NEUROENDOCRINE RESPONSE TO CARDIAC TRANSPLANTATION

OBJECTIVE: The neuroendocrine response to heart transplantation was ch aracterized in 11 patients with special reference to long term effects on plasma hormone concentration. DESIGN: Multiple serial measurements of preload, ejection fraction, plasma renin activity (PRA), aldostero ne, atrial natriuretic factor (ANF) and catecholamines were made over time. SETTING: Tertiary care cardiac referral, university based centre . PATIENTS: Eleven adult patients undergoing orthotopic cardiac transp lantation were studied. The group consisted of 10 males and one female (mean age 52+/-2 years). Eight patients had coronary atherosclerosis, two had idiopathic cardiomyopathy and one had valvular heart disease. All patients were in end-stage heart failure (Canadian Cardiovascular Society class IV) and two also had angina. INTERVENTIONS: Right heart catheterization and hormonal assays in blood were performed simultane ously preoperatively and postoperatively at 24 h, 48 h and during each endomyocardial biopsy. An endomyocardial biopsy to detect rejection w as performed weekly for two to four weeks, then every three to four mo nths at one year postoperatively. Hemodynamic measurements included ce ntral venous pressure (CVP) and pulmonary capillary wedge pressures (P CWP). Ejection fraction was measured in each patient using radionuclid e ventriculography preoperatively and serially through the post-operat ive period. MAIN RESULTS: Following transplantation, transient elevati on of intra-cardiac filling pressures occurred. The CVP and PCWP were elevated at 15+/-2 and 17+/-1 mmHg, respectively, early postoperativel y (ie, days 2 to 30 postsurgery). Late postoperatively (ie, more than 30 days postoperatively), the CVP and PCWP decreased to 8+/-1 and 12+/ -1 mmHg, respectively. Systolic function, as measured by radionuclide ejection fraction, did not change significantly from the early to the late postoperative period (60+/-5% early versus 59+/-2% late postopera tively). PRA and plasm aldosterone fell in association with the decrea se in filling pressures (PRA was 2.4+/-0.8 ng/ml/h early versus 1.0+/- 0.2 ng/ml/h late; plasma aldosterone was 122+/-31 pg/mL early versus 1 03+/-16 pg/mL late). Plasma aldosterone levels were similar in the ear ly and late postoperative periods, except during the first day after s urgery during which a transient elevation occurred. ANF remained marke dly elevated despite the fall in filling pressure (323+/-50 pg/mL preo peratively, 360+/-33 pg/mL early postoperatively and 322+/-31 pg/mL la te postoperatively). CONCLUSIONS: The authors conclude that transient cardiac dysfunction occurs following cardiac transplantation with elev ation of filling pressures and continued increased activity of the ren in-angiotensin-aldosterone system (RAAS) and elevated plasma ANF level s. With return of cardiac function and normalization of filling pressu res, the activity levels of the RAAS decrease, but not those of ANF, w hich remain chronically abnormally elevated. It is not clear whether t his persistent elevation of ANF is the result of factors related to th e transplant procedure, such as extrinsic denervation or antirejection therapy, among others, or is the persistence of factors acting preope ratively. However, known interactions of cyclosporine with vascular sm ooth muscle and endothelial cells leading to increased sensitivity to vasopressor hormones and increased circulating levels of endothelin ap pear as the most likely explanation for the chronic elevation of ANF p lasma levels. In this context, ANF may play a key role in moderating t he side effects of cyclosporine treatment.