Peritoneopericardial communication after aortic valve replacement in a peritoneal dialysis patient.

A 73-year-old male undergoing peritoneal dialysis (PD) for end-stage renal disease due to diabetic nephropathy was diagnosed with aortic stenosis and was admitted to our hospital in September, 2009. The patient underwent replacement of the ascending aorta with an artificial blood vessel plus aortic valve replacement without any notable complications. PD was restarted 3 days after the surgery and large amounts of light red fluid from the drain placed in the pericardium were observed just after resumption of PD solution. The patient was diagnosed with peritoneopericardial communication. PD was discontinued and hemodialysis was performed only with intermittent lavage of the peritoneal cavity. The amount of drainage was spontaneously decreased, and on the 17th day after surgery, PD was resumed. The patient is undergoing PD without recurrence of peritoneopericardial communication, 59 months after the onset of symptoms. Peritoneopericardial communication in a patient with PD developing after open-heart surgery is rare because such a case has been documented in only one case report. However, since massive pericardial effusion may cause severe cardiac problems, we consider that the communication between the peritoneal cavity and the pericardium needs to be checked for in patients with PD after cardiac surgery.

[Incidence and clinical outcome of contrast-induced nephropathy in the elderly patients].

BACKGROUND: Aging is an established risk factor for contrast-induced nephropathy (CIN). However, little information is available on the incidence and clinical outcome of CIN for the elderly patients in Japan. OBJECTIVES: We determined the incidence and clinical outcome of CIN in the Japanese elderly patient. METHODS: We studied 292 patients who had mild renal dysfunction (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) at baseline and underwent coronary angiography. Patients were divided into two groups base on their age: the elderly group (age ≥ 75, n=108) and the control group (age<75, n=184). CIN was defined as a 25% increase in serum creatinine or an increase in serum creatinine by>0.5 mg/dl above the baseline value at or within 2 days post procedure. RESULTS: Patients in the elderly group had a higher incidence of CIN (14%) than those in the control group (9%). In patients who developed CIN, there was no significant difference between the two groups in baseline GFR and GFR on days 1, 2, 7 and 30 after the procedure. However, the relative increase in GFR above baseline on day 7 (-4.0 ± 6.1 vs -8.3 ± 8.0 ml/min P=0.096) and day 30 (1.5 ± 9.4 vs -10.1 ± 9.6 ml/min P=0.0017) in the elderly group was higher than that in the control group. Furthermore, death occurred in 3 patients in the elderly group (20%) whereas no patient died in the control group (P=0.092). CONCLUSION: Aging (age ≥ 75) is a risk factor for CIN in Japanese. CIN in the elderly patients may be associated with prolonged renal dysfunction and poor prognosis.

Prognostic value of normal stress-only technetium-99m myocardial perfusion imaging protocol. Comparison with standard stress-rest protocol.

BACKGROUND: Patients with a normal stress image on technetium-99m (Tc-99m) single-photon emission computed tomography (SPECT) have a good prognosis for diagnosing coronary artery disease. However, current guidelines recommend stress and rest imaging to confirm that a stress image is normal. METHODS AND RESULTS: We determined all-cause of cardiac events (acute coronary syndrome and sudden death) in 1,939 patients undergoing stress myocardial perfusion SPECT with Tc-99m radiotracers. Patients with an abnormal stress image were excluded, so we focused on 1,125 patients in whom the stress SPECT study was interpreted as normal. A stress-only protocol was used in 726 patients (adenosine=339; exercise=387), whereas 399 had both stress and rest imaging (adenosine=294; exercise=105). Mean follow-up was 1,252 days. At the end of follow-up, there were 39 cardiac events in the stress-only cohort and 19 in the stress-rest cohort. Kaplan-Meier analysis revealed that there were no differences for the entire cohort of cardiac events not only between the stress-only and stress-rest protocols but also for stressor modality, despite the fact that the stress-rest cohort showed higher coronary risk factors. CONCLUSIONS: Patients determined as having a normal SPECT on the basis of stress imaging alone have a similar cardiac event rate as those who have a normal SPECT on the basis of evaluation of both stress and rest images. This imaging strategy will significantly reduce radiation exposure in a substantial number of patients.

Granulocyte colony-stimulating factor does not enhance recruitment of bone marrow-derived cells in rats with acute myocardial infarction.

