Effects of atorvastatin and ezetimibe on endothelial function in dyslipidemic patients with chronic kidney disease

Backgroud

Chronic kidney disease (CKD) is a staple risk factor not only for renal failure but also for cardiovascular diseases. In addition, because dyslipidemia facilitates atherosclerosis and renal dysfunction, antihyperlipidemic treatment is important to prevent cardiac and renal events in CKD patients.

Methods

We compared the effects of a statin and an intestinal cholesterol transporter inhibitor in 20 dyslipidemic patients with CKD presenting with proteinuria and/or glomerular filtration rate <60 mL/min/1.73 m². Either 5–10 mg atorvastatin or 10 mg ezetimibe was given for 3 months each in a randomized crossover manner and the parameters of oxidative stress, inflammation and endothelial function were compared.

Results

Atorvastatin lowered serum low-density lipoprotein (LDL) cholesterol more prominently than ezetimibe (103 ± 38 vs 130 ± 45 mg/dL, p < 0.001), while serum γ-glutamyl transpeptidase was higher in atorvastatin than in ezetimibe (29 ± 16 vs 25 ± 11 U/L, p = 0.013). On the other hand, serum oxidized LDL and high-sensitivity C-reactive protein were lower in the atorvastatin treatment period than in the ezetimibe treatment period (109 ± 38 vs 146 ± 67 U/L, p = 0.002; 1.02 ± 1.46 vs 1.47 ± 1.77 µg/mL, p = 0.003). Although serum adiponectin was not significantly different between the two drugs, the reactive hyperemia index, an index of endothelial function, was higher in atorvastatin than in ezetimibe (1.94 ± 0.58 vs 1.60 ± 0.44, p = 0.023).

Conclusion

It is concluded that atorvastatin is more potent than ezetimibe in improving the serum lipid profile, reducing oxidative stress, suppressing inflammation and preserving endothelial function, while ezetimibe may be advantageous in reducing the hepatic lipid load.     

Antegrade selective cerebral perfusion with mild hypothermic systemic circulatory arrest during thoracic aortic surgery

Objective Antegrade selective cerebral perfusion (ASCP) and retrograde cerebral perfusion (RCP) have proven to be reliable methods of brain protection during aortic surgery. These techniques are usually accompanied by systemic circulatory arrest with moderate hypothermia (24–28°C) or deep hypothermia (18–24°C). However, hypothermia can lead to various problems. The present study therefore reports results for thoracic aorta replacement using ASCP with mild hypothermic systemic arrest (28–32°C).

Design Between 1995 and 2003, 68 consecutive patients underwent repair of the ascending aorta and/or aortic arch. Mild hypothermic ASCP was utilized in 31 cases, moderate hypothermic ASCP in 20, and deep hypothermic RCP in 17. Various parameters were compared between the mild hypothermic ASCP, moderate hypothermic ASCP, and RCP.

Results Hospital mortality was 10.3%, with no significant differences observed between any groups. Permanent neurological dysfunction was 8.8%, and no significant differences were observed between any groups. Mild hypothermic ASCP displayed significantly decreased transfusion volume, intubation time, and ICU stay.

Conclusions Use of ASCP with mild hypothermic systemic circulatory arrest during aortic surgery resulted in acceptable hospital mortality and neurological outcomes. ASCP with mild hypothermic arrest allows decreased transfusion volume and reduced duration of intubation and ICU stay.     

Prediction of morbidity after lung resection with risk factors using treadmill exercise test.

OBJECTIVE: To predict accurate morbidity after lung resection using treadmill exercise test. METHODS: A total of 130 patients (108 men and 22 women, with mean age 67.1+/-11.4 years (range, 34-78 years)) of 1129 patients underwent standard lobectomy were performed both treadmill exercise test and spirometry preoperatively. We measured maximum oxygen uptake/body weight (VO2max/BW) and change in arterial blood oxygen pressure from rest to symptom-limited maximum loading (delta aPaO2) and calculated exercise-induced hypoxemia (delta PaO2/delta VO2/BW), and retrospectively compared these parameters for patients with and without complications. RESULTS: There were five patients with severe postoperative complications, including three requiring use of a respirator, two with home oxygen therapy. %Vital capacity, VC (%, 80.2+/-13.2 vs. 92.5+/-20.9, P=0.026), delta PaO2 (Torr, -29.3+/-4.3 vs. -13.2+/-10.8, P=0.0004), VO2max/BW (ml/min/kg, 16.5+/-2.9 vs. 20.6+/-5.1, P=0.018) and delta PaO2/delta VO2/BW (Torr/ml/min/kg, -1.98+/-0.26 vs. -0.57+/-0.47) were significantly associated with worse outcome. All the five patients with complications had delta PaO2/delta VO2/BW<-1.7. CONCLUSIONS: Treadmill exercise testing is a good method for assessment of cardiopulmonary reserve. Limited resection must be performed if delta PaO2/delta VO2/BW is under -1.7.     

