Myocardial blood flow, metabolism, and inotropic reserve in dogs with dysfunctional noninfarcted collateral-dependent myocardium.

There is intense controversy as to the mechanisms underlying chronic but reversible left ventricular (LV) ischemic dysfunction. The aim of this study was to investigate the physiology underlying this condition in a canine model of noninfarcted collateral-dependent myocardium. METHODS: Six mongrel dogs were instrumented with ameroid constrictors on the left circumflex and right coronary arteries and a partial occluder on the left anterior descending coronary artery. The animals were followed up for 6 mo. Every 6 wk, measurements of regional wall thickening (M-mode echo), myocardial blood flow ((13)N-ammonia PET), oxygen consumption ((11)C-acetate PET), and glucose uptake ((18)F-FDG PET) were obtained. After 6 mo, myocardial blood flow reserve (during adenosine infusion) and regional contractile reserve (during infusion of a low dose of dobutamine) were also investigated. RESULTS: Following ameroid implantation, regional thickening decreased in the posterior wall (to 34% +/- 13% of baseline; P < 0.001) but not in the septum. Resting myocardial blood flow (56 +/- 10 vs. 58 +/- 15 mL.[min.100 g](-1)), myocardial oxygen consumption (21 +/- 3 vs. 22 +/- 3 J.[beat.100 g](-1)), and insulin-stimulated glucose uptake (39 +/- 8 vs. 42 +/- 11 micromol.[min.100 g](-1)) were similar among dysfunctional and normal segments. Myocardial blood flow reserve was blunted in dysfunctional versus normal segments (3.7 +/- 0.5 vs. 5.2 +/- 1.5; P = 0.06). With dobutamine, wall thickening (to 69% +/- 8% and 77% +/- 11%, respectively) and oxygen consumption (to 36 +/- 5 and 39 +/- 5 J.[beat.100 g](-1), respectively) improved to the same extent in both segments. As a consequence, mechanical efficiency decreased in septal but remained unchanged in posterior segments during infusion of dobutamine. Biopsy specimens from both walls were free from any morphological alterations. CONCLUSION: Our data indicate that ameroid occlusion in dogs induces sustained reduction in regional contraction, which occurs despite normal levels of transmural blood flow and recruitable inotropic reserve. Since myocardial perfusion reserve was blunted, such perfusion-contraction mismatch could reflect repetitive stunning.     

Reduced septal glucose metabolism predicts response to cardiac resynchronization therapy

Background  

Up to 50% of patients do not respond to Cardiac Resynchronization Therapy (CRT). Recent work has focused on quantifying mechanical dyssynchrony and left ventricular scar. Septal reverse-mismatch (R-MM) (reduced FDG uptake vs perfusion) has been observed in patients with cardiomyopathy and prolonged QRS duration. We hypothesized that a greater quantity of septal R-MM would indicate a greater potential for reversibility of the cardiomyopathy, when the dyssynchrony is improved with CRT. Therefore, this study’s objective was to assess whether greater septal R-MM pattern predicts response to CRT.     

PET imaging of oxidative metabolism abnormalities in sympathetically denervated canine myocardium.

This study was designed to test the hypothesis that regional sympathetic denervation produces perfusion and metabolic alterations in myocardial tissue under resting conditions. METHODS: PET studies of myocardial sympathetic innervation, myocardial perfusion and oxygen utilization using [11C]hydroxyephedrine (HED), [13N]ammonia and 1-[11C]acetate, respectively, were performed before and approximately 2 and 8 wk after surgical left thoracotomy and regional chemical sympathetic denervation (n = 5). A second group of animals underwent the same surgical procedure but, so that they could serve as a sham control group, were not sympathetically denervated (n = 5). The second group of animals was imaged before and 2 wk after surgery. Images of the retention of [11C]HED taken from 50 to 60 min postinjection were used to differentiate sympathetically innervated and denervated regions of the left ventricle. Regions of interest were defined on polar plots of the [11C]HED retention, including the sympathetically denervated territory and normally innervated regions. Regions defined on the HED polar plots were then transferred to the [13N]ammonia and 1-[11C]acetate image data, and tracer kinetic models were fit to the regional time-activity curves to generate estimates of myocardial perfusion and oxidative metabolism. RESULTS: The average percentage of the left ventricle denervated in the group I animals was 13.1% +/- 7.3%. Significant reductions in oxidative metabolism were observed in the sympathectomized tissue both at 2 and 8 wk after surgery (22% and 15% reductions, respectively). Significant alterations in regional perfusion were not observed. No significant changes in oxidative metabolism or perfusion were observed in the sham control group. CONCLUSION: Regional sympathetic denervation alters oxidative metabolism but not perfusion in the denervated region of the heart.     

Assessment of myocardial oxidative metabolic reserve with positron emission tomography and carbon-11 acetate

We have previously demonstrated that positron emission tomography (PET) with [11C]acetate allows noninvasive regional quantification of myocardial oxidative metabolism. To assess the metabolic response of normal myocardium to increased work (oxidative metabolic reserve), clearance of myocardial 11C activity after administration of [11C]acetate i.v. was measured with PET in seven normal subjects at rest and during dobutamine infusion. At rest, clearance of 11C was monoexponential and homogeneous. The rate constant of the first phase of 11C clearance, k1, averaged 0.054 +/- 0.014 min-1 at a rate-pressure produce (RPP) of 7329 +/- 1445 mmHg X bpm. During dobutamine infusion, RPP increased by an average of 141% to 17,493 +/- 3582 mm Hg Z bpm. Clearance of 11C became biexponential and remained homogeneous. k1 averaged 0.198 +/- 0.043 min-1 with a mean coefficient of variation of 16%.. k1 and RPP correlated closely (r = 0.91; p less than 0.001), and the slope of the k1/RPP relation remained consistent in all subjects (1.48 +/- 0.42). These findings suggest that PET with [11C]acetate and dobutamine stress may provide a promising approach for evaluation of regional myocardial oxidative metabolic reserve in patients with cardiac diseases of diverse etiologies and for assessment of the efficacy of interventions designed to enhance the recovery of metabolically comprised myocardium.     

Reduced resting metabolic rate in athletes with menstrual disorders.

PURPOSE: This study investigated metabolic and nutritional determinants in association with menstrual disorders in athletes. Athletes with normal menstrual function (AN; N = 21) and athletes with menstrual disorders (AD: N = 12) participated in this study. METHODS: The quality of the menstrual cycle was judged according to salivary progesterone concentrations. Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) were measured by indirect calorimetry. Body composition, energy intake and restrained eating scores were obtained. RESULTS: When adjusted for body composition by ANCOVA, RMR was significantly (approximately 460 kJ, P < 0.02) lower in athletes with menstrual disorders than in athletes without menstrual disorders. The DIT and the daily energy intake of the groups did not differ. Athletes with menstrual disturbances scored significantly higher on the Restraint Eating Scale (TFEQ). Thyroid hormones (fT3 and fT4), analyzed by a competitive chemiluminescent immunoassay, were in the normal range and not different between groups. CONCLUSIONS: The results provide evidence that restrained eating and low RMR are associated with menstrual cycle disturbances in athletes.     

Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy

Purpose

The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR).

Methods

Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25?±?10 %) were studied with ¹³N-ammonia and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to ¹³N-ammonia activity ratios.

Results

Rest MBF was reduced in viable (0.42?±?0.18 ml/min per g) and nonviable regions (0.32?±?0.09 ml/min per g) relative to remote regions (0.68?±?0.23 ml/min per g, p?<?0.001) and to normals (0.63?±?0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p?<?0.05) and stress (p?<?0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p?>?0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39?±?0.56 vs 1.70?±?0.45, p?>?0.05) but were significantly lower in nonviable regions (1.23?±?0.43, p?<?0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40?±?0.14 vs 0.90?±?0.20, p?<?0.001) and in nonviable regions (1.13?±?0.21, p?<?0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r?=?0.424, p?<?0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions.

Conclusion

As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.     

糖代谢异常对原发性高血压患者肾脏微血管病变的影响

目的探讨糖代谢异常(IGM)对原发性高血压(EH)患者肾脏微血管病变所致的肾功能损伤的影响。方法检测并对比46例单纯EH患者[平均年龄(77.1±5.6)岁]与36例合并2型糖尿病(T2DM)EH患者[平均年龄(79.3±5.9)岁]之间的血糖、血脂参数及血清同型半胱氨酸(Hcy)、胱抑素C(Cys C)、尿微量白蛋白(UM)浓度差异,同时分析血糖参数、血清Hcy、Cys C及UM浓度之间的相关性。结果与单纯EH患者相比,合并T2DM的EH患者的BMI、空腹血糖(FBG)、餐后2 h血糖(PBG)、糖化血红蛋白(Hb A1c)、血三酰甘油、低密度脂蛋白胆固醇、载脂蛋白B、尿酸及纤维蛋白原等代谢参数均显著高于单纯EH患者(P<0.05),而且血清Hcy分别为(16.35±2.86)μmol/L与(12.59±2.37)μmo/L,P<0.01;Cys C浓度(1.40±0.30)mg/L与(1.02±0.16)mg/L,P<0.01及UM水平(3 3.0 8±1 0.5 5)mg/L与(19.40±5.22)mg/L,P<0.01,也均显著增高;相关分析显示,在合并T2DM的EH患者中,血清Hcy浓度分别与FBG(r=0.645,P<0.01)、Hb A1c(r=0.652,P<0.01)正相关,UM也分别与FPG(r=0.387,P<0.05)、Hb A1c(r=0.635,P<0.01)正相关;而且,血清Hcy与Cys C浓度(r=0.841,P<0.01)、血清Hcy浓度与UM水平(r=0.655,P<0.01)、血清Cys C浓度与UM水平之间(r=0.479,P<0.01)均显著正相关。结论 IGM加重EH患者肾脏微血管病变,影响肾小球滤过功能,改善其血糖代谢可有助于延缓肾微血管病变的发生并进展至肾功能不全阶段。     

Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability: A PET study.

SPECT with 99mTc-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasodilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on the changes in blood flow are lacking in SPECT but can be provided by PET. The aim of the present study was to use PET to evaluate whether nitrate administration increases blood flow to chronically dysfunctional but viable myocardium. METHODS: 13N-Ammonia PET was used to quantitatively assess blood flow, and 18F-FDG PET was used as the gold standard to detect viable myocardium. Twenty-five patients with chronic ischemic left ventricular dysfunction underwent 13N-ammonia PET at rest and after nitrate administration. RESULTS: A significant increase in nitrate-enhanced blood flow was observed in viable segments (from 0.55 +/- 0.15 to 0.68 +/- 0.24 mL/min/g, P < 0.05). No statistically significant change in blood flow was observed in nonviable segments (0.60 +/- 0.20 vs. 0.55 +/- 0.18 mL/min/g). A ratio of at least 1.1 for nitrate-enhanced flow to resting flow allowed optimal detection of viable myocardium, yielding a sensitivity of 82% with a specificity of 100%. CONCLUSION: 13N-Ammonia PET showed a significant increase in nitrate-enhanced blood flow in viable myocardium, whereas blood flow remained unchanged after nitrate administration in nonviable myocardium. Nitrate use during myocardial perfusion imaging will lead to improved assessment of myocardial viability.     

Myocardial sympathetic innervation, function, and oxidative metabolism in non-infarcted myocardium in patients with prior myocardial infarction

Objective

The purpose of this study was to investigate the relationship between sympathetic innervation, contractile function, and the oxidative metabolism of the non-infarcted myocardium in patients with prior myocardial infarction.

Methods

In 19 patients (14 men, 5 women, 65 ± 9 years) after prior myocardial infarction, sympathetic innervation was assessed by ¹¹C-hydroxyephedrine (HED) positron emission tomography (PET). Oxidative metabolism was quantified using ¹¹C-acetate PET. Left ventricular systolic function was measured by echocardiography with speckle tracking technique.

Results

The ¹¹C-HED retention was positively correlated with left ventricular ejection fraction (LVEF) (r = 0.566, P < 0.05), and negatively with peak longitudinal strain in systole in the non-infarcted myocardium (r = ?0.561, P < 0.05). Kmono, as an index of oxidative metabolism, was significantly correlated with rate pressure product (r = 0.649, P < 0.01), but not with ¹¹C-HED retention (r = 0.188, P = 0.442). Furthermore, there was no significant correlation between Kmono and LVEF (r = 0.106, P = 0.666) or peak longitudinal strain in systole (r = ?0.256, P = 0.291) in the non-infarcted myocardium. When the patients were divided into two groups based on the median value of left ventricular end-systolic volume index (LVESVI) (41 mL), there were no significant differences in age, sex, and rate pressure product between the groups. However, the large LVESVI group (>41 mL) was associated with reduced ¹¹C-HED retention and peak longitudinal strain in systole, whereas Kmono was similar between the groups.

Conclusions

This study indicates that remodeled LV after myocardial infarction is associated with impaired sympathetic innervation and function even in the non-infarcted myocardial tissue. Furthermore, oxidative metabolism in the non-infarcted myocardium seems to be operated by normal regulatory mechanisms rather than pre-synaptic sympathetic neuronal function.     

Left ventricular diastolic function in type 2 diabetes mellitus is associated with myocardial triglyceride content but not with impaired myocardial perfusion reserve

Purpose:

To study myocardial perfusion reserve and myocellular metabolic alterations indicated by triglyceride content as possible causes of diastolic dysfunction in patients with type 2 diabetes mellitus, preserved systolic function, and without clinically evident coronary artery disease.

Materials and Methods:

Patients with type 2 diabetes mellitus (n = 42) underwent cardiac magnetic resonance (CMR) for quantification of 1) myocardial contractility by strain‐encoded MR (SENC); 2) myocardial triglyceride content by proton magnetic resonance spectroscopy (¹H‐MRS); and 3) myocardial perfusion reserve during pharmacologic hyperemia. Age‐matched healthy volunteers (n = 16) also underwent CMR to acquire normal values for myocardial strain and perfusion reserve.

Results:

Stress CMR procedures were successfully performed in all subjects, and no regional inducible perfusion defects were observed in type 2 diabetes mellitus patients. Diastolic strain rate and myocardial perfusion reserve were significantly impaired in patients with type 2 diabetes mellitus compared to control subjects (P < 0.001 for both). Interestingly, impaired diastolic function in type 2 diabetes mellitus was not associated with impaired myocardial perfusion reserve (r = 0.12, P = NS). Conversely a significant association was observed between diastolic dysfunction and myocardial triglyceride content (r = ?0.71, P < 0.001), which proved to be independent of age, gender, diabetes duration, blood pressure, and fasting blood glucose.

Conclusion:

Myocardial steatosis may represent an early marker of diabetic heart disease, triggering subclinical myocardial dysfunction irrespective of myocardial perfusion reserve. J. Magn. Reson. Imaging 2012;35:804–811. © 2011 Wiley Periodicals, Inc.

     

Long but dysfunctional telomeres correlate with chromosomal radiosensitivity in a mouse AML cell line.

PURPOSE: To compare the chromosomal radiosensitivity of C3H mouse acute myeloid leukaemia (AML) cell lines 7926 and 8709 and to investigate the mechanistic basis of the radiosensitivity observed in 7926. MATERIALS AND METHODS: Yields of chromosome aberrations following X-irradiation were determined in Giemsa-stained metaphases. Cell cycle phase distributions were determined by BrdU incorporation and microscopy, apoptosis was assessed by caspase assays. Telomerase activity (TRAP assay), telomere length (Q-FISH and Southern blotting) and telomere function (Robertsonian-like fusion formation) were also examined. The expression levels of telomerase components, telomerase regulators and DNA PKcs were determined on Northern blots. RESULTS: A total of 4.5-7.6-fold elevated chromosome aberration yields were found in 7926 by comparison with 8709 3-24h after 0.5 and 1 Gy X-ray exposure. This difference could not be accounted for by differences in chromatid break-rejoining rates, cell cycle phase distribution or the induction of apoptosis. Telomeres and telomerase were dysfunctional in 7926. However, average telomere length was approximately two-fold greater than in 8709. CONCLUSION: Defective telomere function in 7926 correlates with chromosomal radiosensitivity. This implicates telomere function in addition to telomere length as a determinant of chromosomal radiosensitivity.     

