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1.
Intern Med ; 60(1): 73-77, 2021.
Article in English | MEDLINE | ID: mdl-33390471

ABSTRACT

The case was a 76-year-old man with chronic limb-threatening ischemia. Plain old balloon angioplasty (POBA) was performed on the popliteal artery. Subsequently, he suffered from cellulitis around the POBA site, followed by reocclusion. Staphylococcus aureus was detected in a blood culture. After re-revascularization with POBA, both purulent gonitis and an infected popliteal aneurysm were observed to occur. We performed aneurysmectomy and bypass grafting with the saphenous vein and then continued antibiotic therapy. Although treatment consisted of endovascular therapy (EVT) with nothing left behind, management was difficult because of secondary infectious complications. We conclude that prophylactic antibiotics before EVT should be considered in such cases.


Subject(s)
Angioplasty, Balloon , Aged , Angioplasty , Angioplasty, Balloon/adverse effects , Humans , Ischemia , Male , Popliteal Artery/diagnostic imaging , Popliteal Artery/surgery , Treatment Outcome , Vascular Patency
2.
Endocr J ; 67(1): 95-98, 2020 Jan 28.
Article in English | MEDLINE | ID: mdl-31597815

ABSTRACT

A 59-year-old woman unaware of having diabetes was transferred due to coma. Upon discovery at home, her consciousness on the Glasgow Coma Scale was E1V2M4, BP 95/84 mmHg, body temperature 34.7°C. On arrival at ER, height was 1.63 m, weight 97 kg, plasma glucose (PG) 1,897 mg/dL, HbA1c 13.6%, osmolality 421 mosm/kg, arterial pH 7.185, lactate 6.34 mmol/L, ß-hydroxybutyrate 7.93 mmol/L. With saline and regular insulin infusion, PG was lowered to 1,440 mg/dL at 2 hours and then to 250 mg/dL by Day 3, and consciousness normalized by Day 5. On admission, serum immunoreactive insulin (IRI) was undetectable (<0.03 U/mL), C-peptide immunoreactivity (CPR) undetectable (<0.003 ng/mL), and anti-glutamic acid decarboxylase antibody negative. Following the above-described treatment, fasting PG was 186 mg/dL and CPR 1.94 ng/mL, respectively, on Day 14; 2-h post-breakfast PG 239 mg/dL and CPR 6.28 ng/mL, respectively, on Day 18. The patient discharged on Day 18 with 1,800 kcal diet, 32 U insulin glargine and 40 mg gliclazide. Fifteen months later at outpatient clinic, her HbA1c was 6.9% and 2-h post-breakfast PG 123 mg/dL and CPR 5.30 ng/dL with 750 mg metformin, 10 mg gliclazide and 18 U insulin glargine. Transient, but total cessation of insulin secretion was documented in a patient with type 2 diabetes under severe metabolic decompensation. Swift, sustained recovery of insulin release indicated that lack of insulin at the time of emergency was due to secretory failure, i.e., unresponsive exocytotic machinery or depletion of releasable insulin, rather than loss of beta cells.


Subject(s)
C-Peptide/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Coma/metabolism , Insulin/metabolism , Acidosis, Lactic/complications , Acidosis, Lactic/metabolism , Acidosis, Lactic/therapy , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Diabetic Coma/etiology , Diabetic Coma/therapy , Female , Fluid Therapy , Glycated Hemoglobin/metabolism , Humans , Hyperglycemia/complications , Hyperglycemia/metabolism , Hyperglycemia/therapy , Hypoglycemic Agents/therapeutic use , Insulin Secretion , Insulin-Secreting Cells/metabolism , Ketosis/complications , Ketosis/metabolism , Ketosis/therapy , Middle Aged , Pancreatitis/etiology , Pancreatitis/metabolism
3.
Cardiovasc Interv Ther ; 32(3): 206-215, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27311986

