Effects of BDF 9198 on left ventricular contractility in advanced spontaneously hypertensive rats with heart failure.
In the first part of this study, we characterized 24-month-old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), their heart weights, and the responses of the isolated left ventricles to electrical stimulation. In the main part of the study, we tested whether the positive inotropic effects of BDF 9198, which prevents the closure of the cardiac sodium channel, were present in senescence and heart failure. Thus, we studied the effects of BDF 9198 on the left ventricle strips of 24-month-old WKy rats (senescence) and SHRs using contractility methods. In comparison with WKY rats, the left ventricles of 24-month-old SHRs were hypertrophied and had prolonged times to peak contraction. BDF 9198 (10(-8) to 10(-6) M) was a positive inotrope on the left ventricles of WKY rats, with a maximum augmenting effect of 122% with BDF 9198 at 10(-7) M. The magnitude of the augmenting effects of BDF 9198 were reduced in SHR heart failure, with a maximum augmenting effect of 26% at 10(-7) M. BDF 9198 at 10(-6) M attenuated the responses of the SHR left ventricle to electrical stimulation. In conclusion, the potential of drugs that prevent closure of the sodium channel as positive inotropes in the treatment of heart failure should be further considered.
Faculty of Medicine and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. s.doggrell@mailbox.uq.edu.au
Sheila A
SA
Doggrell
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000662:veterinary; D006352:Heart Ventricles / Q000187:drug effects*; D006984:Hypertrophy; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects; D016276:Ventricular Function
D002316:Cardiotonic Agents; D015222:Sodium Channels