Despite the potential benefit of granulocyte colony-stimulating factor (G-CSF) therapy in patients with acute myocardial infarction (MI), the efficacy of G-CSF in regenerating the heart after MI remains controversial. The authors hypothesize that the limited efficacy of G-CSF is related to its inhibitory effect on recruitment of bone marrow-derived cells (BMCs) to the infarcted tissue. MI was induced in rats with intrabone marrow-bone marrow transplantation from syngenic rats expressing green fluorescence protein to track BMCs. G-CSF was administered for five days after the onset of MI. G-CSF increased the number of CD45(+) cells in the peripheral circulation but did not increase their recruitment to the heart. G-CSF had no effect on myocardial stromal-derived factor-1 alpha and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in mononuclear cells in the peripheral blood and CXCR4(+) cells in the heart. G-CSF had no effect on angiogenesis, myocardial fibrosis or left ventricular function four weeks after MI. These results suggest that G-CSF mobilizes BMCs to the peripheral circulation but does not increase recruitment to the infarcted myocardium despite preservation of the stromal-derived factor-1 alpha/CXCR4 axis.

Atypical morphology and myocardial perfusion of mid-ventricular ballooning: A case report.

Although some atypical types of transient left ventricular apical ballooning syndrome have been reported, only a few atypical types of transient mid-ventricular ballooning have been reported. A 70-year-old female underwent surgery for urothelial carcinoma. At day 5 after the surgery, she was admitted to our department without cardiac symptoms because of ST elevation in leads I, II, III, aVF and V1-V6 indicating acute coronary syndrome. She was diagnosed with stress induced cardiomyopathy based on an angiographically normal coronary artery, newly developed extensive wall motion abnormality (hyperbasal contraction and akinesis from the mid-left ventricle to the apex without hypercontraction of the small area adjacent to the apex) based on left ventriculography, and a small elevation of myocardial enzymes incongruous with the area of contraction abnormality. Myocardial scintigraphy with 99mTc-tetrofosmin showed a severely reduced myocardial perfusion in an extensive mid-ventricular area without a left ventricular base and top of apex, in accord with a wall motion abnormality different from typical apical ballooning or typical mid-ventricular ballooning previously diagnosed in our hospital. This is the first report presenting an atypical mid-ventricular ballooning based on the myocardial atypical perfusion findings.

Sepiapterin enhances angiogenesis and functional recovery in mice after myocardial infarction.

Uncoupling of nitric oxide synthase (NOS) has been implicated in left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). We hypothesized that inducible NOS (iNOS) plays a crucial role in LV remodeling after MI, depending on its coupling status. MI was created in wild-type, iNOS-knockout (iNOS(-/-)), endothelial NOS-knockout (eNOS(-/-)), and neuronal NOS-knockout (nNOS(-/-)) mice. iNOS and nNOS expressions were increased after MI associated with an increase in nitrotyrosine formation. The area of myocardial fibrosis and LV end-diastolic volume and ejection fraction were more deteriorated in eNOS(-/-) mice compared with other genotypes of mice 4 wk after MI. The expression of GTP cyclohydrolase was reduced, and tetrahydrobiopterin (BH(4)) was depleted in the heart after MI. Oral administration of sepiapterin after MI increased dihydrobiopterin (BH(2)), BH(4), and BH(4)-to-BH(2) ratio in the infarcted but not sham-operated heart. The increase in BH(4)-to-BH(2) ratio was associated with inhibition of nitrotyrosine formation and an increase in nitrite plus nitrate. However, this inhibition of NOS uncoupling was blunted in iNOS(-/-) mice. Sepiapterin increased capillary density and prevented LV remodeling and dysfunction after MI in wild-type, eNOS(-/-), and nNOS(-/-) but not iNOS(-/-) mice. N(ω)-nitro-L-arginine methyl ester abrogated sepiapterin-induced increase in nitrite plus nitrate and angiogenesis and blocked the beneficial effects of sepiapterin on LV remodeling and function. These results suggest that sepiapterin enhances angiogenesis and functional recovery after MI by activating the salvage pathway for BH(4) synthesis and increasing bioavailable nitric oxide predominantly derived from iNOS.

