The role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries in chronically instrumented awake dogs was studied by examining the consequences of inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NGmonomethyl-L-arginine (L-NMMA). In four awake dogs, coronary dimension crystals were chronically implanted on the circumflex artery for the measurement of epicardial coronary diameter, and Doppler flow probes were implanted for quantitation of phasic coronary blood flow (vasomotion of distal regulatory resistance vessels). Basal epicardial coronary diameter, acetylcholine-stimulated endothelium-dependent dilation, and flow-induced endothelium-dependent dilation of the epicardial arteries and phasic blood flow were recorded before, and after 5, 15, 50, and 120 mg/kg of L-NMMA. L-NMMA induced a dose-related increase in basal epicardial coronary vasomotor tone. There was an accompanying increase in aortic pressure and a decrease in heart rate. At doses 2 50 mg/kg, rest phasic coronary blood flow was also decreased. Left ventricular enddiastolic pressure and contractility were not significantly changed. In contrast, the flow-induced or acetylcholine-stimulated endothelium-dependent responses were attenuated only after infusion of the highest doses of L-NMMA (120 mg/kg). The changes in the basal vasomotor tone and acetylcholinestimulated endothelium-dependent responses returned towards the control states in the presence of L-arginine (660 mg/kg). These data support the view that nitric oxide plays a significant role in modulating basal vasomotion and endothelial-dependent dilation stimulated by acetylcholine or increase in blood flow in epicardial coronary arteries and also influence the regulation of coronary blood flow during physiologic conditions. (J. Clin.

There is no gold standard for the measurement of pulmonary regurgitation (PR) severity. Two-dimensional (2D) transthoracic echocardiography is most commonly used to quantify PR severity using color Doppler criteria for aortic regurgitation. However, this method is limited by visualization of only one or two dimensions of the proximal PR jet or vena contracta (VC) precluding accurate assessment of its shape or size. This limitation would be expected to be obviated by three-dimensional (3D) transthoracic echocardiography, which could provide a more accurate quantitative assessment of PR severity. This study evaluated 82 adult patients with PR using 2D and 3D. PR VC area by 3D was obtained by planimetry by positioning the cropping plane exactly parallel to the VC, which was viewed en face by cropping of the 3D data set. Regurgitant volumes were calculated by 2D (assuming a circular VC) and by 3D as a product of the VC and velocity time integral obtained by color Doppler-guided conventional Doppler interrogation of the PR jet.The 3D VC area correlated with 2D jet width (JW)/right ventricular outflow tract (RVOT) width (r = 0.71) and 2D VC area (r = 0.79). 3D JW/RVOT width correlated with 2D JW/RVOT (r = 0.87). 3D regurgitant volumes also correlated with 2D regurgitant volumes (r = 0.76). The 3D VC values of <0.20, 0.20-0.45, 0.46-1.15, and >1.15 cm(2) and regurgitant volumes of <15 ml, 15-50 ml, 51-115 ml, and >115 ml were effective as cutoffs for grades 1, 2, 3, and 4 PR, respectively. In conclusion, quantification of 3D VC area and regurgitant volumes correlate reasonably well with the current 2D methods for measurement of PR. Since 3D visualizes PR VC in three dimensions, it would be expected to provide a more accurate and more quantitative assessment of PR severity as compared to 2D.

This study evaluates the role of endogenous nitric oxide in the modulation of basal coronary vasomotor tone by studying the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide formation from L-arginine, on resting epicardial coronary diameter and coronary flow. L-NMMA (5 mg/kg) was infused in seven awake dogs chronically instrumented with coronary dimension crystals for measurement of epicardial coronary diameter, and Doppler flow probes for quantitation of phasic coronary flow (vasomotion of distal regulatory resistance coronary vessels). Epicardial coronary diameter decreased 5.5% from 3.47 +/- 0.17 to 3.28 +/- 0.15 mm (mean +/- SE). The diameter change was gradual, reaching a maximum at 13 +/- 2 min after infusion, and persistent, lasting greater than 90 min. Phasic coronary flow did not change. Mean aortic pressure significantly increased from 99 +/- 3 to 111 +/- 3 mmHg and heart rate decreased from 56 +/- 4 to 46 +/- 3 beats/min. Left ventricular end-diastolic pressure and contractility were not significantly altered. L-Arginine (66 mg/kg) but not D-arginine reversed all hemodynamic parameters. These data support an important role of nitric oxide in modulating basal epicardial coronary vasomotor tone and systemic vascular resistance.

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The effects of atrial natriuretic peptide (ANP) on transmural myocardial blood flow distribution and the reactive hyperemic response in the presence and absence of flow-limiting coronary stenosis were examined in chronically instrumented conscious dogs. Ten-second coronary occlusion without subsequent flow restriction resulted in marked reactive hyperemic responses (Doppler flow probes), mean flow debt repayment was 481 +/- 55%. When the 10-second coronary occlusions were followed by a 20-second partial restriction that allowed normal preocclusion coronary inflow, the subsequent reactive hyperemia was significantly augmented, mean flow debt repayment was 938 +/- 91% (p less than 0.05). Pretreatment with ANP (3 micrograms/kg) did not alter the flow debt repayment after a 10-second occlusion without restriction (474 +/- 30%, NS) but attenuated the augmentation of reactive hyperemia resulting from the 20-second inflow restriction, flow debt repayment (613 +/- 66%, NS). Regional myocardial blood flow to the ischemic region was measured during restricted inflow after a 10-second coronary occlusion before and after ANP pretreatment. Before ANP, subendocardial flow decreased (0.54 +/- 0.04 ml/min/g) and subepicardial flow significantly increased (1.03 +/- 0.12 ml/min/g) when compared with the nonischemic zone (subendocardial, 1.03 +/- 0.09 ml/min/g; subepicardial, 0.87 +/- 0.09 ml/min/g, p less than 0.05), indicating maldistribution of the restricted inflow. The resultant subendocardial-to-subepicardial ratio in the ischemic region was significantly decreased when compared with the nonischemic region (0.56 +/- 0.03 vs. 1.18 +/- 0.04, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)