Skip to main content

Advertisement

SpringerLink
Log in

Randomized controlled trial of landiolol, a short-acting beta-1 adrenergic receptor blocker, illustrating changes in high-molecular weight adiponectin levels after elective percutaneous coronary intervention

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Adiponectin (APN) has cardioprotective properties and bisoprolol has been reported to increase myocardial APN expression and reduce myocardial damage. Administration of landiolol, which has a higher cardio-selectivity and shorter half-life than bisoprolol, during the percutaneous coronary intervention (PCI) may increase serum APN and high-molecular weight (HMW)-APN, an active form of APN, in patients with stable angina pectoris (SAP). We recruited 70 patients with SAP and randomized them to intravenous landiolol during PCI (N = 35) or control group (N = 35). The primary endpoint was serum APN and HMW-APN level 3 days after PCI. There was no difference in the primary endpoint between the landiolol and control groups (8.93 ± 5.24 vs. 10.18 ± 5.81 μg/mL, p = 0.35 and 3.36 ± 2.75 vs. 4.28 ± 3.13 μg/mL, p = 0.20) for APN and HMW-APN levels, respectively. APN and HMW-APN level were significantly decreased 1 day after PCI [−0.55 ± 0.92 μg/mL (9.87–9.32 μg/mL), p < 0.001 and −0.20 ± 0.45 μg/mL (3.89–3.69 μg/mL), p < 0.001, respectively]. Additionally, the absolute change in HMW-APN was significantly smaller in the landiolol group compared to the control group (−0.08 ± 0.27 vs. −0.31 ± 0.55 μg/mL, p = 0.031). Multiple linear regression analysis showed that use of landiolol was an independent predictor of change in HMW-APN (β = 0.276, p = 0.014). Serum APN and HMW-APN level 3 days after PCI were similar between patients treated with and without landiolol. APN and HMW-APN decreased 1 day after PCI in the SAP and landiolol mitigated decrease in HMW-APN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AV block:

Atrioventricular block

APN:

Adiponectin

CAD:

Coronary artery disease

eGFR:

Estimated glomerular filtration rate

HMW-APN:

High molecular weight adiponectin

PCI:

Percutaneous coronary intervention

SYNTAX:

SYNergy between PCI with TAXUS™ and Cardiac Surgery

SAP:

Stable angina pectoris

SD:

Standard deviation

SE:

Standard error

VT:

Ventricular tachycardia

References

  1. Morishima I, Sone T, Okumura K, Tsuboi H, Kondo J, Mukawa H, Matsui H, Toki Y, Ito T, Hayakawa T (2000) Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol 36(4):1202–1209

    Article  CAS  Google Scholar 

  2. Kiyokuni M, Konishi M, Sakamaki K, Kawashima C, Narikawa M, Doi H, Iwata K, Tomari S, Nakayama N, Komura N, Mitsuhashi T, Yano H, Sugano T, Ishigami T, Endo T, Ishikawa T, Yamanaka T, Kimura K (2016) Beneficial effect of early infusion of landiolol, a very short-acting beta-1 adrenergic receptor blocker, on reperfusion status in acute myocardial infarction. Int J Cardiol 221:321–326

    Article  Google Scholar 

  3. Iguchi S, Iwamura H, Nishizaki M, Hayashi A, Senokuchi K, Kobayashi K, Sakaki K, Hachiya K, Ichioka Y, Kawamura M (1992) Development of a highly cardioselective ultra short-acting beta-blocker, ONO-1101. Chem Pharm Bull (Tokyo) 40(6):1462–1469

    Article  CAS  Google Scholar 

  4. Park H, Otani H, Oishi C, Fujikawa M, Yamashita K, Okazaki T, Sato D, Ueyama T, Iwasaka J, Yamamoto Y, Iwasaka T (2011) Efficacy of intracoronary administration of a short-acting beta-blocker landiolol during reperfusion in pigs. Int J Cardiol 146(3):347–353

    Article  Google Scholar 

  5. Hagiwara S, Iwasaka H, Maeda H, Noguchi T (2009) Landiolol, an ultrashort-acting beta1-adrenoceptor antagonist, has protective effects in an LPS-induced systemic inflammation model. Shock 31(5):515–520

    Article  CAS  Google Scholar 

  6. Kimura-Kurosawa S, Kanaya N, Kamada N, Hirata N, Nakayama M, Namiki A (2007) Cardioprotective effect and mechanism of action of landiolol on the ischemic reperfused heart. J Anesth 21(4):480–489