Differences in the mode of presentation for acute coronary syndrome by pre-hospitalization medication, in relation to coronary risk factors, East-Osaka acute coronary syndrome (EACS) registry.

BACKGROUND: Pre-hospitalization medication such as aspirin and nitrates has been shown to affect the mode of presentation in acute coronary syndrome (ACS). However, it is not formally assessed whether other cardiovascular medications may be contributed to the differences in the mode of presentation, especially in relation to coronary risk factors. METHODS AND RESULTS: We conducted a registration study of patients (M/F 850/323) with either ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA), and examined the differences in the mode of presentation, pre-hospitalization medication, and coronary risk factors. The ratio of the incidence of STEMI and NSTEMI/UA was significantly reduced in patients having pre-hospitalization medication with aspirin, nitrates or statins, but not with other medications such as beta-blockers in multivariate analysis. Pre-hospitalization medication with aspirin and nitrates was significantly associated with the same reduction of the ratio in patients with male gender, hypertension, diabetes mellitus and a history of coronary artery disease. However, in patients who smoked, were obese and hypercholesterolemic, pre-hospitalization medication with nitrates was significantly associated with the reduced ratio. The ratio was significantly low in patients with males and hypercholesterolemia treated with statins before admission. CONCLUSION: Depending on their coronary risk factors, pre-hospitalization medication with aspirin, nitrates or statins was associated with a different presentation and evolution of ACS.

Ascorbic acid and N-acetyl cysteine prevent uncoupling of nitric oxide synthase and increase tolerance to ischemia/reperfusion injury in diabetic rat heart.

Oxidative stress may cause a loss of tetrahydrobiopterin (BH4), a co-factor of nitric oxide synthase (NOS), decrease the bioavailability of NO and aggravate ischemia/reperfusion (I/R) injury in diabetic heart. We hypothesized that ascorbic acid (AA) and N-acetyl cysteine (NAC) protect the diabetic heart from I/R injury by increasing BH4/dihydrobiopterin (BH2) ratio and inhibiting uncoupling of NOS. Diabetes mellitus was induced in rats by streptozotocin treatment, and the hearts were isolated and perfused. BH4 and BH4/BH2 ratio decreased in the diabetic heart associated with increased production of superoxide and nitrotyrosine (NT). Treatment with AA or NAC significantly increased BH4/BH2 ratio in the diabetic heart associated with decreased production of superoxide and NT and increased generation of nitrate plus nitrite (NOx). Pre-treatment with AA or NAC before 30 min ischemia followed by 120 min reperfusion improved left ventricular (LV) function and reduced infarct size in the diabetic but not non-diabetic hearts. The NOS inhibitor, L-NAME, inhibited the increase in the generation of superoxide, NT and NOx, but aggravated LV function and increased infarct size in the diabetic heart. L-NAME also abrogated the increase in NOx and improvement of LV function and the infarct size-limiting effect induced by AA or NAC in the diabetic heart. These results suggest that AA and NAC increase BH4/BH2 ratio and prevent NOS uncoupling in the diabetic heart. Resultant increase in the bioavailability of NO renders the diabetic heart toleratant to I/R injury.

A new protocol using sodium bicarbonate for the prevention of contrast-induced nephropathy in patients undergoing coronary angiography.

Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality rates. Although a previous study reported that pretreatment with sodium bicarbonate is more effective than sodium chloride for prophylaxis of CIN, this has not been a universal finding. We performed a prospective randomized trial to investigate whether CIN can be avoided using sodium bicarbonate. In total 155 patients with a glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) who were undergoing coronary angiography were enrolled. We assigned patients to sodium chloride plus sodium bicarbonate (bicarbonate group, n = 78) or sodium chloride alone (chloride group, n = 77). Infusion of sodium bicarbonate at 1 ml/kg/hour continued from 3 hours before to 6 hours after coronary angiography. CIN was defined as a 25% increase in serum creatinine from baseline value or an absolute increase of ≥0.5 mg/dl, which appeared within 2 days of contrast. Baseline GFR was not significantly different between the 2 groups. Patients in the bicarbonate group had a higher GFR than those in the chloride group on day 2 (45.8 ± 13.4 vs 40.9 ± 14.6 ml/min/1.73 m(2), p = 0.031) and at 1 month (49.5 ± 14.7 vs 43.7 ± 15.5 ml/min/1.73 m(2), p = 0.019). CIN occurred in 10 patients (13%) in the chloride group but in only 2 patients (2.6%) in the bicarbonate group (p = 0.012). Sodium chloride plus sodium bicarbonate is more effective than sodium chloride alone for prophylaxis of CIN and can lead to retention of better long-term renal function.

