Effect of NO donors on LV diastolic function in patients with severe pressure-overload hypertrophy.
BACKGROUND
Previous experimental studies have shown that nitric oxide (NO) modulates cardiac function by an abbreviation of systolic contraction and an enhancement of diastolic relaxation. However, the response to NO donors of patients with severe pressure-overload hypertrophy and diastolic dysfunction is unknown.


RESULTS
Intracoronary NO donors were given to 17 patients with severe aortic stenosis. A dose-response curve was obtained with nitroglycerin (30, 90, and 150 microg) in 11 patients and sodium nitroprusside (1, 2, and 4 microg/min) in 6. Left ventricular (LV) high-fidelity pressure measurements with simultaneous LV angiograms were performed at baseline and after the maximal dose of NO. The dose-response curve for intracoronary NO donors showed a marked fall in LV end-diastolic pressure, from 23 to 14 mm Hg (-39%; P<0.0001), whereas LV peak systolic pressure fell only slightly, from 206 to 196 mm Hg (-4%; P<0.01). End-diastolic chamber stiffness decreased from 0.12 to 0.07 mm Hg/mL (P<0.0001) and end-systolic stiffness from 1.6 to 1.3 mm Hg/mL (P<0.01). Heart rate, right atrial pressure, LV ejection fraction, the time constant of isovolumic pressure decay (tau), and LV filling rates remained unchanged.


CONCLUSIONS
In patients with severe pressure-overload hypertrophy, intracoronary NO donors exert a marked decrease in LV end-diastolic pressure without affecting LV systolic pump function. Thus, the hypertrophied myocardium appears to be particularly susceptible to NO donors, with a marked improvement in diastolic function.
D000328:Adult; D000368:Aged; D001024:Aortic Valve Stenosis / Q000150:complications*; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D003971:Diastole / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000627:therapeutic use*; D009599:Nitroprusside / Q000008:administration & dosage / Q000627:therapeutic use*; D013599:Systole / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure