Delayed Right Ventricular Pacemaker Lead Perforation 9 Years After Implantation.

BACKGROUND Cardiac perforation is a rare complication of cardiac implantable electronic devices, with a reported incidence ranging from 0.1% to 5.2%. Delayed perforation, defined as perforation occurring more than 1 month after implantation, is more uncommon. In this report, we present a case of cardiac perforation involving the right ventricle wall that occurred 9 years after pacemaker implantation. CASE REPORT A 79-year-old woman presented with symptoms of dyspnea and was subsequently admitted to a hospital. She had undergone pacemaker implantation for a complete atrioventricular block 9 years prior to the presentation. The patient had right ventricular failure to capture and a resultant complete atrioventricular block. Computed tomography imaging revealed that the right ventricular lead had clearly protruded outside the heart; however, no pericardial effusion was observed. When the patient underwent open surgical repair, the ventricular tined lead was noted to be traversing the right ventricular apex. Device interrogation revealed a sudden increase followed by a gradual decrease in the right ventricular pacing threshold over the course of 2 months, indicating that the lead had slowly traversed the right ventricular muscle before ultimately rupturing through it. CONCLUSIONS This study described the case of a delayed right ventricular pacemaker lead perforation that occurred 9 years after implantation, which was managed via open surgical repair.

Impact of adaptive cardiac resynchronization therapy in patients with systolic heart failure: Beyond QRS duration and morphology.

BACKGROUND: Mechanical and electrical restoration by cardiac resynchronization therapy (CRT) with adaptive pacing algorithm (aCRT) in heart failure patients with a moderately wide (120-149 ms) QRS has not been fully evaluated. The purpose of this study was to investigate the therapeutic effect of aCRT compared with conventional biventricular CRT (BiV-CRT) regardless of QRS morphology. METHODS: Seventeen consecutive patients with a QRS ≥120 ms, regardless of morphology, underwent CRT device implantation with an aCRT pacing algorithm. Propensity score matched analysis was performed to evaluate the impact of aCRT on the improvement in mechanical and electrical parameters after CRT device implantation using historical controls (HC) from the clinical registry of BiV-CRT (START trial). RESULTS: Left ventricular (LV) volume significantly decreased after CRT in all patients in both the aCRT and HC groups. The difference in relative reduction of LV end-systolic volume (LVESV) was not significantly different between the 2 arms. QRS shortening after CRT was significantly greater in the aCRT group than in the BiV-CRT group, and the difference was prominent in patients with a moderately wide QRS (120-149 ms). In patients with a moderately wide QRS, the relative reduction in LVESV [39 (29-47)% vs. 2 (-6-20)%, p = 0.04] and proportion of LV volume responders (90% vs. 38%, p = 0.04) were significantly greater in the aCRT group than in the HC group. The proportion of volume responders was not significantly different in patients with a wide QRS (≥150 ms). CONCLUSIONS: The aCRT algorithm improved electrical and mechanical parameters in patients with a moderately wide QRS, regardless of QRS morphology.

A Rare Case of Chronic Expanding Intrapericardial Hematoma with Refractory Right-sided Heart Failure 30 Years after the Surgical Repair of Tetralogy of Fallot.

We herein report the case of a 79-year-old man who presented with right-sided heart failure (HF) 27 years after undergoing surgery for tetralogy of Fallot. The HF did not respond well to oral diuretics. Transthoracic echocardiography and chest X-ray failed to determine the cause of the HF for three years. An intrapericardial mass located just behind the sternum, was finally identified on computed tomography. The mass had compressed the right ventricle, causing right-sided HF. Pre-surgical diagnostic images led to suspicion of a chronic expanding intrapericardial hematoma (CEIH), and the CEIH was surgically removed. The patient's symptoms improved markedly.

[Refractory Hypertension and Intermittent Claudication Caused by Distal Elephant Trunk Stenosis 10 Years After Total Arch Replacement for Stanford Type A Aortic Dissection;Report of a Case].

A 49-year-old man was admitted to our hospital because of intermittent claudication and refractory hypertension 10 years after surgery to Stanford type A acute aortic dissection. He underwent total arch replacement with an elephant trunk of 22 mm in diameter. Transesophageal echocardiography revealed that distal end of the elephant trunk was stenosed. Systolic blood pressure gradient over this portion reached to more than 100 mmHg. Folding of elephant trunk and thrombus formation were considered to be the cause. Thoracic endovascular aortic repair relieved stenosis and intermittent claudication, and enabled better blood pressure control.

Comparison of clinical outcomes following percutaneous coronary intervention versus optimal medical therapy based on gray-zone fractional flow reserve in stable angina patients with intermediate coronary artery stenosis (COMFORTABLE prospective study): Study protocol for a multicenter randomized controlled trial.

BACKGROUND: Even in the current drug-eluting stent era, revascularization for coronary stenosis with fractional flow reserve (FFR) between 0.75 and 0.80, the so-called "gray zone," is a matter of debate. Previous studies have reported conflicting results regarding outcomes of revascularization versus deferral for coronary stenosis when FFR values are in the gray zone, but these studies have had differing designs and populations. We therefore will investigate whether medical therapy plus percutaneous coronary intervention (PCI) is superior to medical therapy alone in reducing major cardiovascular events in patients presenting with coronary stenosis with gray zone FFR values. METHODS/DESIGN: This is a prospective, multicenter, open-label, parallel group, randomized, controlled, superiority study. A total of 410 eligible participants will be recruited and randomized to either the medical therapy plus PCI group or the medical therapy alone group. The primary endpoint is 1-year major adverse cardiac events (MACEs), defined as a combined endpoint of all-cause death, nonfatal myocardial infarction (MI), or unplanned target vessel revascularization (TVR). Secondary endpoints include MACE at 2 and 5 years. Moreover, each individual component of the primary endpoint, cardiovascular death, target vessel-related and non-target vessel-related MI, all MI, clinically driven TVR or non-TVR, all revascularization, stent thrombosis, and angina symptom status will be evaluated at 1, 2, and 5 years. DISCUSSION: This is the first prospective, multicenter, randomized, controlled study to investigate the superiority of medical therapy plus PCI over medical therapy by itself in reducing major cardiovascular events in patients presenting with coronary stenosis with "gray zone" FFR values. The results will help interventional cardiologists in making revascularization decisions regarding coronary stenosis with gray zone FFR values. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000031526 . Registered on 1 March 2018.

Effect of strut thickness on neointimal atherosclerotic change over an extended follow-up period (≥ 4 years) after bare-metal stent implantation: intracoronary optical coherence tomography examination.

BACKGROUND: Neointima inside the bare-metal stents (BMSs) can transform into atherosclerotic tissue during an extended follow-up because of a persistent inflammatory reaction to the metal. We sought to investigate whether strut thickness may impact on the atherosclerotic change in neointima 4 years or more after BMS implantation using optical coherence tomography. METHODS: Forty-six stented lesions of 41 patients with BMS ≥ 4 years after implantation who underwent optical coherence tomography were enrolled in the study. The strut was defined as thin when less than 100 µm and thick when ≥ 100 µm. According to these criteria, stents were divided into 2 groups (thin strut n = 19, thick strut n = 27). Neointimal tissue was categorized into normal neointima, characterized by a signal-rich band without signal attenuation, or lipid-laden intima, with marked signal attenuation and a diffuse border. Intimal disruption, thrombus, and neovascularization were also evaluated. RESULTS: The mean period after implantation was 98.2 ± 25.8 months in the thin-strut group and 91.1 ± 22.8 months in the thick-strut group (P = .330). Lipid-laden intima (70% vs 32%, P = .016), thin-cap fibroatheroma-like intima (59% vs 16%, P = .0056), and intimal disruption (48% vs 16%, P = .031) were observed more frequently in the thick-strut group than in the thin-strut group, but no significant difference was observed in the frequency of thrombus. Although peristrut neovascularization was a common finding in both groups (thick vs thin 81% vs 79%, P = 1.000), the frequency of intraintima neovascularization tended to be higher in the thick-strut group (67% vs 42%, P = .135). CONCLUSIONS: A thinner strut thickness may have favorable effects on neointimal atherosclerotic changes after BMS implantation.

Comparison of contrast media and low-molecular-weight dextran for frequency-domain optical coherence tomography.