Type 2 iodothyronine deiodinase is expressed in human preadipocytes.

BACKGROUND: Type 2 iodothyronine deiodinase (D2) is an enzyme that catalyzes the production of triiodothyronine (T3) from thyroxine (T4) and plays a critical role in providing the local intracellular T3. Although D2 is highly expressed in brown adipose tissue, it was thought that D2 is hardly expressed in white adipose tissue. In the present study, we examined whether D2 is expressed in human preadipocytes, using human mesenteric and subcutaneous preadipocytes (HMPA and HSCPA, respectively). METHODS: HMPA and HSCPA were purchased and cultured in the preadipocyte medium containing 10% fetal bovine serum. We measured D2 activity and mRNA level in HMPA and HSCPA incubated with or without dibutyryl cyclic adenosine monophosphate [(Bu)2cAMP]. RESULTS: D2 activity and mRNA were detectable in human HMPA and HSCPA. The apparent Michaelis-Menten constant (K(m)) value for T4 in HMPA was 2.1 ± 0.2 nM, and the maximum velocity (V(max)) value was 333.3 ± 28.0 femtomols of I⁻ released/mg protein/hour, respectively. On the other hand, the apparent K(m) value for T4 in HSCPA was 2.0 ± 0.2 nM and the V(max) value was 91.2 ± 8.7 femtomols of I⁻ released/mg protein/hour, respectively. D2 activities in HMPA and HSCPA incubated with 1 mM (Bu)2cAMP for 24 hours were 7-fold (HMPA) and 3-fold (HSCPA) higher than those without (Bu)2cAMP, respectively. D2 mRNA levels in HMPA and HSCPA incubated with 1 mM (Bu)2cAMP for 3 hours were 10-fold (HMPA) and 5-fold (HSCPA) higher than those without (Bu)2cAMP, respectively. CONCLUSIONS: In the present study, we have clearly demonstrated that D2 activity and mRNA are present in the human preadipocytes from both mesenteric and subcutaneous adipose tissue. Our experiments are the first ones that identify human preadipocytes as one of the sources of T3 production.

A Japanese case of proteinase 3 antineutrophil cytoplasmic autoantibody-associated pauci-immune-type crescentic glomerulonephritis without valvular endocarditis.

A 74-year-old male without recent medical treatment visited our hospital complaining of fever and lack of appetite. Upon examination severe azotemia, proteinuria, and urinary occult blood were noted, and the patient was admitted. Results of a blood test showed that his proteinase 3 antineutrophil cytoplasmic autoantibody (PR3-ANCA) level was high. A transthoracic echocardiogram indicated normal cardiac function and no valvular regurgitation or stenosis. Necrotizing glomerulonephritis accompanied by cellular crescentic bodies, but not granuloma, was noted on renal biopsy. An immunofluorescence study demonstrated no immunofluorescence staining in the glomerulus or in the tubulointerstitial or vascular compartments. No lesion was present in the lung or upper respiratory tract. The patient was diagnosed with PR3-ANCA-associated pauci-immune-type crescentic glomerulonephritis and treated with steroids. This treatment resulted in rapid normalization of C-reactive protein, and the PR3-ANCA level slowly decreased and converted to negative. The renal function, however, did not improve, and maintenance dialysis was introduced. No pulmonary or upper airway lesion has developed during 18 months of follow-up. PR3-ANCA-positive crescentic glomerulonephritis accompanied by valvular endocarditis has been described by several reports in Japan; however, this case was not complicated by valvular endocarditis. To our knowledge, this is the 4th case report describing PR3-ANCA-associated crescentic glomerulonephritis in Japan.

Phenotypic modulation and turnover of bone marrow-derived cells after myocardial infarction in rats.

