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BY-NC-ND 3.0 license Open Access Published by De Gruyter Open Access December 16, 2010

Light-dark dependence of electrocardiographic changes during asphyxia and reoxygenation in a rat model

Ivana Bačová, Pavol Švorc, Martin Kundrík and Benjamin Fulton
From the journal Open Medicine


The aim of this study was to evaluate the effect of ventilation on electrocardiographic time intervals as a function of the light-dark (LD) cycle in an in vivo rat model. RR, PQ, QT and QTc intervals were measured in female Wistar rats anaesthetized with both ketamine and xylazine (100 mg/15 mg/kg, i.m., open chest experiments) after adaptation to the LD cycle (12:12h) for 4 weeks. Electrocardiograms (ECG) were recorded before surgical interventions; after tracheotomy, and thoracotomy, and 5 minutes of stabilization with artificial ventilation; 30, 60, 90 and 120 seconds after the onset of apnoea; and after 5, 10, 15, and 20 minutes of artificial reoxygenation. Time intervals in intact animals showed significant LD differences, except in the QT interval. The initial significant (p<0,001) LD differences in PQ interval and loss of dependence on LD cycle in the QT interval were preserved during short-term apnoea-induced asphyxia (30–60 sec) In contrast, long-term asphyxia (90–120 sec) eliminated LD dependence in the PQ interval, but significant LD differences were shown in the QT interval. Apnoea completely abolished LD differences in the RR interval. Reoxygenation restored the PQ and QT intervals to the pre-asphyxic LD differences, but with the RR intervals, the LD differences were eliminated. We have concluded that myocardial vulnerability is dependent on the LD cycle and on changes of pulmonary ventilation.

[1] Henry R., Casto R., Printz M.P., Diurnal cardiovascular patterns in spontaneously hypertensive and Wistar-Kyoto rats, Hypertension., 1990, 16, 422–428 10.1161/01.HYP.16.4.422Search in Google Scholar

[2] Portaluppi F., Hermida R.C., Circadian rhythms in cardiac arrhythmias and opportunities for their chronotherapy, Chronobiol., 2007, 59, 9–10 10.1016/j.addr.2006.10.011Search in Google Scholar

[3] Waterhouse J., Witte K., Huser L., Nevill A., Atkinson G., Reilly T., Lemmer B., Sensitivity of heart rate and blood pressure to spontaneous activity in transgenic rats, Biol. Rhythm. Res., 2000, 31, 146–159;1-U;FT14610.1076/0929-1016(200004)31:2;1-U;FT146Search in Google Scholar

[4] Zhang B.L., Sannajust F., Diurnal rhythmsn of blood pressure, heart rate and locomotor activity in adult and old male Wistar rats, Physiol. Behav., 2000, 70, 375–380 in Google Scholar

[5] Švorc P., Beňačka R., Petrášová D., Effect of systemic hypoxia and reoxygenation on electrical stability of the rat myocardium: Chronophysiological study, Physiol. Res., 2005, 54, 319–325 10.33549/physiolres.930604Search in Google Scholar

[6] Steinbigler P., Haberl R., Jilge G., Steinbeck G., Circadian variability of late potential analysis in Holter electrocardiograms, PACE., 1999, 22, 1448–1456 10.1111/j.1540-8159.1999.tb00348.xSearch in Google Scholar

[7] Fries R., Konig J., Schonecke O., Schafers H.J., Bohm M., Daily activities and circadian variation of ventricular tachyarrhythmias in patients with implanted defibrilator, Deut. Med. Wochenschr., 2001, 126, 1385–1390 in Google Scholar

[8] Taneda K., Aizawa Y., Absence of a morning peak in ventricular tachycardia and fibrillation events in nonischemic heart disease: analysis of therapies by implantable cardioverter defibrillators, PACE., 2001, 24, 1602–1606 10.1046/j.1460-9592.2001.01602.xSearch in Google Scholar

[9] Fichter J., Bauer D., Arampatzis S., Fries R., Heisel A., Sybrecht G.W., Sleep-related breathing disorders are associated with ventricular arrhythmias in patients with an implantable cardioverter-defibrilator, Chest., 2002, 122(2), 398–399 10.1378/chest.122.2.558Search in Google Scholar

[10] Mehra R., Benjamin E.J., Shahar E., Gottlieb D.J., Nawabit R., Kirchner H.L., Sahadevan J., Redline S., Sleep Heart Health Study: Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study, Am. J. Respir. Crit. Care. Med., 2006, 173(8), 910–916 in Google Scholar

[11] Arias M.A., Sanches A.M., Obstructive sleep apnea and its relationship to cardiac arrhythmias, J. Cardiovasc. Electr., 2007, 18(9), 1006–1014 in Google Scholar

[12] Patel N.P., Rosen I., Sleep apnea and cardiovascular disease: association, causation and implication, Clin. Pul. Med., 2007, 14(4), 225–231 in Google Scholar

[13] Daccarett M., Segerson N.M., Hamdan A.L., Hill B., Hamdan M.H., Relation of daytime bradyarrhythmias with high risk features of sleep apnea, Am. J. Cardiol., 2008, 101(8), 1147–1150 10.1016/j.amjcard.2007.11.068Search in Google Scholar PubMed

[14] Thorman J., Schlepper M., Kramer W., Diurnal changes and reproducibility of corrected sinus node recovery time, Cathet. Cardiovasc. Diagn., 1983, 9, 439–451 in Google Scholar PubMed

[15] Mitsuoka T., Ueyama C., Matsumoto Y., Hashiba K., Influences of autonomic changes on the sinus node recovery time in patients with sick sinus syndrome, Jpn. Heart. J., 1990, 31, 645–660 10.1536/ihj.31.645Search in Google Scholar PubMed

[16] Cinca J., Moya A., Bardaji A., Rius J., Soler J., Circadian variations of electrical properties of the heart. Ann. NY. Acad. Sci., 1990, 601, 222–233 in Google Scholar PubMed

[17] Kujaník Š., Sninčák M., Vokál J., Podhradský J., Kovaľ J., Periodicity of arrhythmias in healthy elderly men at the moderate altitude, Physiol. Res., 2000, 49, 285–287 Search in Google Scholar

[18] Štimmelová J., Švorc P., Bračoková I., ECG parameters changes in the dependence on the alteration of light and dark in female Wistar rats, Physiol. Res., 2002, 51, 43 Search in Google Scholar

[19] Štimmelová J., Švorc P., Bračoková I., Richtáriková Z., Hypoventilation and amplitude changes of ECG in the dependence on the light/dark cycle in female Wistar rats, Physiol. Res., 2004, 53, 38 Search in Google Scholar

[20] Graf A.V., Maslova M.V., Maklakova A.S., Sokolova N.A., Kudryashova N.Y., Krushinskaya Y.V., Gencharenko E.N., Neverova M.E., Fidelina O.V., Effect of hypoxia during early organogenesis on cardiac activity and noradrenergic regulation in the postnatal period, Bull. Exp. Biol. Med., 2006, 142(5), 543–555 in Google Scholar PubMed

[21] Overgaard J., Gesser H., Wang T., Tribute To P.L.Lutz., Cardiac performance and cardiovascular regulation during anoxia/hypoxia in freshwater turtles, J. Exp. Biol., 2007, 15, 1687–1699 in Google Scholar PubMed

[22] Švorc P., Bračoková I., Podlubný I., Relation of ventricular fibrillation threshold to heart rate during normal ventilation and hypoventilation in female Wistar rats: a chronophysiological study, Physiol. Res., 2000, 49, 711–719 Search in Google Scholar

[23] Bishop B., Silva G., Krasney L., Salloum A., Roberts A., Nakano H., Shucard D., Rifkin D., Farkas G., Circadian rhythms of body temperature and activity levels during 63 h of hypoxia in the rat, Am. J. Physiol., 2000, 279, 1378–1385 10.1152/ajpregu.2000.279.4.R1378Search in Google Scholar PubMed

[24] Jarsky T.M., Stephenson R., Effect of hypoxia and hypercapnia on circadian rhythms in the golden hamster, J. Appl. Physiol., 2000, 89, 2130–2138 10.1152/jappl.2000.89.6.2130Search in Google Scholar PubMed

[25] Kujaník Š., Wilk P., Tomčová D., Changes in the vulnerable period of the rat myocardium during hypoxia, hyperventilation and heart failure, Physiol Bohemoslov., 1984, 33, 470–480 Search in Google Scholar

[26] Tomori Z., Beňačka R., Tkáčová R., Donič V., Disorders of heart rhythm and ECG changes in experimental apnoeic states, Bratisl. Lek. Listy., 1997, 98, 531–538 Search in Google Scholar

[27] Tomori Z., Beňačka R., Donič V., Jakuš J., Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation, Monaldi. Arch. Chest. Dis., 2000, 55, 398–403 Search in Google Scholar

[28] Surawicz B., Ventricular fibrillation and dispersion of repolarization, J. Cardiovasc. Electrophysiol., 1997, 8, 1009–1012 in Google Scholar PubMed

[29] Han J., Moe G.K., Nonuniform recovery of excitability in ventricular muscle, Circ. Res., 1964, 14, 44–60 10.1161/01.RES.14.1.44Search in Google Scholar

[30] Han J., deJalon G. P., Moe G. K., Adrenergic effects on ventricular vulnerability, Circ. Res., 1964, 14, 516–524 10.1161/01.RES.14.6.516Search in Google Scholar

[31] Han J., deJalon G. P., Moe G.K., Fibrillation threshold of premature ventricular responses, Circ. Res., 1966, 18, 18–25 10.1161/01.RES.18.1.18Search in Google Scholar

[32] Ohoi I., Takeo S., Involvement of superoxide and nitric oxide in the genesis of reperfusion arrhythmias in rats, Eur. J. Pharmacol., 1996, 306, 123–131 in Google Scholar

[33] Tanno K., Kobayashi Y., Adachi T., Ryu S., Asano T., Obara C., Baba T., Katagiri T., Onset heart rate and microvolt t-wave alternans during atrial pacing, Am. J. Cardiol., 2000, 86, 877–880 in Google Scholar

[34] Prudian F., Gantenbein M., Pelissier A.L., Attolini L., Bruguerolle B., Daily rhythms of heart rate temperature and locomor activity are modified by anaesthetics in rats: a telemetric study, NS Arch. Pharmacol., 1997, 355, 774–778 in Google Scholar

[35] Pelissier A.L., Gantenbein M., Prudian F., Bruguerolle B., Influence of general anaesthetics on circadian rhythms of heart rate, body temperature and locomotor activity in rats, Sci. Tech. Anim. Lab., 1998, 23, 91–98 Search in Google Scholar

[36] Gantenbein M., Attolini L., Bruguerolle B., Nicorandil affect diurnal rhythms of body temperature, heart rate and locomotor activity in rats, Eur. J. Pharmacol., 1998, 346, 125–130 in Google Scholar

[37] Hsu W. H., Bellin S.I., Dellmann H. D., Habil V., Hanson C. E., Xylasine-ketamine-induced anaesthesia in rats and its antagonism by yohimbine, Jamma., 1986, 189, 1040–1043 Search in Google Scholar

[38] Cope D. K., Impastato W. K., Cohen M. V., Downey J. M., Volatile anaesthetics protect the ischemic rabbit myocardium from infarction, Anaesthesiology, 1998, 86, 699–709 in Google Scholar PubMed

[39] Morita Y., Murakami T., Iwase T., Nagai K., Nawada R., Kouchi I, Akao M., Sasayama S., KATP channels contribute to the cardioprotection of preconditioning independent of anaesthesia in rabbit heart, J. Mol. Cell. Cardiol., 1997, 29, 1267–1276 in Google Scholar PubMed

[40] Švorc P., Bračoková I., Bačová I., Švorcová E., Acid-base balance and artifitial controlled ventilation in Wistar rats, Chronobiological view, Abstract book from The third International Congress of Applied Chronobiology and Chronomedicine, Akko Israel, 2009, 67 Search in Google Scholar

[41] Carmeliet E., The slow inward current: nonvoltage-clamp studies. In: The slow invard current and cardiac arrhythmias. (Eds.) E. Anries, R. Stroobandt, Elsevier Science Publishers B. V., 1986, 9–20 Search in Google Scholar

[42] Amitzur G., Schoels W., Visokovsky A., Lev-ran V., Novikov I., Mueller M., Kraft P., Kaplinsky E., Eldar M., Role of sodium channels in ventricular fibrillation: A study in nonischemic isolated hearts, J. Cardiovasc. Pharmacol., 2000, 36, 785–793 in Google Scholar PubMed

[43] Gunes Y., Tuncer M., Guntekin U., Akdag S., Gumrukcuoglu H.A, Lacko f diurnal variation of P-wave and QT dispersions in patients with heart failure, Pace., 2008, 31(8), 974–978 10.1111/j.1540-8159.2008.01124.xSearch in Google Scholar

[44] Froldi G., Pandolfo L., Chinellato A., Ragazzi E., Caparrotta L., Fassina G., Protection of atrial function in hypoxia by high potassium concentration, Gen. Pharmacol., 1994, 25, 401–407 10.1016/0306-3623(94)90187-2Search in Google Scholar

