ACUTE EFFECTS OF NITRIC-OXIDE ON LEFT-VENTRICULAR RELAXATION AND DIASTOLIC DISTENSIBILITY IN HUMANS - ASSESSMENT BY BICORONARY SODIUM-NITROPRUSSIDE INFUSION

Background In isolated mammalian cardiomyocytes, papillary muscle prep arations, and ejecting hearts, nitric oxide (NO) or other cyclic GMP-e levating interventions increase diastolic cell length and reduce peak contractile performance by hastening onset of myocardial relaxation. I n the present study, the effect of NO on left ventricular (LV) relaxat ion and diastolic distensibility was investigated in humans. Methods a nd Results The NO donor substance sodium nitroprusside was infused dur ing cardiac catheterization in the global coronary bed of the LV of pa tients (n=13) investigated for chest pain who were without evidence of obstructive coronary artery or other cardiac disease. Sodium nitropru sside was infused intracoronarily at a dosage (less than or equal to 4 mu g/min) that was previously shown to be devoid of systemic effects when infused into the brachial artery to investigate the reactivity of the forearm vascular bed. The effect of this global intracoronary inf usion of the NO donor sodium nitroprusside was assessed by sequential LV angiograms and tip-micromanometer pressure recordings. During globa l intracoronary nitroprusside infusion, there was a decrease in heart rate from 78+/-11 to 76+/-12 beats per minute (P<.05), in LV peak syst olic pressure from 161+/-18 to 146+/-18 mm Hg (P<.001), and in time to onset of LV relaxation (interval from Q wave on the ECG to LV dP/dt(m in)) from 432+/-36 to 419+/-36 milliseconds (P<.01). In 7 patients in whom adequate sequential LV angiograms could be obtained, LV end-diast olic volume increased from 158+/-34 to 165+/-40 mL (P<.05), whereas LV end-diastolic pressure fell from 18+/-5 to 12+/-3 mm Hg (P<.02), and in 5 of these 7 patients, a downward shift of the diastolic LV pressur e-volume relation was observed. In 5 patients, a right atrial infusion of sodium nitroprusside was performed either before (n=2) or after th e global intracoronary infusion. The decrease in LV peak systolic pres sure observed during right atrial infusion was significantly smaller ( P<.01) than during global intracoronary infusion. Conclusions The pres ent study reveals reduced LV pressure development, an LV relaxation-ha stening effect, and improved LV diastolic distensibility during global intracoronary infusion of the NO donor substance sodium nitroprusside . These effects appeared to be unrelated to systemic vasodilation or t o pericardial constraint and could be explained by a direct myocardial effect of NO, probably through activation of guanylyl cyclase to incr ease cyclic GMP or through modification of other cellular proteins.