title: Age-related effects of dexmedetomidine on myocardial contraction and coronary circulation in isolated guinea pig hearts.
abstract: Dexmedetomidine is a selective α2 adrenergic agonist. Although dexmedetomidine is widely used for sedation and analgesia, it frequently produces hypotension and bradycardia. The present study aimed to evaluate the effects of dexmedetomidine on cardiac function and coronary circulation using Langendorff-perfused guinea pig hearts. Coronary perfusion pressure (CPP) and left ventricular pressure (LVP) were continuously monitored, and electric field stimulation (EFS) was applied to stimulate sympathetic nerve terminals. Dexmedetomidine almost completely inhibited the EFS-induced increase in LVP at all ages. The effect of dexmedetomidine on coronary artery resistance varied according to postnatal age, i.e., dexmedetomidine had little effect on CPP in young hearts (<4 weeks) but increased CPP by 10 mmHg at 4-8 weeks and by 15 mmHg at >8 weeks. The increase in CPP in adult hearts was inhibited by imiloxan, an α2B antagonist, and prazosin, an α1 antagonist. The results suggest that dexmedetomidine acts on α2 adrenergic receptors at sympathetic nerve terminals to suppress the release of norepinephrine. In addition, the findings suggest that dexmedetomidine directly affects α1 adrenoceptors and/or α2B adrenoceptors on coronary smooth muscles to increase CPP. The age-related changes in α adrenoceptor subtypes may be linked to the cardiodepressant effects of dexmedetomidine.
authors.affiliation: Department of Cell Physiology, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Hongo
authors.affiliation: Department of Cell Physiology, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Fujisawa
authors.affiliation: Department of Cell Physiology, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Cell Physiology, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Shimbo
authors.affiliation: Department of Critical Care Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Cell Physiology, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohba
authors.affiliation: Department of Cell Physiology, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan. Electronic address: onok@med.akita-u.ac.jp.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ono
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D020927:Dexmedetomidine / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018712:Analgesics, Non-Narcotic; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine
keywords: Cardiac function; Coronary circulation; Dexmedetomidine; Langendorff perfusion; α(2)-adrenoceptor