Coronary remodeling plays a significant role in lumen loss in transplant allograft vasculopathy (TxCAD), but the determinants of remodeling are unknown. We assessed the relationship between ...remodeling and plaque topography, coronary compliance, and blood flow in TxCAD.
One artery in each of 27 transplant patients was investigated with simultaneous intravascular ultrasound and coronary flow measurements (basal and hyperemic by Doppler flow wire). At 4 to 8 different cross sections (mean 5.1+/-1. 2), plaque topography (concentric or eccentric) was determined, and total vessel area, lumen area, and intimal/medial area (IMA) were measured. Mean remodeling ratio (vessel area/IMA) in eccentric lesions (E, n=28) was significantly larger than that in concentric lesions (C, n=70) (E 5.87+/-0.93 versus C 3.58+/-0.62; P<0.001), despite similar IMA (E 3.89+/-0.68 versus C 3.90+/-0.41; P=NS) and distribution of imaged segments. Remodeling ratio was consistently larger in eccentric lesions in all 3 vessel segments when analyzed separately, and mean remodeling ratio for each artery was larger in vessels with predominantly eccentric lesions. Coronary compliance (Delta lumen area/diastolic lumen area/Delta mean arterial pressure x 10(3)) was also significantly greater in eccentric lesions versus concentric lesions (proximal 1.00+/-0.39 versus 0.22+/-0.04; mid 0.71+/-0.17 versus 0.21+/-0.10; distal 0.43+/-0.13 versus 0. 01+/-0.08; all P<0.01). Coronary flow reserve was also significantly higher in coronary arteries with primarily eccentric lesions (E 2. 49+/-0.64 versus C 1.87+/-0.28; P<0.01).
Vessel remodeling in transplant vasculopathy is significantly greater in eccentric lesions than in concentric lesions, possibly due to greater coronary compliance and resistive vessel function.
Objectives. The aim of this study was to use Doppler catheterization and sequential dynamic positron emission tomography (PET) to investigate the role and time course of abnormal coronary resistive ...vessel function in the impairment of the coronary vasodilator response (maximal/basal coronary blood flow) after successful coronary angioplasty.
Background. The coronary vasodilator response may be impaired immediately after coronary angioplasty, despite successful dilation of a flow-limiting stenosis.
Methods. Twelve men (mean age 52 ± 10 years) with singlevessel coronary artery disease and normal left ventricular function were studied. The coronary vasodilator response to intravenous dipyridamole (0.5 mg·kg−1over 4 min) was determined from intracoronary Doppler measurement of coronary How velocity, before and after successful angioplasty. Basal and maximal myocardial blood flow in the angioplasty region and a normal region were determined in nine patients with positron emission tomography with H215O at 1 day (PET1), 7 days (PET2) and 3 months (PET3) after angioplasty.
Results. The coronary vasodilator response, measured by Doppler catheterization, was similar before and immediately after angioplasty, 1.63 ± 0.41 and 1.62 ± 0.55, respectively (p = NS). After angioplasty, in seven of nine patients without restenosis, basal myocardial blood flow at PET1, PET2and PET3was 0.98 ± 0.16, 0.94 ± 0.09 and 0.99 ± 0.13 ml·min−1·g−1, respectively, in the remote region and 1.19 ± 0.23 (p < 0.01 vs. remote region), 1.17 ± 0.19 (p < 0.01 vs. remote region) and 1.10 ± 0.08 ml·min-1·g−1(p = NS vs. remote region), respectively, in the angioplasty region. Myocardial blood flow after dipyridamole at PET1, PET2and PET3was 3.04 ± 0.68, 3.00 ± 0.71 and 3.00 ± 0.60 ml·ml·min−1g−1, respectively, in the remote region and 2.11 ± 0.80 (p < 0.01 vs. remote region), 2.28 ± 0.73 (p = NS vs. remote region) and 3.06 ± 0.86 ml · min−1· g−1(p = NS vs. remote region), respectively, in the angioplasty region. The coronary vasodilator response at PET1, PET2and PET3was 3.15 ± 0.85, 3.18 ± 0.68 and 3.08 ± 0.75, respectively, in the remote region and 1.80 ± 0.68 (p < 0.01 vs. remote region), 1.94 ± 0.49 (p < 0.01 vs. remote region) and 2.77 ± 0.74 (p = NS vs. remote region), respectively, in the angioplasty region.
Conclusions. After successful angioplasty, basal myocardial blood flow is increased for ≥7 days in the angioplasty region, with a reduction in the dipyridamole · induced increase in maximal myocardial blood flow for ≥24 h after the procedure. Thus, the coronary vasodilator response is impaired for ≥7 days after angioplasty, indicating that there is abnormal resistive vessel function in the coronary vascular bed distal to a coronary artery stenosis that persists for 7 days to 3 months.
Arterial remodeling may increase or decrease the luminal encroachment of atherosclerotic plaques in the coronary circulation. However, the factors determining the nature and consequences of the ...remodeling process remain poorly characterized. The study aims were to assess whether the pattern of vascular remodeling influences the physical and vasomotor responses of the coronary arteries in vivo in man.
Coronary vessel area, distensibility and stiffness were determined in positively, negatively and non-remodeled arterial segments using intravascular ultrasound and Doppler flow measurement. Epicardial vasomotor responses were determined following intracoronary boluses of acetylcholine (10(-6) and 10(-4) M), adenosine (24-30 microg) and nitroglycerin (200 microg).
Fifty-six coronary arterial segments were studied in 25 patients. In comparison to non- and positively remodeled segments, negatively remodeled segments had a higher stiffness index (67+/-16 vs. 33+/-5 and 38+/-8, respectively; P<0.02) and appeared to have lower compliance and distensibility (0.66+/-0.17 vs. 1.65+/-0.54 and 0.94+/-0.18/mmHg; P=NS). Non-remodeled segments had a greater change in vessel area with 10(-6) M acetylcholine (4.9+/-0.8%), compared to positively and negatively remodeled segments (0.6+/-1.8% and -4.9+/-1.8%, respectively, P<0.05). A significant degree of preservation of vasodilatation to 10(-6) M acetylcholine was evident in positively remodeled compared with negatively remodeled segments (P<0.05). Nitroglycerin caused greater vasodilatation in non-remodeled segments (7.2+/-3.8%) than either positively or negatively remodeled segments (4.7+/-0.9 and 3.7+/-0.6%, respectively, P<0.05).
Vascular remodeling is an important and major determinant of local epicardial vasomotor responses. Both structural and functional abnormalities are associated with negative remodeling that may contribute to the adverse effects of such lesions.
Intravascular ultrasound allows accurate assessment of the arterial vessel, including vessel luminal diameter and assessment of vessel disease in terms of plaque morphology, plaque volume and extent ...of calcification. Recently published trials highlight the role of intravascular ultrasound in monitoring disease progression in a clinical setting.
NG-Monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis, was used to determine the effects of inhibition of nitric oxide synthesis in the human coronary circulation.
Twelve ...patients (mean age, 52 +/- 2 years) with normal epicardial coronary arteries were studied. The surface ECG, systemic blood pressure, and coronary venous oxygen saturation (coronary SvO2), an index of coronary blood flow, were monitored continuously. Coronary artery diameter was measured by quantitative arteriography. L-NMMA was given as intracoronary infusions at 2 mL/min via the diagnostic arteriography catheter. In two patients, low doses (0.01 to 5 mumol/min) of L-NMMA were infused into the nondominant right coronary artery. There was no evidence of ischemia in these patients, who were not included in the final analysis. In 10 patients, higher doses of L-NMMA (4, 10, and 25 mumol/min, each for 5 minutes) were infused into the left coronary artery. In six patients, incremental doses of acetylcholine were infused (1, 10, and 100 nmol/min, each for 3 minutes) before and after the L-NMMA infusion. Finally, in all patients, sodium nitroprusside, a nitric oxide donor, was infused. No patient developed myocardial ischemia. The heart rate and systemic blood pressure remained unchanged throughout the infusions. L-NMMA (25 mumol/min), compared with the control saline infusion, caused a significant reduction in distal (-5.9 +/- 2.1%, P = 0.021) but not proximal left anterior descending coronary artery (LAD) diameter and a fall in coronary SvO2 from 37.5 +/- 2.8% to 34.3 +/- 2.8% (P = 0.019). Sodium nitroprusside dilated the proximal (17.8 +/- 6.9%, P = 0.033) and distal (24.5 +/- 6.5%, P = 0.006) LAD and increased the coronary SvO2 to 61.6 +/- 5.0% (P = 0.0002). Acetylcholine caused significant dilatation of the distal (13.8 +/- 5.4%, P = 0.049) but not proximal LAD and a significant increase in coronary SvO2 from 36.5 +/- 3.5% to 59.2 +/- 2.8% (P < 0.0001). After L-NMMA, acetylcholine-induced dilatation of the distal LAD was abolished, but the rise in coronary SvO2 was unchanged.
Inhibition of nitric oxide synthesis in the human coronary circulation caused a decrease in basal distal LAD diameter and basal coronary blood flow assessed by coronary SvO2, indicating that there is a small basal release of nitric oxide in the distal epicardial coronary arteries and resistive vessels. Distal epicardial coronary artery dilatation in response to acetylcholine is nitric oxide dependent, but coronary resistive vessel dilatation is not.
We aimed to characterise and to identify the predominant plaque type
in vivo using unprocessed radiofrequency (RF) intravascular ultrasound (US) backscatter, in remodelled segments of human ...atherosclerotic coronary arteries. A total of 16 remodelled segments were identified using a 30-MHz intravascular ultrasound (IVUS) scanner
in vivo. Of these, 9 segments were classified as positively remodelled (> 1.05 of the total vessel area in comparison with the proximal and distal reference segments) and 7 as negatively remodelled (< 0.95 of reference segment area). Spectral parameters (maximum power, mean power, minimum power and power at 30 MHz) were determined and plaque type was defined as mixed fibrous, calcified or lipid-rich. Positively remodelled segments had a larger total vessel area (16.5 ± 1.1 mm
2 vs. 8.7 ± 0.9 mm
2,
p < 0.01) and plaque area (7.3 ± 1.1 mm
2 vs. 4.4 ± 0.8 mm
2,
p = 0.05) than negatively remodelled segments. Both positively and negatively remodelled segments had a greater percentage of fibrous plaque (
p < 0.01) than calcified or lipid-rich plaque. Comparing positively and negatively remodelled segments, there was no significant difference between the proportion of fibrous, calcified or lipid-rich plaque. We have been able to characterise and to identify plaque composition
in vivo in human atherosclerotic coronary arteries. Our data suggest that remodelled segments are predominantly composed of fibrous plaque, as identified by RF analysis, although plaque composition is similar, irrespective of the remodelling type. (E-mail: a.mcleod@ed.ac.uk)
Summary Background The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary ...artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers18 F-sodium fluoride (18 F-NaF) and18 F-fluorodeoxyglucose (18 F-FDG). Methods In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent18 F-NaF and18 F-FDG PET-CT, and invasive coronary angiography.18 F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of18 F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction. Findings In 37 (93%) patients with myocardial infarction, the highest coronary18 F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 IQR 1·40–2·25 vs highest non-culprit 1·24 1·06–1·38, p<0·0001). By contrast, coronary18 F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 1·40–2·13 vs 1·58 1·28–2·01, p=0·34). Marked18 F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal18 F-NaF uptake (maximum tissue-to-background ratio 1·90 IQR 1·61–2·17) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 1·09–1·19 vs 1·01 0·94–1·06; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% 21–29 vs 18% 14–22, p=0·001). Interpretation18 F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease. Funding Chief Scientist Office Scotland and British Heart Foundation.
Objectives. The aim of this study was to investigate coronary vasodilator reserve and metabolism in myocardium subtended by angiographically normal arteries remote from ischemia.
Background. After ...infarction, structural and functional changes occur in remote myocardium often subtended by normal arteries. Whether changes occur in regions remote from ischemic but noninfarcted myocardium is unknown.
Methods. Coronary vasodilator reserve was measured with positron emission tomography in 12 patients with single-vessel disease using intravenous dipyridamole (0.56 mg/kg for 4 min). In another 10 patients, simultaneous arterial/great cardiac vein catheterization was performed during atrial pacing to measure myocardial metabolism in regions subtended by diseased or normal arteries.
Results. Basal myocardial blood flow in stenosis-related regions was comparable to that in remote regions but was lower after dipyridamole administration (1.73 ± 0.91 vs. 2.89 ± 0.93 ml/min per g, p < 0.01), giving coronary vasodilator reserve values of 1.80 ± 0.82 and 2.73 ± 0.89 (p < 0.01). In normal control subjects, basal myocardial blood flow was 0.92 ± 0.13 and 3.67 ±0.94 ml/min per g in the basal state and after dipyridamole (both p < 0.05 vs. values in remote regions), and coronary vasodilator reserve was 4.07 ± 0.98 (p < 0.01 vs. values in remote regions). During pacing there was net lactate release in diseased regions (−18 ± 27%, p < 0.05 vs. values in remote regions and control subjects) and extraction in remote regions (38 ± 17%) and in normal control subjects (26 ± 11%). Glucose and alanine extraction were increased in diseased (8 ± 6% and 6 ± 6%) and remote regions (6 ± 3% and 4 ± 3%), compared with values in normal control subjects (2 ± 3% and −1 ± 3%, both p < 0.05 vs. diseased and remote regions).
Conclusions. Coronary vasodilator reserve is reduced and glucose and alanine metabolism is abnormal in regions subtended by normal arteries remote from ischemic but noninfarcted myocardium.
Effect of Aging on Myocardial Perfusion Reserve Uren, Neal G; Camici, Paolo G; Melin, Jacques A ...
The Journal of nuclear medicine (1978),
11/1995, Letnik:
36, Številka:
11
Journal Article
Recenzirano
Myocardial perfusion reserve (hyperemic divided by basal myocardial blood flow) describes vasodilator responsiveness of coronary-resistive vessels. The effect of aging and gender on myocardial ...perfusion reserve remains controversial.
We studied 56 normal volunteers (21 women, 35 men; aged 50 +/- 20 yr, range 21-86 yr) with 15O-water PET to measure myocardial blood flow during basal and hyperemic states with intravenous dipyridamole (0.56 mg/kg, n = 46) or adenosine (140 micrograms/kg/min, n = 10). For comparative analysis, patients were grouped according to age: < 30 yr (n = 11), 30-49 yr (n = 18), 50-69 yr (n = 15) and > or = 70 yr (n = 12).
Overall, basal flow was 1.00 +/- 0.26 ml/min/g and hyperemic flow was 3.31 +/- 1.38 ml/min/g, resulting in a myocardial perfusion reserve of 3.38 +/- 1.35. There was an increase in basal flow with age (r = 0.45, p < 0.025), although hyperemic flow was only lower in patients > or = 70 yr, causing a significant reduction in myocardial perfusion reserve: 3.54 +/- 0.96 in < 30 yr, 4.23 +/- 1.35 in 30-49 yr, 3.51 +/- 1.21 in 50-69 yr and 1.94 +/- 0.46 in > or = 70 yr (p < 0.05 versus all groups < 70 yr).
Myocardial blood flow during basal and hyperemia conditions are roughly comparable up to 60 yr of age. Above this age, there is significant increase in basal flow associated with an increase in systolic blood pressure. Above 70 yr, there is a significant reduction in hyperemic flow, and thus myocardial perfusion reserve independent of hemodynamic response to vasodilator stress.
Calcitonin gene related peptide (CGRP) is a potent vasodilator found in sensory nerve endings in coronary arteries. The effect of intravenous CGRP on myocardial ischaemia, cardiovascular ...haemodynamics, and epicardial coronary artery stenoses was studied in patients with angina to investigate the possible role of CGRP in the control of vasodilation in the coronary circulation.
12 patients (mean age 60 years) performed exercise tests on consecutive days during intravenous infusions of placebo or CGRP (at 50 pmol.min-1). At cardiac catheterisation (6 patients), consecutive 20 min intravenous infusions of placebo and CGRP were given at a fixed heart rate, with measurement of haemodynamic variables and quantitative arteriography.
The time to 0.1 mV ST depression increased from 475(SD 245) to 546(193) s (p < 0.05), and time to 0.2 mV ST segment depression, from 634(266) to 694(202) s (p < 0.05), on placebo and CGRP respectively. Rate-pressure product at 0.1 mV ST segment depression was 18,410(4590) and 20,750(7270) mm Hg.min-1 (p < 0.05), and at 0.2 mV ST depression it was 21,510(6470) and 24,080(7380) mm Hg.min-1 (p < 0.01), with placebo and CGRP, respectively. At catheterisation, diastolic blood pressure fell from 93(11) to 83(8) mm Hg (p < 0.05), systemic vascular resistance fell from 26.2(9.4) to 20.7(9.0) units (p < 0.05), and cardiac output increased from 5.94(1.10) to 6.73(1.04) litre.min-1 (p < 0.05), on placebo and CGRP respectively. Minimum luminal diameter increased from 0.66(0.23) to 1.11(0.15) mm (p < 0.01) with CGRP.
Intravenous CGRP is a systemic arterial vasodilator which dilates coronary arteries at the site of atheromatous stenoses and delays the onset of myocardial ischaemia during treadmill exercise testing in patients with chronic stable angina.
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