In isolated rabbit hearts, dipyridamole accumulates in the myocardium and reduces myocardial contractility and efficiency.
May reduce contractility via myocardial accumulation; hypothesis-generating for human dosing and relevance.
The myocardial accumulation and disposition pharmacokinetics of the antithrombotic drug dipyridamole were investigated in isolated perfused and spontaneously beating rabbit hearts. The rabbit myocardium behaved pharmacokinetically as a two-compartment system with regard to the drug. The half-lives of the alpha-phase of distribution and of the beta-phase of disposition were about 1.4 and 6.3 min., respectively. Perfusion with a modified Krebs-Henseleit solution containing 5.1 microgram ml-1 of dipyridamole caused an accumulation of about 140 micrograms g-1 of myocardial tissue at steady state. The initial measured pharmacokinetic parameters were unchanged after perfusion with the drug for 60 min. The accumulating dipyridamole in the rabbit heart caused a progressive decrease in myocardial contractility to about 65%. This was accompanied by a decrease in the ratio of contraction rate to oxygen consumption to about 0.7 as an expression of reduced myocardial efficiency. The coronary flow rate was not significantly increased. The heart beating frequency decreased only slightly and no dromotropic effects were observed.
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Nielsen‐Kudsk et al. (1981) studied this question.
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