Effects of Atrial Natriuretic Peptide on Left Ventricular Performance in Conscious Dogs Before and After Pacing-Induced Heart Failure1
Abstract
Atrial natriuretic peptide (ANP) has potent vasodilatory and natriuretic actions and may have therapeutic benefit in congestive heart failure (CHF). These benefits may be offset by a negative inotropic effect of ANP seen in isolated preparations. However, ANP’s integrated effect on left ventricular (LV) contraction and relaxation, independent of loading conditions, both under normal conditions and after CHF, is not known. We studied six conscious dogs, instrumented to measure LV and left atrial pressures and to determine LV volume from three dimensions. ANP produced significant (P < .05) decreases in LV end-systolic pressure (101.2 ± 11.8 versus 91.7 ± 11.2 mm Hg, P < .05) in normal dogs and in dogs with CHF (93.1 ± 6.4 versus 87.1 ± 4.4 mm Hg,P < .05). ANP also caused significant reductions of the slope of end-systolic pressure-end-systolic volume relation both before (7.0 ± 1.5 versus 6.3 ± 1.5 mm Hg/ml) and after CHF (4.8 ± 1.3 versus 4.4 ± 1.2 mm Hg/ml, P< .05). Both before and after CHF, ANP slowed LV relaxation at matched end-systolic pressure. Before CHF, steady-state stroke volume and peak LV filling rate (dV/dtmax) were reduced. However, after CHF, the fall in end-systolic pressure more than offset the load-independent LV depression, as stroke volume, the rate LV relaxation, and dV/dtmax were increased and minimum LV pressure reduced. ANP has negative effects on LV contractility and relaxation both before and after CHF. However, after CHF, afterload reduction with ANP overcomes its negative effects, resulting in net improvement of LV ejection and relaxation. Thus, the direct cardiodepressant effects of ANP should not limit its usefulness in CHF.
Footnotes
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Send reprint requests to: Dr. Che-Ping Cheng, Section of Cardiology,Wake Forest University School of Medicine, Bowman Gray Campus, Medical Center Blvd., Winston-Salem, NC 27157. E-mail:ccheng{at}wfubmc.edu
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↵1 This study was supported in part by Grants HL45258 and HL53541 from the National Institutes of Health, Grant 9640189 from the American Heart Association, and a grant from the Alcohol Beverage Medical Research Foundation.
- Abbreviations:
- ANP
- atrial natriuretic peptide
- CHF
- congestive heart failure
- LV
- left ventricular
- LA
- left atrial
- PED
- end-diastolic pressure
- PES
- end-systolic pressure
- VED
- end-diastolic volume VES, end-systolic volume
- VLV
- LV volume
- P-V
- pressure volume
- SW
- stroke work
- SV
- stroke volume
- T
- time constant of LV relaxation
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- Received February 3, 1999.
- Accepted June 25, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