BACKGROUND: Bone marrow-derived cells (BMCs) are critically involved in inflammation and regeneration after myocardial infarction (MI). However, the participation of BMCs in the reconstruction of infarcted myocardium remains unclear. In this study, we investigated phenotypic modulation of BMCs and their turnover in the heart following MI. METHODS AND RESULTS: MI was produced in rats with intra-bone marrow-bone marrow transplantation from the syngenic rats expressing green fluorescence protein (GFP). The number of GFP-positive BMCs recruited to the infarcted myocardium peaked at 3 days after MI, and the majority of BMCs recruited to the heart after MI underwent turnover within 2 weeks. This turnover rate was unchanged for up to 16 weeks after MI, although the number of BMCs recruited to the infarcted myocardium rapidly decreased between 2 and 8 weeks after MI. A small number of BMCs recruited to the heart were positive for CD31 and α-smooth muscle actin, and the majority of these were positive for vimentin at 3 days and 4 weeks after MI. None of BMCs expressed α-actinin or von Willebrand factor 4 weeks after MI. CONCLUSIONS: These results suggest that BMCs recruited to the heart underwent phenotypic modulation to a fibroblastic cell type and turnover within 2 weeks after MI without differentiating into cardiomyocytes or endothelial cells, and that although the number of BMCs in the infarcted myocardium decreased over time, the rate of turnover remained relatively constant during the chronic phase of MI.

Inhibition of contractile activity during postconditioning enhances cardioprotection by restoring sarcolemmal dystrophin through phosphatidylinositol 3-kinase.

BACKGROUND: Although ischemic postconditioning (IPost) confers cardioprotection by protecting the mitochondria though the activation of phosphatidylinositol 3-kinase (PI3K), a potential drawback of IPost is impairment of aerobic ATP generation during reperfusion by repeated ischemia. This decrease in ATP might inhibit the restoration of sarcolemmal dystrophin, which is translocated during ischemia, and render cardiomyocytes susceptible to contraction-induced oncosis. METHODS AND RESULTS: Isolated rat hearts were subjected to 30 min ischemia and 120 min reperfusion. IPost induced by 20 cycles of 10-s reperfusion and 10-s ischemia enhanced the activation of PI3K as evidenced by the increased phosphorylation of Akt, but had no effect on myocardial ATP, restoration of sarcolemmal dystrophin, or cardiomyocyte oncosis during IPost. Administration of the contractile blocker, 2,3-butanedione monoxim (BDM), during IPost increased myocardial ATP and facilitated the redistribution of dystrophin to the sarcolemma. This led to reduced cardiomyocyte oncosis and infarct size, and improved the left ventricular function. The anti-oncotic effect of BDM occurred without changing the anti-apoptotic effect of IPost. The PI3K inhibitor, LY294002, prevented the phosphorylation of Akt, decreased the recovery of ATP and restoration of sarcolemmal dystrophin, and blocked the anti-oncotic and anti-apoptotic effects of IPost. CONCLUSIONS: These results suggest that the inhibition of contractile activity during IPost prevents cardiomyocyte oncosis and enhances cardioprotection through PI3K-dependent restoration of sarcolemmal dystrophin.

Contrast-induced nephropathy in patients undergoing emergency percutaneous coronary intervention for acute coronary syndrome.

Contrast-induced nephropathy (CIN) is associated with significantly increased morbidity and mortality after coronary angiography and percutaneous coronary intervention (PCI). The aim of the present study was to assess the clinical features and in-hospital outcomes of CIN after emergency PCI. The serum creatinine (SCr) concentration was measured from days 0 to 30 in 338 consecutive patients with acute coronary syndrome undergoing emergency PCI. CIN was defined as an increase in SCr of >25% or >0.5 mg/dl within 2 days after PCI. Overall, 94 patients (28%) developed CIN. The mean SCr on admission was not significantly different between patients with CIN and those without CIN. The CIN group had significantly greater SCr at days 1, 2, and 30 than did the no CIN group. Multivariate analysis showed female gender (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.12 to 5.07, p = 0.025), a culprit lesion in the left anterior descending artery (OR 2.37, 95% CI 1.31 to 4.27, p = 0.0042), contrast agent volume >200 ml (OR 3.60, 95% CI 1.96 to 6.62, p <0.001) and end-diastolic pulmonary arterial pressure >15 mm Hg (OR 2.03, 95% CI 1.02 to 4.04, p <0.01) to all correlate independently with CIN. The in-hospital mortality rate was greater in the CIN group than in the no CIN group (9.6% vs 3.3%, respectively; p = 0.025). In conclusion, CIN is a frequent complication of emergency PCI for acute coronary syndrome and is associated with a greater mortality rate and persistent renal dysfunction.

