Abstract
Purpose
The authors examined the cardioprotective effect of landiolol, an ultra short-acting, highly selective β1-blocker, and its role in cardiac work, antioxidative effect, and sarcoplasmic reticulum (SR) function in hearts subjected to ischemia-reperfusion.
Methods
Isolated guinea pig hearts were subjected to ischemia-reperfusion by stopping the perfusion for 45 min and reperfusing. Before the ischemia, hearts were treated with landiolol (20, 100, or 500 µM) for 15 min (LAN group). In another set of experiments, before ischemia, hearts were washed out for 15 min after treatment with landiolol (WO group). In other hearts, the tissue concentration of malondialdehyde was measured after reperfusion. We also examined the phosphorylation of phospholamban at Ser16 and Thr17residues to evaluate the SR function.
Results
After 90 min of reperfusion, left ventricular pressure (LVP) was restored significantly in the LAN-500 µM group regardless of heart rate. However, the improvement in recovery in LVP disappeared in the WO group. The tissue malondialdehyde levels were decreased in the LAN group compared with those in the control group. In the control group, the phosphorylation of phospholamban at Ser16 and Thr17 residues was markedly increased after reperfusion. Landiolol at 500 µM suppressed the increase of phosphorylation at Ser16 residues.
Conclusion
The present study demonstrated that landiolol had a lipid peroxidation-reducing effect and suppressed the increase in phospholamban phosphorylation at the Ser16 residue in hearts subjected to ischemia-reperfusion. These findings indicate that landiolol may have an anti-ischemic effect, via an antioxidant effect and/or via preserving SR function during the ischemic period.
Similar content being viewed by others
References
S Iguchi H Iwamura M Nishizaki A Hayashi K Senokuchi K Kobayashi K Sakaki K Hachiya Y Ichioka M Kawamura (1992) ArticleTitleDevelopment of a highly cardioselective ultra short-acting beta-blocker, ONO-1101 Chem Pharm Bull 40 1462–1469 Occurrence Handle1356643 Occurrence Handle1:CAS:528:DyaK38Xmtleqt7w%3D
S Kurosawa N Kanaya Y Niiyama M Nakayama S Fujita A Namiki (2003) ArticleTitleLandiolol, esmolol and propranolol protect from ischemia/reperfusion injury in isolated guinea pig hearts Can J Anaesth 50 489–494 Occurrence Handle12734159 Occurrence Handle10.1007/BF03021062
GJ Gross JD Buch DC Warltier HF Hardman (1982) ArticleTitleRole of autoregulation in the beneficial action of propranolol on ischemic blood flow distribution and stenosis severity in the canine myocardium J Pharmacol Exp Ther 222 635–640 Occurrence Handle7108768 Occurrence Handle1:CAS:528:DyaL38XlslCktb4%3D
J Imagawa GF Baxter DM Yellon (1998) ArticleTitleMyocardial protection afforded by nicorandil and ischemic preconditioning in a rabbit infarct model in vivo J Cardiovasc Pharmacol 31 74–79 Occurrence Handle9456280 Occurrence Handle10.1097/00005344-199801000-00011 Occurrence Handle1:CAS:528:DyaK1cXjtVyltQ%3D%3D
JR Kersten TJ Schmeling PS Pagel GJ Gross DC Warltier (1997) ArticleTitleIsoflurane mimics ischemic preconditioning via activation of KATP channels: reduction of myocardial infarct size with an acute memory phase Anesthesiology 87 361–370 Occurrence Handle9286901 Occurrence Handle10.1097/00000542-199708000-00024 Occurrence Handle1:CAS:528:DyaK2sXlvFejtbg%3D
