Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting.

The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS). The fatty livers were retrieved and preserved for 4 h using either CS in histidine-tryptophan-ketoglutarate or SMP in polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 h at 37°C. SMP resulted in significant reductions in not only parenchymal alanine aminotransferase (p < 0.001), but also mitochondrial glutamate dehydrogenase (p < 0.001) enzyme release. Moreover, portal venous pressure (p = 0.047), tissue adenosine triphosphate (p = 0.001), bile production (p < 0.001), high-mobility group box protein-1 (p < 0.001), lipid peroxidation, and tissue glutathione were all significantly improved by SMP. Electron microscopy revealed that SMP alleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMP could protect 50-60% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools.

Dopamine as a novel antioxidative agent for rat vascular smooth muscle cells through dopamine D(1)-like receptors.

BACKGROUND: To elucidate the roles of vascular D(1)-like receptors in atherosclerosis, the effects of the specific D(1)-like agonists on platelet-derived growth factor (PDGF)-BB-mediated oxidative stress in vascular smooth muscle cells (VSMCs) were studied. METHODS AND RESULTS: Immunohistochemical studies demonstrated the coexistence of D(1A) and D(1B) dopamine receptors in VSMCs. Western blotting revealed a band of approximately 70 kDa for D(1A) and D(1B) dopamine receptors. VSMCs stimulated by PDGF-BB exhibited increased oxidative stress directly measured by flow cytometry. These effects were prevented by dopamine, SKF 38393, or YM 435, and this prevention was reversed by Sch 23390. These effects were blocked by a specific protein kinase A (PKA) inhibitor, N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H 89). The PDGF-BB-mediated increase in oxidative stress of VSMCs was significantly suppressed by the indirect phospholipase D (PLD) inhibitor suramin or the specific protein kinase C (PKC) inhibitor calphostin C. Both antisense but neither sense nor scrambled oligonucleotides to D(1A) and D(1B) receptors inhibited dopamine-induced suppression of increase in oxidative stress of VSMCs induced by PDGF-BB. CONCLUSIONS: These findings suggest that vascular D(1)-like receptors (D(1A) and D(1B) receptors) inhibit any increase in oxidative stress of VSMCs, possibly through activation of PKA and suppression of PLD and PKC.

Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.

BACKGROUND: There is accumulating data that acute coronary syndromes relate to recent onset activation of inflammation affecting atherosclerotic plaques. Increased blood levels of oxidized low density lipoprotein (ox-LDL) could play a role in these circumstances. METHODS AND RESULTS: Ox-LDL levels were measured in 135 patients with acute myocardial infarction (AMI; n=45), unstable angina pectoris (UAP; n=45), and stable angina pectoris (SAP; n=45) and in 46 control subjects using a sandwich ELISA method. In addition, 33 atherectomy specimens obtained from a different cohort of patients with SAP (n=10) and UAP (n=23) were studied immunohistochemically for ox-LDL. In AMI patients, ox-LDL levels were significantly higher than in patients with UAP (P<0.0005) or SAP (P<0.0001) or in controls (P<0.0001) (AMI, 1.95+/-1.42 ng/5 microgram LDL protein; UAP, 1.19+/-0.74 ng/5 microgram LDL protein; SAP, 0.89+/-0.48 ng/5 microgram LDL protein; control, 0.58+/-0.23 ng/5 microgram LDL protein). Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In the atherectomy specimens, the surface area containing ox-LDL-positive macrophages was significantly higher in patients with UAP than in those with SAP (P<0.0001). CONCLUSIONS: This study demonstrates that ox-LDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of ox-LDL-positive macrophages. These observations suggest that increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions.

Noninvasive assessment of left internal mammary artery graft patency using duplex Doppler echocardiography from supraclavicular fossa.

OBJECTIVES: The purpose of this study was to clarify the usefulness of duplex Doppler echocardiography from the supraclavicular fossa for assessment of left internal mammary artery graft patency. BACKGROUND: A noninvasive method to assess coronary artery bypass graft patency would be useful for clinical diagnosis and long-term follow-up of graft outcome. METHODS: Duplex Doppler echocardiography from the supraclavicular fossa was performed in 56 consecutive patients who underwent postoperative cardiac catheterization studies, including quantitative angiography. All patients underwent coronary artery bypass graft surgery using the left internal mammary artery graft to the left anterior descending coronary artery. RESULTS: The left internal mammary artery graft and its flow were detected in 55 (98%) of the 56 patients with duplex Doppler echocardiography from the supraclavicular fossa. According to the quantitative angiographic data, the patients were assigned to three groups: group A (36 patients) with a normal left internal mammary artery graft (< 50% diameter stenosis), group B (9 patients) with intermediate (50% to 75% diameter) graft stenosis and group C (10 patients) with severe (> 75% diameter) graft stenosis. The diastolic/systolic peak velocity ratio was smaller in group C than in groups A and B (p < 0.05), but there was no significant difference between groups A and B. A diastolic/systolic peak velocity ratio < 0.6 predicted severe left internal mammary artery graft stenosis (> 75% diameter stenosis) with a sensitivity and specificity of 100% and 80%, respectively. The diastolic fraction of time-velocity integral was smaller in group C than in groups A and B (p < 0.05), but there was no significant difference between groups A and B. A diastolic fraction < 0.5 predicted significant left internal mammary artery graft stenosis (> 75% diameter stenosis) with a sensitivity and specificity of 90% and 100%, respectively. CONCLUSIONS: Duplex Doppler echocardiography from the supraclavicular fossa is useful for noninvasive assessment of left internal mammary artery graft patency.

Noninvasive diagnosis of coronary artery fistula by Doppler color flow mapping.

Sixteen patients with coronary artery fistula proved by coronary angiography or surgery were studied using two-dimensional echocardiography and Doppler color flow mapping. The coronary artery fistula drained into the right atrium in 4 patients, the right ventricle in 2 and the pulmonary artery in 10. The dilated coronary artery was visualized in 7 of the 16 patients with a fistula, as compared with none of the 40 control subjects. These 7 patients included 5 of 6 patients with a fistula draining into the right atrium or right ventricle and only 2 of 10 patients with a fistula draining into the pulmonary artery. Abnormal flow signals in the dilated coronary artery were visualized with Doppler color flow mapping in five of these seven patients. Color flow imaging visualized abnormal flow signals with mosaic appearance in the pulmonary artery in eight patients, the right atrium in four and the right ventricle in two. The chamber in which abnormal signals were detected corresponded with the entry site of the fistula by angiography. Intraoperative imaging during surgical repair was needed in two cases to confirm ligation of all arteries feeding into the fistula network. In conclusion, Doppler color flow imaging is diagnostically useful to visualize shunt flows originating from the opening or exit of a coronary artery fistula. Furthermore, intraoperative use of this technique may provide confirmation of successful surgical ligation of the fistula.

Improved diagnosis and characterization of left ventricular pseudoaneurysm by Doppler color flow imaging.

Three patients with a left ventricular pseudoaneurysm are presented. Doppler color flow imaging helped to establish the diagnosis and was able to show additional blood flow abnormalities. The guided continuous wave Doppler interrogation of the shunting blood flow through the communication between the pseudoaneurysm and the left ventricle allowed the identification of a specific diagnostic flow pattern. Doppler color flow imaging offers advantages in patients with equivocal two-dimensional echocardiographic findings for elucidating confusing clinical findings and demonstrating additional and unsuspected flow abnormalities.

Value of acceleration flow signals proximal to the leaking orifice in assessing the severity of prosthetic mitral valve regurgitation.

To test the value of acceleration flow signals proximal to the leaking orifice in assessing the severity of prosthetic mitral valve regurgitation, 39 consecutive patients undergoing left ventriculography were examined by Doppler color flow imaging. Acceleration flow signals proximal to the regurgitant orifice were detected in 27 of the 31 patients who had prosthetic mitral regurgitation by left ventriculography (sensitivity 87%). All four patients without acceleration flow signals had mild prosthetic mitral regurgitation by angiography. No acceleration flow signals were detected in any patient without prosthetic regurgitation by left ventriculography (specificity 100%). Individual values of the maximal area of acceleration flow signals obtained from three orthogonal planes in seven patients with mild prosthetic mitral regurgitation by angiography ranged from 0 to 17 mm2 (mean 4 +/- 6). In 8 patients with moderate prosthetic mitral regurgitation by angiography, the maximal area of acceleration flow signals ranged from 21 to 58 mm2 (mean 33 +/- 15), whereas the maximal area of acceleration flow signals in 16 patients with severe prosthetic regurgitation ranged from 20 to 173 mm2 (mean 102 +/- 41). The maximal area of the acceleration flow signals from three planes correlated well with the angiographic grade of prosthetic mitral regurgitation. There was a significant difference in the maximal area of acceleration flow signals between mild and moderate (p less than 0.001), moderate and severe (p less than 0.001) and mild and severe (p less than 0.001) prosthetic mitral regurgitation. Thus, measurement of acceleration flow signals by Doppler color flow imaging is useful in assessing the severity of prosthetic mitral regurgitation.

Planimetry and transthoracic two-dimensional echocardiography in noninvasive assessment of aortic valve area in patients with valvular aortic stenosis.

OBJECTIVES: The aim of this study was to evaluate the reliability of transthoracic two-dimensional echocardiography in measuring aortic valve area (AVA) by planimetry. BACKGROUND: Planimetry of AVA using two-dimensional transesophageal echocardiographic images has been reported to be a reliable method for measuring AVA in patients with aortic stenosis. Recent advances in resolution of two-dimensional echocardiography permit direct visualization of an aortic valve orifice from the transthoracic approach more easily than before. METHODS: Forty-two adult patients with valvular aortic stenosis were examined. A parasternal short-axis view of the aortic valve was obtained with transthoracic two-dimensional echocardiography. AVA was measured directly by planimetry of the inner leaflet edges at the time of maximal opening in early systole. AVA was also measured by planimetry using transesophageal echocardiography, by the continuity equation and by cardiac catheterization (Gorlin formula). RESULTS: In 32 (76%) of the 42 study patients, AVA could be detected by using the transthoracic planimetry method. There were good correlations between results of transthoracic two-dimensional echocardiographic planimetry and the continuity equation (y = 0.90x + 0.09, r = 0.90, p < 0.001, SEE = 0.09 cm2), transesophageal echocardiographic planimetry (y = 1.05x - 0.02, r = 0.98, p < 0.001, SEE = 0.04 cm2) and the Gorlin formula (y = 1.02x + 0.05, r = 0.89, p < 0.001, SEE = 0.10 cm2). CONCLUSIONS: Transthoracic two-dimensional echocardiography provides a feasible and reliable method in measuring AVA in patients with aortic stenosis.

Direct visualization of ruptured chordae tendineae by transesophageal two-dimensional echocardiography.

To determine the value of transesophageal echocardiography in the detection of ruptured chordae tendineae, 28 patients who had surgical therapy for pure mitral regurgitation were evaluated prospectively by conventional transthoracic and transesophageal two-dimensional echocardiography. Seventeen patients (Group I) had ruptured chordae tendineae and 11 (Group II) had intact chordae tendineae. Transthoracic echocardiography detected ruptured chordae tendineae in 6 patients from Group I (sensitivity 35%) and flail leaflets in 11 patients from Group I (sensitivity 65%). Transesophageal echocardiography disclosed ruptured chordae tendineae in all 17 Group I patients (sensitivity 100%); the sensitivity was significantly higher than that of transthoracic echocardiography. No abnormal chordal echoes were visualized in any patient from Group II by either transthoracic or transesophageal echocardiography (specificity 100%). Transesophageal echocardiography is a highly sensitive method for detecting ruptured chordae tendineae and is superior to transthoracic echocardiography in establishing its diagnosis.

Assessment of coronary flow velocity with transthoracic Doppler echocardiography during dobutamine stress echocardiography.

OBJECTIVES: The purpose of this study was to evaluate the feasibility of measuring coronary flow velocity (CFV) by transthoracic Doppler echocardiography (TTDE) in the left anterior descending coronary artery (LAD) during contrast-enhanced dobutamine stress echocardiography (DSE). We also assessed the value of TTDE for detecting stress-induced myocardial ischemia in the LAD territory. BACKGROUND: Noninvasive assessment of both CFV and wall motion during DSE would enhance the diagnostic accuracy of DSE. METHODS: One hundred forty-four consecutive patients underwent CFV recording in the distal LAD by TTDE during contrast-enhanced DSE. Regional wall motion score index (WMSI) in the LAD territory and CFV ratio at peak stress (CFV ratio peak), defined as a ratio of CFV at peak stress to basal CFV, were obtained. RESULTS: Coronary flow velocity was successfully recorded in 129 patients (90%) at baseline and during dobutamine infusion. Mean value of CFV ratio peak was 2.39 +/- 0.83 (range: 0.84 to 4.40). There was good correlation between WMSI at peak stress and CFV ratio peak (r = 0.62, p < 0.001). Coronary flow velocity ratio peak was significantly lower in patients who developed stress-induced wall motion abnormality (WMA) in the LAD territory than it was in those patients without WMA (1.51 +/- 0.51 vs. 2.76 +/- 0.65, p < 0.001). A CFV ratio peak <2.1 had a sensitivity of 92% and a specificity of 86% for detecting the presence of stress-induced WMA. CONCLUSIONS: Assessment of CFV in the distal LAD during DSE is feasible in the majority of cases and provides a CFV ratio for detecting stress-induced myocardial ischemia in the LAD territory.

Temporal resolution of mitral regurgitation in patients with mitral valve prolapse: a phonocardiographic and Doppler echocardiographic study.

To assess the timing and duration of mitral regurgitation in mitral valve prolapse, 20 patients with a mid-systolic click or late systolic murmur, or both (Group 1) and 16 patients with a pansystolic murmur with late systolic accentuation (Group 2) were studied with phonocardiography and echocardiography including various Doppler techniques. The subjects' ages ranged from 15 to 73 years. Mitral valve prolapse with mitral regurgitation was observed in 15 of 20 patients in Group 1 and in all 16 patients in Group 2. M-mode Doppler color echocardiography demonstrated a mitral regurgitant signal throughout systole and isovolumic relaxation in all but 1 of these 31 patients regardless of the pattern of the systolic murmur. The regurgitant signal was recorded after the click in only one patient with mitral valve prolapse in Group 1. Two of the five patients in Group 1 without two-dimensional echocardiographic findings of mitral valve prolapse had the early systolic signal of mitral regurgitation. The timing and duration of the mitral regurgitant signal detected in patients in Group 1 with pulsed or continuous wave Doppler ultrasound varied with the site of the sample volume or beam direction. In the patients in Group 2, however, the signal was demonstrated throughout systole and isovolumic relaxation by both Doppler methods. Compared with M-mode Doppler color echocardiography, therefore, pulsed and continuous wave Doppler methods were less sensitive and thus inadequate to investigate the timing and duration of mitral regurgitation in mitral valve prolapse, especially in patients with a mid-systolic click or a late systolic murmur, or both, who had mild or eccentric mitral regurgitant jets.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow capacity of internal mammary artery grafts: early restriction and later improvement assessed by Doppler guide wire. Comparison with saphenous vein grafts.

OBJECTIVES: The purpose of this study was to assess flow dynamics and flow capacities of internal mammary artery and saphenous vein grafts to the left anterior descending coronary artery. BACKGROUND: The postoperative flow capacity of internal mammary artery grafts to the left anterior descending coronary artery has been reported to be restricted compared with that of saphenous vein grafts in studies using radionuclide angiography. A recently developed Doppler guide wire has been used to analyze the flow dynamics of bypass grafts and to clarify the mechanism of this limited flow capacity. METHODS: Phasic flow velocity recordings were obtained in the midportion of the bypass graft and within the native left anterior descending artery, using a 0.018-in. (0.046-cm) 12-MHz Doppler guide wire, in 53 patients: 27 patients with an internal mammary artery graft (16 with a new graft assessed 1 month postoperatively and 11 with an old graft assessed at 1 year) and 26 patients with a saphenous vein graft (13 with a new graft assessed 1 month postoperatively and 13 with an old graft assessed at 1 year). All patients were studied at baseline rest and during hyperemia induced by intravenous infusion of dipyridamole, 0.56 mg/kg body weight, over 4 min. RESULTS: In the left anterior descending artery itself, systolic and diastolic peak velocities, the time average of the instantaneous spectral peak velocity (time-averaged peak velocity), vessel diameter and the calculated flow volume did not differ significantly among the four graft groups. The time-averaged peak velocity was significantly greater for new than for old arterial grafts or for new or old vein grafts (mean +/- SD 27 +/- 9 vs. 19 +/- 6, 11 +/- 5 and 12 +/- 6 cm/s, respectively, p < 0.01). However, because the diameter of new arterial grafts was significantly smaller than that of the other three grafts (2.4 +/- 0.1 vs. 2.9 +/- 0.2 [p < 0.05], 3.6 +/- 0.6 [p < 0.01] and 3.4 +/- 0.5 mm [p < 0.01], respectively), there was no difference in calculated flow volumes at rest (62 +/- 17 vs. 58 +/- 15, 61 +/- 18 and 58 +/- 19 ml/min, respectively, p = NS) between new arterial grafts and the other grafts. Although the maximal time-averaged peak velocity during hyperemia was significantly greater in new than in old arterial grafts or new or old vein grafts (47 +/- 17 vs. 40 +/- 7, 31 +/- 8 and 34 +/- 12 cm/s, respectively, p < 0.01), the flow reserve of new arterial grafts was significantly smaller than that of the other three groups (1.8 +/- 0.3 vs. 2.6 +/- 0.3, 2.8 +/- 0.5 and 3.0 +/- 0.6, respectively, p < 0.01) because the baseline time-averaged peak velocity of these new grafts was far greater than that of the other groups. CONCLUSIONS: Internal mammary artery graft flow early after operation is characterized by a higher rest velocity than that of vein graft flow. This high velocity maintains flow volume at baseline condition in compensation for the smaller diameter. Although flow reserve does not differ significantly between new and old vein grafts, that for internal mammary artery grafts is significantly reduced soon after bypass surgery. This restricted flow capacity improves late postoperatively because of an increase in diameter and a decrease in flow velocity from baseline levels.

Retinopathy identifies marked restriction of coronary flow reserve in patients with diabetes mellitus.

OBJECTIVES: This study sought to assess the differences in coronary flow reserve in patients with and without diabetic retinopathy. BACKGROUND: Microvascular abnormalities throughout the body and impairment of coronary flow reserve have been described in patients with diabetes mellitus. However, the relation between diabetic retinopathy and coronary microvascular disease has not been investigated. METHODS: The study included 29 patients with diabetes mellitus (18 with and 11 without diabetic retinopathy) and 15 control patients with chest pain and normal coronary arteries. Diabetic retinopathy was nonproliferative in all 18 patients with this disorder (8 had background, 10 preproliferative retinopathy). Five minutes after injection of 3 mg of isosorbide dinitrate, phasic flow velocities were recorded in the proximal segment of the angiographically normal left anterior descending coronary artery at rest and during hyperemia (0.14 mg/kg body weight per min of adenosine infused intravenously) using a 0.014-in. 15-MHz Doppler guide wire. Coronary blood flow was calculated, and coronary flow reserve was obtained from the hyperemic/baseline flow ratio. RESULTS: Coronary blood flow was significantly lower during hyperemia ([mean +/- SD] 107 +/- 23 and 116 +/- 18 vs. 136 +/- 17 ml/min, respectively) and higher at baseline (58 +/- 16 and 45 +/- 12 vs. 37 +/- 10 ml/min, respectively) in diabetic patients with and without retinopathy than in control subjects (p < 0.05 for both diabetic groups). As a result, coronary flow reserve in both groups of diabetic patients was significantly lower than in control patients (1.9 +/- 0.4 and 2.8 +/- 0.3 vs. 3.3 +/- 0.4, respectively, p < 0.01 for both diabetic groups), and its reduction was greater in patients with than without retinopathy (p < 0.01). Furthermore, in patients with diabetic retinopathy, maximal hyperemic coronary flow (102 +/- 11 vs. 114 +/- 16 ml/min, p < 0.05) and flow reserve (1.6 +/- 0.2 vs. 2.3 +/- 0.2, p < 0.01) were significantly lower in those with preproliferative than background retinopathy. CONCLUSIONS: Coronary flow reserve is significantly restricted in patients with diabetes mellitus, and its reduction is more marked in those with diabetic retinopathy, especially in advanced retinopathy. Thus, diabetic retinopathy should identify marked restriction of coronary flow reserve in patients with diabetes mellitus.

Noninvasive evaluation of pulmonary capillary wedge pressure in patients with acute myocardial infarction by deceleration time of pulmonary venous flow velocity in diastole.

OBJECTIVES: This study investigates the correlation between deceleration time of diastolic pulmonary venous flow (PV-DT) and of early filling mitral flow (LV-DT), and pulmonary capillary wedge pressure (PCWP) in patients with acute myocardial infarction (AMI). BACKGROUND: An earlier study suggests that Doppler-derived LV-DT provides an accurate means of estimating PCWP in postinfarction patients with left ventricular systolic dysfunction. Furthermore, recent studies have suggested that PCWP correlates better with PV-DT than with LV-DT. However, the value of PV-DT and LV-DT for assessment of PCWP in patients with AMI has not been evaluated. METHODS: In 141 consecutive patients with AMI, we measured PV-DT and LV-DT by Doppler echocardiography, and compared these variables with PCWP measured using a Swan-Ganz catheter. RESULTS: There was a weak negative correlation between the LV-DT and PCWP (r = -0.54). Although the sensitivity of < or =130 ms in LV-DT in predicting > or =18 mm Hg in PCWP was high (86%), its specificity was low (59%). On the other hand, a very close negative correlation was found between PV-DT and PCWP (r = -0.89). The sensitivity and specificity of < or =160 ms in PV-DT in predicting > or =18 mm Hg in PCWP were 97% and 96%, respectively. CONCLUSIONS: In patients with AMI, Doppler-derived PV-DT showed a stronger correlation with PCWP than LV-DT.

Valvular regurgitation in heart-lung transplant recipients: a Doppler color flow study.

To assess the frequency and degree of valvular regurgitation in combined heart and lung transplant recipients, 50 patients were investigated using Doppler color flow echocardiography 20 to 909 days (mean 369) after heart-lung transplantation. The mean age (+/- SD) of the patients was 25 +/- 9 years. No patient had evidence of rejection at the time of the study. Fifty normal volunteers acted as control subjects. Tricuspid, mitral and pulmonary regurgitation were commonly observed in the patients undergoing heart-lung transplantation (78%, 52% and 68%, respectively), but were not significantly more frequent than in the normal subjects (68%, 42% and 70%, respectively). Aortic regurgitation was uncommon in both groups (4% and 2%, respectively). However, tricuspid and mitral regurgitant jet areas were significantly greater (p less than 0.01) in heart-lung transplant recipients than in normal subjects (156 +/- 120 and 84 +/- 52 mm2 compared with 40 +/- 38 and 28 +/- 26 mm2, respectively); pulmonary regurgitant jet area was not significantly different in the two groups (32 +/- 26 and 28 +/- 26 mm2, respectively). Regurgitant jet area was not significantly correlated with patient or donor age, donor organ total ischemic time, time after operation, use of steroids for immunosuppression or total number of rejection episodes. These results show that valvular regurgitation is not significantly more frequent after heart-lung transplantation than in normal subjects, but atrioventricular (AV) valve regurgitation, when present, is significantly greater in degree. This suggests that the degree but not the frequency of AV valve regurgitation is related to transplantation.

Modulation of coronary flow velocity reserve by gender, menstrual cycle and hormone replacement therapy.

OBJECTIVES: The purpose of this study was twofold: 1) to examine the relationship between menstrual cycle and coronary flow velocity reserve (CFVR) in young healthy women, and 2) to evaluate the effect of hormone replacement therapy by estrogen on CFVR in postmenopausal women, using transthoracic color Doppler echocardiography (TTCDE). BACKGROUND: Although the incidence of cardiovascular disease is lower in women before menopause compared with men, postmenopausal women have an incidence of coronary artery disease similar to that of men of the same age. This is mainly dependent upon estrogen deficiency. However, no clinical report has yet examined the effect of estrogen on CFVR, which is one index of coronary microcirculation. METHODS: We examined 15 male and both 15 premenopausal and 10 postmenopausal female healthy volunteers. We measured coronary flow velocity of the left anterior descending coronary artery at baseline and hyperemic conditions during adenosine triphosphate infusion by TTCDE and determined CFVR. Each premenopausal woman was studied two times (menstrual [M] and follicular [F] phases) in one menstrual cycle. Fifteen men were also studied at a time corresponding to women's menstrual cycle. The postmenopausal women were studied before and two hours after oral administration of conjugated estrogen (CE). RESULTS: Serum 17beta-estradiol level in premenopausal women increased in the F phase and decreased to the same levels as in men, as in the M phase and as in postmenopausal women (123 +/- 9 pg/ml vs. 28 +/- 6 pg/ml, 25 +/- 9 pg/ml and 19 +/- 11 pg/ml; p < 0.0001, respectively). The CFVR increased in the F phase compared with that in the M phase (4.8 +/- 0.4 vs. 3.7 +/- 0.8, p < 0.0001). We found that CFVR in men remained unchanged (3.7 +/- 0.6 vs. 3.8 +/- 0.5). After CE administration, CFVR increased compared with baseline in postmenopausal women (4.1 +/- 0.8 vs. 3.4 +/- 0.8, p < 0.005). CONCLUSIONS: In premenopausal women, CFVR determined by TTCDE varied during the menstrual cycle, and in postmenopausal women, CFVR increased after acute estrogen replacement.

Physiologic assessment of coronary artery stenosis by coronary flow reserve measurements with transthoracic Doppler echocardiography: comparison with exercise thallium-201 single piston emission computed tomography.

OBJECTIVES: We evaluated the value of coronary flow reserve (CFR), as determined by transthoracic Doppler echocardiography (TTDE), for physiologic assessment of coronary artery stenosis severity, and we compared TTDE measurements with those obtained by exercise thallium-201 (Tl-201) single-photon emission computed tomography (SPECT). BACKGROUND: Coronary flow reserve measurements by TTDE have been reported to be useful for assessing angiographic left anterior descending coronary artery (LAD) stenosis. However, discrepancies exist between angiographic and physiologic estimates of coronary lesion severity. METHODS: We studied 36 patients suspected of having coronary artery disease. The flow velocity in the distal LAD was measured by TTDE both at rest and during intravenous infusion of adenosine. Coronary flow reserve was calculated as the ratio of hyperemic to basal peak (peak CFR) and mean (mean CFR) diastolic flow velocities. The CFR measurements by TTDE were compared with the results of Tl-201-SPECT. RESULTS: Complete TTDE data were acquired for 33 of 36 study patients. Of these 33 patients, Tl-201-SPECT confirmed reversible perfusion defects in the LAD territories in 12 patients (group A). Twenty-one patients had normal perfusion in the LAD territories (group B). Peak CFR and mean CFR (mean value +/- SD) were 1.5 +/- 0.6 and 1.5 +/- 0.7 in group A and 2.8 +/- 0.8 and 2.7 +/- 0.7 in group B, respectively. Both peak and mean CFR < or = 2.0 predicted reversible perfusion defects, with a sensitivity and specificity of 92% and 90%, respectively. CONCLUSIONS: Noninvasive measurement of CFR by TTDE provides data equivalent to those obtained by Tl-201-SPECT for physiologic estimation of the severity of LAD stenosis.

Value of acceleration flow and the prestenotic to stenotic coronary flow velocity ratio by transthoracic color Doppler echocardiography in noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty.

OBJECTIVES: The study evaluated the value of coronary flow velocity measurement by transthoracic color Doppler echocardiography (TTCDE) for the noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty (PTCA) for left anterior descending coronary artery (LAD) lesions. BACKGROUND: Recent advances in TTCDE provide coronary flow velocity measurements in the LAD under the guidance of color flow mapping. METHODS: We studied 53 patients who underwent successful PTCA for LAD lesions and follow-up coronary angiography (18 patients with restenosis [Group-R], 35 patients without restenosis [Group-N]). We searched localized color aliasing corresponding to local flow acceleration to obtain coronary flow velocity at PTCA sites in the LAD. When localized aliasing was detected, we measured coronary flow velocity at the aliasing (stenotic site) and the prestenotic site. RESULTS: Using TTCDE, it was possible to measure mean diastolic velocity (MDV) in the LAD in 41 (77%) of 53 patients (14 of 18 patients in Group-R; 27 of 35 patients in Group-N). Localized aliasing was displayed by color flow mapping in 14 (100%) of 14 patients in Group-R, and 15 (56%) of 27 patients in Group-N. Stenotic MDV in Group-R was significantly higher than that in Group-N (60.3 +/- 21.1 vs. 35.1 +/- 7.6 cm/s, p < 0.01), although prestenotic MDV did not differ between Group-R and Group-N (20.2 +/- 3.0 vs. 19.6 +/- 2.3 cm/s). There were significant differences in the prestenotic to stenotic MDV ratio between Group-R and Group-N (0.36 +/- 0.10 vs. 0.57 +/- 0.09, p < 0.001). Localized aliasing with the prestenotic to stenotic MDV ratio <0.45 as the optimal cutoff value had a sensitivity of 86% and a specificity of 93% for the presence of restenosis in LAD lesions. CONCLUSIONS: Detection of localized color aliasing and measurement of the prestenotic to stenotic MDV ratio in the LAD by TTCDE are useful in the noninvasive diagnosis of restenosis after PTCA for LAD lesions.

Restricted coronary flow reserve in patients with mitral regurgitation improves after mitral reconstructive surgery.