不同糖调节受损人群的餐后血糖波动特点研究

目的 采用动态血糖监测系统(CGMS)研究不同糖调节受损人群的餐后血糖波动特征.方法 根据连续2次75g口服葡萄糖耐量检查(OGTT)结果,选取北京地区稳定人群中正常糖耐量(NGT)组22例,单纯空腹血糖受损(HFG)15例、单纯糖耐量低减(I-IGT)19例、空腹血糖受损合并糖耐量低减(IFG/IGT)组11例,新诊断2型糖尿病(T2DM)组21例.所有受试对象均行72hCGMS监测,分析比较各组餐后血糖峰值(PPG)、达峰时间(△t).餐后血糖波动幅度(PPGE)、餐后血糖波动持续时间(DPE)、曲线下面积(AUC)和其增量(△AUC).结果 I-IGT、IFG/IGT和T2DM组的餐后PPG、餐后PFGE较NGT或I-IFG明显升高,HGT和T2DM组DPE明显延长,T2DM组△t较NGT组明显延迟(P<0.05);从NGT、I-IGT、IFG/IGT到T2DM组,餐后血糖对全天高血糖的贡献率(△PAUCI)逐渐下降;且I-IFG、IRG/IGT和T2DM组较NGT有显著性差异(P<0.05);当糖化血蛋白(HbA1C)≥7%时,空腹对全天高血糖的贡献率首次逆转为大于餐后贡献率,且与HbA1C<5.5%组比较,△PAUC1开始有显著性差异;HbA1C与餐后总曲线下面积(AUC1)、全天总曲线下面积(AUC2)、空腹总曲线下面积(AUC3)、OGTT葡萄糖负荷后2h血糖(2hPBG)和3餐血糖峰值均值(MPPG)显著相关(γ分别为0.743、0.687、0.504、0.708和0.732,P<0.001);以HbA1C为因变量,以曲线下面积和血糖水平为自变量分别进行多元逐步回归分析,只有AUC1、AUC2和2hPBG、中餐后PPG最终分别进入2个方程(决定系数r2为0.552和0.614,P<0.01).结论 IGR三组分中I-IFG的餐后特征与NGT最为接近,I-IGT组与T2DM最相似;除I-IFG组外,随着糖调节受损程度的加重,餐后血糖对全天高血糖的贡献率逐渐下降;当HbA1C<7%时,应以控制餐后血糖为主,餐后2h血糖为推荐的简单评价指标;而HbA1C≥7%时,还应重视空腹血糖.     

Repetitive supply-demand ischemia with dobutamine increases glucose uptake in postischemic and remote myocardium.

The goal of this study was to determine whether myocardial glucose uptake after repetitive ischemia differs in response to coronary occlusion-reperfusion versus supply-demand ischemia induced by dobutamine. Although glucose metabolism is increased after myocardial ischemia, the metabolic effect of supply-demand ischemia induced by dobutamine may increase glucose metabolism within remote myocardium. This would make it difficult to discriminate postischemic from remote myocardium with glucose tracers. METHODS: Eighteen swine with a hydraulic occluder and flow probe on the circumflex artery underwent repetitive ischemia. In group 1 (n = 9), the circumflex artery was occluded, whereas in group 2 (n = 9), circumflex flow was decreased by 30% before dobutamine (40 micro g/kg/min intravenously). Each pig underwent 15 min of ischemia, twice per day for 5 d. Echocardiography and PET to determine myocardial glucose ((18)F-FDG) uptake were performed after final ischemia, and tissue was later analyzed for activation of Akt, p38 mitogen-activated protein, and adenosine monophosphate (AMP) kinase. RESULTS: Wall thickening in the circumflex region was lower than in remote regions in both groups. (18)F-FDG uptake in the circumflex region was similar in groups 1 and 2 (0.22 +/- 0.03 and 0.23 +/- 0.04 micro mol/min/g, respectively; not statistically significant). In the remote region, (18)F-FDG uptake was lower than in the circumflex region in group 1 (0.14 +/- 0.03 micro mol/min/g; P < 0.05) but was similar to that in the circumflex region in group 2 (0.20 +/- 0.03 micro mol/min/g; not statistically significant). AMP kinase activity in the remote region was significantly lower than in the circumflex region in group 1 but was similar to that in the circumflex region in group 2. CONCLUSION: Unlike repetitive coronary artery occlusion-reperfusion, repetitive supply-demand ischemia with dobutamine alters glucose uptake within the remote myocardium, possibly as a result of AMP kinase activation. Clinically, these data suggest that (18)F-FDG studies have a limited role in discriminating postischemic from remote myocardium after dobutamine stress.     