ABSTRACT

Little is known about the mid-term outcomes of patients with atrial fibrillation (AF) who undergo coronary stenting in the second-generation drug-eluting stent (DES) era. We evaluated the 1-year outcomes of AF patients undergoing percutaneous coronary intervention (PCI) with second-generation DES. This retrospective cohort analysis used integrated data from the SHINANO registry, a prospective observational multicenter cohort study, which enrolled 1923 consecutive patients undergoing PCI for any coronary artery disease. We retrospectively recruited 917 of these patients (mean age, 71.3 ± 10.0 years; male, 77 %) who received PCI with 2nd generation DES. The primary endpoint was net adverse clinical events (NACE: cardiac death, stroke, MI, stent thrombosis, and major bleeding) at 1 year. The secondary endpoints were major adverse cardiovascular events (MACE: cardiac death, stroke, and MI), stroke, MI, and major bleeding at 1 year. One-year follow-up was completed in 871 (94.9 %) patients, of whom 85 had AF. The incidence of NACE (15.4 vs. 7.3 %, P = 0.008), MACE (10.6 vs. 5.4 %, P = 0.047), and major bleeding (6.0 vs. 2.3 %, P = 0.049) were all significantly higher in AF compared to non-AF patients. On multivariate analysis, AF was an independent predictor of NACE (HR 2.32, 95 % CI 1.24-4.34, P = 0.008). In the second-generation DES era, patients with AF undergoing PCI still have a poorer prognosis, with more thrombotic and bleeding events, than those without AF. More attention should be paid to the thrombotic and bleeding risk in AF patients undergoing PCI.


Subject(s)
Atrial Fibrillation/surgery , Blood Vessel Prosthesis , Coronary Disease/surgery , Drug-Eluting Stents , Aged , Atrial Fibrillation/complications , Coronary Disease/complications , Female , Humans , Male , Registries , Retrospective Studies , Treatment Outcome
4.
J Cardiol ; 70(2): 147-154, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27908505

ABSTRACT

BACKGROUND: This study compared adenosine stress computed tomography myocardial perfusion (CTP) with single-photon emission computed tomography (SPECT) in the diagnosis of functionally significant coronary artery stenosis using fractional flow reserve (FFR) as reference standard. METHODS: We included a total of 93 coronary arteries from 31 patients in whom at least one vessel with ≥50% stenosis was detected with computed tomography coronary angiography. All patients underwent both SPECT and adenosine stress CTP, followed by invasive coronary angiography (ICA) and FFR. Diagnostic accuracy between CTP and SPECT was compared according to positive findings of either ≥99% stenosis on ICA or FFR ≤0.8. RESULTS: Among 78 vessels eligible for the quantitative analyses, significant coronary artery disease (CAD) was diagnosed in 22 vessels of 19 patients. Comparison of CTP vs. SPECT for sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in detecting significant CAD were 59% vs. 18%, 96% vs. 93%, 87% vs. 50%, 86% vs. 74%, and 86% vs. 72%, respectively. CONCLUSIONS: CTP demonstrated a significant diagnostic advantage over SPECT in the identification of significant CAD, especially in terms of sensitivity and PPV. Adenosine stress CTP is useful for the noninvasive diagnosis of functionally significant CAD.


Subject(s)
Myocardial Ischemia/diagnostic imaging , Myocardial Perfusion Imaging/methods , Tomography, X-Ray Computed/methods , Aged , Female , Fractional Flow Reserve, Myocardial , Humans , Male , Middle Aged , Myocardial Ischemia/physiopathology , Sensitivity and Specificity
5.
Angiology ; 68(8): 688-697, 2017 Sep.
Article in English | MEDLINE | ID: mdl-27856669

ABSTRACT

BACKGROUND: We evaluated the 1-year outcomes of percutaneous coronary intervention (PCI) for elderly patients (aged ≥ 80 years) in the second-generation drug-eluting stent (DES) era. METHODS AND RESULTS: Between August 2012 and July 2013, 1923 consecutive patients (mean age, 71 ± 11 years; ≥80 years, 23%; men, 77%) who underwent 2250 elective/urgent PCI procedures were enrolled in the Shinshu Prospective Multicenter Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention registry. The primary end point was major adverse cardiovascular events (MACEs; cardiovascular death, myocardial infarction, and stroke) at 1 year. The 1-year incidence of MACEs, cardiac death, and stroke was significantly higher in elderly patients than in nonelderly patients (12.4% vs 5.3%, P < .0001; 7.8% vs 2.2%, P < .0001; and 2.8% vs 1.3%, P = .033, respectively). However, no significant difference in elective PCI procedures was detected. In elderly patients, the incidence of cardiac death and target lesion revascularization was significantly lower for DES than for non-DES (2.7% vs 10.5%, P = .0001 and 4.1% vs 8.6%, P = .029, respectively). CONCLUSION: Although elderly patients had a significantly poorer prognosis than younger patients, the adverse events rate was comparable in those patients who underwent elective PCI in the second-generation DES era.


