Relationship between blood flow and fatty acid metabolism in subacute myocardial infarction: a study by means of99mTc-Sestamibi and23I-β-methyl-iodo-phenyl pentadecanoic acid

Contradictory data have been published on the relative behaviour of fatty acids and flow tracers during the subacute stage of myocardial infarction. Therefore, the present study was set up (1) to investigate the potential occurrence of mismatches between -methyl-iodophenyl pentadecanoic acid (BMIPP), a fatty acid analogue, and Sestamibi, and to describe their nature, and (2) to relate these mismatches to clinical characteristics such as whether or not thrombolysis or percutaneous transluminal coronary angioplasty (PTCA) had been performed. Twenty-six patients were studied within 2 weeks after myocardial infarction. Sestamibi and BMIPP single-photon emission tomography (SPET) were performed within 4 days of one another. Activity of both tracers was scored in 16 basal, 16 midventricular and 8 apical segments, using a four-point grading system: 3 = normal (65% of maximum activity), 2 = mildly decreased (45%–64%), 1 = moderately decreased (25%–44%), 0 = severely decreased (0%–24%). Coronary arteriography was obtained during the same hospital stay. Four hundred and seventy-seven segments out of 1040 studied were abnormal for at least one tracer: 197 with higher Sestamibi activity (group I), 226 with equal scores for Sestamibi and BMIPP (group II) and 54 with higher BMIPP activity (group III). Seventy-five percent of group I segments and 84% of group III segments were found in infarct-related artery territories. Group I segments were associated with acute thrombolysis and/or PTCA (P < 0.01), and with the absence of prior infarction in the territory of the infarct-related artery (P < 0.001). Group III segments were associated with the absence of thrombolysis or PTCA (P < 0.001), with occlusion of the infarct-related artery (P < 0.001), with previous infarction in the same territory (P < 0.001) and with a- or dyskinesia in this territory (P < 0.001). These data could support the interpretation that areas in which the uptake of BMIPP is more decreased than that of Sestamibi (group I) are due to delayed recovery of fatty acid metabolism after reperfusion, whereas those with higher BMIPP than Sestamibi activity (group III) are accounted for by the enhanced metabolism induced by passive systolic wall stretch.     

Relationship between evaluation by quantitative fatty acid myocardial scintigraphy and response to β-blockade therapy in patients with dilated cardiomyopathy

Predicting the effect of #-blockade therapy on the clinical outcome of patients with dilated cardiomyopathy (DCM) is difficult prior to the initiation of therapy. Myocardial fatty acid metabolism has been shown to be impaired in patients with DCM. We examined whether the extent of myocardial injury, as assessed by iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy, is related to the response of patients with DCM to #-blockade therapy. Thirty-seven patients with DCM were examined using BMIPP myocardial scintigraphy before and after 6 months of treatment with metoprolol. Myocardial BMIPP uptake (%BM uptake) was estimated quantitatively as a percentage of the total injected count ratio. The left ventricular end-diastolic and end-systolic dimensions (LVDd, LVDs) and ejection fraction (LVEF) were also evaluated. The patients were divided into two groups according to their functional improvement (>10% elevation of LVEF) after 6 months of metoprolol therapy. Twenty-eight patients responded to the therapy, while nine did not. Prior to the therapy, no significant differences in LVDd, LVDs or LVEF were observed between the responders and non-responders. However, the %BM uptake was significantly lower in the non-responders than in the responders (1.0%ǂ.2% vs 2.1%ǂ.5%, P<0.001). The %BM uptake could be used to distinguish the responders from the non-responders with a sensitivity of 0.93 and a specificity of 1.00 at a threshold value of 1.4. After the metoprolol therapy, the %BM uptake improved significantly in the responders (2.5%ǂ.5%, P<0.01) but did not change in the non-responders. These results indicate that myocardial BMIPP uptake could predict the response of DCM patients to #-blockade therapy.     