Reverse blood flow-glucose metabolism mismatch indicates preserved oxygen metabolism in patients with revascularised myocardial infarction

Purpose

Positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) has been reported to be unreliable for identifying viable myocardium in acute myocardial infarction (AMI), especially in areas with discordance in myocardial blood flow (MBF) and glucose metabolism. In myocardium with decreased FDG uptake but preserved MBF, referred to as exhibiting reverse mismatch, myocardial viability remains controversial and little is known about the metabolic state. The aims of this study were to clarify substrate use and to estimate myocardial viability in infarct areas exhibiting reverse mismatch.

Methods

Eighteen AMI patients with successful revascularisation were included in this study. Two weeks after onset, ¹¹C-acetate and ¹⁸F-FDG PET were performed to evaluate regional oxygen consumption (k _mono), MBF and glucose metabolism. Free fatty acid (FFA) metabolism was evaluated with ¹²³I-15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT). To assess wall motion, movement in left ventricular endocardial surface was calculated using ECG-gated ^99mTc-tetrofosmin SPECT.

Results

The %k _mono values in reverse mismatch segments (52.6?±?13.6 %) were not significantly different from those in non-infarct segments (60.4?±?12.8 %, p?=?0.071) and normal match segments (preserved MBF and FDG uptake) (58.6?±?11.6 %, p?=?0.396), although regional wall motion was more severely impaired (3.06?±?2.52 mm vs 6.78?±?3.17 mm, p?<?0.0001, and vs 5.30?±?2.33 mm, p?=?0.042, respectively). Compared to segments with reduced match (reduced MBF and FDG uptake), %k _mono and %BMIPP uptake were significantly higher in reverse mismatch segments (52.6?±?13.6 % vs 37.4?±?8.9 %, p?=?0.0002, and 58.8?±?10.6 % vs 40.2?±?10.7 %, p?<?0.0001).

Conclusion

Reverse mismatch in reperfused AMI patients, high oxygen consumption and FFA metabolism were observed despite decreased glucose metabolism. We conclude that reverse mismatch indicated the myocardium with early restoration of MBF and aerobic FFA metabolism.     

Relationship between contractile reserve,Tl-201 uptake,and collateral angiographic circulation in collateral-dependent myocardium: Implications regarding the evaluation of myocardial viability

