A comparison of the cardiovascular effects of dobutamine and a new dopamine derivative (D4975) during shock induced by E. coli endotoxin.
1 The effects of a newly developed dopamine-xanthine derivative, 7-propyl-theophylline-dopamine (D4975) and of dobutamine have been examined in anaesthetized cats before and after the induction of shock with E. coli endotoxin. 2 Both D4975 and dobutamine caused dose-related increases in left ventricular (LV) dP/dtmax (and LVdP/dt at fixed isovolumic pressures. Significantly smaller increases in LVdP/dtmax occurred as early as 0.5 to 1 h after endotoxin, with maximal attenuation at 1 to 2 h and some improvement in sensitivity in cats surviving 2 to 4 h. The maximum response to each drug was markedly reduced in shock. 3 Neither D4975 nor dobutamine had significant effects on heart rate. D4975 caused dose-related increases in systemic arterial blood pressure which were smaller during shock, the changes in responsiveness following those in LVdP/dtmax. 4 Possible mechanisms responsible for changing myocardial sensitivity to these and other agents are discussed. It is concluded that D4975 may be more useful in the treatment of shock than either dopamine or dobutamine because (a) it is more potent during shock than dobutamine (perhaps as a result of phosphodiesterase inhibition by the theophylline component of D4975); (b) its action is longer-lasting than dobutamine or dopamine and (c) like dobutamine, its effect on heart rate is insignificant.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000494:pharmacology*; D002415:Cats; D004280:Dobutamine / Q000494:pharmacology*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004731:Endotoxins; D004926:Escherichia coli; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D012772:Shock, Septic / Q000188:drug therapy*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D002395:Catecholamines; D004731:Endotoxins; D004280:Dobutamine; C021942:7-propyltheophylline dopamine; D013806:Theophylline; D004298:Dopamine