Summary
This review deals with the principal mechanisms which are known to play a role in positive inotropism: 1) The myoplasmic Ca2+ concentration may be increased by increases in cyclic AMP. Beside receptor-mediated stimulation (isoprenaline) or direct stimulation (forskolin) of the adenylate cyclase, the cyclic AMP may be increased by phosphodiesterase inhibition; 2) Cyclic AMP-independent activation of Ca2+ channels can be brought about by alpha-adrenergic agents (phenylephrine) or so-called calcium agonists; 3) Only a small increase in myoplasmic Na+ concentration can greatly enhance the force of contraction by an increase in the intracellular Ca2+ concentration. This is possible by inhibition of the Na+/K+-ATPase (glycosides) or by prolongation of the open state of Na channels (DPI 201-106); 4) A direct inhibition of the Na+/Ca2+ exchange has been discussed for amiloride; 5) A prolongation of the action potential induced by K+ channel-inhibiting agents such as 4-amino-pyridine may increase the myoplasmic Ca2+ concentration by a prolongation of the slow Ca2+ inward current; 6) An increased Ca2+ sensitivity of the contractile proteins has been demonstrated for a number of compounds in vitro; the contribution of such an effect to the overall positive inotropism is unknown because a calcium sensitizer without any effects on calcium or sodium movements is not yet available.
The increase in the force of myocardial contraction is ultimately due to one of two mechanisms (Fig. 1): an increase in intracellular free Ca2+ concentration, <Ca2+> i, to interact with the contractile proteins (① in Fig. 1) or to an increased sensitivity of the myofilaments for Ca2+ (② in Fig. 1), or both (9). It will be discussed in detail in this section how these variables might be affected by various inotropic drugs.
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References
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© 1989 Springer-Verlag Berlin Heidelberg
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Scholz, H. (1989). Introduction: Mechanisms of positive inotropic effects. In: Just, H., Holubarsch, C., Scholz, H. (eds) Inotropic Stimulation and Myocardial Energetics. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-662-07908-9_1
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DOI: https://doi.org/10.1007/978-3-662-07908-9_1
Publisher Name: Steinkopff, Heidelberg
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