Ventricular-vascular coupling and central arterial pulse pressure

• Main Author: Fok, Henry Wing Hang
• Other Authors: Chowienczyk, Philip Jan
• Published: King's College London (University of London) 2015
• Subjects: 615.1
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677206

Central pulse pressure (cPP), a product of ventricular-arterial interaction, is an important determinant of cardiovascular outcomes in hypertension. The aim of this thesis is to advance the understanding of pulsatile haemodynamics and to explore mechanisms that may selectively reduce cPP. The conventional view is that cPP comprises a component determined by the direct interaction of myocardial contraction with the impedance of the proximal arterial tree (closely related to pulse wave velocity, PWV) and a component ‘augmentation pressure’ generated by pressure wave reflections from muscular conduit arteries. Surprisingly little is known regarding regulation of conduit artery tone despite its potential influence on cPP. In the first part of this thesis, muscular large arterial tone was examined using a human forearm blood flow model. Vasoactive substances were infused locally into the brachial artery and vasodilator responses of the radial artery, as a muscular conduit artery, and forearm resistance microvasculature were examined. Nitric oxide donors, in particular, glyceryl trinitrate (GTN) were found to have the most selective action on conduit arteries compared to other vasodilators. In the second part of the thesis, I examined whether the action of GTN to reduce augmentation pressure could be accounted for by this selective dilation of muscular arteries. GTN was given systemically and by intra-coronary infusion in patients undergoing cardiac catheterisation. Invasive aortic blood pressure and flow velocity were analysed in the time domain by wave intensity analysis. This allows separation of pressure into a forward component generated by myocardial contraction and a backward component generated by ‘reflection’ from the peripheral arterial tree. A surprising finding was that changes induced by GTN were mainly attributable to a reduction in forward rather than backward pressure waves. That this resulted from a change in myocardial contractility was confirmed by local intracoronary injection of GTN. The final part of the thesis examines the relative contribution of forward and backward pressure waves in hypertension. An elevated cPP in hypertensive compared to normotensive subjects was accounted for primarily by an increased forward pressure wave. That this was due to increased myocardial contractility was confirmed by examining whether the pattern of wave intensity seen in hypertension could be reproduced, in normotensive subjects, by the inotrope dobutamine (when compared to the vasoconstrictor norepinephrine used as a control). This thesis thus provides novel insight into a) regulation of conduit artery tone, and b) pulsatile haemodynamics, highlighting the contribution of left ventricular ejection characteristics in determining pressure augmentation and cPP.