Intracoronary ET-1 elicited positive inotropic effects (end-systolic elastance increased from 0.94 to 1.48) and negative lusitropic effects (tau increased from 41.5 to 58.1) in a pig model.
Does endothelin receptor agonism alter myocardial contractility and relaxation in an in vivo pig model?
Endothelin-1 exerts positive inotropic effects via ET(A) receptors and negative lusitropic effects via ET(B) receptors in an in vivo pig model.
The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to 1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4 +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (tau from 43.3 +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.
Konrad et al. (Sat,) reported a other. Intracoronary infusions of ET-1 and sarafotoxin 6c was evaluated on Myocardial contractile status and left ventricular isovolumic relaxation. Intracoronary ET-1 elicited positive inotropic effects (end-systolic elastance increased from 0.94 to 1.48) and negative lusitropic effects (tau increased from 41.5 to 58.1) in a pig model.
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