Subject(s)
Coronary Artery Disease/drug therapy , Coronary Artery Disease/surgery , Percutaneous Coronary Intervention , Aged , Aged, 80 and over , Combined Modality Therapy , Drug-Eluting Stents , Endpoint Determination , Female , Humans , Japan , Male , Patient Safety , Prognosis , Prospective Studies , Registries , Treatment Outcome
6.
Heart Vessels ; 32(4): 399-407, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27709325

ABSTRACT

Although coronary artery disease (CAD) is common in patients with heart failure (HF), little is known about the prognostic significance of coronary lesion complexity in patients with prior HF undergoing percutaneous coronary intervention (PCI). The aim of this study was to investigate whether the coronary Synergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery (SYNTAX) score could improve risk stratification in HF patients with CAD. Two hundred patients (mean age 73 ± 11 years, left ventricular ejection fraction 49 ± 15 %) with prior HF who underwent PCI were divided into two groups stratified by SYNTAX score (median value 12) and tracked prospectively for 1 year. The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for worsening HF. Adverse events were observed in 39 patients (19.5 %). Patients with high SYNTAX scores (n = 100) showed worse prognoses than those with low scores (n = 100) (26.0 vs. 13.0 %, respectively, P = 0.021). In multivariate Cox-regression analysis, SYNTAX score ≥12 was significantly associated with MACE (hazard ratio: 1.99, 95 % confidence interval: 1.02-3.97; P = 0.045). In patients with prior HF and CAD, high SYNTAX scores predicted a high incidence of MACE. These results suggest that the SYNTAX score might be a useful parameter for improving risk stratification in these patients.


Subject(s)
Coronary Artery Disease/surgery , Heart Failure/epidemiology , Myocardial Infarction/epidemiology , Percutaneous Coronary Intervention , Stroke/epidemiology , Aged , Aged, 80 and over , Cause of Death , Drug-Eluting Stents , Female , Heart Failure/etiology , Hospital Mortality , Humans , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/etiology , Postoperative Complications/epidemiology , Proportional Hazards Models , Registries , Retrospective Studies , Risk Assessment , Severity of Illness Index , Stroke/etiology , Treatment Outcome
7.
Am J Cardiol ; 117(2): 179-85, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26684515

ABSTRACT

The Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score is effective in predicting clinical outcome after percutaneous coronary intervention (PCI). However, its prediction ability is low because it reflects only the coronary characterization. We assessed the predictive value of combining the ankle-brachial index (ABI) and SYNTAX score to predict clinical outcomes after PCI. The ABI-SYNTAX score was calculated for 1,197 patients recruited from the Shinshu Prospective Multi-center Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention (SHINANO) registry, a prospective, observational, multicenter cohort study in Japan. The primary end points were major adverse cardiovascular and cerebrovascular events (MACE; all-cause death, myocardial infarction, and stroke) in the first year after PCI. The ABI-SYNTAX score was calculated by categorizing and summing up the ABI and SYNTAX scores. ABI ≤ 0.49 was defined as 4, 0.5 to 0.69 as 3, 0.7 to 0.89 as 2, 0.9 to 1.09 as 1, and 1.1 to 1.5 as 0; an SYNTAX score ≤ 22 was defined as 0, 23 to 32 as 1, and ≥ 33 as 2. Patients were divided into low (0), moderate (1 to 2), and high (3 to 6) groups. The MACE rate was significantly higher in the high ABI-SYNTAX score group than in the lower 2 groups (low: 4.6% vs moderate: 7.0% vs high: 13.9%, p = 0.002). Multivariate regression analysis found that ABI-SYNTAX score independently predicted MACE (hazards ratio 1.25, 95% confidence interval 1.02 to 1.52, p = 0.029). The respective C-statistic for the ABI-SYNTAX and SYNTAX score for 1-year MACE was 0.60 and 0.55, respectively. In conclusion, combining the ABI and SYNTAX scores improved the prediction of 1-year adverse ischemic events compared with the SYNTAX score alone.


Subject(s)
Ankle Brachial Index/methods , Coronary Artery Disease/diagnosis , Percutaneous Coronary Intervention , Registries , Risk Assessment/methods , Aged , Coronary Angiography , Coronary Artery Disease/mortality , Coronary Artery Disease/surgery , Drug-Eluting Stents , Female , Humans , Japan/epidemiology , Kaplan-Meier Estimate , Male , Predictive Value of Tests , Prospective Studies , Risk Factors , Survival Rate/trends , Treatment Outcome
8.
Heart Asia ; 7(2): 12-18, 2015.
Article in English | MEDLINE | ID: mdl-26345318

ABSTRACT

OBJECTIVE: Little is known about the relationship between body composition indicators, including body mass index (BMI), fat mass index (FMI) and lean BMI (LBMI), and adverse outcomes after percutaneous coronary intervention (PCI) in Asian populations. The aim of this study was to clarify this relationship. METHODS: The SHINANO registry is a prospective, observational, multicenter cohort registry that enrolled 1923 consecutive patients with coronary heart disease (CHD) from August 2012 to July 2013; 66 patients were excluded because of missing data. We evaluated 1857 patients with CHD who underwent PCI (aged 70±11 years; 23% women; BMI 23.8±3.5 kg/m2; LBMI 18.3±1.8 kg/m2; FMI 5.4±2.2 kg/m2). Patients were divided into three groups, based on BMI, LBMI and FMI tertiles, to assess the prognostic value of the three indicators. The primary endpoint was major adverse cardiac events (MACE), including all cause death, non-fatal myocardial infarction and ischaemic stroke at 1 year. RESULTS: Over a 1 year follow-up period (1776 patients, 95.6%), the cumulative MACE incidence was 8.7% (161 cases). Using Kaplan-Meier analysis, the MACE incidence was significantly higher in patients with lower BMI values (13.4-22.2 kg/m2) (p=0.002) and lower LBMI values (11.6-17.6 kg/m2) (p<0.001); this trend was not observed for FMI. Multivariate Cox regression analysis showed that lower LBMI but not lower BMI values were predictive of a higher MACE incidence (HR 1.55; 95% CI 1.05 to 2.30). CONCLUSIONS: Lower LBMI values are associated with adverse outcomes in an Asian population with CHD undergoing PCI. LBMI is a better predictor of MACE than BMI or FMI. CLINICAL TRIAL REGISTRATION: UMIN-ID; 000010070.

9.
Circ J ; 78(5): 1097-103, 2014.
Article in English | MEDLINE | ID: mdl-24662401

ABSTRACT

BACKGROUND: The clinical outcomes of elderly patients (≥80 years old) undergoing percutaneous coronary intervention (PCI) has not been well established, despite recent advances in both devices and techniques. METHODS AND RESULTS: We recruited patients from the SHINANO Registry, a prospective, observational, multicenter, cohort study. From August 2012 to July 2013, a total of 1,923 consecutive patients with 2,250 elective/urgent PCIs (2,105 admissions) (mean age, 71±11 years; ≥80 years, 23%; men, 77%) were enrolled. The primary endpoint was procedural success. The secondary endpoints were in-hospital death and in-hospital major adverse cardiovascular events (MACE). The procedural success rate was significantly lower (83.7% vs. 89.1%, P=0.0001), and the rates of in-hospital mortality and MACE were significantly higher in elderly than in non-elderly patients (3.6% vs. 1.5%, P=0.005; 4.4% vs. 2.3%, P=0.016, respectively). For elective PCI, the rates of procedural success and in-hospital MACE were similar between groups (90.3% vs. 91.3%, P=0.65, 2.3% vs. 1.2%, P=0.2, respectively). On multivariate analysis, being elderly was not an independent predictor of procedural failure (OR, 1.15; CI, 0.81-1.61; P=0.43). CONCLUSIONS: In elderly patients, PCI is safe and feasible. The presence of comorbidities is a more important factor than age alone.


