The transplanted heart will not be able to respond to drugs that act by blocking the parasympathetic system because these connections were severed during the transplant. Therefore, treating bradycardia would have to be done with agents such as isoproterenol, glucagon, epinephrine, norepinephrine (drugs that have a direct effect on the heart). Isoproterenol is most commonly used for increasing heart rate in cardiac transplant recipients. Epinephrine/Norepinephrine may have exaggerated beta mimetic effects on the heart rate because the increase in blood pressure will not lead to a reflex slowing of the heart rate via the baroreceptor reflex (i.e., efferent vagus nerve). Implanted mechanical pacemakers work normally in heart transplant recipients since the cardiac leads are placed directly into myocardium.
Transplanted hearts have no baseline parasympathetic innervation and thus don’t have the normal tachycardia and increased contractility response to hypotension/hypovolemia. Reflex venous contriction response to hypotension still exists. Thus intravascular volume is even more important. Circulating catecholes will have cause a delayed increase in rate and contractility. Indirect drugs that affect rate will not be effective (antimuscarinics, anticholinesterases, pancuronium, digoxin). Use direct acting agents (isoproterenol, epinephrine). Lack of vagal tone will result in baseline rate of 90-100. Vagal bradycardic reflexes will also be absent (laryngoscopy, hypertension, carotid sinus massage).
About 25% of patients will develop a bradycardia that will require implantation of a permanent pacemaker.
Denervated heart: exercise physiology
Definition
Donor heart, which is completely denervated, does not respond to manipulations of the parasympathetic nervous system (including reductions in parasympathetic outflow, ex. anticholinergics, anticholinesterases, or increases on PNS outflow, ex. phenylephrine), or neuronal SNS outflow (ex. cardioaccelerator fibers, although systemic epinephrine may still affect the heart). Furthermore, denervation impairs the response to changes in cardiac filling pressures as well as the renin-angiotensin-aldosterone system. Resting heart rate is increased, the heart rate does not respond to hypovolemia, vasodilation, or exercise. Diabetes is the most common cause of denervation in the non-cardiac surgery population.
Denervated Heart
Resting HR 90-110
No response to hypovolemia, vasodilation, or exercise
Impaired response to changes in cardiac filling pressures
Impaired renin-angiotensin-aldosterone system
Normal resting inotropic state
Despite these changes, inotropic state and myocardial blood flow are normal at rest. Beta receptors may be upregulated, leading to an exaggerated response to systemic catecholamines. Afferent sensation is absent (and thus subsequent myocardial disease is asymptomatic).
Cardiac transplantation surgery results in postganglionic denervation. Note that preganglionic denervation (as occurs during spinal cord injury, Shy-Drager syndrome, etc.) will leave some reflexes intact.