[45] Cutler M.J., Hamdam A.L., Hamdam M.H., Ramaswamy K., Smith M.L, Sleep apnea: from the nose to the heart, J. Am. Board. Fam. Pract., 2002, 15(2), 128–141 Search in Google Scholar

[46] Yamashita J., Nomura M., Uehara K., Nakaya Y., Uemura E., Iga A., Sawa Y., Nishikado A., Saito K., Ito S., Influence of sleep apnea on autonomic nervous activity and QT dispersion in patients with essential hypertension and old myocardial infarction, Electrocardiol., 2004, 37(1), 31–40 in Google Scholar

[47] Bounhoure J.P., Galinier M., Didier A., Leophonte P., Sleep apnea syndromes and cardiovascular disease, Bull. Acad. Natl. Med., 2005, 189(3), 445–459 10.1016/S0001-4079(19)33558-7Search in Google Scholar

[48] Dunai A., Musci I., Juhasz J., Novak M., Obstructive sleep apnea andcardiovascular disease, Orv. Hetil., 2006, 147(48), 2303–2311 Search in Google Scholar

[49] Bayram N.A., Diker E., Obstructive sleep apnea syndrome and cardiac arrhythmias, Turk. Kardiyol. Dern. Ars., 2008, 36(1), 44–50 Search in Google Scholar

[50] Grešová S., Tomori Z., Kurpas M., Marossy A., Vrbenska A., Kundrik M., Donic V., Blood pressure increase detected by ambulatory monitoring cerrelates with hypoxemia reflecting sleep apnea severity, Cent. Eur. J. Med., 2009, 4, 222–232 in Google Scholar

[51] Mortola J.P., Hypoxia and circadian patterns, Respir. Physiol. Neurobiol., 2007, 158(2–3), 274–279 in Google Scholar

[52] Nishimura M., Tanaka H., Homma N., Matsuzawa Y., Ionic mechanisms of the depression of automaticity and conduction in the rabbit atrioventricular node caused by hypoxia or metabolic inhibition and protective action of glucose and valine, Amer. J. Cardiol., 1989, 64, 24J–28J in Google Scholar

[53] Sawanobori T., Adaniya H., Yukisada H., Hiraoka M., Role for ATP-sensitive K+ channel in the development of A-V block during hypoxia, J. Mol. Cell. Cardiol., 1995, 27, 647–657 in Google Scholar

[54] Xu J., Wang L., Hurt C.M., Pelleg A., Endogenous adenosine does not activate ATP-sensitive pottasium channels in the hypoxic guinea pig ventricle in vivo, Circulation., 1994, 89, 1209–1216 10.1161/01.CIR.89.3.1209Search in Google Scholar

[55] Leone R., Jr., Merrill G. F., Inhibition of adenosine deaminase and administration of adenosine increase hypoxia induced ventricular ectopy, Basic. Res. Cardiol., 1995, 90, 234–239 in Google Scholar PubMed

[56] Perchenet L., Kreher P., Mechanical and electrophysiological effects of preconditioning in isolated ischemic/reperfused rat heart, J. Cardiovasc. Pharmacol., 1995, 26, 831–840 in Google Scholar PubMed

[57] Bugge E., Gamst T.M., Hegstad A.C., Andreasen T., Ytrehus K., Mepacrine protects the isolated rat heart during hypoxia and reoxygenation - but not by inhibition of phospholipase A2, Basic. Res. Cardiol., 1997, 92, 17–24 10.1007/BF00803753Search in Google Scholar PubMed

[58] Griffiths E.J., Ocampo C.J., Savage J.S., Stern M.D., Silverman H.S., Protective effects of low and high doses of cyclosporin A against reoxygenation injury in isolated rat cardiomyocytes are associated with differrential effects on mitochondrial calcium levels, Cell. Calcium., 2000, 27, 87–95 in Google Scholar PubMed

[59] Mukai M., Terada H., Sugiyama S., Satoh H., Hayashi H., Effects of a selective inhibitor of Na+/Ca2+ exchange, KB-R7943, on reoxygenation - induced injuries in Guinea pig papillary muscles, J. Cardiovasc. Pharmacol., 2000, 35, 121–128 in Google Scholar PubMed

[60] Lubbe W.F., Bricknell O.L., Marzagao C., Ventricular fibrillation threshold and vulnerable period in the isolated perfused rat heart, Cardiovasc. Res., 1975, 9, 613–620 in Google Scholar PubMed

Published Online: 2010-12-16
Published in Print: 2011-2-1

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