The Nitric Oxide Donor ITF 1129 Augments Subendocardial Blood Flow During Exercise-Induced Myocardial Ischemia

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Abstract
The effect of the nitric oxide donor ITF 1129 and nitroglycerin (NTG) on myocardial blood flow was examined in dogs with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD). Studies were performed during treadmill exercise in the presence of a coronary artery stenosis. The effects of ITF 1129 in doses of 3 and 10 micrograms/kg/min i.v. were compared with NTG (2 micrograms/kg/min i.v.). Neither ITF 1129 nor NTG caused significant alteration of heart rate, arterial blood pressure, or left ventricular systolic pressure. During partial inflation of the occluder to decrease distal coronary pressure to 55 +/- 2 mm Hg, mean myocardial blood flow measured with microspheres was 0.72 +/- 0.14 ml/min/g in the region perfused by the stenotic coronary artery compared with 2.93 +/- 0.40 ml/min/g in a normally perfused control region. With no change in distal coronary pressure, ITF 1129 increased mean myocardial blood flow in the stenosis perfused region to 1.15 +/- 0.24 ml/min/g (3 micrograms/kg/min i.v.) and to 1.20 +/- 0.28 ml/ min/g (10 micrograms/kg/min i.v.), whereas NTG (2 micrograms/kg/min iv) increased blood flow to 1.16 +/- 0.22 ml/min/g (each p < 0.05). The increase in myocardial blood flow produced by ITF 1129 or NTG occurred principally in the deeper myocardial layers with no change in subepicardial flow. As a result, the subendocardial/subepicardial blood flow ratio (ENDO/EPI) increased from 0.44 +/- 0.09 during control stenosis to 0.85 +/- 0.13 after ITF 1129 (10 micrograms/kg/min i.v.) and to 0.81 +/- 0.12 after NTG. Neither ITF 1129 nor NTG significantly altered myocardial blood flow in the normally perfused control region. The effect of ITF 1129 and NTG on myocardial perfusion occurred without alterations of distal coronary pressure or left ventricular diastolic pressure, indicating a primary effect on the intramural coronary microvasculature.