Subject(s)
Coronary Artery Disease/mortality , Coronary Artery Disease/surgery , Hospital Mortality , Percutaneous Coronary Intervention , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Factors
10.
Int Heart J ; 52(4): 197-202, 2011.
Article in English | MEDLINE | ID: mdl-21828943

ABSTRACT

The in-hospital mortality rate of acute myocardial infarction (AMI) is improving. In Japan, little information exists concerning the incidence and mortality of AMI. Therefore, our population-based analysis examined the incidence and mortality rate in AMI cases in individuals that lived in the Matsumoto region in 2002. We studied 169 AMI patients who were admitted within 14 days after a non-out-of-hospital cardiac arrest (non-OHCA group) and 63 patients with an AMI-related out-of-hospital cardiac arrest (OHCA group). The in-hospital mortality rate of the non-OHCA group was 9.5% (reperfusion therapy [+] 3.4%, [-] 22.7%, P < 0.0001). The rate of return of spontaneous circulation and the survival rate were 21% and 1.6%, respectively, in the OHCA group. The incidence of AMI in the non-OHCA and OHCA groups combined was 55.2 to 63.1 events/100,000 people annually and the mean age of AMI patients was 70 ± 13 years. The population-based mortality rate of AMI was 34% to 42%. The mortality rate of AMI remains high, and most deaths occur outside of the hospital. Prehospital care may lower the mortality rate of AMI.


Subject(s)
Myocardial Infarction/epidemiology , Out-of-Hospital Cardiac Arrest/epidemiology , Population Surveillance , Aged , Female , Hospital Mortality/trends , Humans , Incidence , Japan/epidemiology , Male , Myocardial Infarction/complications , Out-of-Hospital Cardiac Arrest/etiology , Retrospective Studies , Survival Rate/trends
11.
Circ J ; 75(1): 59-66, 2011.
Article in English | MEDLINE | ID: mdl-21099124

ABSTRACT

BACKGROUND: Acute aortic dissection (AAD) classically presents as sudden, severe chest, back, or abdominal pain. However, there have been several documented cases presenting with atypical features. The clinical characteristics and outcomes of patients with painless AAD were investigated. METHODS AND RESULTS: The study group comprised 98 patients (53 males, 45 females; 66 ± 12 years) with AAD admitted to hospital from 2002 to 2007: 16 patients (17%) had no pain (painless group) and 82 patients had pain (painful group). In 81% of the painless group and 70% of the painful group there was a type A dissection. The painless group more frequently had a persistent disturbance of consciousness (44% vs. 6%, P < 0.001), syncope (25% vs. 1%, P < 0.001) and a focal neurologic deficit (19% vs. 2%, P = 0.006) as presenting symptoms. Imaging study findings were not significantly different. Cerebral ischemia (50% vs. 1%, P < 0.001) and cardiac tamponade (38% vs. 13%, P = 0.01) were more frequent complications in the painless group. In-hospital mortality was not significantly different (19% vs. 15%). However, the painless group had a more unfavorable functional outcome on overall performance category (P < 0.001). CONCLUSIONS: Painless AAD may be more frequent than previously reported. Painless AAD patients often present with a disturbance of consciousness or a neurologic deficit, and have a higher morbidity than painful AAD patients.


Subject(s)
Aortic Aneurysm/diagnosis , Aortic Aneurysm/therapy , Aortic Dissection/diagnosis , Aortic Dissection/therapy , Pain/etiology , Acute Disease , Aged , Aortic Dissection/complications , Aortic Dissection/mortality , Aortic Aneurysm/complications , Aortic Aneurysm/mortality , Asymptomatic Diseases , Brain Ischemia/etiology , Cardiac Tamponade/etiology , Consciousness Disorders/etiology , Female , Hospital Mortality , Humans , Japan , Male , Middle Aged , Nervous System Diseases/etiology , Retrospective Studies , Syncope/etiology , Time Factors , Treatment Outcome
12.
J Cardiol Cases ; 1(2): e71-e74, 2010 Apr.
Article in English | MEDLINE | ID: mdl-30615759

ABSTRACT

The clinical diagnosis of cardiac sarcoidosis can be elusive, because the clinical manifestations are non-specific, and the sensitivity and specificity of diagnostic modalities are limited. A 60-year-old woman suffered atrial flutter and diffuse thickening of the left atrial wall accompanied with gallium-67 uptake, both of which were successfully treated with corticosteroid therapy. The diagnosis of cutaneous sarcoidosis had been made two years previously; therefore, we diagnosed the patient as having atrial involvement of cardiac sarcoidosis, and discuss here the importance of noninvasive evaluation of cardiac sarcoidosis using echocardiography.

