Effects of amlodipine and adenosine on coronary haemodynamics: in vivo study and numerical simulation

Amlodipine (AMLO) is a calcium channel blocker with vasodilating properties, in which the specific effects on the coronary circulation are not fully known. Coronary flow velocity-pressure (F/P) curves were obtained at rest and during administration of AMLO (10 mg to 20 mg iv) or adenosine (ADO, 1 mg ic) in 10 normal subjects (six women, age 48 ± 14 years). F/P curves were reproduced in a numerical simulator of systemic and coronary circulations (CARDIOSIM(©)) by adjustment of coronary resistance ( > or < 100 μm diameter vessels) and extravascular resistance applied to smaller vessels at endocardial (ENDO), middle and epicardial (EPI) myocardial layers. Best matching of in silico to in vivo curves was achieved by trial and error approach. ADO induced 170% and 250% increase in coronary flow velocity CFV and F/P diastolic slope as compared to 80% and 25-30% increase induced by AMLO, respectively. In the cardiovascular model, AMLO effects were predicted by progressive reduction of>100 μm vessels resistance from EPI to ENDO. ADO effects were mimicked by reducing resistance of both>100 μm and < 100 μm vessels, progressively from EPI to ENDO in the latter. Additional reduction in extravascular resistance avoided to impose a transmural gradient of vasodilating effect for both drugs. Numerical simulation predicts vasodilating effects of AMLO mainly on larger arteries and of ADO on both>and < 100 μm vessels. In vivo F/P loops could be completely reproduced in silico by adding extravascular resistance reduction for both drugs. Numerical simulator is useful tool for exploring the coronary effects of cardioactive drugs.