Article

Increase in myofibrillar Ca2+ sensitivity induced by UD-CG 212 Cl, an active metabolite of pimobendan, in canine ventricular myocardium.

Department of Pharmacology, Yamagata University School of Medicine, Japan.
Journal of Cardiovascular Pharmacology (Impact Factor: 2.11). 03/2001; 37(2):209-18. DOI: 10.1097/00005344-200102000-00008
Source: PubMed

ABSTRACT We performed experiments in canine ventricular trabeculae loaded with aequorin to elucidate the mechanism of positive inotropic effect of UD-CG 212 Cl (4,5-dihydro-6-[2-(4-hydroxyphenyl)-1H-benzimidazole-5-yl]-5-methyl-3(2H)-pyridazinone), an active metabolite of pimobendan. The maximum response to UD-CG 212 Cl achieved at 10(-5) M was 18% of ISOmax and it was associated with an increase in Ca2+ transients of 7% of ISOmax. For a given increase in force, the increase in Ca2+ transients induced by UD-CG 212 Cl was less than that induced by elevation of [Ca2+]o. The positive inotropic effect of UD-CG 212 Cl was not associated with an impairment of relaxation and it was abolished by carbachol. In conclusion, UD-CG 212 Cl has a positive inotropic effect partly due to an increase in myofibrillar Ca2+ sensitivity that is exerted via cross talk with a signal transduction pathway that involves cAMP.

0 Followers
 · 
59 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die Mitralklappenendokardiose – Aktueller Stand der Diagnose und Therapie Die Mitralklappenendokardiose ist die häufigste erworbene Herzerkrankung beim Hund. Zusammenfassung Die Mitralklappenendokardiose ist die häufigste erworbene Herzerkrankung beim Hund. In den letzten Jahren wurden die diagnostischen Methoden weiterentwickelt und verschiedene therapeutische Optionen anhand einer Vielzahl von Studien untersucht. Das CHIEF-Klassifikationsschema ermöglicht eine eindeutige Einteilung von Hunden in verschiedene Stadien ihrer Herzerkrankungen und erleichtert damit Therapieentscheidungen. Während für die Behandlung symptomatischer Hunde (Stadium CHIEF_C) ein Konsens hinsichtlich der Therapie besteht, ist die optimale Therapie für asymptomatische Hunde (Stadium CHIEF_B) nicht endgültig geklärt. Ziel dieses Artikels ist es, den aktuellen Stand der Wissenschaft zu diskutieren, um eine bestmögliche Versorgung des Patienten mit Mitralklappenendokardiose zu ermöglichen. Schlüsselwörter Herzinsuffizienz, Behandlung, Graduierung, CHIEF-Klassifikation Summary Degenerative mitral valve disease – Current state of diagnosis and therapy Degenerative mitral valve disease is the most common acquired heart disease in dogs. In recent years, the diagnostic methods have advanced and therapeutic options have been evaluated in several studies. To be able to classify and treat this disease uniformly, it is strongly advised to use the four-stage CHIEF (Canine Heart Failure International Expert Forum) classification scheme. While there is consent regarding the treatment of symptomatic dogs (CHIEF C), the optimal treatment of asymptomatic dogs (CHIEF B) has not been agreed upon. The aim of this article is to present and discuss current scientific knowledge enabling the best possible care of dogs with degenerative mitral valve disease.
    Kleintierpraxis 06/2014; 59(6):329–352. DOI:10.2377/0023-2076-59-329 · 0.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of Ca2+ in cardiac excitation-contraction (E-C) coupling has been established by simultaneous measurements of contractility and Ca2+ transients by means of aequorin in intact myocardium and Ca2+ sensitive fluorescent dyes in single myocytes. The E-C coupling process can be classified into 3 processes: upstream (Ca2+ mobilization), central (Ca2+ binding to troponin C) and downstream mechanism (thin filament regulation and crossbridge cycling). These mechanisms are regulated differentially by various inotropic interventions. Positive force-frequency relationship and effects of beta-adrenoceptor stimulation, phosphodiesterase 3 inhibitors and digitalis are essentially exerted via upstream mechanism. Alpha-adrenoceptor stimulation, endothelin-1, angiotensin II, and clinically available Ca2+ sensitizers, such as levosimendan and pimobendan, act by a combination of the upstream and central/downstream mechanism. The Frank-Starling mechanism and effects of Ca2+ sensitizers such as EMD 57033 and Org 30029 are primarily induced via the central/downstream mechanism. Whereas the upstream and central mechanisms are markedly suppressed in failing myocytes and under acidotic conditions, Ca2+ sensitizers such as EMD 57033 and Org 30029 can induce cardiotonic effects under such conditions. Ca2+ sensitizers have high therapeutic potential for the treatment of contractile dysfunction in congestive heart failure and ischemic heart diseases, because they have energetic advantages and less risk of Ca2+ overload and can maintain effectiveness under pathological conditions.
    Circulation Journal 01/2009; 72(12):1915-25. DOI:10.1253/circj.CJ-08-0838 · 3.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective-To assess survival time and adverse events related to the administration of pimobendan to cats with congestive heart failure (CHF) secondary to hypertrophic cardiomyopathy (HCM) or hypertrophic obstructive cardiomyopathy (HOCM). Design-Retrospective case-control study. Animals-27 cats receiving treatment with pimobendan and 27 cats receiving treatment without pimobendan. Procedures-Medical records between 2003 and 2013 were reviewed. All cats with HCM or HOCM treated with a regimen that included pimobendan (case cats) were identified. Control cats (cats with CHF treated during the same period with a regimen that did not include pimobendan) were selected by matching to case cats on the basis of age, sex, body weight, type of cardiomyopathy, and manifestation of CHF. Data collected included signalment, physical examination findings, echocardiographic data, serum biochemical values, and survival time from initial diagnosis of CHF. Kaplan-Meier survival curves were constructed and compared by means of a log rank test. Results-Cats receiving pimobendan had a significant benefit in survival time. Median survival time of case cats receiving pimobendan was 626 days, whereas median survival time for control cats not receiving pimobendan was 103 days. No significant differences were detected for any other variable. Conclusions and Clinical Relevance-The addition of pimobendan to traditional treatment for CHF may provide a substantial clinical benefit in survival time for HCM-affected cats with CHF and possibly HOCM-affected cats with CHF.
    Journal of the American Veterinary Medical Association 09/2014; 245(5):534-9. DOI:10.2460/javma.245.5.534 · 1.67 Impact Factor