Clinical significance of reduced regional myocardial glucose uptake in regions with normal blood flow in patients with chronic coronary artery disease

Objectives. The objective of this study was to assess the clinical significance of reduced regional fluorine-18 (¹⁸F) fluorodeoxyglucose uptake with normal flow in patients with chronic coronary artery disease.Background. In patients with ischemic left ventricular dysfunction, ¹⁸F-fluorodeoxyglucose uptake may be reduced in some myocardial regions despite normal flow. The significance of this finding to unclear and has not been investigated systematically.Methods. Twenty-three patients with coronary artery disease and impaired ventricular function (mean ejection fraction (±1 SD) 28 ± 10%) underwent positron emission tomography with ¹⁸F-fluorodeoxyglucose and oxygen-15-labeled water at rest, exercise thallium-201 tomographic imaging with rest reinjection and gated magnetic resonance imaging to measure end-diastolic wall thickness and systolisc wall thickening.Results. Of 168 regions with normal flow (≥0.7 ml/g per min), 125 (74%) had normal ¹⁸F-fluorodeoxyglucose uptake (98 ± 10%), and the remaining 43 (26%) showed moderately reduced ¹⁸F-fluorodeoxyglucose uptake (69 ± 8%). Systolic wall thickening was absent at rest in 14% of regions with normal ¹⁸F-fluorodeoxyglucose uptake compared with 32% of regions with reduced ¹⁸F-fluorodeoxyglucose uptake (p < 0.01). Reversible thallium abnormalities were observed in 45 (36%) of 125 regions with normal ¹⁸F-fluorodeoxyglucose uptake compared with 27 (63%) of 43 regions with reduced ¹⁸F-fluorodeoxyglucose uptake (p < 0.01). This difference was accounted for by a higher proportion of partially reversible defects in regions with reduced ¹⁸F-fluorodeoxyglucose uptake compared with regions with normal ¹⁸F-fluorodeoxyglucose uptake (42% vs. 18%, respectively, p < 0.01).Conclusions. Thus, regions with moderately reduced ¹⁸F-fluorodeoxyglucose uptake with normal flow occur commonly in patients with ischemic left ventricular dysfunction. The majority of these regions show impaired systolic function at rest and exercise-induced thallium abnormalities that are only partially reversible. These observations suggest that such regions represent an admixture of fibrotic and reversibly ischemic myocardium.     

Improvement of resting myocardial asynergy with cessation of upright bicycle exercise

Exercise generally aggravates ischemic myocardial dysfunction, presumably by increasing tissue oxygen demand out of proportion to the increase in supply. Nevertheless, resting left ventricular (LV) wall motion abnormalities can improve dramatically after upright exercise. To investigate this "paradoxical" phenomenon, we performed upright bicycle exercise equilibrium radionuclide ventriculography in 93 patients with angiographic coronary artery disease. Immediately after exercise, LV end-diastolic volume was similar to the resting level (1 +/- 22% of rest value), but end-systolic volume (ESV) was significantly below (p less than 0.05) that at rest (-11 +/- 32%) and LV ejection fraction increased significantly compared with rest (0.57 +/- 0.16 vs 0.51 +/- 0.13, p less than 0.05). Improvement in resting myocardial asynergy was frequent (115 of 330 abnormal segments), and was observed more commonly in patients without pathologic Q waves and in segments manifesting mild rather than severe asynergy. In 60 additional patients with resting asynergy who were also studied after nitroglycerin (NTG), there was 89% concordance of wall motion response in asynergic segments after exercise and NTG: 71 of 85 segments manifesting improvement with NTG also improved after exercise, and 157 of 172 segments without improvement with NTG also failed to improve after exercise. Despite the similar wall motion response, the mechanism of improvement is probably different from that produced by NTG. With NTG, preload (end-diastolic volume) and afterload (systolic blood pressure) were significantly lower than their resting control levels (p less than 0.05). These changes did not occur after exercise. Instead, an isolated, significant reduction in ESV was noted. These data support the hypothesis that catecholamine stimulation is responsible for paradoxical wall motion improvement after upright exercise.     

Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans

OBJECTIVE: Absolute myocardial blood flow (MBF) is not well-defined in large normal populations, and appears to be heterogeneous in both humans and animals. These factors contribute to the difficulties in defining resting MBF to hibernating myocardium. We therefore assessed absolute baseline and hyperemic MBF in a large population of normal humans. METHODS: MBF was quantified by positron emission tomography with oxygen-15-labeled water at baseline and during hyperemia induced by either adenosine or dipyridamole in 131 men and 38 women, aged 21-86 (mean 46+/-12) years. MBF was corrected for workload using the rate-pressure product (RPP). RESULTS: Uncorrected baseline MBF ranged from 0.590 to 2.050 (mean 0.985+/-0.230) ml/min/g (coefficient of variation=27%), and corrected MBF from 0.736 to 2.428 (mean 1.330+/-0.316) ml/min/g (coefficient of variation=24%). MBF in the inferior region was significantly (P<0.0001) lower than either the anterior or lateral regions. Baseline MBF in females was significantly (P<0.001) higher than in males. CONCLUSIONS: These results confirm the heterogeneity of MBF in normals and highlight the difficulty in establishing the lower limit of normal MBF.     

Metabolic evidence of viable myocardium in regions with reduced wall thickness and absent wall thickening in patients with chronic ischemic left ventricular dysfunction.

Reduced end-diastolic wall thickness with absent systolic wall thickening has been reported to represent nonviable myocardium in patients with chronic coronary artery disease. To assess whether reduced regional end-diastolic wall thickness and absent wall thickening accurately identify nonviable myocardium, 25 patients with ischemic left ventricular dysfunction (ejection fraction at rest 27 +/- 10%) underwent positron emission tomography with oxygen-15-labeled water and 18fluorodeoxyglucose to assess metabolic activity and spin-echo gated nuclear magnetic resonance imaging to measure regional end-diastolic wall thickness and wall thickening. The presence of metabolic activity was defined as 18fluorodeoxyglucose uptake (corrected for partial volume) greater than 50% of that in normal regions. Of 355 myocardial regions evaluated, 266 were hypokinetic or normokinetic at rest and 89 were akinetic (that is, absent wall thickening). 18Fluorodeoxyglucose uptake was observed in 97% of the hypokinetic and normokinetic regions and in 74% of the akinetic regions. End-diastolic wall thickness was greater in akinetic regions with than in those without 18fluorodeoxyglucose uptake (11 +/- 4 vs. 7 +/- 3 mm, p less than 0.01). The highest values for sensitivity and specificity of end-diastolic wall thickness in predicting the absence of metabolic activity in akinetic regions were 74% and 79%, respectively, and corresponded to an end-diastolic threshold of 8 mm. However, the positive predictive accuracy was only 55% and did not improve for other end-diastolic wall thickness values. In all myocardial regions, there was only a weak correlation between 18fluorodeoxyglucose activity and either end-diastolic wall thickness (r = 0.17) or wall thickening (r = 0.32). Thus, metabolic activity is present in many regions with reduced end-diastolic wall thickness and absent wall thickening. These data indicate that assessment of regional anatomy and function may be inaccurate in distinguishing asynergic but viable myocardium from nonviable myocardium.     

Relationship between blood flow to ischemic regions and extent of myocardial infarction. Serial measurement of blood flow to ischemic regions in dogs.

