Lack of parallelism between the positive inotropic effects of various cardiac stimulants and their activities to produce the slow channels in the depolarized myocardium.
Positive inotropic actions in the normal guinea pig cardiac muscle and the activities required to produce electrical and mechanical responses in the depolarized muscle were examined using epinephrine, dopamine, metanephrine, aminophylline, histamine, serotonin, tyramine, tetraethylammonium (TEA), tetramethylammonium (TMA), and X-537A, a calcium ionophore. In the normal cardiac muscle, histamine produced the greatest positive inotropic action, followed by epinephrine, dopamine and TEA. In the cardiac muscle made inexcitable by the elevated potassium (30 mM), all of the agents tested produced electrical and mechanical responses. Aminophylline was the most potent in the activity to produce the mechanical response in the depolarized muscle; the potencies of histamine, dopamine, X-537A, epinephrine and TEA were much the same. From these results, it was concluded that the positive inotropic effects of the cardiac stimulants are not produced solely through the mechanisms related to the slow channels, but that other mechanisms must be involved in the normal condition where the fast sodium channels are functioning.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D013268:Stimulation, Chemical
D002316:Cardiotonic Agents; D002395:Catecholamines; D007473:Ion Channels; D000628:Aminophylline; D006632:Histamine