β-methyl-p-(123I)-iodophenyl pentadecanoic acid single-photon emission computed tomography in cardiomyopathy

-Methyl-p-(123I)-iodophenyl pentadecanoic acid (BMIPP) is one of the branched-chain free fatty acids, which has suitable characteristics for myocardial SPECT because of higher uptake and longer retention in the myocardium. Recent advances of BMIPP myocardial SPECT for evaluating cardiomyopathy were reviewed. BMIPP defects were observed in 80% patients with hypertrophic cardiomyopathy (HCM). Moreover, BMIPP uptake was reduced at sites that corresponded with hypertrophic areas, where thallium uptake was increased. The correlations between severity score and septal wall thickness and LV function were better with BMIPP SPECT, suggesting that BMIPP is more suitable for the assessment of myocardial integrity in HCM. The dissociation between BMIPP and thallium defects was not observed frequently in dilated cardiomyopathy (DCM). We carried out BMIPP myocardial SPECT to evaluate the therapeutic effects of co-enzyme Q10 on DCM patients. Hearts to the mediastinum ratio and BMIPP defect scores were significantly decreased after co-enzyme Q10 treatment. BMIPP myocardial SPECT was confirmed to be sensitive in evaluating the therapeutic effect for the perspective of metabolic SPECT imaging. Recently, a lack of myocardial uptake of BMIPP has been found in a small subset of patients (0.3%–1.2%). Cardiac radionuclide imaging using BMIPP and 18F-FDG were performed on patients with type I CD36 deficiency. The percent dose uptake of 18F-FDG was significantly higher than in normal controls. CD functions as a major myocardial long-chain fatty acid transporter and its absence may lead to a compensatory up-regulation of myocardial glucose uptake. An increased frequency of CD36 deficiency was demonstrated in cardiomyopathy. Therefore, fatty acid transport proteins and their related gene defects in relation to BMIPP uptake may become an important issue in the future.     

Improvement in cardiac function and free fatty acid metabolism in a case of dilated cardiomyopathy with CD36 deficiency

A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of 123I-beta-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: 18F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.     

Asymmetrical septal hypertrophy in patients with hypertension: A type of hypertensive left ventricular hypertrophy or hypertrophic cardiomyopathy combined with hypertension?

To determine whether asymmetrical septal hypertrophy (ASH) in patients with essential hypertension (HT) is a type of hypertensive left ventricular (LV) hypertrophy or hypertrophic cardiomyopathy (HCM) combined with HT, we investigated a group of 7 hypertensive patients with ASH compared with 12 HCM patients and 10 healthy controls using radionuclide angiography and right ventricular endomyocardial biopsy. The LV time-volume curve and its first and second derivative curves were constructed from cardiac output and time-activity curves constructed by combined forward and reverse-gating from the R wave. The LV wall thickness and ejection fraction were significantly greater in both the HT and HCM groups than in the control group, whereas there were no differences in these indices between the HT and HCM groups. Rapid filling volume index and rapid filling fraction showed significantly lower values in the HCM group than in the control group (p < 0.005). In contrast to the HCM group, these indices in the HT group did not differ from those in the control group. The time to peak filling rate was prolonged in the control, hypertension, and HCM groups in increasing order. Histopathological study revealed a higher incidence of myocardial cell disarray in the HCM than in the HT group. The above results suggest that ASH in hypertensive patients is a type of hypertensive LV hypertrophy.     

Hypertrophic cardiomyopathy with left ventricular dilatation

There is increasing interest in the notion that some patients with hypertrophic cardiomyopathy (HCM) progress to morphological and functional manifestations similar to those of dilated cardiomyopathy (DCM). From 165 consecutive patients with HCM, 20 patients with left ventricular dilatation (left ventricular end-diastolic diameter greater than or equal to 50 mm) were selected and designated as dilated HCM. The diagnosis of HCM was established in these patients either by detection of the classical form of HCM in family members, with 2-dimensional echocardiographic evidence of asymmetric septal hypertrophy (ASH; septal thickness greater than or equal to 15 mm and a ratio of septal to posterior wall thickness greater than or equal to 1.3); or by demonstrating myocardial fiber disarray in autopsy or biopsy samples. The clinical manifestations of these patients with dilated HCM were then compared with those of other forms of HCM without left ventricular dilatation; 1) 40 patients with hypertrophic obstructive cardiomyopathy (HOCM) who had resting intraventricular pressure gradients of 20 mmHg or more, 2) 80 patients with non-obstructive HCM, each of whom had ASH of the entire ventricular septum (typical ASH), and 3) 25 non-obstructive patients whose hypertrophy was localized to the apical region of the ventricular septum (apical ASH). Patients having apical hypertrophy with a spade-like configuration on the left ventriculogram were excluded from the study. Compared with HOCM and typical ASH groups, the patients with dilated HCM had family histories of significantly more frequent HCM and less frequent hypertension. The patients with dilated HCM also had significantly less fractional shortening (FS), decreased interventricular septal thickness, greater left ventricular end-diastolic pressure (LVEDP), and left ventricular dilatation. During the follow-up period (average: 3.5 years), seven patients (35%) with dilated HCM died; five from congestive heart failure (CHF), one suddenly, and one three days following mitral valve replacement. The other five patients had CHF at the time of their follow-up examination. The patients with apical ASH had clinical features similar to those of dilated HCM; a higher familial frequency, less marked septal hypertrophy, and higher LVEDP. They tended to develop left ventricular dilatation, associated with reduced fractional shortening, although left ventricular diameter at end-diastole did not exceed 50 mm. These findings suggested that dilated HCM is not a rare condition. It is observed in 12% of consecutive patients with HCM.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influence of CD36 deficiency on heart disease in children.

BACKGROUND: The physiological role of the CD36 molecule in pediatric heart disease has not been fully investigated. METHODS AND RESULTS: The CD36 antigen in platelets and monocytes was measured by flow cytometry in 189 patients with various heart diseases; 15 (7.9%) had a diagnosis of CD36 deficiency (type I: 2[1 boy, 1 girl], type II: 13 [6 boys, 7 girls]). The prevalence in each heart disease was as follows: group A (congenital heart disease) 7.6% (9/118, type II: 9 [6 boys, 3 girls]); group B (myocardial disease) 20.0% (3/15, I: 1 girl, II: 2[1 boy, 1 girl]), group C (Kawasaki disease) 4.9% (2/41, II: 2 [1 boy, 1 girl]), group D (arrhythmia): 6.7% (1/15, I: 1 boy). Three patients in group B had transient myocardial damage, which was thought to be related to abnormal myocardial long-chain fatty acid metabolism. CONCLUSION: The frequency of CD36 deficiency in childhood heart disease was almost identical to that of healthy individuals. Some patients with CD36 deficiency may be susceptible to myocardial damage in the presence of disadvantageous conditions, such as serious infections or massive steroid therapy.     

Cardiac muscle cell disorganization in apical hypertrophic cardiomyopathy: a cardiac biopsy study

Apical hypertrophic cardiomyopathy has been divided into two entities: apical asymmetric septal hypertrophy (apical ASH) and apical symmetric hypertrophy (AH). The latter differs clinically from hypertrophic cardiomyopathy (HCM) with ASH, and it is unclear whether AH represents a distinct subtype of HCM. In the present study, the presence or absence and the extent of cardiac muscle cell disorganization, a histologic characteristic of HCM, were compared in patients with AH (n = 10) and ASH (n = 29) in whom cardiac biopsy specimens were obtained from the left ventricular apex and interventricular septum. Disorganization was graded as (1+) in only 1 patient in the AH group and (-) in the remaining 9. In contrast, in the ASH group disorganization was graded as (1+) in 15 patients, (2+) in 7, (3+) in 3, and (-) in only 4 (P < 0.0001). Thus, it was observed that in AH disorganization is virtually absent or at most limited to a very narrow area. It is concluded from a histological stand point as well that the type of apical hypertrophic cardiomyopathy showing apical symmetric hypertrophy differs from usual HCM.     

Scintigraphic evidence for a specific long-chain fatty acid transporting system deficit and the genetic background in a patient with hypertrophic cardiomyopathy.

The mechanism of cardiac uptake of long-chain free fatty acids has not been fully determined. We encountered a hypertrophic cardiomyopathy patient who showed a lack of cardiac uptake of 2 different types of long-chain fatty acid analogues on the scintigraphic images. Flow cytometric analysis revealed no platelet or monocyte CD36 molecule expression (type I CD36 deficiency) and his CD36 gene showed homozygous mutation for 478C to T substitution, leading to an abnormal CD36 amino acid sequence. These findings strongly suggest that a specific transporting system rather than a simple diffusion is commonly involved in the cardiac uptake of long-chain free fatty acids in humans, and that the CD36 protein is the most likely candidate for the specific transporter and to explain scintigraphic defects on fatty acid imaging.     

Cardiac sympathetic activity in the asymmetrically hypertrophied septum in patients with hypertension or hypertrophic cardiomyopathy

BACKGROUND: In patients with essential hypertension (HT), proportional (symmetric) left ventricular hypertrophy (LVH) is common. In contrast, hypertrophic cardiomyopathy (HCM) is characterized by disproportional LVH and, in particular, asymmetric septal hypertrophy (ASH); however, some hypertensive patients also develop ASH. It has not been determined whether such cases represent a distinct type of hypertensive LVH or HCM combined with hypertension. HYPOTHESIS: The study was undertaken to evaluate sympathetic activity in the interventricular septum in patients with HT and ASH or in patients with HCM. METHODS: The patients were evaluated by I-123 meta-iodobenzylguanidine (MIBG) and thallium-201 (201Tl) single-photon emission computed tomography (SPECT), respectively. They were divided into three groups: patients with essential HT and symmetric septal hypertrophy (Group A), patients with HT and ASH (Group B), and patients with HCM and ASH (Group C). RESULTS: Compared with the lateral wall, early uptake of MIBG in the septum was significantly higher in Group B than in Group A, but not significantly different between Groups A and C. Compared with the lateral wall, early uptake of 201Tl in the septum did not differ among the three groups. No significant difference in the MIBG clearance in the lateral wall was seen among the three groups. By contrast, MIBG clearances in the septum and apex were significantly greater in Group C than in Groups A and B. There was an inverse correlation between systolic thickening and MIBG clearance in the septum. CONCLUSION: These findings suggest that sympathetic activity in the septum differs between patients with HT and ASH and patients with HCM.     

Can serum carnitine levels distinguish hypertrophic cardiomyopathy from hypertensive hearts?

Although echocardiography is a useful diagnostic tool in hypertrophic cardiomyopathy (HCM), it is sometimes difficult to differentiate it from hypertensive heart disease (HHD): some patients with HCM show symmetrical hypertrophy, whereas patients with HHD sometimes show asymmetrical septal hypertrophy. We used a radioiodinated long-chain fatty acid tracer to visualize the altered myocardial fatty acid metabolism of HCM and HHD. Carnitine is the essential substance for the beta-oxidation of long-chain fatty acids. We recently reported that serum free carnitine levels in HCM were elevated and that they were significantly correlated with the severity of myocardial fatty acid metabolic disorder. Therefore, we investigated serum carnitine levels in patients with HCM and HHD, which can contribute to the differentiation of each other. We studied 56 patients with HCM and 20 patients with essential hypertension. Serum free carnitine levels were significantly higher in patients with HCM than those with HHD (HCM 52.5+/-9.5 nmol/mL, HHD 46.6+/-6.4 nmol/mL, P<0.01), but they showed no statistical difference between patients with HHD and normal subjects. Serum acylcarnitine levels were significantly lower in patients with HCM than those with HHD (HCM 10.1+/-4.0 nmol/mL, HHD 14.5+/-4.9 nmol/mL, P<0.0005), although they did not differ between patients with HHD and normal subjects. Scintigraphic analyses with a long-chain fatty acid analog revealed that myocardial tracer uptake was much reduced in patients with HCM compared with that in patients with HHD (quantitative analysis: HCM 2.11+/-0.12, HHD 2.22+/-0.17, P<0.05; semiquantitative analysis: HCM 13.6+/-6.3, HHD 2.0+/-1.5, P<0.0001). In conclusion, the differences in serum carnitine levels between HCM and HHD reflect altered myocardial fatty acid metabolic impairment, and the levels can help to distinguish these 2 diseases.     

Mechanism of development of asymmetric septal hypertrophy in patients with essential systemic hypertension

In order to understand the mechanism of development of asymmetric septal hypertrophy (ASH) in hypertension, 290 patients with essential hypertension (HT) were examined echocardiographically. Out of them 84 cases of advanced left ventricular hypertrophy (LVH) [37 cases of symmetric hypertrophy (HT-SH group) and 47 cases of ASH (HT-ASH group)] were compared in their clinical and echocardiographic findings with hypertrophic cardiomyopathy (HCM). In the 290 HT cases, the highest systolic pressure in each patient's history was found to correlate with left ventricular (LV) posterior wall thickness (PWT), but not with the septal wall thickness (IVST). There were no differences in LV thickness (IVST + PWT) among patients in the HT-ASH, HT-SH and HCM groups. While the HCM group patients showed no significant differences in IVST and PWT from those in the HT-ASH group, they did have greater IVST and smaller PWT than HT-SH group patients. The rapid filling rate (RFR) was also not much different in the HCM and HT-ASH groups, but was significantly lower in the HCM group than in the HT-SH group. Furthermore, HT-ASH group patients has a milder degree of hypertension and a higher incidence of familial occurrence of HCM than did those in the HT-SH group. After treatment for HT, the HT-SH group showed a significant decrease in wall thickness during long-term observation, while the HT-ASH and HCM groups, failed to exhibit such changes. Moreover, the degree of myocardial disarrangement in the HT-ASH group did not differ significantly from that in the HCM group. These results suggested that LVH in HT is related not only to pressure load but also to genetic factors similar to that in HCM.     

CD36 genotype and long-chain fatty acid uptake in the heart.

Homozygous or compound heterozygous mutation of the CD36 gene (CD36-/-) in humans results in severe defects of the uptake of long-chain fatty acids (LCFAs) in the heart. Because the effect of a single mutation of this gene (CD36+/-) on the LCFA uptake is not known, it was evaluated in 29 subjects with the CD36 wild-type gene (WT) (6 healthy subjects, 10 patients with heart disease), CD36+/- (4 healthy subjects, 5 patients) and CD36-/- (4 patients). The CD36 genotype was identified in the coding region of genomic DNA, and the expression of CD36 protein was examined by flow cytometry after staining with monoclonal anti-CD36 antibody. The LCFA uptake in the heart was assessed as the radioactivity accumulation ratio of heart to mediastinum after intravenous administration of iodine-123 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (H/M ratio). The H/M ratios in WT, CD36+/- and CD36-/- were 2.28 +/- 0.10, 1.90 +/- 0.06 and 1.40 +/- 0.11, respectively (p < 0.0001, among groups). The H/M ratio between healthy subjects and patients with heart disease for WT and CD36+/- did not differ significantly (ie, those of WT and CD36+/- in healthy subjects and patients were 2.29 +/- 0.08 vs 2.27 +/- 0.12 and 1.90+/- 0.07 vs 1.89 +/- 0.05, respectively). Not only CD36-/- but also CD36+/- resulted in a significant reduction of the LCFA uptake in the heart independent of heart disease, suggesting genotype dependency and that CD36 might be a fundamental determinant of myocardial LCFA uptake.     

Potential application of tissue Doppler imaging to assess regional left ventricular diastolic function in patients with hypertrophic cardiomyopathy: comparison with 123I-beta-methyl iodophenyl pentadecanoic acid myocardial scintigraphy

BACKGROUND: Tissue Doppler imaging (TDI) has been utilized to evaluate left ventricular myocardial dysfunction in patients with hypertrophic cardiomyopathy (HCM); however, no clear explanation for the abnormality of TDI variables has been forthcoming. HYPOTHESIS: Peak negative myocardial velocity gradient (MVG) derived from TDI may correlate with a disorder of fatty acid metabolism in patients with HCM. METHODS: Tissue Doppler imaging and 123I-beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP) myocardial scintigraphy were performed in 15 patients with asymmetric septal hypertrophy (mean age 47 +/- 18 years) and in 12 healthy controls (mean age 43 +/- 10 years). RESULTS: In early 123I-BMIPP images, accumulation defects were observed in the ventricular septum in 12 patients and in the posterior wall in 8 patients with HCM. Peak negative MVG in the ventricular septum (1.1 +/- 0.5 vs. 2.8 +/- 0.5, p < 0.0001) and posterior wall (5.2 +/- 1.4 vs. 6.7 +/- 0.8, p < 0.01 ) was significantly lower in the HCM group than in the controls; also, these parameters were significantly lower in patients with than in those without a defect in the region in question. The peak negative MVG in the ventricular septum and posterior wall correlated inversely with the washout rate in all subjects. CONCLUSIONS: Peak negative MVG according to TDI is related to disorder of fatty acid metabolism in the regional left ventricular myocardium of patients with HCM.     

Ventricular Tachyarrhythmia Associated with Hypertrophic Cardiomyopathy: Incidence,Prognosis, and Relation to Type of Hypertrophy

VT Associated with HCM . Objective: To assess the incidence, characteristics, and prognosis of ventricular tachyarrhythmia in hypertrophic cardiomyopathy (HCM). Patients: The study consisted of 66 consecutive patients with HCM who were admitted to Niigata University Hospital between 1992 and 2005. Their clinical characteristics and ECG morphology were investigated according to the type of HCM. Results: The type of HCM was asymmetric hypertrophy (ASH) in 34 patients (51%), obstructive HCM (HOCM) in 9 (14%), apical HCM (ApHCM) in 14 (21%), and midventricular obstruction (MVO) in 9 (14%). The cause of admission was ventricular tachyarrhythmia in 25 patients (38%), unexplained syncope in 11 (17%), and heart failure in 30 (45%). Sustained monomorphic ventricular tachycardia (SMVT) occurred in 19 patients and ventricular fibrillation in 6. In the 19 patients with SMVT, 12 had MVO and 3 of these had previous apHCM. Six of the 19 patients with SMVT had ASH, and 3 had abnormal apical wall motion. In 14 patients, the SMVT appeared to originate from the apical aneurysm based on the morphology of the tachycardia. Ventricular tachyarrhythmia recurred in 14 of the 25 patients (56%), and 4 of the 18 patients with an ICD had electrical storm. ASH with abnormal wall motion of the LV apex or MVO was recognized in the 4 patients with electrical storm; they commonly had abnormal Q waves and ST elevation in leads V4–V6. Conclusion: Ventricular tachyarrhythmia was responsible for 38% of hospitalizations in HCM, and SMVT occurred in patients with MVO and/or with abnormal wall motion of the LV apex. Electrical storm was more common in patients with ST elevation in precordial leads V4–V6. (J Cardiovasc Electrophysiol, Vol. 21, pp. 991‐999, September 2010)     

Correlation of Electrocardiographic Changes and Myocardial Fibrosis in Patients With Hypertrophic Cardiomyopathy Detected by Cardiac Magnetic Resonance Imaging

Background:

Despite several electrophysiologic and pathologic studies, the cause of electrocardiographic (ECG) changes in patients with hypertrophic cardiomyopathy (HCM) remains unclear. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging can detect myocardial fibrosis. We aimed to assess the relationship between ECG findings and LGE in such patients.

Hypothesis:

Myocardial LGE may be associated with ECG changes in HCM.

Methods:

Seventy consecutive patients with HCM (mean age, 55.5 ± 10.7 years; 47 males) underwent CMR and 12‐lead ECG. The subjects were divided into 3 groups according to the type of hypertrophy: the asymmetric septal hypertrophy group (ASH group, n = 31), the apical hypertrophy group (AP group, n = 22), and concentric hypertrophy group (CH group, n = 17). The transmural and segmental extent, pattern, and location of myocardial LGE were assessed and analyzed in relation to ECG changes.

Results:

All of the subjects showed some degree of LGE on CMR. The AP group showed significantly higher prevalence of negative T‐wave (P = 0.028) and deep negative T‐wave inversion (P = 0.001) than the ASH and CH groups. The total volume of LGE did not show any significant association with ECG changes. LGE detected at the interventricular septum was associated with increased QRS duration (P = 0.009) and was found in 94% of the ASH group, 59% of the AP group, and 77% of the CH group. LGE at the apex of the heart was present in 32% of the ASH group, 73% of the AP group, and 35% of the CH group and was also associated with negative T‐wave (P = 0.006) and deep negative T‐wave inversion (P = 0.018). Multifocal LGE lesions were associated with increased QRS duration (P = 0.039) as opposed to single nodular or patchy pattern of presence.

Conclusions:

The location of myocardial LGE in HCM shows significant association with various ECG changes. This may be useful information for initially evaluating subjects with HCM and adds pathophysiological insight into understanding ECG changes in myocardial diseases that cannot be explained otherwise. Clin. Cardiol. 2011 DOI: 10.1002/clc.22062 The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Difference in the response to isoproterenol between asymmetric septal hypertrophy and symmetric hypertrophy in patients with hypertrophic cardiomyopathy

The response to isoproterenol was studied in 9 patients with hypertrophic cardiomyopathy (HCM) and asymmetric septal hypertrophy (ASH), 9 patients with HCM and symmetric hypertrophy (SH), and 9 normal controls (NC), using digitized M-mode echocardiography. There was no significant difference in fractional shortening (FS) between ASH and SH, nor between SH and NC before isoproterenol infusion. During isoproterenol infusion, however, FS was significantly greater in ASH (60 +/- 6%) than in SH (53 +/- 7%) and NC (49 +/- 5%) (p less than 0.05, p less than 0.01, respectively), and normalized peak rate of change of left ventricular dimension during systole (pVs) was greater in ASH (7.7 +/- 1.5/s) than in SH (5.2 +/- 0.8/s) and in NC (4.9 +/- 0.8/s) (p less than 0.001, p less than 0.001, respectively). This study shows that the response to isoproterenol of ASH differs from those of SH and of NC and suggests hypersensitivity of the beta-adrenergic receptor system in ASH and the possibility that ASH is a different clinical entity than SH.     

Distribution of myocardial damage in patients with hypertrophic cardiomyopathy: evaluation by exercise thallium-201 scintigraphy]

The characteristic of myocardial damage in hypertrophic cardiomyopathy (HCM) was evaluated as to whether the damage is limited to the hypertrophied wall or extends throughout the entire wall. The myocardial damage was detected by exercise thallium-201 (Tl-201) scintigraphy and was evaluated using circumferential profile analysis, calculation of initial uptake and washout rate. Eleven patients with asymmetrical hypertrophy (ASH), whose septal and posterior wall thickness ratio exceeded 1.3 on left ventriculography and biventriculography, and 13 age-matched control subjects without heart disease were studied. The mean values of initial uptake in both groups did not differ significantly, but the washout rate for the entire heart was significantly decreased only in the HCM group (p < 0.05). All of the regional washout rates (antero-septal, apical and postero-lateral) were significantly decreased in the HCM group (p < 0.05), without any difference between the hypertrophied wall and the non-thickened free wall being noted. These results demonstrated that the analysis of myocardial damage by exercise Tl-201 scintigraphy using calculation of the washout rate is a very sensitive means of detecting myocardial damage in HCM, and that such myocardial damage is not restricted to the hypertrophied wall, but rather extends to the entire wall, including the free wall which is not thickened.     

Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification

Aims/hypothesis Changes in cardiac substrate utilisation leading to altered energy metabolism may underlie the development of diabetic cardiomyopathy. We studied cardiomyocyte substrate uptake and utilisation and the role of the fatty acid translocase CD36 in relation to in vivo cardiac function in rats fed a high-fat diet (HFD). Methods Rats were exposed to an HFD or a low-fat diet (LFD). In vivo cardiac function was monitored by echocardiography. Substrate uptake and utilisation were determined in isolated cardiomyocytes. Results Feeding an HFD for 8 weeks induced left ventricular dilation in the systolic phase and decreased fractional shortening and the ejection fraction. Insulin-stimulated glucose uptake and proline-rich Akt substrate 40 phosphorylation were 41% (p < 0.001) and 45% (p < 0.05) lower, respectively, in cardiomyocytes from rats on the HFD. However, long-chain fatty acid (LCFA) uptake was 1.4-fold increased (p < 0.001) and LCFA esterification into triacylglycerols and phospholipids was increased 1.4- and 1.5-fold, respectively (both p < 0.05), in cardiomyocytes from HFD compared with LFD hearts. In the presence of the CD36 inhibitor sulfo-N-succinimidyloleate, LCFA uptake and esterification were similar in LFD and HFD cardiomyocytes. In HFD hearts CD36 was relocated to the sarcolemma, and basal phosphorylation of a mediator of CD36-trafficking, i.e. protein kinase B (PKB/Akt), was increased. Conclusions/interpretation Feeding rats an HFD induced cardiac contractile dysfunction, which was accompanied by the relocation of CD36 to the sarcolemma, and elevated basal levels of phosphorylated PKB/Akt. The permanent presence of CD36 at the sarcolemma resulted in enhanced rates of LCFA uptake and myocardial triacylglycerol accumulation, and may contribute to the development of insulin resistance and diabetic cardiomyopathy. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

肥厚型心肌病患者核素心肌灌注/代谢显像的研究

目的:观察肥厚型心肌病(HCM)患者的核素心肌灌注/代谢显像的变化,以进一步揭示HCM的病理生理改变,为今后患者的预后分析提供基础.方法:采用单光子发射计算机断层成像双核素心肌灌注/代谢显像的方法对93例(男65例,女28例,年龄16~68岁)HCM患者行99mTc-甲氧基异丁基异腈(99mTc-MIBI)心肌灌注显像和18F-脱氧葡萄糖(18F-FDG)心肌代谢显像.患者均为空腹状态下,静脉注射99mTc-MIBI 20 mCi、18F-FDG 4 mCi,1小时后行双核素心肌显像.采用半定量评分法分析左心室室壁各节段的灌注及葡萄糖显像情况.结果:93例HCM患者99mTc-MIBI心肌灌注显像结果:左心室心肌放射性摄取增高患者90例(97%),其中间隔部82例,前壁20例,心尖部15例,外侧壁4例,下后壁3例.93例HCM患者18F-FDG心肌代谢显像结果:31例(33%)患者心肌未见明显显影;13例(14%)患者左心室显影清晰,左心室室壁各心肌节段均可见放射性摄取或明显摄取(得分为-1或-2);49例(53%)患者心肌部分节段有放射性分布,其中间隔36例,前壁35例,心尖部20例,外侧壁33例,下后壁32例.结论:肥厚型心肌病患者心肌灌注/代谢显像异常表现具有多样性,灌注显像的异常主要表现为心肌放射性摄取增高,最多累及部位为间隔部;而代谢显像表现不均一性较为明显,左心室室壁各心肌节段约可见放射性摄取的患者有14%,心肌部分节段可见放射性摄取的患者有53%,而左心室心肌各节段均未见放射性摄取的占33%.