Effects of B-type natriuretic peptide (nesiritide) on coronary epicardial arteries, systemic vasculature and microvessels.
BACKGROUND
Nesiritide is recombinant human B-type natriuretic peptide, used in the treatment of decompensated heart failure. Ischemic heart disease remains the major underlying cause for congestive heart failure, however, the effects of intravenous and intracoronary nesiritide on coronary circulation have not been adequately studied.


METHODS
Fourteen Yorkshire pigs were used to systematically evaluate the effects of intravenous and intracoronary nesiritide on microvascular function, coronary blood flow, and epicardial and microvascular reactivity using in vivo hemodynamic parameters, Doppler flow assessment (average peak velocity, APV) and intravascular ultrasound (cross-sectional area, CSA), and in vitro microvascular function.


RESULTS
The clinically used dose of nesiritide caused a small (not statistically significant) decrease in blood pressure at 10 minutes (p = 0.6411); blood pressure returned to baseline at 30 minutes and did not affect coronary flow or diameter. Intracoronary nesiritide (100 mcg) resulted in a slight increase (trend) in coronary flow (increase from 15.8 to 19 cm/s; p = 0.6), but no change in CSA. Nesiritide caused significant microvascular relaxation in vitro (p = 0.009), attenuated by pretreatment with L-NAME indicating that vasodilation is partially nitric oxide-dependent.


CONCLUSIONS
Intravenous and intracoronary nesiritide do not result in adverse effects on the normal coronary circulation in pigs. In contrast it has profound effects on microvessels with potentially beneficial effects on the myocardial perfusion at the tissue level. Further studies are needed to assess its effects on diseased coronary circulation and its safety in patients with ischemic heart disease.
Wu
Gui Fu
GF
Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA. rlaham@bidmc.harvard.edu.
Wykrzykowska
Joanna J
JJ
Rana
Jamal S
JS
Pinto
Duane S
DS
Gibson
C Michael
CM
Li
Jian
J
Sellke
Frank W
FW
Laham
Roger J
RJ
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D015150:Echocardiography, Doppler; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008833:Microcirculation / Q000187:drug effects; D045283:Natriuretic Agents / Q000494:pharmacology*; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects*; D013552:Swine
D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain