Cardiovascular Journal of Africa • SAHS Biennial Congress 2024 15 AFRICA Submission ID: 1634 Introduction Heart rate-reducing agents such as β-blockers and ivabradine (IVB) are frequently used in the management of patients with cardiovascular disease. However, reductions in heart rate (HR) are associated with increases in central aortic pulse pressure (PPc), but not peripheral PP. The inverse HR-PPc relationship, and the mechanisms thereof, have been identified primarily in cross-sectional studies. Hence, intervention studies are required to establish causality and the primary mechanisms. The aim of my intervention study in rats, was to assess the effect of changes in HR on PPc, and the impact of the determinants of PPc on the HR-PPc relationship. Methods Male spontaneously hypertensive rats (SHR) (n=15) and Wistar Kyoto (WKY) normotensive rats (n=12), at 17 months of age, were studied. To induce changes in blood pressure (BP) and HR, approximately 7 doses of a vasoconstrictor, phenylephrine (PE) (0.5 mg/kg per dose), followed by about 6 doses of IVB (0.5 mg/kg per dose) were administered to anaesthetised rats. Central aortic pressures (carotid catheter and high-resolution pressure transducer paired with PowerLab Lab Chart 8 system) and aortic outflow tract diameter and flow velocity (echocardiography) were systematically acquired for each anaesthetised rat at baseline and then during the administration of PE and then IVB. The aortic pressure waves were coupled with the aortic flow waves, and wave separation analysis performed to obtain the various determinants of PPc (backward wave pressure [Pb], forward wave pressure [Pf], reflected pressure, re-reflected pressure, aortic flow [Q], aortic characteristic impedance [Zc], the pressure generated by the product of flow and characteristic impedance [QxZc]), using standard formulae. Bivariate and multivariate correlation analyses were performed to determine the relationship between HR and PPc, and the impact of determinants of PPc on this relationship respectively. Results Heart rate was inversely associated with PPc (p<0.0001), backward wave pressure (Pb) (p<0.0001), forward wave pressure (Pf) (p<0.0001), reflected pressure (p<0.0001), and re-reflected pressure (p<0.0001). On the contrary, aortic flow (Q), aortic characteristic impedance (Zc), and the pressure generated by the product of flow and characteristic impedance (QxZc) were not related to heart rate. The slope of the relationship between HR and PPc was diminished by adjustments for Pf, and markedly diminished by adjustments for Pb, reflected pressure, or re-reflected pressure (p<0.05 to p<0.0001). Conclusion In an intervention study in rats, we confirm the inverse relationship between HR and PPc, and show that wave reflection and re-reflection are the primary mechanisms responsible for the HR-PPc relationship. These data suggest that in individuals who require HR-reducing agents, wave-reflection and re-reflection should be targeted, such as by intensive lowering of BP. Name: Presenting Author Information Article Category Abstract Title University of the Witwatersrand 1474838@students.wits.ac.za English Abstract Students - Currently enrolled postgraduate students Impact of determinants of aortic pulse pressure on the relationship between heart rate and aortic pulse pressure: an intervention study in rats Author Affiliation: Email: Katleho Khanye Science Theme Basic Authors Name & Surname Title Expertise Affiliation Email Country Katleho Khanye Mr Physiology University of the Witwatersrand 1474838@students.wits.ac.za South Africa Angela Woodiwiss Professor Physiology University of the Witwatersrand angela.woodiwiss@wits.ac.za South Africa Vernice Peterson Dr Physiology University of the Witwatersrand vernice.peterson@wits.ac.za South Africa Nonhlanhla Mthembu Dr Physiology University of the Witwatersrand nonhlanhla.mthembu@yahoo.com South Africa ORAL PRESENTATION
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