    Article  Google Scholar 

  7. Zhang S, He B, Goldstein S, Ge J, Wang Z, Ruiz G (2011) Changes in adiponectin expression in acute myocardial infarction rats and the significance of bisoprolol intervention. Can J Physiol Pharmacol 89(2):109–115

    Article  CAS  Google Scholar 

  8. Achari AE, Jain SK (2017) Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int J Mol Sci 18(6):1321

    Article  Google Scholar 

  9. Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H, Imai Y, Nagai R, Kadowaki T (2006) Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care 29(6):1357–1362

    Article  CAS  Google Scholar 

  10. Liu G, Ding M, Chiuve SE, Rimm EB, Franks PW, Meigs JB, Hu FB, Sun Q (2016) Plasma levels of fatty acid-binding protein 4, retinol-binding protein 4, high-molecular-weight adiponectin, and cardiovascular mortality among men with type 2 diabetes: a 22-year prospective study. Arterioscler Thromb Vasc Biol 36(11):2259–2267

    Article  CAS  Google Scholar 

  11. Macheret F, Bartz TM, Djousse L, Ix JH, Mukamal KJ, Zieman SJ, Siscovick DS, Tracy RP, Heckbert SR, Psaty BM, Kizer JR (2015) Higher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults. Heart 101(17):1368–1374

    Article  CAS  Google Scholar 

  12. von Eynatten M, Humpert PM, Bluemm A, Lepper PM, Hamann A, Allolio B, Nawroth PP, Bierhaus A, Dugi KA (2008) High-molecular weight adiponectin is independently associated with the extent of coronary artery disease in men. Atherosclerosis 199(1):123–128

    Article  Google Scholar 

  13. Liang S, Li H, Shen X, Liu R (2019) Increased serum adiponectin predicts improved coronary flow and clinical outcomes in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention. J Clin Lab Anal 33(5):e22864

    Article  Google Scholar 

  14. Kalisz M, Baranowska B, Wolinska-Witort E, Maczewski M, Mackiewicz U, Tulacz D, Gora M, Martynska L, Bik W (2015) Total and high molecular weight adiponectin levels in the rat model of post-myocardial infarction heart failure. J Physiol Pharmacol 66(5):673–680

    CAS  PubMed  Google Scholar 

  15. Li J, Elrashidi MY, Flammer AJ, Lennon RJ, Bell MR, Holmes DR, Bresnahan JF, Rihal CS, Lerman LO, Lerman A (2013) Long-term outcomes of fractional flow reserve-guided vs. angiography-guided percutaneous coronary intervention in contemporary practice. Eur Heart J 34(18):1375–1383

    Article  CAS  Google Scholar 

  16. Manjunath G, Aravindhakshan R, Varghese S (2019) Effect of fasting during Ramadan on thermal stress parameters. East Mediterr Health J 25(1):34–39

    Article  Google Scholar 

  17. Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, van den Brand M, Van Dyck N, Russell ME, Mohr FW, Serruys PW (2005) The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention 1(2):219–227

    PubMed  Google Scholar 

  18. Hanada K, Higuma T, Nishizaki F, Sukekawa T, Yokota T, Yamada M, Saito S, Kushibiki M, Oikawa K, Abe N, Tomita H, Osanai T, Okumura K (2012) Randomized study on the efficacy and safety of landiolol, an ultra-short-acting beta1-adrenergic blocker, in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Circ J 76(2):439–445

    Article  CAS  Google Scholar 

  19. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators Developing the Japanese Equation for Estimated GFR (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53(6):982–992

    Article  CAS  Google Scholar 

  20. Trifunovic D, Stankovic S, Marinkovic J, Beleslin B, Banovic M, Djukanovic N, Orlic D, Tesic M, Vujisic-Tesic B, Petrovic M, Nedeljkovic I, Stepanovic J, Djordjevic-Dikic A, Giga V, Ostojic M (2015) Time-dependent changes of plasma adiponectin concentration in relation to coronary microcirculatory function in patients with acute myocardial infarction treated by primary percutaneous coronary intervention. J Cardiol 65(3):208–215

    Article  Google Scholar 

  21. Shibata R, Sato K, Kumada M, Izumiya Y, Sonoda M, Kihara S, Ouchi N, Walsh K (2007) Adiponectin accumulates in myocardial tissue that has been damaged by ischemia-reperfusion injury via leakage from the vascular compartment. Cardiovasc Res 74(3):471–479

