Author + information
- Received December 23, 2003
- Revision received March 31, 2004
- Accepted April 20, 2004
- Published online September 15, 2004.
- John M. McCurley, MD*,
- Stephen U. Hanlon, MD*,
- Shao-kui Wei, MD*,
- Erich F. Wedam, MD†,
- Michael Michalski, MD‡ and
- Mark C. Haigney, MD*,* ()
- ↵*Reprint requests and correspondence:
Dr. Mark C. Haigney, Division of Cardiology, Uniformed Services University of the Health Sciences, Room A3060, 4301 Jones Bridge Road, Bethesda, Maryland 20814
Objectives We tested the hypothesis that furosemide accelerates the progression of left ventricular systolic dysfunction in a tachycardia-induced porcine model of heart failure.
Background Furosemide activates the renin-angiotensin-aldosterone system in patients with congestive heart failure (CHF). Such activation may contribute to CHF progression, but prospective data are lacking.
Methods Thirty-two Yorkshire pigs were randomized to furosemide (1 mg/kg intramuscularly daily, mean 16.1 ± 0.9 mg) or placebo. Thereafter, a pacing model of heart failure was utilized to produce systolic dysfunction in both sets of animals (fractional shortening <0.16 by echocardiogram). The goal was to determine if furosemide would accelerate the progression of left ventricular dysfunction in the “treated” group. After sacrifice, sodium-calcium exchanger currents and their responsiveness to isoproterenol were measured during voltage clamp. All investigators were blinded to treatment assignment.
Results Furosemide shortened the time to left ventricular dysfunction (35.1 ± 5.1 days in placebo versus 21.4 ± 3.2 days for furosemide animals; p = 0.038, log-rank test). By day 14, aldosterone levels were significantly higher in furosemide animals (43.0 ± 11.8 ng/dl vs. 17.6 ± 4.5 ng/dl; p < 0.05). Serum sodium was reduced (133.0 ± 0.9 mmol/l furosemide vs. 135.7 ± 0.8 mmol/l placebo; p < 0.05), but no difference in norepinephrine, potassium, magnesium, creatinine, or urea nitrogen was present. Basal sodium-calcium exchanger currents were significantly increased and isoproterenol responsiveness depressed by furosemide.
Conclusions Tachycardic pigs given furosemide had significant acceleration of both contractile and metabolic features of CHF, including left ventricular systolic dysfunction, elevated serum aldosterone levels, and altered calcium handling in a controlled experimental model of heart failure.
Drs. McCurley and Hanlon contributed equally to this work. The views expressed in this paper reflect the opinions of the authors only and are not the official policy of the Uniformed Services University, the United States Navy, or the Department of Defense.
- Received December 23, 2003.
- Revision received March 31, 2004.
- Accepted April 20, 2004.
- American College of Cardiology Foundation