BACKGROUND: Although an intracoronary frequency-domain optical coherence tomography (FD-OCT) system overcomes several limitations of the time-domain OCT (TD-OCT) system, the former requires injection of contrast media for image acquisition. The increased total amount of contrast media for FD-OCT image acquisition may lead to the impairment of renal function. The safety and usefulness of the non-occlusion method with low-molecular-weight dextran L (LMD-L) via a guiding catheter for TD-OCT image acquisition have been reported previously. The aim of the present study was to compare the image quality and quantitative measurements between contrast media and LMD-L for FD-OCT image acquisition in coronary stented lesions. METHODS AND RESULTS: Twenty-two patients with 25 coronary stented lesions were enrolled in this study. FD-OCT was performed with the continuous-flushing method via a guiding catheter. Both contrast media and LMD-L were infused at a rate of 4 ml/s by an autoinjector. With regard to image quality, the prevalence of clear image segments was comparable between contrast media and LMD-L (97.9% vs. 96.5%, P=0.90). Furthermore, excellent correlations were observed between both flushing solutions in terms of minimum lumen area, mean lumen area, and mean stent area. The total volumes of contrast media and of LMD-L needed for OCT image acquisition were similar. CONCLUSIONS: FD-OCT image acquisition with LMD-L has the potential to reduce the total amount of contrast media without loss of image quality.

Optical coherence tomography analysis of attenuated plaques detected by intravascular ultrasound in patients with acute coronary syndromes.

Background. Recent intravascular ultrasound (IVUS) studies have demonstrated that hypoechoic plaque with deep ultrasound attenuation despite absence of bright calcium is common in acute coronary syndrome. Such "attenuated plaque" may be an IVUS characteristic of unstable lesion. Methods. We used optical coherence tomography (OCT) in 104 patients with unstable angina to compare lesion characteristics between IVUS-detected attenuated plaque and nonattenuated plaque. Results. IVUS-detected attenuated plaque was observed in 41 (39%) patients. OCT-detected lipidic plaque (88% versus 49%, P < 0.001), thin-cap fibroatheroma (48% versus 16%, P < 0.001), plaque rupture (44% versus 11%, P < 0.001), and intracoronary thrombus (54% versus 17%, P < 0.001) were more often seen in IVUS-detected attenuated plaques compared with nonattenuated plaques. Conclusions. IVUS-detected attenuated plaque has many characteristics of unstable coronary lesion. The presence of attended plaque might be an important marker of lesion instability.

Virtual histology intravascular ultrasound compared with optical coherence tomography for identification of thin-cap fibroatheroma.

Virtual histology intravascular ultrasound (VH-IVUS) allows detailed assessment of plaque composition in the clinical setting. Optical coherence tomography (OCT) has been developed as a high-resolution imaging method, which might be a promising technique to identify thin-cap fibroatheroma (TCFA) in vivo. The purpose of the present study was to evaluate the diagnostic accuracy of VH-IVUS to identify TCFA as determined by OCT.We examined 96 target lesions in patients with stable angina pectoris by using VH-IVUS and OCT. VH-IVUS derived TCFA was defined as a focal necrotic core-rich lesion without evident overlying fibrous tissue. OCT derived TCFA was defined as a plaque with a fibrous cap of < 65 µm. VH-IVUS correctly identified 16 TCFA and 67 non-TCFA but misclassified 2 TCFA and 11 non-TCFA as determined by OCT. The sensitivity, specificity, and positive and negative predictive values of VH-IVUS to identify TCFA as determined by OCT were 89%, 86%, 59%, and 97%, respectively.VH-IVUS showed an acceptable sensitivity and specificity to identify TCFA as determined by OCT. Although the positive predictive value was low reflecting a high number of false positives, the negative predictive value was notably high. Our results suggest a potential role for VH-IVUS to exclude high risk lesions for future coronary events.

Impact of hinge motion on in-stent restenosis after sirolimus-eluting stent implantation.

BACKGROUND: A tortuous lesion with hinge motion is reportedly a risk factor for in-stent restenosis (ISR) after bare metal stent implantation. Sirolimus-eluting stents (SESs) implantation has dramatically reduced ISR. However, SES is a closed-cell design stent, which has low conformability and flexibility. Several studies have reported a relationship between tortuous lesions and stent fracture, which is one of the causes of ISR. The efficacy of SES in a tortuous lesion with hinge motion has not been fully evaluated. The aim of this study was to investigate the relationship between tortuous lesions and ISR after SES implantation. METHODS AND RESULTS: Three year clinical follow-up data after SES implantation, including 6-9 month scheduled follow-up coronary angiography in 399 consecutive patients with 537 lesions, were obtained. Δangle was defined as the difference in the angle of the target lesion between the diastole and systole before the procedure. The incidence of ISR was 8.2%. The mean maximal angle and Δangle were larger in the ISR group (47 ± 22° vs. 37 ± 21°, P=0.004 and 20 ± 13° vs. 13 ± 10°, P < 0.0001, respectively). Independent predictors of ISR were Δangle, hemodialysis, aortic ostium stenting, and diabetes mellitus. Hinge motion-associated ISR (Δangle ≥ 16°) occurred in 28 lesions: stent fracture in 9, stent recoil in 6, edge injury in 10, and others in 3. CONCLUSIONS: The amount of hinge motion in tortuous lesions should be considered in the selection of drug eluting stent types.

Difference of culprit lesion morphologies between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome: an optical coherence tomography study.

OBJECTIVES: The aim of this study was to investigate the difference of culprit lesion morphologies assessed by optical coherence tomography (OCT) between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTEACS). BACKGROUND: Autopsy studies have reported that rupture of a thin-cap fibroatheroma and subsequent thrombus formation is the most important mechanism leading to acute coronary syndrome (ACS). Optical coherence tomography is a high-resolution imaging modality that is capable of investigating detailed coronary plaque morphology in vivo. METHODS: We examined the culprit lesion morphologies by OCT in 89 consecutive patients with acute coronary syndrome (STEMI = 40; NSTEACS = 49). RESULTS: The incidence of plaque rupture, thin-cap fibroatheroma, and red thrombus was significantly higher in STEMI compared with NSTEACS (70% vs. 47%, p = 0.033, 78% vs. 49%, p = 0.008, and 78% vs. 27%, p < 0.001, respectively). Although the lumen area at the site of plaque rupture was similar in the both groups (2.44 ± 1.34 mm(2) vs. 2.96 ± 1.91 mm(2), p = 0.250), the area of ruptured cavity was significantly larger in STEMI compared with NSTEACS (2.52 ± 1.36 mm(2) vs. 1.67 ± 1.37 mm(2), p = 0.034). Furthermore, the ruptured plaque of which aperture was open-wide against the direction of coronary flow was more often seen in STEMI compared with NSTEACS (46% vs. 17%, p = 0.036). CONCLUSIONS: The present OCT study demonstrated the differences of the culprit lesion morphologies between STEMI and NSTEACS. The morphological feature of plaque rupture and the intracoronary thrombus could relate to the clinical presentation in patients with acute coronary disease.

Prevalence and clinical significance of papillary muscle infarction detected by late gadolinium-enhanced magnetic resonance imaging in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The frequency of papillary muscle infarction (PapMI) without rupture has not been fully investigated in vivo. Furthermore, the relationship between papillary muscle dysfunction and mitral regurgitation (MR) has been controversial in patients with ST-segment elevation myocardial infarction. Therefore, the aim of this study was to assess the frequency and clinical characteristics of PapMI without rupture using late gadolinium-enhanced magnetic resonance imaging (MRI) in patients with ST-segment elevation myocardial infarction. METHODS AND RESULTS: One hundred eighteen ST-segment elevation myocardial infarction patients with primary percutaneous coronary intervention underwent cardiac MRI twice 9±4 days and 8±1 months (n=104) after myocardial infarction. MR was categorized by echocardiography. Of these patients, 40% were found to have late gadolinium enhancement of papillary muscle, in which the posterior papillary muscle was involved more frequently than the anterior papillary muscle (77% versus 26%; P<0.001). PapMI was encountered more frequently in patients with left circumflex and right coronary artery lesions compared with left anterior descending artery lesion (78%, 48%, and 13%; P<0.001). By multiple logistic regression analysis, only coaptation height was identified as an independent predictor of the presence of MR. The second cardiac magnetic resonance imaging showed that the infarct size had a positive correlation with left ventricular end-diastolic volume (r=0.41, P<0.001) and that PapMI was not associated with left ventricular remodeling (P=0.31). Deterioration of MR was not observed in patients with PapMI. CONCLUSIONS: PapMI is more frequent than previously thought yet appears to have significant clinical latency. The size of the myocardial infarction, but not the presence of PapMI, seems to affect left ventricular remodeling, and PapMI is not obligatorily associated with MR.