    Article  CAS  Google Scholar 

  22. Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R (2001) Adiponectin gene expression is inhibited by beta-adrenergic stimulation via protein kinase A in 3T3-L1 adipocytes. FEBS Lett 507(2):142–146

    Article  CAS  Google Scholar 

  23. Pizarro G, Fernandez-Friera L, Fuster V, Fernandez-Jimenez R, Garcia-Ruiz JM, Garcia-Alvarez A, Mateos A, Barreiro MV, Escalera N, Rodriguez MD, de Miguel A, Garcia-Lunar I, Parra-Fuertes JJ, Sanchez-Gonzalez J, Pardillos L, Nieto B, Jimenez A, Abejon R, Bastante T, Martinez de Vega V, Cabrera JA, Lopez-Melgar B, Guzman G, Garcia-Prieto J, Mirelis JG, Zamorano JL, Albarran A, Goicolea J, Escaned J, Pocock S, Iniguez A, Fernandez-Ortiz A, Sanchez-Brunete V, Macaya C, Ibanez B (2014) Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction). J Am Coll Cardiol 63(22):2356–2362

    Article  CAS  Google Scholar 

  24. Ibanez B, Macaya C, Sanchez-Brunete V, Pizarro G, Fernandez-Friera L, Mateos A, Fernandez-Ortiz A, Garcia-Ruiz JM, Garcia-Alvarez A, Iniguez A, Jimenez-Borreguero J, Lopez-Romero P, Fernandez-Jimenez R, Goicolea J, Ruiz-Mateos B, Bastante T, Arias M, Iglesias-Vazquez JA, Rodriguez MD, Escalera N, Acebal C, Cabrera JA, Valenciano J, Perez de Prado A, Fernandez-Campos MJ, Casado I, Garcia-Rubira JC, Garcia-Prieto J, Sanz-Rosa D, Cuellas C, Hernandez-Antolin R, Albarran A, Fernandez-Vazquez F, de la Torre-Hernandez JM, Pocock S, Sanz G, Fuster V (2013) Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial. Circulation 128(14):1495–1503

    Article  CAS  Google Scholar 

  25. Chang J, Li Y, Huang Y, Lam KS, Hoo RL, Wong WT, Cheng KK, Wang Y, Vanhoutte PM, Xu A (2010) Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathway. Diabetes 59(11):2949–2959

    Article  CAS  Google Scholar 

  26. Guo BY, Li YJ, Han R, Yang SL, Shi YH, Han DR, Zhou H, Wang M (2011) Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression. Acta Pharmacol Sin 32(4):449–455

    Article  CAS  Google Scholar 

  27. Merl V, Peters A, Oltmanns KM, Kern W, Born J, Fehm HL, Schultes B (2005) Serum adiponectin concentrations during a 72-hour fast in over- and normal-weight humans. Int J Obes (Lond) 29(8):998–1001

    Article  CAS  Google Scholar 

  28. Rizza S, Cardellini M, Farcomeni A, Morabito P, Romanello D, Di Cola G, Canale MP, Federici M (2018) Low molecular weight adiponectin increases the mortality risk in very old patients. Aging Dis 9(5):946–951

    Article  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

    Masayoshi Kiyokuni, Masaaki Konishi, Kiwamu Iwata, Naohiro Komura, Teruyasu Sugano, Tomoaki Ishigami, Toshiyuki Ishikawa, Kouichi Tamura & Kazuo Kimura

  2. Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan

    Yusuke Saigusa & Takeharu Yamanaka

  3. Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan

    Naoki Nakayama

Authors
  1. Masayoshi Kiyokuni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masaaki Konishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yusuke Saigusa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kiwamu Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naoki Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naohiro Komura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Teruyasu Sugano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tomoaki Ishigami
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Toshiyuki Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Takeharu Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kouichi Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kazuo Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masaaki Konishi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kiyokuni, M., Konishi, M., Saigusa, Y. et al. Randomized controlled trial of landiolol, a short-acting beta-1 adrenergic receptor blocker, illustrating changes in high-molecular weight adiponectin levels after elective percutaneous coronary intervention. Heart Vessels 35, 1510–1517 (2020). https://doi.org/10.1007/s00380-020-01637-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-020-01637-6

Keywords

Search

Navigation