Neuroendocrine response to cardiac transplantation

The neuroendocrine response to heart transplantation was characterized in 11 patients with special reference to long term effects on plasma hormone concentration.

Multiple serial measurements of preload, ejection fraction, plasma renin activity (PRA), aldosterone, atrial natriuretic factor (ANF) and catecholamines were made over time.

Tertiary care cardiac referral, university-based centre.

Eleven adult patients undergoing orthotopic cardiac transplantation 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.

Right heart catheterization and hormonal assays in blood were performed simultaneously preoperatively and postoperatively at 24 h, 48 h and during each endomyocardial biopsy. An endomyocardial biopsy to detect rejection was performed weekly for two to four weeks, then every three to four months at one year postoperatively. Hemodynamic measurements included central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP). Ejection fraction was measured in each patient using radionuclide ventriculography preoperatively and serially through the postoperative period.

Following transplantation, transient elevation of intracardiac filling pressures occurred. The CVP and PCWP were elevated at 15 +/- 2 and 17 +/- 1 mmHg, respectively, early postoperatively (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 postoperatively). PRA and plasma aldosterone fell in association with the decrease 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 103 +/- 16 pg/mL late). Plasma aldosterone levels were similar in the early and late postoperative periods, except during the first day after surgery during which a transient elevation occurred. ANF remained markedly elevated despite the fall in filling pressures (323 +/- 50 pg/mL preoperatively, 360 +/- 33 pg/mL early postoperatively and 322 +/- 31 pg/mL late postoperatively).

The authors conclude that transient cardiac dysfunction occurs following cardiac transplantation with elevation of filling pressures and continued increased activity of the renin-angiotensin-aldosterone system (RAAS) and elevated plasma ANF levels. With return of cardiac function and normalization of filling pressures, the activity levels of the RAAS decrease, but not those of ANF, which remain chronically abnormally elevated. It is not clear whether this persistent elevation of ANF is the result of factors related to the transplant procedure, such as extrinsic denervation or antirejection therapy, among others, or is the persistence of factors acting preoperatively. However, known interactions of cyclosporine with vascular smooth muscle and endothelial cells leading to increased sensitivity to vasopressor hormones and increased circulating levels of endothelin appear as the most likely explanation for the chronic elevation of ANF plasma levels. In this context, ANF may play a key role in moderating the side effects of cyclosporine treatment.