A patient with refractory nephrotic syndrome withdrawn from peritoneal dialysis.

A 67-year-old woman was admitted to our hospital because of anasarca due to refractory nephrotic syndrome and chronic renal insufficiency. Laboratory data indicated serum total protein of 4.8 g/dl, albumin of 1.5 g/dl, creatinine of 1.9 mg/dl and BUN of 17 mg/dl. Urinary protein excretion was 7.8 g/day. Because of severe atrophy of both kidneys, neither renal biopsy nor immunosuppressive treatment was performed. Since conservative management including bed rest, diet therapy, limitation of water intake and administration of diuretics was not effective, peritoneal dialysis therapy using icodextrin only at night was started. The amount of water removal was steadily secured without progressing renal dysfunction or decreasing urine volume. From day 290 onward, the urinary protein excretion was decreased to show complete remission and urine volume increased. On day 528, peritoneal dialysis was discontinued, and thereafter only peritoneal lavage was performed. On day 858, the catheter was removed from the abdominal cavity, and thereafter diuretics could be discontinued. The reason for the dramatic reduction of urinary protein in this patient is unclear. However, it is possible that the primary disease such as membranous nephritis showed remission while the patient was undergoing icodextrin peritoneal dialysis, which preserves renal function but not extracorporeal ultrafiltration or hemodialysis. Icodextrin peritoneal dialysis may be an alternative to hemodialysis for refractory fluid overload in patients with nephrotic syndrome and may have the advantage of preserving renal function.

Soluble TRAIL prevents RANTES-dependent restenosis after percutaneous coronary intervention in patients with coronary artery disease.

Some factors play pathogenic roles in the development of restenosis after percutaneous coronary intervention (PCI). We measured and compared the ratio of elevated levels of regulated on activation normally T-cell expressed and secreted (RANTES), soluble (s) P-selectin, sE-selectin, s vascular cell adhesion molecule (VCAM)-1, s interleukin-2 receptor (IL-2R) and s tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) after PCI. Plasma levels of chemokines and soluble markers were measured before and 30 days after PCI in 85 patients (61 males and 24 females, aged 61 +/- 7 years) who underwent PCI and who had repeated angiograms at a 6-month follow-up. Restenosis occurred in 29 (34.1%) patients. The significant and time-dependent increases in RANTES, sIL-2R and sVCAM-1 were observed in the restenosis group. However, there were no significant differences in sP-selectin and sE-selectin levels with or without restenosis. sTRAIL levels in patients with coronary artery disease were significantly higher than levels in normal controls. Furthermore, unlike the restenosis group, sTRAIL levels after PCI were significantly increased in the non-restenosis group, and sTRAIL levels correlated significantly with sVCAM-1 and sE-selectin. These findings suggest that restenosis development after PCI in patients with coronary artery disease involve the participation of RANTES and activated T-lymphocyte expressing CD25 after PCI, and sTRAIL may prevent this RANTES-dependent restenosis.

Prevention of contrast-induced nephropathy by chronic pravastatin treatment in patients with cardiovascular disease and renal insufficiency.

BACKGROUND: Contrast-induced nephropathy (CIN) is known to increase morbidity and mortality of cardiovascular disease. Recent studies have shown statins prevented CIN after contrast media exposure, but optimal statin type and dosage are still unknown. PURPOSE: The aims of the present study were to evaluate whether chronic pravastatin treatment before scheduled coronary angiography or percutaneous coronary intervention could reduce the incidence of CIN and to elucidate the factors related to CIN in patients with renal insufficiency. METHODS: We studied 431 consecutive patients with renal insufficiency. One hundred ninety-four patients were receiving pravastatin treatment as standard chronic treatment of hypercholesterolemia. Serum creatinine levels were measured at baseline (pre-procedure) and within 48 h after contrast media exposure (peak post-procedure). CIN was defined as an increase in the serum creatinine values of > or = 25% or > or = 0.5 mg/dl after contrast media exposure. Logistic regression analysis was performed to evaluate the important factors related to CIN using four variables: age, pravastatin, pre-procedure serum creatinine, and contrast volume. RESULTS: CIN was observed in 36 patients (8.4%). Patients without pravastatin (p<0.01), high level pre-procedure serum creatinine (p<0.01), and high contrast volume (p=0.034) had a significantly higher incidence of CIN. Logistic regression analysis revealed that pravastatin treatment (chi(2)=6.549, p=0.011, odds ratio=0.34), pre-procedure serum creatinine (chi(2)=6.294, p=0.009, odds ratio=2.78), and contrast volume (chi(2)=4.484, p=0.034, odds ratio=1.01) were independently related to the decreased risk of CIN. CONCLUSIONS: Chronic pravastatin treatment before contrast media exposure was important for preventing CIN in patients with renal insufficiency. Also, reducing the dose of contrast media was important for preventing CIN in patients with high-baseline serum creatinine levels.

