrial myocytes from patients in sinus rhythm but with a high risk of atrial fibrillation,” Eur. Heart J., vol. 29, no. 9, pp. 1190–1197, 2008.
D. V Abramochkin, N. N. Haertdinov, M. V Porokhnya, A. L. Zefirov, and G. F. Sitdikova, “Carbon monoxide affects electrical and con-tractile activity of rat myocardium,” J. Bio-med. Sci., vol. 18, no. 1, p. 40, 2011.
R.-Y. Zhang, J.-B. Du, Y. Sun, S. Chen, H.-J. Tsai, L. Yuan, L. Li, C.-S. Tang, and H.-F. Jin, “Sulfur dioxide derivatives depress L-type calcium channel in rat cardiomyocytes,” Clin. Exp. Pharmacol. & Physiol., vol. 38, no. 7, pp. 416–422, Jul. 2011.
A. Nie and Z. Meng, “Study of the interaction of sulfur dioxide derivative with cardiac sodi-um channel,” Biochim. Biophys. Acta - Biomembr., vol. 1718, no. 1–2, pp. 67–73, Dec. 2005.
M. Courtemanche, “Ionic targets for drug therapy and atrial fibrillation-induced electri-cal remodeling: insights from a mathematical model,” Cardiovasc. Res., vol. 42, no. 2, pp. 477–489, May 1999.
J. Kneller, R. Zou, E. J. Vigmond, Z. Wang, L. J. Leon, and S. Nattel, “Cholinergic atrial fi-brillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties.,” Circ. Res., vol. 90, no. 9, pp. E73--87, 2002.
J. L. Scragg, M. L. Dallas, J. a Wilkinson, G. Varadi, and C. Peers, “Carbon monoxide in-hibits L-type Ca2+ channels via redox modu-lation of key cysteine residues by mitochon-drial reactive oxygen species.,” J. Biol. Chem., vol. 283, no. 36, pp. 24412–24419, 2008.
L. Andre, J. Boissière, C. Reboul, R. Perrier, S. Zalvidea, G. Meyer, J. Thireau, S. Tanguy, P. Bideaux, M. Hayot, F. Boucher, P. Obert, O. Cazorla, and S. Richard, “Carbon monoxide pollution promotes cardiac remodeling and ventricular arrhythmia in healthy rats,” Am. J. Respir. Crit. Care Med., vol. 181, no. 6, pp. 587–595, Mar. 2010.
B. Trenor, K. Cardona, J. Saiz, S. Rajamani, L. Belardinelli, and W. R. Giles, “Carbon monoxide effects on human ventricle action potential assessed by mathematical simula-tions,” Front. Physiol., vol. 4, no. 282, pp. 1–11, 2013.
D. V Vassallo, E. C. Lebarch, C. M. Moreira, G. A. Wiggers, and I. Stefanon, “Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardi-um,” Brazilian J. Med. Biol. Res., vol. 41, no. 9, pp. 789–795, 2008.
Z. Parvin, J. Mahyar, F. Seyed Mohamamd, and M. Fereshteh, “The effect of lead (Pb2+) on electrophysiological properties of calcium currents in F77 neuron in Helix aspersa,” Physiol Pharmacol, vol. 4, no. 2, pp. 145–160, 2000.
S. Jeong, B. Park, J.-W. Lee, and J.-H. Lee, “Divalent metals differentially block cloned T-type calcium channels,” Neuroreport, vol. 14, no. 11, pp. 1537–1540, 2003.
K. A. Miller, D. S. Siscovick, L. Sheppard, K. Shepherd, J. H. Sullivan, G. L. Anderson, and J. D. Kaufman, “Long-Term Exposure to Air Pollution and Incidence of Cardiovascular Events in Women,” N. Engl. J. Med., vol. 356, no. 5, pp. 447–458, 2007.
R. D. Brook, B. Franklin, W. Cascio, Y. Hong, G. Howard, M. Lipsett, R. Luepker, M. Mit-tleman, J. Samet, S. C. Smith, and I. Tager, “Air pollution and cardiovascular disease: A statement for healthcare professionals from the expert panel on population and preven-tion science of the American Heart Associa-tion,” Circulation, vol. 109, no. 21. pp. 2655–2671, 2004.
M. M. Finkelstein, “Pollution-Related Mortal-ity and Educational Level,” JAMA J. Am. Med. Assoc., vol. 288, no. 7, pp. 830–830, Aug. 2002.
C. A. Pope, R. T. Burnett, M. J. Thun, E. E. Calle, D. Krewski, K. Ito, and G. D. Thurston, “Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution.,” JAMA, vol. 287, no. 9, pp. 1132–1141, 2002.
United Nations Environment Programme, Air Pollution: World’s Worst Environmental Health Risk. 2014.
M. S. Link, H. Luttmann-Gibson, J. Schwartz, M. A. Mittleman, B. Wessler, D. R. Gold, D. W. Dockery, and F. Laden, “Acute exposure to air pollution triggers atrial fibrillation,” J. Am. Coll. Cardiol., vol. 62, no. 9, pp. 816–825, 2013.
Descargas