IT Mak WB Weglicki (1988) ArticleTitleProtection by beta-blocking agents against free-radical mediated sarcolemmal lipid peroxidation Circ Res 63 262–266 Occurrence Handle2898307 Occurrence Handle1:CAS:528:DyaL1cXks1KltL8%3D
E Roth B Torok (1991) ArticleTitleEffect of the ultrashort-acting beta-blocker Brevibloc on free-radical-mediated injuries during the early reperfusion state Basic Res Cardiol 86 422–433 Occurrence Handle1685083 Occurrence Handle10.1007/BF02190710 Occurrence Handle1:STN:280:DyaK387hsl2msg%3D%3D
IT Mak CM Arroyo WB Weglicki (1989) ArticleTitleInhibition of sarcolemmal carbon-centered free radical formation by propranolol Circ Res 65 1151–1156 Occurrence Handle2551530 Occurrence Handle1:CAS:528:DyaL1MXmtVyksrk%3D
RM Temsah C Dyck T Netticadan D Chapman V Elimban NS Dhalla (2000) ArticleTitleEffect of β-adrenoceptor blockers on sarcoplasmic reticular function and gene expression in the ischemic-reperfused heart J Pharmacol Exp Ther 293 15–23 Occurrence Handle10734148 Occurrence Handle1:CAS:528:DC%2BD3cXkvFGht7w%3D
T Suzuki JH Wang (1986) ArticleTitleStimulation of bovine cardiac sarcoplasmic reticulum Ca2+ pump and blocking of phospholamban phosphorylation and dephosphorylation by a phospholamban monoclonal antibody J Biol Chem 261 7018–7023 Occurrence Handle2939076 Occurrence Handle1:CAS:528:DyaL28XktVagsL4%3D
M Tada M Yamada M Kodama M Inui F Ohomori (1986) ArticleTitleCalcium transport by cardiac sarcoplasmic reticulum and phosphorylation of phospholamban Mol Cell Biochem 46 73–95
Y Nakae S Fujita A Namiki (2001) ArticleTitleIsoproterenol enhances myofilament Ca2+ sensitivity during hypothermia in isolated guinea pig beating hearts Anesth Analg 93 846–852 Occurrence Handle11574344 Occurrence Handle10.1097/00000539-200110000-00009 Occurrence Handle1:CAS:528:DC%2BD3MXnslKmu7g%3D
H Estebauer RJ Schaur H Zollner (1991) ArticleTitleChemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes Free Radic Biol Med 11 81–128 Occurrence Handle10.1016/0891-5849(91)90192-6
BK Podesser S Schwazacher W Zwoelfer TM Binder E Wolner R Seitelberger (1995) ArticleTitleComparison of perioperative myocardial protection with nifedipine versus nifedipine and metoprolol in patients undergoing elective coronary artery bypass grafting J Thorac Cardiovasc Surg 110 1461–1469 Occurrence Handle7475198 Occurrence Handle10.1016/S0022-5223(95)70069-2 Occurrence Handle1:STN:280:DyaK28%2FnsVeqtA%3D%3D
S Takeo H Yamada K Tanonaka M Hayashi N Sunagawa (1990) ArticleTitlePossible involvement of membrane-stabilizing action in beneficial effect of beta adrenoceptor blocking agents on hypoxic and posthypoxic myocardium J Pharmacol Exp Ther 254 847–856 Occurrence Handle1975623 Occurrence Handle1:CAS:528:DyaK3cXlvVCnurY%3D
A Wallace B Layug I Tateo J Li M Hollenberg W Browner D Miller DT Mangano (1998) ArticleTitleProphylactic atenolol reduces postoperative myocardial ischemia. McSPI Research Group Anesthesiology 88 7–17 Occurrence Handle9447850 Occurrence Handle10.1097/00000542-199801000-00005 Occurrence Handle1:CAS:528:DyaK1cXnsFWhsg%3D%3D
K Ichihara Y Abiko (1983) ArticleTitleEffects of diltiazem and propranolol on irreversibility of ischemic cardiac function and metabolism in the isolated perfused rat heart J Cardiovasc Pharmacol 5 745–751 Occurrence Handle6195460 Occurrence Handle10.1097/00005344-198309000-00007 Occurrence Handle1:CAS:528:DyaL3sXmtVGrsbk%3D
