A 57-year-old man with hypertension, elevated serum cholesterol, and mild renal insufficiency presented for laparoscopic cholecystectomy. His past medical history was significant for heart transplantation at age 55 for idiopathic dilated cardiomyopathy. His medications included nifedipine, tacrolimus, azathioprine, prednisone, atorvastatin, and omeprazole.
Explain the physiology of transplanted hearts.
The donor heart is denervated during harvesting, and once it is transplanted into the recipient, there is neither direct efferent nor afferent neural innervation of the graft through autonomic or somatic pathways. Although denervation results in inability of the transplanted heart to respond to extrinsic neural signals, intrinsic myocardial mechanisms and reflexes remain intact. Although the transplanted heart functions in isolation from the nervous system, it retains the ability to respond to humoral factors circulating in the blood (e.g., catecholamines) directly through myocardial receptors. The overall result is a predictable physiology.
The results of cardiac denervation are as follows:
Lack of tonic vagal input to the transplanted heart results in relative tachycardia, usually around 90 to 100 beats per minute.
All autonomic reflexes that would normally alter the heart rate are gone. One should expect no change in heart rate with carotid massage, from acute hypertension or hypotension, or from a Valsalva maneuver.
Drugs that alter the heart rate indirectly (i.e., via the autonomic nervous system), either by intent or by side effect, do not have their usual effects on a transplanted heart. One should not expect an increased heart rate from drugs with vagolytic actions (e.g., atropine, pancuronium, meperidine), and similarly one should not expect a decreased heart rate from drugs with vagotonic actions (e.g., acetylcholinesterase inhibitors, opioids). Drugs that have both direct and indirect actions maintain their direct effects on the denervated heart. Digoxin maintains its positive inotropic effects on the graft but does not slow the heart rate through its parasympathetic mediated effects on the atrioventricular (AV) node.
Because of lack of direct sympathetic innervation of the heart, there are delayed and decreased sympathetic responses to laryngoscopy, intubation, painful stimuli, and light anesthesia. However, if a stimulus is prolonged, increasing levels of circulating catecholamines eventually result in an appropriate tachycardia or perhaps an exaggerated one through direct stimulation of myocardial adrenergic receptors.
Despite denervation, intrinsic myocardial mechanisms remain intact in the transplanted heart, as follows:
The denervated myocardium responds normally to circulating or administered catecholamines (e.g., epinephrine, norepinephrine) and direct-acting sympathomimetic agents (e.g., isoproterenol, dobutamine) through direct stimulation of myocardial adrenergic receptors. In this regard, one should be aware that denervation appears to induce a downregulation of β 1 receptors, so most β-adrenergic receptors on the denervated myocardium tend to be of the β 2 subtype.
The Frank-Starling mechanism (i.e., increased preload results in increased stroke volume) remains intact and is the primary mechanism for increased cardiac output in response to exercise or stress. For this reason, it is important to maintain adequate preload in a patient after heart transplantation. Because they already have an elevated heart rate, the only way patients after heart transplantation can initially increase cardiac output in response to increased metabolic demand is through increased stroke volume. Any further increases in heart rate and cardiac output with prolonged exercise or stress are the results of increased levels of circulating catecholamines and are slightly delayed in onset (and resolution).
Metabolic autoregulation of coronary blood flow in response to changes in acid-base status (pH) and carbon dioxide tension remains intact.
There is normal electrical impulse formation and conductivity in the transplanted heart along the usual pathways from the donor sinoatrial (SA) node, but first-degree AV block is a common finding. Previous techniques for heart transplantation involved leaving behind cuffs of native right and left atrial tissue to facilitate the anastomoses. As a result, two P waves were seen on the electrocardiogram (ECG), one from the native heart and the other from the donor heart ( Figure 10-1 ). The electrical discharge from the native SA node was unable to cross the suture line and did not result in depolarization of the donor heart. Current surgical technique involves bicaval anastomoses, so there is no native SA node left behind, and subsequently only a single P wave is expected to be seen on the ECG. The cuff of left atrial tissue contains the entry site for the four pulmonary veins.
Is reinnervation of the transplanted heart a concern?
Whether or not significant reinnervation occurs in transplanted human hearts remains to be determined. There is laboratory evidence of varying levels of functional reinnervation in nonhuman experimental models of cardiac transplantation, and there are some reports in the literature supporting varying degrees of apparent sympathetic reinnervation late in the posttransplantation period (>5 years postoperatively) in human patients. However, reinnervation appears to be incomplete at best in the human graft, and there is no evidence at the present time that reinnervation of transplanted human hearts is a clinically important phenomenon in the first few years after transplantation.