BACKGROUND: The aim of this study was to compare collateral angiographic circulation (CC), thallium 201 single photon emission computed tomography (SPECT), low-dose dobutamine echocardiography (LDDE), and their combination in identifying viable myocardium beyond a chronic occlusion. METHODS AND RESULTS: We studied 33 consecutive patients with a chronic occluded coronary artery and regional ventricular dysfunction who underwent dobutamine infusion (5-10 microg x kg(-1) x min(-1)), Tl-201 SPECT, and coronary revascularization (15 patients underwent coronary artery bypass grafting and 18 patients percutaneous transluminal coronary angioplasty). Echocardiography and Tl-201 SPECT at rest were repeated 90 +/- 48 days after revascularization. For viability assessment, Tl-201 SPECT showed the best sensitivity and accuracy (77% and 72%, respectively) compared with LDDE (64% and 63%, respectively) and CC (74% and 55%, P < .05 vs Tl-201 SPECT). Specificity was significantly better for both Tl-201 SPECT (65%) and LDDE (62%) compared with collateral circulation (27%, P < .001 vs Tl-201 SPECT and LDDE). Furthermore, combined Tl-201 SPECT and LDDE data improved specificity (from 88% to 92%) and positive predictive power (from 75% to 78%) but not global accuracy. A direct relationship between the number of viable segments and global functional recovery after revascularization was found only in the case of Tl-201 SPECT (r = 0.48, P = .04). CONCLUSIONS: This study demonstrates that CC has a very low specificity in the evaluation of viability in collateral-dependent myocardium and that LDDE has a very low sensitivity, whereas Tl-201 SPECT is the most reliable method, particularly in akinetic segments, and optimally identifies patients who will mostly benefit from revascularization in terms of ventricular functional improvement. No additional advantages in terms of accuracy were found when Tl-201 SPECT and LDDE data were combined.     

Myocardial oxidative metabolism in normal subjects in fasting,glucose loading and dobutamine infusion states

Experimental studies indicated the clearance rate constant of 11C-acetate as an index of regional myocardial oxygen consumption. To assess the response of the clearance rate from the left ventricular (LV) myocardium to the change in plasma substrate levels and to the increase in the cardiac work load in normal subjects, a total of 18 dynamic positron emission tomographic studies were performed at rest in the fasting state (control) (n = 7), after oral glucose administration (n = 4), and during dobutamine infusion (n = 7) in 7 normal volunteers. The clearance rate constant (Kmono) was similar in the control (0.065 +/- 0.017 min-1) and glucose loading states (0.059 +/- 0.008 min-1), whereas a significant increase in Kmono was observed during dobutamine infusion (0.106 +/- 0.018 min-1) (p < 0.01) in relation to the increase in the pressure-rate product with a correlation coefficient of 0.873 (p < 0.01). When the LV myocardium was divided into 6 segments, there were no significant differences among the segments in Kmono values in any condition. These normal responses should be valuable for assessing oxidative metabolic reserve and regional changes in oxidative metabolism in patients with coronary artery disease.     

Myocardial perfusion reserve and contractile pattern after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy

Background  

In Idiopathic Dilated Cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. The ensuing subclinical myocardial ischemia may contribute to progressive deterioration of LV function. β-blocker is the therapy of choice in these patients. However, not all patients respond to the same extent. The aim of this study was to elucidate whether differences between responders and non-responders can be identified with respect to regional myocardial perfusion reserve (MPR) and contractile performance.     

Metabolic reserve in normal myocardium assessed by positron emission tomography with C-11 palmitate

Positron emission tomography (PET) with C-11 palmitate has been used in estimating the myocardial utilization of free fatty acid. To assess the metabolic reserve in normal subjects, a PET study was performed at control and during dobutamine infusion at 2 hour intervals in 5 normal subjects. Following monoexponential curve fitting of the time activity curve of the myocardium, the clearance half time (min) and residual fraction (%) were calculated as indices of beta-oxidation of free fatty acid. A significant increase in the heart rate and systolic blood pressure were observed during dobutamine infusion (65 +/- 5 vs 100 +/- 29 bpm, p less than 0.05 and 119 +/- 12 vs 144 +/- 16 mmHg, p less than 0.01, respectively). The clearance half time and the residual fraction were significantly decreased (23.4 +/- 2.6 vs 15.8 +/- 2.3 min and 67.0 +/- 2.5 vs 58.6 +/- 4.0%, P less than 0.05, each). When the left ventricular myocardium was divided into 4 segments, these indices were similar at control and uniformly decreased without regional differences during dobutamine infusion. These data suggest that beta-oxidation of free fatty acid may be uniformly increased in the left ventricular myocardium in relation to the increase in cardiac work in normal subjects. PET with C-11 palmitate at control and during dobutamine infusion is considered to be promising in assessing metabolic reserve in the myocardium.