The effect of lipid and inflammatory profiles on the morphological changes of lipid-rich plaques in patients with non-ST-segment elevated acute coronary syndrome: follow-up study by optical coherence tomography and intravascular ultrasound.

OBJECTIVES: The aim of this study was to determine the relationship between the morphological changes of nonculprit lipid-rich plaques and several clinical profiles in patients with non-ST-segment elevated acute coronary syndrome (NSTEACS). BACKGROUND: Identification of coronary lesion with morphological characteristics of rupture-prone plaques is still difficult. METHODS: Eighty-two consecutive patients with NSTEACS who underwent percutaneous coronary intervention were enrolled. The changes in total atheroma volume (TAV) of residual nonculprit lipid-rich plaques and the changes in the corresponding fibrous cap thickness (FCT) were assessed by intravascular ultrasound and optical coherence tomography, respectively, at baseline and after 9 months. RESULTS: The percentage changes in TAV (mm(3)) of lipid-rich plaques and in the corresponding FCT (microm) over the 9-month follow-up period were 3.1 +/- 11% and 15 +/- 17%, respectively. There was no significant correlation between the changes in TAV and those in FCT. The change in TAV showed a significant correlation with reduction of the low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio (r = 0.42, p < 0.01). In contrast, the change in FCT showed no correlation with LDL/HDL ratio but had a significant positive correlation with changes in high-sensitivity C-reactive protein (r = 0.44, p < 0.01). Furthermore, in multivariate logistic analysis, statin use was an independent predictor of changes in well-stabilized plaques that showed both TAV reduction and FCT increase. CONCLUSIONS: The changes in TAV and FCT of coronary plaques over a 9-month observation period were related to 2 different independent factors (i.e., reduction of LDL-cholesterol and high-sensitivity C-reactive protein, respectively). Furthermore, lipid-lowering therapy with statin has the potential to stabilize these parameters by both plaque reduction and FCT.

Left ventricular apical aneurysm due to unrecognized sarcoidosis.

A 47-year-old woman was hospitalized for syncope. An electrocardiogram showed complete right bundle branch block and T-wave inversion in leads III, aVF, and V2-4. Cardiac catheterization was performed since the echocardiogram demonstrated the existence of a left ventricular apical aneurysm and apical thrombus. Coronary angiography revealed normal coronary arteries. An endomyocardial biopsied specimen from the right ventricular apical wall demonstrated typical noncaseating granulomas with giant cells. There was no evidence suggesting the involvement of other systemic organs. The patient was diagnosed as having cardiac sarcoidosis. Cardiac sarcoidosis should be considered within a spectrum of diseases that cause left ventricular apical aneurysm.

Effects of mild aerobic physical exercise on membrane fluidity of erythrocytes in essential hypertension.

1. The present study was undertaken to investigate the effects of aerobic physical exercise on membrane function in mild essential hypertension. 2. Hypertensive patients were divided into an exercise group (n = 8) and a non-exercise (control) group (n = 8). Physical exercise within the intensity of the anaerobic threshold level was performed twice a week for 6 months. Membrane fluidity of erythrocytes was examined by means of electron paramagnetic resonance (EPR) and spin-labelling methods before and after the trial period in both groups. 3. After physical exercise, blood pressure decreased significantly. 4. Compared with the non-exercise group, in the exercise group both the order parameter (S) and the peak height ratio (ho/h-1) in the EPR spectra of erythrocytes were significantly reduced (S, 0.717 +/- 0.004 vs 0.691 +/- 0.008, respectively (n = 8), P < 0.05; ho/h-1, 5.38 +/- 0.06 vs 4.89 +/- 0.06, respectively (n = 8), P < 0.05). These findings indicated that exercise increased membrane fluidity and improved the membrane microviscosity of erythrocytes. 5. There was no direct correlation between blood pressure reduction and the exercise-induced increase in membrane fluidity of erythrocytes. 6. In the non-exercise (control) group, blood pressure and membrane fluidity were not changed after a 6 month follow-up period. 7. The results show that aerobic physical exercise increased erythrocyte membrane fluidity and improved the rigidity of cell membranes in hypertensive patients. The improvement of rheological properties of erythrocytes may explain, in part, the cellular mechanisms for the beneficial effects of physical exercise in hypertension.

