Describe the physiology of transplanted hearts.
The donor heart is denervated during harvesting. Consequently, the recipient lacks efferent and afferent innervation. The transplanted heart does not receive auto-nomic or somatic input. Although denervation prevents responses to extrinsic neural signals, intrinsic myocardial mechanisms and reflexes remain intact. While transplanted hearts function in isolation from the nervous system, they respond to humoral factors (e.g., catecholamines) circulating in blood.
The results of cardiac denervation are:
· Relative tachycardia from absent vagal input to the trans-planted heart. Heart rates approximate 90–100 beats per minute.
· Loss of rapid heart rate responses to autonomic reflexes. Heart rates remain unchanged with carotid mas-sage, acute hyper- or hypotension, and from Valsalva maneuvers.
· Absence of many pharmacologic effects. Drugs which alter the heart rate indirectly, via the autonomic nervous system, will not have their usual effects on the trans-planted heart. Vagolytic drugs, such as atropine, pan-curonium, and meperidine, will not increase heart rate. Vagotonic drugs, such as acetylcholinesterase inhibitors and opioids, will not decrease heart rate. Medications with both direct and indirect cardiac actions will maintain their direct effects on the denervated heart. Digoxin, for example, maintains its positive inotropic effects on the graft, but will not slow heart rate through its parasympa-thetically mediated effects on the atrioventricular (AV) node.
· Delayed and attenuated responses to laryn-goscopy, intubation, painful stimuli, and light anesthe-sia because direct sympathetic innervation of the heart no longer occurs. However, prolonged stimulation results in rising levels of circulating catecholamines that will eventually induce an increase in heart rate, or even an exaggerated one, directly through myocardial adrenergic receptors.
· Inability to perceive angina. Despite sporadic case reports to the contrary, which have been touted as evidence of reinnervation, the majority of post-transplantation patients do not perceive angina.
Despite denervation, intrinsic myocardial mechanisms remain intact in the transplanted heart:
· The denervated myocardium responds normally to circulating or administered catecholamines (e.g., epi-nephrine, norepinephrine) and direct-acting sympath-omimetic agents (e.g., isoproterenol, dobutamine) directly through myocardial adrenergic receptors. In this regard, denervation appears to induce downregulation of β1 receptors, so most β-adrenergic receptors on the denervated myocardium will be β2 subtypes.
· The Frank-Starling mechanism (increased preload results in increased stroke volume) remains intact, and is the primary mechanism for increased cardiac output during exercise or stress. For this reason, it is important to maintain adequate preload in post-transplantation patients. Since they already have elevated heart rates, the only way a post-transplant patients can initially increase cardiac output is through the Frank-Starling mechanism. Any further increases in heart rate and cardiac output with prolonged exercise or stress are the result of increased levels of circulating catecholamines, and are therefore slightly delayed in onset (and in resolution).
· Metabolic autoregulation of coronary blood flow in response to changes in pH and pCO2 remains intact.
· Normal electrical impulse formation and conductivity along the usual pathways is maintained in the trans-planted heart. Classic orthotopic heart transplantation techniques leave cuffs of native right and left atrial tissue behind in the recipient, to facilitate surgical anasto-moses. The native sinoatrial (SA) node is contained in the right atrial cuff. Impulses continue to emanate from the native SA node, but these can not cross atrial suture lines and do not depolarize the transplanted heart. Frequently, two independent p-waves are dis-cernible on the post-transplant electrocardiogram (ECG) (Fig. 12.1).
Physiology of the Transplanted Heart
· Resting tachycardia of 90–100 beats/min
· Due to vagus nerve denervation
· Absence of autonomic reflexes
· No change in heart rate to:
§ carotid massage
§ Valsalva maneuver
§ acetylcholinesterase inhibitors
o Delayed tachycardic response to:
§ painful stimuli
§ light anesthesia (mediated through cate-cholamine release)
o Phenomenon of reinnervation remains speculative
· Intrinsic myocardial mechanisms
· Normal response to:
o Circulating catecholamines (epinephrine, norepinephrine)
o Direct-acting sympathomimetics (isoproterenol, dobutamine)
· Frank-Starling mechanism remains intact:
o Primary mechanism to increase cardiac output
o Important to maintain adequate preload
· Metabolic autoregulation of coronary blood flow:
o Responds to local pH and pCO2 Normal electrical impulse formation and
· Action potentials from native SA node do not cross suture line and are not propagated to donor heart