Effects of primary PCI and facilitated PCI on myocardial viability and ventricular systolic synchrony in acute myocardial infarction patients

Effects of primary PCI and facilitated PCI on myocardial viability and ventricular systolic synchrony in acute myocardial infarction patients!石家庄050000$河北医科大学第二医院@谷新顺 !石家庄050000$河北医科大学第二医院@傅向华 !石家庄050000$河北医科大学第二医院@马宁     

Studies of chemical and biological properties of 99mTc-DMS (dimercaptosuccinic acid) — Renal imaging agent

Studies of the chemistry of preparation of tin chelate 2.3-dimercaptosuccinic acid (DMS) complexed with ^99mTc with respect to its biological properties have been made. We have varied molar ratio of reactants (DMS:Sn/II/), concentration of Sn-DMS chelate and pH of ^99mTc-DMS injection solution and examined their influence on biodistribution. Biodynamics of labeled solution at time intervals of from 0.5 to 4 h have also been measured. Animal experiments were carried out on mice and rats.Radiochemical purity was checked by paper chromatography, thin-layer chromatography, and gel-filtration through Bio-Gel P-2.A sterile, pyrogen-free lyophilized kit for labeling, stable for 6 months, was made on the basis of achieved results.The results of its clinical application are also reported.Report presented at the I European Congress of Nuclear Medicine, Lausanne, May 12/15, 1976     

Potential prognostic implications of myocardial thallium-201 and iodine-123-beta-methylpentadecanoic acid dual scintigraphy in patients with Anderson–Fabry disease

Annals of Nuclear Medicine - Information on the relationship between myocardial damage assessed by myocardial scintigraphy and prognosis in patients with Anderson–Fabry disease (AFD) is...     

Lactic acid and exercise performance : culprit or friend?

This article critically discusses whether accumulation of lactic acid, or in reality lactate and/or hydrogen (H+) ions, is a major cause of skeletal muscle fatigue, i.e. decline of muscle force or power output leading to impaired exercise performance. There exists a long history of studies on the effects of increased lactate/H+ concentrations in muscle or plasma on contractile performance of skeletal muscle. Evidence suggesting that lactate/H+ is a culprit has been based on correlation-type studies, which reveal close temporal relationships between intramuscular lactate or H+ accumulation and the decline of force during fatiguing stimulation in frog, rodent or human muscle. In addition, an induced acidosis can impair muscle contractility in non-fatigued humans or in isolated muscle preparations, and several mechanisms to explain such effects have been provided. However, a number of recent high-profile papers have seriously challenged the 'lactic acid hypothesis'. In the 1990s, these findings mainly involved diminished negative effects of an induced acidosis in skinned or intact muscle fibres, at higher more physiological experimental temperatures. In the early 2000s, it was conclusively shown that lactate has little detrimental effect on mechanically skinned fibres activated by artificial stimulation. Perhaps more remarkably, there are now several reports of protective effects of lactate exposure or induced acidosis on potassium-depressed muscle contractions in isolated rodent muscles. In addition, sodium-lactate exposure can attenuate severe fatigue in rat muscle stimulated in situ, and sodium lactate ingestion can increase time to exhaustion during sprinting in humans. Taken together, these latest findings have led to the idea that lactate/H+ is ergogenic during exercise.It should not be taken as fact that lactic acid is the deviant that impairs exercise performance. Experiments on isolated muscle suggest that acidosis has little detrimental effect or may even improve muscle performance during high-intensity exercise. In contrast, induced acidosis can exacerbate fatigue during whole-body dynamic exercise and alkalosis can improve exercise performance in events lasting 1-10 minutes. To reconcile the findings from isolated muscle fibres through to whole-body exercise, it is hypothesised that a severe plasma acidosis in humans might impair exercise performance by causing a reduced CNS drive to muscle.     

