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Interaction between cardiac sympathetic drive and heart rate in heart failure

Modulation by adrenergic receptor genotype

David M. Kaye, MD, PhD, FRACP, FACC^*,*, Belinda Smirk, BSc^*, Samara Finch, BSc^*, Carolyn Williams, PhD and Murray D. Esler, MD, PhD, FRACP

^* Wynn Department of Metabolic Cardiology
Alfred Baker Genebank, Melbourne, Australia
Human Neurotransmitter Laboratory, Baker Heart Research Institute, Melbourne, Australia

View larger version (18K): [in a new window]   Figure 1 Scatterplots show the relationship between heart rate and plasma norepinephrine (NE) (top panel), total systemic norepinephrine spillover rate (SR) (middle panel), and cardiac norepinephrine spillover rate (lower panel). The relationship between heart rate and total norepinephrine spillover (middle panel) is influenced by an outlying patient; when removed r = 0.22, p = 0.10. bpm = beats/min.

View larger version (23K): [in a new window]   Figure 2 Scatterplots demonstrate the relationship between cardiac norepinephrine spillover (NE SR) and heart rate. The top panel indicates the relationship according to ß2-adrenoceptor genotype at position 16 and the lower panel represents position 27. The dashed line in the top panel indicates the regression line for Arg/Arg individuals and the solid line in the top panel indicates the regression line for the combined Arg/Gly and Gly/Gly patients. The slope of the line is significantly different (p = 0.02). bpm = beats/min.

View larger version (22K): [in a new window]   Figure 3 Scatterplots demonstrating the relationship between cardiac norepinephrine spillover (NE SR) and heart rate. The top panel indicates the relationship according to ß1-adrenoceptor genotype at position 49 and the lower panel represents position 389.

View larger version (20K): [in a new window]   Figure 4 Scatterplots demonstrate the relationship between cardiac norepinephrine spillover rate (NE SR) and pulmonary capillary wedge pressure (PCWP) (top panel), mean arterial (Art.) pressure (middle panel), and cardiac output (lower panel).

View larger version (30K): [in a new window]   Figure 5 Scatterplot shows the relationship between pulmonary capillary wedge pressure (PCWP) and cardiac norepinephrine spillover rate (NE SR) according to 2C-adrenoceptor genotype (top panel), ß2-adrenoceptor genotype at position 16 (middle panel), and ß2-adrenoceptor genotype at position 27 (lower panel).