OBJECTIVES: The purpose of this study was to assess coronary flow characteristics in patients with chronic mitral regurgitation (MR). BACKGROUND: Coronary flow reserve (CFR) has been reported to be restricted in cases with left ventricular (LV) volume overload caused by aortic regurgitation and increased LV preload. METHODS: The study populations consisted of 31 patients with nonrheumatic chronic MR. Eleven with chest pain and normal coronary arteries served as control subjects. Phasic coronary flow velocities were obtained in the proximal segment of the angiographically normal left anterior descending coronary artery at rest and during hyperemia (0.14 mg/kg/min adenosine infusion intravenously) using a 0.014-in. (0.036 cm), 15-MHz Doppler guide wire. Coronary flow reserve was obtained from the ratio of hyperemic/baseline time-averaged peak velocity (APV). Thirteen cases who underwent mitral valve reconstructive surgery were also studied 1 month after surgery. RESULTS: Compared with control subjects, CFR was significantly reduced in cases with MR (2.1+/-0.5 vs. 33+/-0.6, respectively, p < 0.01) because baseline APV was significantly greater (28+/-8 vs. 19+/-6 cm/s, respectively, p < 0.01), although maximal hyperemic APV was not significantly different (56+/-14 vs. 61+/-16 cm/s, respectively, p = NS). Significant correlations were obtained between CFR and LV end-diastolic pressure (LVEDP) (r = 0.70, p < 0.01), LV mass index (r = 0.42, p < 0.01), LV end-diastolic volume (r = 038, p = 0.04) and MR volume (r = 0.39, p = 0.03), and stepwise regression analysis showed LVEDP was the most important determinant of CFR in MR (r2 = 0.49, p < 0.0001). This restricted CFR improved significantly after mitral valve reconstructive surgery (2.1+/-0.5 vs. 3.1+/-0.6, respectively, p < 0.01) because of reduction of baseline APV (28+/-8 vs. 21+/-8 cm/s, respectively, p < 0.01). CONCLUSIONS: Coronary flow reserve is limited in cases with MR because of elevation of baseline resting flow velocity. This reduction of CFR correlates well with increase in LV preload, mass and volume overload, especially with increase in LV preload, and this restricted CFR improves after mitral valve surgery.

Flow dynamics of angiographically no-flow patent internal mammary artery grafts.

OBJECTIVES: This study sought to assess the flow dynamics of internal mammary artery grafts (IMAGs) in no-flow situations by use of a Doppler guide wire. BACKGROUND: Functionally no-flow and anatomically patent IMAGs have been reported by angiography in patients with a patent recipient coronary artery. METHODS: The study included 12 patients with an IMAG to the left anterior descending coronary artery (LAD) in whom no-flow patency of the graft was suspected angiographically. Thirteen patients with a normally functioning IMAG whose LAD was occluded in the proximal portion and was supplied only from the graft served as control patients. Phasic flow velocities were recorded in the distal portion of the graft and the recipient LAD using a 0.014-in., 15-MHz Doppler guide wire at rest and during hyperemia (0.14-mg/kg body weight per min intravenous adenosine infusion). RESULTS: There were no significant differences in systolic (15+/-3 vs. 19+/-6 cm/s, p = NS), diastolic (35+/-11 vs. 37+/-7 cm/s, p = NS) and time-averaged peak velocities at rest (20+/-5 vs. 21+/-5 cm/s, p = NS), during hyperemia (51+/-12 vs. 54+/-8 cm/s, p = NS) and in coronary flow velocity reserve (2.8+/-0.9 vs. 2.7+/-0.3, NS) in the native LAD in patients with a no-flow patent graft versus control patients. Within the graft, to and fro signals with systolic reversal and diastolic anterograde flow were seen in the no-flow patent grafts, although anterograde flow signals were recorded in systole and diastole in control patients. Systolic (-28+/-19 vs. 22+/-9 cm/s, p < 0.01), diastolic (18+/-17 vs. 44+/-14 cm/s, p < 0.01) and time-averaged (-2+/-6 vs. 26+/-9 cm/s, p < 0.01) peak velocities at rest were significantly smaller in the no-flow patent grafts than in control grafts. During hyperemia, anterograde flow became predominant, with a reduction in retrograde systolic flow signal and an increase in diastolic flow velocity and time-averaged peak velocity in the no-flow patent grafts, and no-flow situations disappeared temporarily. CONCLUSIONS: Functionally no-flow situations of IMAGs manifesting to and fro signals with systolic flow reversal and diastolic antegrade low flow velocity are temporary conditions in certain hemodynamic circumstances, and these grafts function as conduits during hyperemic states.