Poly-L-lactic acid — hydroxyapatite (PLLA-HA) bioabsorbable interference screws for tibial graft fixation in anterior cruciate ligament (ACL) reconstruction surgery: MR evaluation of osteointegration and degradation features

Purpose

We evaluated with magnetic resonance imaging (MRI) the degradation and osteointegration features of a new type of bioabsorbable interference (BioRCI) screw composed of poly-L-lactic acid and hydroxyapatite (PLLA-HA) used for tibial graft fixation in anterior cruciate ligament (ACL) reconstruction.

Materials and methods

Thirty-one patients underwent arthroscopic surgery for ACL reconstruction using doubled gracilis and semitendinosus tendons fixed to the tibial tunnel with PLLA-HA (BioRCI-HA) screws. Two groups of patients were evaluated, one group 10–13 months after surgery and the other after 30–40 months. The standard knee ligament evaluation form of the International Knee Documentation Committee (IKDC) was used for clinical assessment and MRI for the radiological assessment.

Results

MRI after 10–13 months revealed findings referable to healing and integration of the bone-graft-screw system, findings that disappeared at later follow-up examinations. The BioRCI-HA screw remained constantly visible in all patients, although with changes in signal intensity over time.

Conclusions

BioRCI-HA screws allow adequate primary stability and superior osteoconduction and biocompatibility in comparison with plain PLLA screws. The absence of ferromagnetic artefacts allows accurate MRI follow-up and adequate evaluation of ligament synovialisation, screw degradation and graft osteointegration.     

Cardiac β-adrenergic receptor density and myocardial systolic function in the remote noninfarcted region after prior myocardial infarction with left ventricular remodelling

Purpose

After myocardial infarction (MI), left ventricular (LV) remodelling is observed in noninfarcted LV myocardium. LV remodelling is closely associated with systolic heart failure. Since myocardial dysfunction is related to the downregulation of cardiac postsynaptic beta-adrenergic receptors (β-AR), we hypothesized that a reduction in β-AR density may be manifested in the remote noninfarcted region and such reduction may be related to myocardial systolic dysfunction. Accordingly, we assessed β-AR density with a focus on the remote noninfarcted region.

Methods

Cardiac PET was performed in 15 patients with a prior MI and 10 age-matched healthy controls using ¹¹C-CGP 12177, a radioligand for β-receptors. The maximum number of available specific ¹¹C-CGP 12177 binding sites per gram of tissue was calculated in regions of interest using an established graphical method. LV regional systolic function was assessed based on peak systolic myocardial strain on the LV wall in the longitudinal direction using two-dimensional ultrasound speckle tracking imaging. LV volumes and LV ejection fraction (EF) were also measured.

Results

The LV end-diastolic volume index was significantly larger in patients than in controls (67.8?±?16.9 vs. 49.1?±?12.3?ml/m², p?p?p?Conclusion In the remote noninfarcted region in patients, β-AR downregulation was observed, which was related to deterioration of local myocardial systolic function.     

Mucopolysaccharidosis IVA (Morquio A syndrome) and VI (Maroteaux–Lamy syndrome): under-recognized and challenging to diagnose

Objective

Mucopolysaccharidosis IVA (MPS IVA, or Morquio A syndrome) and VI (MPS VI, or Maroteaux–Lamy syndrome) are autosomal recessive lysosomal storage disorders. Skeletal abnormalities are common initial presenting symptoms and, when recognized early, may facilitate timely diagnosis and intervention, leading to improved patient outcomes. Patients with slowly progressing disease and nonclassic phenotypes can be particularly challenging to diagnose. The objective was to describe the radiographic features of patients with a delayed diagnosis of MPS IVA or VI.

Materials and Methods

This was a retrospective study. The records of 5 MPS IVA and 3 MPS VI patients with delayed diagnosis were reviewed. Radiographs were evaluated by a radiologist with special expertise in skeletal dysplasias.

Results

An important common theme in these cases was the appearance of multiple epiphyseal dysplasia (MED) with epiphyseal changes seemingly confined to the capital (proximal) femoral epiphyses. Very few patients had the skeletal features of classical dysostosis multiplex.