This study was designed to measure early sequential changes in blood flow to ischemic regions after acute coronary occlusion and to determine the relationship between blood flow and the extent of subsequent myocardial infarction. Initial studies were carried out on five dogs which verified using radioisotope-labeled microspheres, 7-10 mum in diameter, to measure changes in blood flow in small myocardial regions after acute coronary artery occlusions. Studies then were carried out on 11 awake dogs chronically prepared with dwelling catheters in the aorta and left atrium and occluders on the left circumflex coronary artery. Microspheres were injected via the left atrial catheter 45 seconds and 2, 6, and 24 hours after complete circumflex coronary occlusion. Six days later myocardial blood flow and the extent of histological infarction were determined for multiple samples from four transmural layers of the entire ischemic zone. Average blood flow to the circumflex region was 0.25 +/- 0.03 (SE), 0.39 +/- 0.05, and 0.53 +/- 0.07 ml/min per g at 45 seconds, and 2, 6, and 24 hours, respectively. When samples from each transmuarl layer were grouped according to increasing ranges of blood flow, the extent of infarction in each layer was inversely related to blood flow. When samples in the same range of blood flow were compared, the extent of infarction in endocardial samples exceeded that in epicardial samples. These data indicate that the relationship between a given measurement of regional blood flow after acute coronary occlusion and the extent of subsequent myocardial infarction varies in different transmural layers and is a function of the time after occlusion that blood flow is measured.     

OCs and resting blood flow.

Report findings indicate that the pill appears to reduce resting blood flow in the leg but does not necessarily mean an increased risk of thrombosis. The pill changes the elasticity of the vessel walls and leads to increased rigidity and reduced distensibility. Flow resistance is increased and the volume flow may be reduced, but it is velocity not flow per se that is the crucial factor in thrombosis. Using the tilt table method, venous pressure expected with legs horizontal would be 6-12 cm of water, but with legs verticle, the pressure in the foot and lower calf would be 40-50 cm of water, similar to the occluding cuff in horizontal plethysmography. However, it is not known if the elastic reaction during passive engorgement of the horizontal leg is the same as that caused by hydrostatic pressure during normal flow perfusion.     

Weight changes and obesity predict impaired resting and endothelium-dependent myocardial blood flow in postmenopausal women

BACKGROUND: Obesity has been associated with impaired endothelial function, but the influence of lifetime weight patterns on endothelial function has not been studied. HYPOTHESIS: We hypothesized that coronary vascular reactivity would be diminished in postmenopausal women with a history of obesity and frequent weight swings. METHODS: We performed dynamic N-13 ammonia positron emission tomography in 18 postmenopausal women with cardiac risk factors. Myocardial blood flow (MBF) was measured at rest, after the cold pressor test (CPT), and after adenosine infusion in order to determine baseline and endothelium-dependent and -independent flows, respectively. Myocardial blood flow was corrected for cardiac work by normalizing to the rate-pressure product. Weight history was obtained by standardized questionnaire. RESULTS: Normalized rest (n-rest) MBF correlated negatively with current weight (r = -0.52, p = 0.026) and weight at age 18 (r = -0.47, p = 0.047). Normalized CPT (n-CPT) MBF correlated inversely with current weight (r = -0.55, p = 0.018), weight at age 18 (r = -0.605, p = 0.008), and highest weight (r = -0.62, p = 0.006). Higher waist circumference predicted lower n-rest MBF (r = -0.52, p = 0.028) and n-CPT MBF (r = -0.48, p = 0.04). The same association was found with hip circumference (r = -0.52, p = 0.028; r = -0.49, p = 0.038, respectively), whereas higher body mass index (BMI) predicted lower n-CPT MBF (r = -0.53, p = 0.02). Women with at least four significant weight swings had lower MBF during rest, CPT, and n-CPT (0.88 vs. 1.19 ml/g/min, p = 0.008; 0.76 vs. 1.23 ml/g/min, p < 0.001; 0.74 vs. 1.10 ml/g/min, p = 0.009, respectively). CONCLUSIONS: Increased waist and hip circumference, weight, and frequent weight swings are associated with impaired resting and endothelium-dependent MBF in postmenopausal women. These data suggest that lifetime weight patterns may influence cardiovascular risk in women.     

