Key result
Dopexamine increases contraction force in failing human myocardium only when combined with milrinone.
Why the study?
The study investigated the effects of dopexamine on force of contraction in failing human myocardium despite preserved beta 2-adrenoceptor subpopulation to understand impaired receptor coupling in heart failure.
Does dopexamine increase the force of contraction in failing human myocardium?
Does dopexamine increase the force of contraction in failing human myocardium?
The study provides evidence for impaired coupling of beta-2 adrenoceptors to mechanisms beyond receptor occupation in terminal heart failure, as dopexamine requires phosphodiesterase inhibition (milrinone) to exert a positive inotropic effect.
Dopexamine may require PDE inhibition for inotropy in failing myocardium; hypothesis-generating for beta-2 adrenoceptor uncoupling in terminal HF.
The results of the present study show that the reduction of the total number of beta adrenoceptors affected the beta 1-adrenoceptor subpopulation, whereas the beta 2 adrenoceptors were not detectably altered in the failing heart. Dopexamine had a 9.8-fold greater affinity to beta 2 adrenoceptors than to beta 1 adrenoceptors. In nonfailing myocardium, dopexamine increased force of contraction concentration-dependently. However, dopexamine alone had no effect in papillary muscle strips from moderately (NYHA II-III) and severely (NYHA IV) failing myocardium. However, in the presence of milrinone, it concentration-dependently increased force of contraction. Under this condition, the effectiveness was slightly less pronounced in NYHA IV than in NYHA II-III. Dopexamine concentration-dependently stimulated adenylate cyclase activity. Experiments with the beta 1-selective antagonist CGP 207.12 A and the beta 2-selective antagonist ICI 118.551 showed that both stimulation of adenylate cyclase and the increase of force of contraction are mediated by beta 2 adrenoceptors. It is concluded that although the number of beta 2 adrenoceptors is preserved in the failing myocardium, dopexamine alone does not increase force of contraction. However, the positive inotropic effect of dopexamine, which is observed in the presence of milrinone and the stimulation of adenylate cyclase activity by dopexamine are mediated by beta 2 adrenoceptors. Therefore, beta 2 adrenoceptors exist in the human myocardium, are coupled to adenylate cyclase, and are capable of increasing force of contraction. These results provide evidence for an impaired coupling of beta 2 adrenoceptors to mechanisms beyond receptor occupation in terminal heart failure.
No takes yet. Share an insight, caveat, or question.
Böhm et al. (1989) studied Heart failure (NYHA II-IV). Dopexamine vs. Dopexamine with milrinone / Nonfailing myocardium was evaluated on Force of contraction and adenylate cyclase activity. Dopexamine (which had a 9.8-fold greater affinity for beta-2 than beta-1 adrenoceptors) increased force of contraction in failing human myocardium only in the presence of milrinone.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: