The Influence On Dobutamine Docking Of Blood Flow Around The Sinoatrial Node

Abstract

Traditionally, the docking of drugs onto cell receptors has been considered to occur from the capillaries into the interstitial fluid and thence to the cell receptor. In patients that are unable to exercise, pharmacologic stress testing is performed, either with vasodilatory agents (e.g. adenosine) or Dobutamine, which is a proinotropic and chronotropic drug. This drug docks with the sinoatrial node (SAN) in the upper right atrium of the heart near the superior vena cava. Due to its unique location it is exposed to both the blood flow coming from the right ventricle as well as the flow in the interstitial fluid. The SAN in the human has a surface area of approximately 4.6 mm2 and 0.1-0.2 mm thick and hence has a large surface area to volume ratio. The flow on the outside was simulated by a multiscale model consisting of a continuum flow, a Monte Carlo region and at the inner surface a molecular dynamics model. The simulation of the interstitial fluid contains more unknowns than the external flow. The SAN is relatively thin and thus it does not contain as many capillaries as would be found in normal tissue. The drug molecular dimensions are such that the Dobutamine can readily pass through the spaces between the capillary molecules, usually approximately 40 microns. Due to the number of unknowns involved with the capillary solution a continuum solution involving a diffusion coefficient based on the Lebas molecular volume was undertaken to obtain the order of magnitude of the