Regional myocardial blood flow during cardiac tamponade in hearts with chronic coronary artery occlusion

The effects of increased pericardial pressure on blood flow to collateral dependent and normal myocardium were investigated and the mechanisms responsible for these effects evaluated in 10 anaesthetised dogs after collateral inducement by gradual occlusion of a coronary artery. Regional myocardial blood flows were measured with radioactive microspheres during control conditions, mild tamponade, severe tamponade, and severe tamponade with aortic blood pressure held at the control value by blood volume expansion. Mild tamponade increased heart rate by 10% and decreased aortic blood pressure by 15%. Left atrial and central venous blood pressures were moderately increased, and indices of cardiac function were reduced. Blood flow to collateral dependent and normally perfused myocardium was not significantly altered, but the endocardial to epicardial flow ratio was significantly decreased in collateral dependent myocardium. Severe tamponade decreased aortic blood pressure by 45% and cardiac index by 62%. Left atrial and central venous blood pressures were appreciably increased and cardiac function indices considerably depressed. Blood flow to collateral dependent and normally perfused myocardium was decreased similarly (by 54-57%), but the endocardial to epicardial flow ratio was decreased by a greater degree in collateral dependent myocardium. During severe tamponade at control aortic blood pressure, left atrial and central venous blood pressures were further increased, but blood flow to collateral dependent and normally perfused myocardium returned to within 84% of control and endocardial to epicardial flow ratios were normal. Total peripheral vascular resistance increased during severe tamponade, but coronary vascular resistance remained constant. Thus blood flow to collateral dependent and normally perfused myocardium varied according to net coronary perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Echocardiokimography and scintigraphy with Tc-MIBI in left ventricular asynergy in chronic myocardial infarct. Comparison of these methods

The study compared echocardiography, specially echocardiokimography, and myocardial scintigraphy in the evaluation of the extent of chronic myocardial infarction. Eighteen subjects were enrolled and the following examinations performed: ECG, M- and B-mode echocardiography, echocardiokimography and myocardial scintigraphy with Tc-MIBI, a new perfusion radionuclide agent. We concluded: 1) accordance between the two kinds of methods; 2) specificity of echocardiokimography; 3) advantage in using both methods, specially with MIBI scintigraphy.     

Blood hyperviscosity with reduced skin blood flow in scleroderma

The vascular complications of scleroderma have previously been attributed to the progressive obliteration of small vessels. Our study was carried out to determine whether abnormalities of blood viscosity occur in this disease, thereby contributing to the ischaemic process. Blood viscosity was measured in 20 patients using a rotational viscometer. At a high rate of shear, blood hyperviscosity was found in 35% of the patients and at a low rate of shear, in 70%. In addition there was a significant increase in the plasma viscosity which implicates changes in plasma proteins (fibrinogen, immunoglobulins) as causing the hyperviscosity. Measurement of the hand blood flow by venous occlusion plethysmography showed reduced flow at 32 degrees , 27 degrees , and 20 degrees C. A unique finding was a delayed recovery of the blood flow after cooling. These observations suggest that the increased resistance to blood flow in skin affected by scleroderma may be caused by an interaction between the occlusive vascular lesion and blood hyperviscosity. In addition, blood flow patterns and hyperviscosity could help distinguish scleroderma from primary Raynaud's disease.     

Elevated coronary vascular resistance in the presence of reduced resting blood flow distal to a severe coronary stenosis

