Role of adrenergic beta 2 receptors in pharmacological circulatory support

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09247
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Nagasaki University
• Principal Investigator: Hara Tetsuya 長崎大学, 医歯薬学総合研究科(医学系), 教授 (50304952)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: アドレナリン受容体 / カテコラミン / β遮断薬 / ホスホジエステラーゼ阻害薬 / 心室圧容積曲線

Outline of Final Research Achievements

The purpose of this study was to elucidate the role of cardiac adrenergic β2 receptors in pharmacological circulatory support by evaluating the effects of three β-blockers with different β receptor selectivity on catecholamine-induced tachycardia in pig and rat models.
Regarding the effect of β receptor selectivity on cardiac function under catecholamine treatment, propranolol and esmolol dose-dependently suppressed left ventricular contractile and mechanical efficiency, while the suppression of those parameters in landiolol was significantly lower than in propranolol and esmolol. Cardiac contractile and mechanical efficiency in response to PDEI in β1 receptor blockade tended to be higher with landiolol than with propranolol and esmolol.The effect of β receptor selectivity on intracellular signaling was evaluated in terms of PKA and Akt activity in the myocardium. PKA and Akt activity tended to be higher with landiolol than with propranolol and esmolol.

Free Research Field

周術期全身管理

Academic Significance and Societal Importance of the Research Achievements

周術期、集中治療および救急等の急性期医療における重症患者の循環管理においては、心拍出量や血圧を維持するためにアドレナリン、ノルアドレナリン、ドパミンおよびドブタミン等のカテコラミンを用いた薬理学的循環補助を行う。カテコラミンに代表される強心薬は心筋のアドレナリン受容体を介して強心作用を発揮するため、これらの重症患者においては、洞性頻脈、発作性上室性頻拍、心房細動、心房粗動等の心拍出量低下を招く重症不整脈や、心室頻拍、心室細動といった致死性不整脈を誘発するリスクが高く、頻脈性不整脈の薬理学的制御が重要な問題となる。重症患者の循環管理において、カテコラミンと併用できる抗頻脈薬が明らかとなる。