RBCs distribute oxygen to tissues, but, paradoxically, blood transfusion does not always improve oxygen delivery and is associated with ischemic events. We hypothesized that storage of blood would result in loss of NO bioactivity, impairing RBC vasodilation and thus compromising blood flow, and that repleting NO bioactivity would restore RBC function. We report that S-nitrosohemoglobin (SNO-Hb) concentrations declined rapidly after storage of fresh venous blood and that hypoxic vasodilation by banked RBCs correlated strongly with the amounts of SNO-Hb (r 2 ‫؍‬ 0.90; P < 0.0005). Renitrosylation of banked blood during storage increased the SNO-Hb content and restored its vasodilatory activity. In addition, canine coronary blood flow was greater during infusion of renitrosylated RBCs than during infusion of S-nitrosothiol-depleted RBCs, and this difference in coronary flow was accentuated by hypoxemia (P < 0.001). Our findings indicate that NO bioactivity is depleted in banked blood, impairing the vasodilatory response to hypoxia, and they suggest that SNO-Hb repletion may improve transfusion efficacy.blood preservation ͉ blood transfusion ͉ erythrocytes ͉ hypoxic vasodilation ͉ S-nitrosylation

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.

In previous studies from this laboratory, we found that approximately 30% of women with chest pain and normal coronary arteries demonstrated either a decrease in or a failure to increase radionuclide ejection fraction during exercise. To examine the hypothesis that this apparent abnormality in left ventricular function represents a physiologic difference between men and women, we prospectively studied central and peripheral cardiovascular responses to exercise in 31 age-matched healthy volunteers (16 women and 15 men). A combination of quantitative radionuclide angiography and expired-gas analysis was used to measure ejection fraction and relative changes in end-diastolic counts, stroke counts, count output, and arteriovenous oxygen difference during symptom-limited upright bicycle exercise. Normal male and female volunteers demonstrated comparable baseline left ventricular function and similar aerobic capacity, as determined by weight-adjusted peak oxygen consumption (22.1 ± 5.1 and 22.6 ± 4.3 ml/kg/min, respectively). However, their cardiac responses to exercise were significantly different. Ejection fraction increased from 0.62 ± 0.09 at rest to 0.77 0.07 during exercise in men (p < .001), but was unchanged from 0.63 0.09 at rest to 0.64 0.10 during exercise in women. The ejection fraction increased by 5 points or more in 14 of 15 men, but in only seven of the 16 women. End-diastolic counts increased by 30% in women (p < .001), but was unchanged in men. Because decreases in ejection fraction were matched by increases in end-diastolic counts, relative increases in stroke counts and count output were the same for men and women. These data demonstrate a basic difference between men and women with respect to the mechanism by which they achieve a normal response of stroke volume to exercise; these differences must be taken into account when measurements of cardiac function during exercise stress are used for diagnostic purposes

SUMMARY Seven subjects with rate-dependent left bundle branch block (RDLBBB) and 13 subjects with normal conduction (control group) underwent upright bicycle exercise radionuclide angiography to determine the effects of the development of RDLBBB on global and regional left ventricular function. Six of the seven subjects with RDLBBB had atypical chest pain syndromes; none had evidence of cardiac disease based on clinical examination and either normal cardiac catheterization or exercise thallium-201 scintigraphy. Radionuclide angiograms were recorded at rest and immediately before and after RDLBBB in the test group, and at rest and during intermediate and maximal exercise in the control group. The development of RDLBBB was associated with an abrupt decrease in left ventricular ejection fraction (LVEF) in six of seven patients (mean decrease 6 ± 5%) and no overall increase in LVEF between rest and maximal exercise (65 + 9% and 65 ± 12%, respectively). In contrast, LVEF in the control group was 62 ± 8% at rest and increased to 72 ± 8% at intermediate and 78 ± 7% at maximal exercise. The onset of RDLBBB was associated with the development of asynchronous left ventricular contraction in each patient and hypokinesis in four of seven patients. All patients in the control group had normal wall motion at rest and exercise. These data indicate that the development of RDLBBB is associated with changes in global and regional ventricular function that may be confused with development of left ventricular ischemia during exercise.THE occurrence of rate-dependent left bundle branch block (RDLBBB) during exercise treadmill testing is not uncommon in the evaluation of patients with chest pain syndromes.' Because LBBB effects secondary ST-segment changes, evaluation of myocardial ischemia using established electrocardiographic criteria is precluded. Radionuclide angiography offers a potential diagnostic alternative for assessing ventricular function in patients with RDLBBB and chest pain syndromes because measurements are not dependent on electrocardiographic criteria. However, the value of radionuclide angiography in such patients has not been established because the independent effects of RDLBBB on left ventricular function in the absence of coronary artery disease have not been determined. The purpose of this study was to determine the effects of exercise-induced RDLBBB on left ventricular ejection fraction (LVEF) and regional wall motion in a group of patients without apparent coronary artery disease. Patients with chronic LBBB at rest and no apparent coronary artery disease were also studied at rest and during exercise. Methods Patient PopulationPatients with RDLBBB in the Duke Cardiovascular Data Bank were identified and selected for a prospective study based on the following criteria: (1) normal conduction on a resting ECG and development of typical LBBB morphology with a QRS interval of 120

The objectives of this study were to define the relationship between the first order constant of Gd-DTPA transfer (K1) and the myocardial blood flow (MBF) at rest and to compare it with an equivalent relationship obtained for positron emission tomography (PET). In a canine model of permanent coronary occlusion (n = 4), myocardial and blood time concentration curves obtained by 13N-ammonia PET and Gd-DTPA-enhanced MRI were fitted by a one-compartment model to determine K1. A linear relationship was observed between MRI-derived K1 and MBF measured by microspheres (K1 = 0.88 x flow -0.015, R = 0.95), which compares favorably with the equivalent relationship derived from PET (K1 = 0.74 x flow +0.16, R = 0.88). The results of this preliminary study suggest that, at rest and distal to a permanently occluded coronary artery, myocardial perfusion quantification by MRI is possible and can challenge PET.