Vascular reserve in underperfused myocardium has recently been described. This seemingly paradoxical observation conflicts with older concepts of the coronary circulation which hold that flow deficits do not develop until reserve is fully exhausted. To examine this phenomenon in greater detail in an animal model mimicking a fixed human coronary artery stenosis, we analysed the records of 25 carefully selected, sedated pigs all instrumented with a rigid intralumenal coronary stenosis (82% lumenal diameter reduction). Each animal satisfied the following criteria: 1) perfused myocardial mass beyond the stenosis was within a narrow weight range (16 to 24 g); and 2) post stenosis (distal) epicardial (Epi) and endocardial (endo) flows were less than or equal to 90% of respective flows in a region perfused by the non-stenosed circumflex (CX) coronary artery. Accordingly, distal flow was reduced compared to circumflex zone flow (p less than 0.01) in the Epi (173 +/- 51 to 113 +/- 32 ml . 100g-1 . min-1), Endo (146 +/- 39 to 116 +/- 27) and transmural (Tm) regions (164 +/- 45 to 124 +/- 31). Despite a flow deficit and constant severity of stenosis, distal zone Tm resistance (0.55 +/- 0.21 mmHg/ml . 100 g-1 . min-1) exceeded the minimum level achievable with intravenous infusion of adenosine (0.25 +/- 0.07) in a separate group of eight animals without a stenosis. Distal transmural resistance also varied over a five fold range (0.27 to 1.33) and in 20/25 animals exceeded the highest level (0.37) seen in non-stenosis animals during adenosine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for decreased coronary flow reserve in viable postischemic myocardium

To try to unravel the complexity and heterogeneity of the "no-reflow" phenomenon and its underlying mechanisms, we studied tissue perfusion in reperfused heart muscle by using tracer microspheres in an anesthetized dog model of 90-minute coronary occlusion followed by reperfusion for 2 1/2 hours, 24 hours, or 1 week. Regional myocardial blood flow was determined both in basal flow conditions and during reactive hyperemia. The effect of intracoronary adenosine administration was examined, and the ultrastructure of postischemic myocardium was analyzed. In viable reperfused tissue (as delineated by triphenyltetrazolium chloride staining), reflow in basal conditions is unimpaired. Coronary flow reserve (as approximated by peak reactive hyperemic flow) is intact at the start of reperfusion, decreases by more than half after 2 1/2 hours, and recovers completely within 1 week. This impairment of coronary reserve can be relieved by intracoronary adenosine administration. On ultrastructural examination, the capillaries are patent. On the other hand, in irreversibly damaged myocardium, both the basal reflow impairment and the decrease in coronary flow reserve are severe and permanent. Coronary flow reserve is already decreased at the start of reperfusion, and the pharmacological intervention has no beneficial effect. Ultrastructurally, extracellular and intracellular edema invariably are present, whereas the vascular endothelium is damaged and the capillaries are packed with red blood cells. We conclude that the no-reflow phenomenon (i.e., mechanical obstruction to blood flow) is limited to infarcted tissue. In viable myocardium, however, coronary flow reserve is transiently diminished, probably because of washout and subsequent insufficient availability of the chemical mediator adenosine after breakdown and slow recovery of the precursor ATP pool.     

静息与负荷心肌造影超声心动图识别存活心肌的对比研究

目的探讨负荷心肌造影超声心动图(MCSE)对心肌梗死后存活心肌评价的疗效和安全性。方法选择冠状动脉造影证实的心肌梗死患者30例。首先在静息状态下行心肌造影超声心动图(MCE),MCE心肌灌注结果采用半定量评价。多巴酚丁胺负荷静脉滴注剂量分别为5、10、20μg·kg~(-1)·min~(-1),每期3 min观察心率、血压变化于达到负荷剂量后再次行MCE,并以~(18)F-脱氧葡萄糖正电子发射计算机体层扫描(PET)作为金标准评价其敏感性和特异性。结果 MCE总共评价360个梗死节段,静息MCE评价1、0.5、0分为264、22、74个节段。多巴酚丁胺负荷MCSE评价1、0.5、0分为286、30、44个节段,评价MCE敏感性和特异性分别为38.10%、88.89%,kappa=0.285(P0.01)。评价MCSE敏感性和特异性分别为86.21%、88.89%,kappa=0.746(P0.05)。结论MCE及MCSE安全性良好。MCE及MCSE均与冠状动脉造影心肌梗死部位有较好的相关性,以PET作为金标准,MCSE具有较高的敏感性和特异性,是评价梗死节段内存活心肌的较好方法。