Characterization of Human AVN and SAN – KEDAR ARAS

We will perform dual-sided dual optical mapping studies to simultaneously map the endocardial and epicardial surfaces of isolated SAN preparations, which will be specifically prepared in such a way to preserve the epicardial fat pads that anatomically surround the SAN. Electrical stimulation of the preserved sympathetic and parasympathetic nerve fibers will be performed, and the resulting heart rate changes and leading pacemaker locations will again be recorded. To identify the specific effects of the sympathetic system on the SAN, cholinergic antagonists (e.g. nicotine and muscarine) will be applied to inhibit postganglionic muscarinic receptors while the nerves are electrically excited. Additionally, to isolate the specific effects of the parasympathetic system on the SAN, adrenergic antagonists (e.g. propranolol and phentolamine) will be applied to conversely inhibit adrenergic receptors while the nerves are electrically excited. The questions to answer include: To what degree can the SAN push the range of the intrinsic heart rate with pharmacologic stimulation? With nerve stimulation? How does this range change with age (if at all)? What is the appropriate method for identifying activation times in the human SAN versus the human atrial myocardium (e.g. max dV/dt, 50% of the action potential amplitude upstroke, dV/dt temporal maps, etc.)? How is the human SAN innervated with parasympathetic and sympathetic nerve fibers in three-dimensions? Where are β1, β2, β3, and cholinergic receptors located, and do their anatomical locations correlate to their functional expressions?