13.
Int J Cardiol ; 131(2): 240-5, 2009 Jan 09.
Article in English | MEDLINE | ID: mdl-18199508

ABSTRACT

BACKGROUND: The autoantibodies stimulate the beta1-adrenoreceptors on cardiac myocytes similar to norepinephrine, and are associated with reduced cardiac function. Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) is metabolized similarly to norepinephrine. This study was undertaken to investigate the relationship between cardiac stimulation by anti-beta1-adrenoreceptor autoantibodies and myocardial sympathetic nervous activity in patients with chronic heart failure. METHODS: We screened for the anti-beta1-adrenoreceptor autoantibodies in 52 patients with chronic heart failure by conducting an enzyme-linked immunosorbent assay, and underwent (123)I-MIBG scintigraphy in 27 of the patients. Anterior planar images of (123)I-MIBG were obtained 15 min and 3 h after the injection. We determined the heart to mediastinum radioactivity ratio (H/M), and calculated the rate of washout of (123)I-MIBG from the heart. RESULTS: Patients with New York Heart Association functional class III or IV had higher levels of anti-beta1-adrenoreceptor autoantibodies than those with class I or II (p<0.01). The autoantibody level was significantly correlated with delayed H/M (r=-0.65, p<0.001) and washout rate (r=0.65, p<0.001). Sixteen patients with a cardiac event showed higher levels of the autoantibodies (p<0.05). Cardiac event-free survival was poorer in patients with the autoantibody levels >10 U/ml than that <10 U/ml (log-rank=12.1, p<0.001). CONCLUSION: The anti-beta1-adrenoreceptor autoantibodies are closely associated with cardiac sympathetic nervous activity assessed by (123)I-MIBG and cardiac event in patients with chronic heart failure.


Subject(s)
Autoantibodies/biosynthesis , Heart Failure/metabolism , Myocardium/metabolism , Receptors, Adrenergic, beta-1/immunology , Sympathetic Fibers, Postganglionic/metabolism , Aged , Chronic Disease , Female , Heart Failure/diagnostic imaging , Heart Failure/mortality , Humans , Male , Middle Aged , Radionuclide Imaging , Receptors, Adrenergic, beta-1/metabolism
14.
J Control Release ; 122(2): 189-98, 2007 Sep 26.
Article in English | MEDLINE | ID: mdl-17681632

ABSTRACT

A drug delivery system (DDS) that targets the injured myocardium would serve as a novel therapeutic tool for cardiac diseases. To develop such a DDS, we investigated the interaction of 2 types of glycoside-conjugated liposomes containing a fluorescence substrate with cardiomyocytes. Flow cytometry revealed that cardiomyocytes adequately interact with N-acetylglucosamine-conjugated liposomes (GlcNAc-Ls). Furthermore, to confirm whether the agents encapsulated in GlcNAc-Ls affect the intracellular environment of cardiomyocytes, we prepared GlcNAc-Ls-containing pravastatin and examined the effect of pravastatin on cardiomyocytes. Pravastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor (statin) and is hydrophilic. It is reported that lipophilic statins enhance nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by interleukin-1beta (IL-1beta)-stimulated cardiomyocytes. The hydrophilic nature of pravastatin prevents its entry into cardiomyocytes; therefore, it cannot enhance both these processes. Treatment with GlcNAc-Ls-containing pravastatin specifically enhanced NO production and iNOS expression by IL-1beta-stimulated cardiomyocytes. Based on these results, we found that cardiomyocytes exhibit a high degree of interaction with GlcNAc-Ls, and GlcNAc-Ls-encapsulated agents can be effectively taken up by cardiomyocytes. We suggest that GlcNAc-Ls can be utilized therapeutically as a DDS for the injured myocardium.


Subject(s)
Acetylglucosamine/chemistry , Endocytosis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism , Lipids/chemistry , Liposomes , Myocytes, Cardiac/metabolism , Pravastatin/metabolism , Animals , Animals, Newborn , Cells, Cultured , Chemistry, Pharmaceutical , Drug Compounding , Enzyme Induction , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Interleukin-1beta/metabolism , Myocytes, Cardiac/drug effects , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/biosynthesis , Particle Size , Pravastatin/chemistry , Pravastatin/pharmacology , Rats , Rats, Sprague-Dawley
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