Conclusions

Radiologists should appreciate the wide phenotypic variability of MPS IVA and VI. The cases presented here illustrate the importance of considering MPS in the differential diagnosis of certain skeletal dysplasias/disorders, including MED, some forms of spondylo-epiphyseal dysplasia (SED), and bilateral Perthes-like disease. It is important to combine radiographic findings with clinical information to facilitate early testing and accurate diagnosis.     

Assessment ofTakotsubo (ampulla) cardiomyopathy using99mTc-tetrofosmin myocardial SPECT —Comparison with acute coronary syndrome—

We assessed Takotsubo (ampulla) cardiomyopathy compared with acute coronary syndrome (ACS) using two-dimensional echocardiography and 99mTc-tetrofosmin myocardial SPECT. METHODS: We examined 10 patients with Takotsubo cardiomyopathy and 16 with ACS at the time of emergency admission (acute phase), at three to nine days after the attack (subacute phase) and at one month after the attack (chronic phase). The left ventricle was divided into nine regions on echocardiograms and SPECT images, and the degree of abnormalities in each region was scored in five grades from normal (0) to severely abnormal (4). RESULTS: Coronary angiography revealed total or subtotal occlusion in patients with ACS but no stenotic legions in those with Takotsubo cardiomyopathy. The amount of ST segment elevation (mm) was 7.9 +/- 3.4 in patients with Takotsubo cardiomyopathy and 7.3 +/- 3.7 in those with ACS (N.S.). Abnormal wall motion scores on echocardiograms were 13.8 +/- 4.4, 4.4 +/- 3.8 and 1.8 +/- 2.3 during the acute, subacute and chronic phases in patients with Takotsubo cardiomyopathy, and 13.9 +/- 4.0, 11.7 +/- 3.7, 7.6 +/- 4.2, respectively in patients with ACS. The value of MB fraction of creatine phosphokinase (IU/l) was 34 +/- 23 in patients with Takotsubo cardiomyopathy and 326 +/- 98 in those with ACS (p < 0.001). Abnormal myocardial perfusion scores on 99mTc-tetrofosmin myocardial SPECT were 11.4 +/- 3.2, 3.2 +/- 3.3 and 0.7 +/- 1.1 during the acute, subacute and chronic phases respectively, in patients with Takotsubo cardiomyopathy, and 15.8 +/- 4.1, 13.5 +/- 4.4, 8.2 +/- 4.4, respectively, in those with ACS. The numbers of myocardial segments that did not uptake 99mTc-tetrofosmin during the acute phase were 0.5 +/- 0.8 and 3.6 +/- 2.8 in patients with Takotsubo cardiomyopathy and ACS, respectively. CONCLUSION: Impaired coronary microcirculation might be a causative mechanism of Takotsubo cardiomyopathy.     

Does myocardial fibrosis hinder contractile function and perfusion in idiopathic dilated cardiomyopathy? PET and MR imaging study

PURPOSE: To prospectively evaluate, by using positron emission tomography (PET) and magnetic resonance (MR) imaging, the interrelationships between regional myocardial fibrosis, perfusion, and contractile function in patients with idiopathic dilated cardiomyopathy (DCM). MATERIALS AND METHODS: The study protocol was approved by the hospital ethics committee, and all subjects gave written informed consent. Sixteen patients with idiopathic DCM (mean age, 54 years +/- 11 [standard deviation]; nine men) and six healthy control subjects (mean age, 28 years +/- 2; five men) were examined with PET and MR tissue tagging. Oxygen 15-labeled water and carbon monoxide were used as tracers at PET to assess myocardial blood flow (MBF) and the perfusable tissue index (PTI), which is inversely related to fibrosis. MBF was determined at rest and during pharmacologically induced hyperemia. Maximum circumferential shortening (E(cc)) was determined with MR tissue tagging. Student t tests were performed for comparison of data sets, and linear regression was used to investigate the association between parameters. RESULTS: Mean global hyperemic MBF (2.23 mL/min/mL +/- 0.73), E(cc) (-10.5% +/- 2.9), and PTI (0.95 +/- 0.10) were lower in the patients with DCM than in the control subjects (4.33 mL/min/mL +/- 0.85, -17.4% +/- 0.6, and 1.09 +/- 0.12, respectively; P < .05 for all). In the patients with DCM, regional PTI was related to E(cc) (r = -0.21, P = .009) but not to resting or hyperemic MBF. Furthermore, regional E(cc) was correlated to both resting (r = -0.28, P = .004) and hyperemic MBF (r = -0.29, P < .001). In addition, the ratio of left ventricular end-diastolic volume to mass, as a reflection of wall stress, was related to global hyperemic MBF (r = -0.52, P = .047) and to global E(cc) (r = 0.69, P = .003). CONCLUSION: In idiopathic DCM, the extent of myocardial fibrosis is related to the impairment in contractile function, whereas fibrosis and perfusion do not seem to be interrelated. The degree of impairment of hyperemic myocardial perfusion is related to contractility and end-diastolic wall stress.     

Nuclear chemical transformations of ytterbium and lutetium radionuclides following (n,γ) and beta decay reactions in Tris(2,2,6,6-tetramethyle-3,5-heptanedionato)Yb(III)

The behavior of recoiled radionuclides ¹⁶⁹Yb, ¹⁷⁵Yb, and ¹⁷⁷Lu resulting from the reactions ¹⁶⁸Yb(n,γ)¹⁶⁹Yb, ¹⁷⁴Yb(n,γ)¹⁷⁵Yb, and ¹⁷⁶Yb(n,γ)¹⁷⁷Yb→¹⁷⁷Lu, respectively, in the organometallic Tris(2,2,6,6-tetramethyle-3,5-heptanedionato)Yb(III) compound was investigated. Paper chromatography as well as thin layer chromatography, using different patterns of solvents and developers, are discussed. It was found that the organic and inorganic species were of different types and the species resulting from (n,γ) differed from those resulting from β-decay. The species resulting from β-decay reaction were little affected by the type of paper chromatography, while those resulting from (n,γ) reaction were not affected at all. The retention depended on the type of paper and the pattern of solvent/developer. Paper chromatography gave the best results when the compound was dissolved and developed in toluene. The retention values of ¹⁷⁷Lu in three different cases were determined. The obtained retention values indicated that the compound under investigation was not suitable for the purpose of high specific activity radioisotope production.     

The relationship of myocardial contraction and electrical excitation—the correlation between scintigraphic phase image analysis and electrophysiologic mapping

Background

Phase imaging derived from equilibrium radionuclide angiography presents the ventricular contraction sequence. It has been widely but only indirectly correlated with the sequence of electrical myocardial activation.

Objectives

We sought to determine the specific relationship between the sequence of phase progression and the sequence of myocardial activation, contraction and conduction, in order to document a noninvasive method that could monitor both.

Methods

In 7 normal and 9 infarcted dogs, the sequence of phase angle was correlated with the epicardial activation map in 126 episodes of sinus rhythm and pacing from three ventricular sites.

Results

In each episode, the site of earliest phase angle was identical to the focus of initial epicardial activation. Similarly, the serial contraction pattern by phase image analysis matched the electrical epicardial activation sequence completely or demonstrated good agreement in approximately 85% of pacing episodes, without differences between normal or infarct groups.

Conclusions

A noninvasive method to accurately determine the sequence of contraction may serve as a surrogate for the associated electrical activation sequence or be applied to identify their differences.     

Hypoxia inducible factor (HIF1α and HIF2α) and carbonic anhydrase 9 (CA9) expression and response of head-neck cancer to hypofractionated and accelerated radiotherapy

Purpose: Tumor hypoxia and low intrinsic radiosensitivity may counteract the efficacy of standard radiotherapy for locally advanced head and neck cancer (HNC). We investigated the involvement of hypoxia-regulated proteins (Hypoxia inducible factors HIF1α, HIF2α and carbonic anhydrase CA9) in HNC resistance to accelerated and hypofractionated radiotherapy.

Materials and methods: Thirty-nine patients with locally advanced HNC received 15 daily fractions of 3.4 Gy amounting to a total tumor dose of 51 Gy (equivalent to 63 Gy in four weeks – one week split); this was combined with platinum chemotherapy and amifostine cytoprotection administered subcutaneously. Immunohistochemical analysis of hypoxia-regulated proteins, namely HIF1α, HIF2α and CA9, was performed in formalin-fixed paraffin-embedded tissues obtained prior to radio-chemotherapy.

Results: HIF1α and HIF2α were expressed in the nuclei and cytoplasm of cancer cells, while CA9 had a membrane reactivity. A high expression of HIF1α, HIF2α and CA9 was noted in 21/39 (53.8%), 20/39 (51.3%) and 23/39 (58.9%) cases, respectively. Complete response was obtained in 85.2% of patients and HIF1α was marginally related with persistent disease after RT (p = 0.05). HIF1α was significantly associated with poor local relapse free survival (LRFS) (p = 0.006) and overall survival (p = 0.008), whilst HIF2α was not. A significant association of CA9 expression with poor LRFS was noted (p = 0.01).

Conclusion: In accord with previously reported studies, high levels of the hypoxia regulated proteins HIF1α and CA9 in HNC predict resistance to platinum based radio-chemotherapy. Whether HIF2α expressing tumors are more sensitive to larger radiotherapy fractions, compared to standard radiotherapy fractionation, is an issue that deserves further investigation.     

Correlation of left ventricular dyssynchrony with myocardial stunning using dual single photon emission computed tomography of 123iodine-β-methyl iodophenyl pentadecanoic acid and 201thallium scintigraphy after reperfusion therapy

Objective  

Left ventricular (LV) dyssynchrony after reperfusion therapy has been closely examined as a cause of chronic remodeling, but the details have not been clarified. The present study measured LV dyssynchrony appearing immediately after reperfusion therapy using real-time three-dimensional echocardiography (RT-3DE), and assessed the significance of this phenomenon in relation to dual single photon emission computed tomography (SPECT) of ¹²³iodine β methyliodophenyl pentadecanoic acid (¹²³I-BMIPP) and ²⁰¹thallium (²⁰¹Tl).     

Estimation of the area at risk in myocardial infarction of rats by means of I-123 β-methyliodophenyl pentadecanoic acid imaging

Clinical investigations have suggested that the defects in SPECT images of a free fatty acid analog, I-123 beta-methyliodophenyl pentadecanoic acid (BMIPP) may indicate the ischemic risk area. To elucidate whether I-123 BMIPP can indicate the area at risk of ischemia, ex-vivo autoradiography was performed in rats whose left coronary artery was occluded for 60 min and then reperfused. I-123 BMIPP was injected at the acute stage (n = 10), or the subacute stage (7 days after reperfusion; n = 9). Infarction and the area at risk were identified by triphenyl tetrazolium chloride staining and injection of methylene blue during religation just before sacrifice, respectively. The BMIPP uptake in the risk area was significantly lower than that in the remote area at the acute (risk, 53.7+/-23.3% of the uptake at right ventricle, mean +/- SD; remote, 109.3+/-11.8%; p < 0.01) and subacute (risk, 52.5+/-11.5%; remote, 97.9+/-14.3%; p < 0.01) stages. In addition, the area with reduced uptake of I-123 BMIPP showed a significant correlation with the area at risk both at the acute (r = 0.98, p < 0.01) and subacute (r = 0.92, p < 0.01) stages. In conclusion, the area at risk can be evaluated by I-123 BMIPP both at the acute and subacute stages.