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CLINICAL STUDIES

High dose angiotensin-converting enzyme inhibition prevents fluid volume expansion in heart transplant recipients

Randy W. Braith, PhD^*, Roger M. Mills, MD, FACC, Christopher S. Wilcox, MD, PhD^||, Matthew J. Mitchell, MS^*, James A. Hill, MD, FACC and Charles E. Wood, PhD

^* Center for Exercise Science, College of Health and Human Performance, University of Florida, Gainesville, Florida, USA
Department of Medicine, University of Florida, Gainesville, Florida, USA
Department of Physiology University of Florida, Gainesville, Florida, USA
Cleveland Clinic, Cleveland, Ohio, USA
^|| Department of Medicine, Georgetown University, Washington, DC, USA

Manuscript received October 22, 1999; revised manuscript received February 22, 2000, accepted April 5, 2000.

Reprint requests and correspondence: Dr. Randy W. Braith, P.O. Box 118206, Center for Exercise Science, University of Florida, Gainesville, Florida 32611
rbraith{at}hhp.ufl.edu

OBJECTIVES

We sought to test the hypothesis that plasma volume (PV) expansion in heart transplant recipients (HTRs) is caused by failure to reflexively suppress the renin-angiotensin-aldosterone (RAA) axis.

BACKGROUND

Extracellular fluid volume expansion occurs in clinically stable HTRs who become hypertensive. We have previously demonstrated that the RAA axis is not reflexively suppressed by a hypervolemic stimulus in HTRs.

METHODS

Plasma volume and fluid regulatory hormones were measured in eight HTRs (57 ± 6 years old) both before and after treatment with captopril (225 mg/day). Antihypertensive and diuretic agents were discontinued 10 days before. The HTRs were admitted to the Clinical Research Center (CRC), and, after three days of a constant diet containing 87 mEq/day of Na⁺, PV was measured by using the modified Evans blue dye dilution technique. After approximately four months (16 ± 5 weeks), the same HTRs again discontinued all antihypertensive and diuretic agents; they were progressed to a captopril dose of 75 mg three times per day over 14 days, and the CRC protocol was repeated.

RESULTS

Captopril pharmacologically suppressed (p < 0.05) supine rest levels of angiotensin II (–65%) and aldosterone (–75%). The reductions in vasopressin and atrial natriuretic peptide levels after captopril did not reach statistical significance. The PV, normalized for body weight (ml/kg), was significantly reduced by 12% when the HTRs received captopril.

CONCLUSIONS

Extracellular fluid volume is expanded (12%) in clinically stable HTRs who become hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril (225 mg/day) returned HTRs to a normovolemic state. These findings indicate that fluid retention is partly engendered by a failure to reflexively suppress the RAA axis when HTRs become hypervolemic.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ANOVA = analysis of variance   ANP = atrial natriuretic peptide   AVP = arginine vasopressin   CRC = Clinical Research Center   Hct = hematocrit   HTRs = heart transplant recipients   PV = plasma volume   RAA = renin-angiotensin-aldosterone

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				H. J. Eisen Hypertension in heart transplant recipients: more than just cyclosporine J. Am. Coll. Cardiol., February 5, 2003; 41(3): 433 - 434. [Full Text] [PDF]