Nitric oxide is a determinant of membrane fluidity of erythrocytes in postmenopausal women: an electron paramagnetic resonance investigation.

In the present study, to determine a possible role of nitric oxide (NO) in the regulation of membrane functions, we examined the relationship between plasma NO level and membrane fluidity of erythrocytes in postmenopausal women. We evaluated the membrane fluidity of erythrocytes obtained from hypertensive and normotensive postmenopausal women by means of an electron paramagnetic resonance (EPR) and spin labeling method. The EPR study revealed that the order parameter (S) for 5-nitroxide stearate in erythrocyte membranes was significantly greater in hypertensive postmenopausal women than in normotensive postmenopausal women. The finding indicated that the membrane fluidity of erythrocytes was decreased in hypertensive postmenopausal women compared with normotensive postmenopausal women. The plasma level of the NO metabolites (nitrite and nitrate) while fasting was significantly lower in hypertensive postmenopausal women than in normotensive postmenopausal women. In addition, the order parameter (S) in the EPR spectra of erythrocyte membranes was inversely correlated with the plasma NO metabolite level, which indicated that the lower membrane fluidity of erythrocytes was associated with the lower plasma NO level in postmenopausal women. These results are consistent with the hypothesis that NO may have a crucial role in the regulation of membrane fluidity of erythrocytes in postmenopausal women.

Effect of oestrone on membrane fluidity of erythrocytes is mediated by a nitric oxide-dependent pathway: An electron paramagnetic resonance study.

1. It has been recognized that hormone replacement therapy (HRT) may have a beneficial effect on protection against cardiovascular diseases. Oestrone is the major component of conjugated equiline oestrogens, which are commonly used in HRT. The present study was performed in order to investigate the effects of oestrone on the membrane fluidity of erythrocytes by means of an electron paramagnetic resonance (EPR) and spin-labelling method. 2. In an in vitro study, oestrone significantly decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-nitroxide stearate (16-NS) obtained from EPR spectra of erythrocyte membranes. This finding indicated that oestrone may increase the membrane fluidity and improve the membrane microviscosity of erythrocytes. 3. The effect of oestrone was significantly potentiated by the nitric oxide (NO) donor s-nitroso-N-acetylpenicillamine and the cGMP analogue 8-bromo-cGMP. 4. In contrast, the change in membrane fluidity induced by oestrone was antagonized by the NO synthase inhibitors NG-nitro-l-arginine methyl ester and asymmetric dimethyl-l-arginine. 5. The results of the present study show that oestrone significantly increases membrane fluidity and improves the rigidity of cell membranes, which is partially mediated by a NO- and cGMP-dependent pathway. Furthermore, the data may be consistent with the hypothesis that oestrone could have a beneficial effect on the rheological behaviour of erythrocytes and have a crucial role in the regulation of the microcirculation.

Leptin improves membrane fluidity of erythrocytes in humans via a nitric oxide-dependent mechanism--an electron paramagnetic resonance investigation.

Abnormalities in physical properties of the cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular diseases. Recently, there has been an indication that leptin, the product of the human obesity gene, actively participates not only in the metabolic regulations but also in the control of cardiovascular functions. In the present study, to assess the role of leptin in the regulation of membrane properties, the effects of leptin on membrane fluidity of erythrocytes in humans are examined. The membrane fluidity of erythrocytes in healthy volunteers by means of an electron paramagnetic resonance (EPR) and spin-labeling method is determined. In an in vitro study, leptin decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes in a dose-dependent manner in healthy volunteers. The finding indicated that leptin increased the membrane fluidity and improved the microviscosity of erythrocytes. The effect of leptin on the membrane fluidity was significantly potentiated by the nitric oxide (NO) donors, L-arginine and S-nitroso-N-acetylpenicillamine (SNAP), and a cyclic guanosine monophosphate (cGMP) analog, 8-bromo-cGMP. In contrast, the change evoked by leptin was significantly attenuated in the presence of the NO synthase inhibitors, N(G)-nitro-L-arginine-methyl-ester (L-NAME) and asymmetric dimethyl-L-arginine (ADMA). The results of the present study showed that leptin increased the membrane fluidity and improved the rigidity of cell membranes to some extent via an NO- and cGMP-dependent mechanism. Furthermore, the data also suggest that leptin might have a crucial role in the regulation of rheological behavior of erythrocytes and microcirculation in humans.