Thyroid hormone activation in vascular smooth muscle cells is negatively regulated by glucocorticoid.

BACKGROUND: Type 2 iodothyronine deiodinase (D2) catalyzes the production of triiodothyronine from thyroxine. D2 is present in rat aorta media, and there is a circadian variation in the D2 expression. In rat aorta media, the D2 activity exhibited the maximal value at 1200 hour and low value between 1800 and 2400 hour. To understand the mechanisms that induce the circadian variation in the D2 expression, we examined the effects of glucocorticoid on the D2 activity and mRNA in rat aorta media and cultured vascular smooth muscle cells (VSMCs). METHODS: The effects of intrinsic and extrinsic glucocorticoid on the D2 activity and mRNA in rat aorta media were studied using metyrapone, a corticosterone synthesis inhibitor, and dexamethasone (DEX). Further, the effects of DEX on D2 expression were studied using the cultured rat VSMCs. RESULTS: The trough values of D2 activity and mRNA at 2100 hour were increased by the treatment with metyrapone. On the other hand, the peak values of D2 activity and mRNA were decreased by the treatment with DEX. D2 activity and mRNA in cultured rat VSMCs were increased by the addition of 10(-3) M dibutyryl cyclic adenosine monophosphate [(Bu)(2)cAMP]. The increments were reduced by coincubation with 10(-6) M DEX. CONCLUSIONS: These results suggest that glucocorticoids might directly suppress the D2 expression in rat VSMCs induced by a cAMP-dependent mechanism.

Effects of pitavastatin on monocyte chemoattractant protein-1 in hyperlipidemic patients.

The effects of statins on platelet activation markers, chemokines and adiponectin, were investigated in 135 patients with hyperlipidemia. Of the 135 hyperlipidemic patients, 63 were allocated to the simvastatin group, treated with simvastatin at the dose of 10 mg daily, and the remaining 72 were allocated to the pitavastatin group, treated with pitavastatin at the dose of 2 mg daily. Plasma levels of platelet-derived microparticles (PDMP), cell adhesion molecules (sCD40L and sP-selectin), chemokines [monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normally T-cell expressed and secreted] and adiponectin were measured at the baseline and after 6 months of treatment in both the groups. In addition, we carried out a basic study to investigate the MCP-1-dependent induction of tissue factor expression on a histiocytic cell line (U937 cells). The plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 were higher, whereas those of adiponectin were lower, in the hyperlipidemic patients than in the normolipidemic controls. Plasma PDMP and sCD40L were positively correlated, whereas plasma adiponectin was negatively correlated, with the plasma levels of MCP-1. No significant differences in the plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 measured before and after treatment were observed in either the simvastatin or pitavastatin group. A significant increase of the plasma adiponectin levels was observed after 6 months of treatment with pitavastatin but not after an equal duration of treatment with simvastatin. When pitavastatin-treated patients were divided into two groups according to the adiponectin response to pitavastatin treatment, significant decreases of the plasma MCP-1, PDMP and sCD40L levels were observed after pitavastatin treatment in the responder group. In the aforementioned basic study, MCP-1 by itself did not induce the expression of tissue factor on the U937 cells. However, the recombinant sCD40L-induced expression of tissue factor on U937 was enhanced by the addition of MCP-1. These findings suggest that PDMP, sCD40L and MCP-1 may participate in the development of atherothrombosis in patients with hyperlipidemia and that pitavastatin may exert an adiponectin-dependent antiatherothrombotic effect in hyperlipidemic patients.