FLUID HOMEOSTASIS AFTER HEART-TRANSPLANTATION - THE ROLE OF CARDIAC DENERVATION

Background: Orthotopic heart transplantation may interrupt key neural and humoral homeostatic mechanisms that normally adjust Na+ and fluid excretion to changes in intake. Such an interruption could lead to pla sma volume expansion. Methods: We measured plasma volume and fluid reg ulatory hormones under standardized conditions in ii heart transplant recipients (58 +/- 7 years old; mean +/- standard deviation) months af ter transplantation (cyclosporine control group), and in 7 normal heal thy control subjects (61 +/- 9 years old). Administration of ail diure tics and antihypertensive drugs was discontinued before the study. Aft er 3 days during which subjects are a constant diet containing 87 mEq of Na+ per 24 hours, plasma volume was measured by a modified Evans bl ue dye (T-1824) dilution technique. Renal creatinine clearance was mea sured and blood samples were drawn for determination of plasma levels of vasopressin, angiotensin II, aldosterone, atrial natriuretic peptid e, and plasma renin activity. Results: Supine resting plasma renin act ivity, angiotensin II, and aldosterone (renin-angiotensin-aldosterone axis) and vasopressin levels were not different among the control, hea rt transplant, and liver transplant groups. However, there vas a trend toward elevated angiotensin II (p less than or equal to 0.08) and ald osterone (p less than or equal to 0.08) levels in the heart transplant recipients. Atrial natriuretic peptide Ici els were significantly ele vated two ro threefold in the heart transplant recipients when compare d with those in the two control groups. Blood volume. normalized for b ody weight (milliliters per kilogram), was significantly greater (14%) in the heart transplant recipients when compared with that in liver t ransplant recipients and normal healthy control subjects. Blood volume values did not differ (p greater than or equal to 0.05) between the t wo control groups, Conclusions: Extracellular fluid volume expansion ( +14%) occurs in clinically stable heart transplant recipients who beco me hypertensive. Although hyperactivity of the renin-angiotensin-aldos terone axis is not apparent during supine resting conditions. our data suggest that the renin-angiotensin-aldosterone system is not responsi ve to a hypervolemic stimulus and this is likely a consequence of chro nic cardiac deafferentation. Thus, poor adaptation of the renin-angiot ensin-aldosterone system to fluid retention may be partly responsible for the incidence and severity of posttransplantation hypertension in some heart transplant recipients.