CE Murry RB Jennings KA Reimer (1986) ArticleTitlePreconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium Circulation 74 1124–1136 Occurrence Handle3769170 Occurrence Handle1:STN:280:DyaL2s%2FivVKnuw%3D%3D
RA Kloner K Przyklenk P Whittaker (1989) ArticleTitleDeleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues Circulation 80 1115–1127 Occurrence Handle2553296 Occurrence Handle1:CAS:528:DyaK3cXntFKksA%3D%3D
ML Hess NH Manson (1984) ArticleTitleMolecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury J Mol Cell Cardiol 16 969–985 Occurrence Handle6394765 Occurrence Handle10.1016/S0022-2828(84)80011-5 Occurrence Handle1:CAS:528:DyaL2MXns1Khsw%3D%3D
H Nakaya N Tohse M Kanno (1987) ArticleTitleElectrophysiological derangements induced by lipid peroxidation in cardiac tissue Am J Physiol 253 H1089–1097 Occurrence Handle3688253 Occurrence Handle1:CAS:528:DyaL1cXpt1CrsA%3D%3D
S Kalaycioglu V Sinci Y Imren E Öz (1999) ArticleTitleMetoprolol prevents ischemia-reperfusion injury by reducing lipid peroxidation Jpn Circ J 63 718–721 Occurrence Handle10496488 Occurrence Handle10.1253/jcj.63.718 Occurrence Handle1:CAS:528:DyaK1MXmtFGhu7Y%3D
PA Grace (1994) ArticleTitleIschemia-reperfusion injury Br J Surg 81 637–647 Occurrence Handle8044536 Occurrence Handle10.1002/bjs.1800810504 Occurrence Handle1:STN:280:DyaK2czhvFOqtw%3D%3D
L Vittone C Mundiña-Weilenmann M Said P Ferrero A Mattiazzi (2002) ArticleTitleTime course and mechanisms of phosphorylation of phospholamban residues in ischemia-reperfused rat hearts. Dissociation of phospholamban phosphorylation pathways J Mol Cell Cardiol 34 39–50 Occurrence Handle11812163 Occurrence Handle10.1006/jmcc.2001.1488 Occurrence Handle1:CAS:528:DC%2BD38XntlOhug%3D%3D
JWM Bassani W Yuan DM Bers (1995) ArticleTitleFractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac myocytes Am J Physiol Cell Physiol 268 C1313–1319 Occurrence Handle1:CAS:528:DyaK2MXlvVajtbY%3D
N Sperelakis Z Xiong G Haddad H Masuda (1994) ArticleTitleRegulation of slow calcium channels of myocardial cells and vascular smooth muscle cells by cyclic nucleotides and phosphorylation Mol Cell Biochem 140 103–117 Occurrence Handle7898483 Occurrence Handle10.1007/BF00926749 Occurrence Handle1:CAS:528:DyaK2MXjtVyjs7o%3D
S Takagi Y Kihara T Mitsuiye Z Wang S Sasayama (1997) ArticleTitleEffects of tilisolol, a nonselective beta-adrenergic blocker, on the membrane currents of isolated guinea pig ventricular myocytes J Cardiovasc Pharmacol 29 593–598 Occurrence Handle9213200 Occurrence Handle10.1097/00005344-199705000-00005 Occurrence Handle1:CAS:528:DyaK2sXktl2gsbs%3D
K Muraki H Nakagawa N Nagano S Henmi H Kawasumi T Nakanishi K Imaizumi T Tokuno K Atsuki Y Imaizumi M Watanabe (1996) ArticleTitleEffects of ONO-1101, a novel beta-antagonist, on action potential and membrane currents in cardiac muscle J Pharmacol Exp Ther 278 555–563 Occurrence Handle8768704 Occurrence Handle1:CAS:528:DyaK28XkvFKjs7s%3D
Author information
Authors and Affiliations
Additional information
Presented in part at the annual meeting of the American Society of Anesthesiologists, Las Vegas, Nevada, October 23–27, 2004.
About this article
Cite this article
Kimura-Kurosawa, S., Kanaya, N., Kamada, N. et al. Cardioprotective effect and mechanism of action of landiolol on the ischemic reperfused heart. J Anesth 21, 480–489 (2007). https://doi.org/10.1007/s00540-007-0558-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00540-007-0558-2