CyberKnife stereotactic irradiation for metastatic brain tumors

BACKGROUND: The CyberKnife provides a new technique for performing frameless stereotactic irradiation. So far, few reports have been published on clinical outcomes obtained with the CyberKnife. This report summarizes our clinical experience with CyberKnife irradiation for metastatic brain tumors. MATERIALS AND METHODS: Seventy-seven lesions (48 patients) were evaluated and analyzed, and 66 lesions in 41 patients were treated with stereotactic radiosurgery (SRS). The prescribed dose was 9 to 30 Gy. RESULTS: Freedom from progression of the tumors was more likely with a prescribed dose of at least 24 Gy than with one of less than 20 Gy (p=0.0244; log-rank test). The CR (complete response) rate was significantly higher when D99 was at least 24 Gy (p=0.0045). There were no severe side effects. CONCLUSION: Stereotactic irradiation with the CyberKnife for metastatic brain tumors is effective and safe. D99 should be at least 24 Gy for CyberKnife SRS treatment.     

Serotonin 5‐HT1B receptor‐mediated calcium influx‐independent presynaptic inhibition of GABA release onto rat basal forebrain cholinergic neurons

Modulatory roles of serotonin (5‐HT) in GABAergic transmission onto basal forebrain cholinergic neurons were investigated, using whole‐cell patch‐clamp technique in the rat brain slices. GABA_A receptor‐mediated inhibitory postsynaptic currents (IPSCs) were evoked by focal stimulation. Bath application of 5‐HT (0.1–300 μm ) reversibly suppressed the amplitude of evoked IPSCs in a concentration‐dependent manner. Application of a 5‐HT_1B receptor agonist, CP93129, also suppressed the evoked IPSCs, whereas a 5‐HT_1A receptor agonist, 8‐OH‐DPAT had little effect on the evoked IPSCs amplitude. In the presence of NAS‐181, a 5‐HT_1B receptor antagonist, 5‐HT‐induced suppression of evoked IPSCs was antagonised, whereas NAN‐190, a 5‐HT_1A receptor antagonist did not antagonise the 5‐HT‐induced suppression of evoked IPSCs. Bath application of 5‐HT reduced the frequency of spontaneous miniature IPSCs without changing their amplitude distribution. The effect of 5‐HT on miniature IPSCs remained unchanged when extracellular Ca²⁺ was replaced by Mg²⁺. The paired‐pulse ratio was increased by CP93129. In the presence of ω‐CgTX, the N‐type Ca²⁺ channel blocker, ω‐Aga‐TK, the P/Q‐type Ca²⁺ channel blocker, or SNX‐482, the R‐type Ca²⁺ channel blocker, 5‐HT could still inhibit the evoked IPSCs. 4‐AP, a K⁺ channel blocker, enhanced the evoked IPSCs, and CP93129 had no longer inhibitory effect in the presence of 4‐AP. CP93129 increased the number of action potentials elicited by depolarising current pulses. These results suggest that activation of presynaptic 5‐HT_1B receptors on the terminals of GABAergic afferents to basal forebrain cholinergic neurons inhibits GABA release in Ca²⁺ influx‐independent manner by modulation of K⁺ channels, leading to enhancement of neuronal activities.     

Comparison of the effects of angiotensin II receptor antagonist monotherapy and combination therapy with a diuretic on cardiac function in spontaneously hypertensive rats

Objective

Losartan, an angiotensin II receptor blocker (ARB), has been reported to promote sodium excretion and show an enhanced antihypertensive effect when used in combination with hydrochlorothiazide (HCTZ). We investigated the effects of losartan monotherapy and combination therapy together with HCTZ on cardiac function in hypertensive rats using echocardiography.

Methods

Spontaneously hypertensive rats (n?=?21) fed on high-salt diet (8?% NaCl) for 13?weeks were randomly assigned to rats without medication (HS, n?=?7), those medicated with ARB (ARB, losartan 30?mg/kg/day, n?=?8), and those with ARB and HCTZ (ARB?+?HCTZ, losartan 30?mg/kg/day?+?HCTZ 10?mg/kg/day, n?=?6). Blood pressure measurements and echocardiography were performed at 13, 17, and 29?weeks of age. After the end of the protocol, the proportion of cardiac muscle fibrosis was measured histologically.

Results

In the HS group, blood pressure and left ventricular mass/body weight (LV mass/BW) increased, and % fractional shortening (%FS) and early diastolic mitral annular velocity (e??) decreased significantly with age. In the ARB group, although blood pressure and %FS were maintained, LV mass/BW increased with age as in the HS group, and e?? decreased. In the ARB?+?HCTZ group, blood pressure decreased and LV mass/BW, %FS, and e?? were maintained. The progression of myocardial fibrosis was clearly prevented in rats treated with ARB.

Conclusion

ARB was shown to inhibit systolic disorder and myocardial fibrosis in hypertensive rats. Combination therapy proved to be more effective than monotherapy and is also effective in inhibiting diastolic disorders.     

Interaction between ESRα polymorphisms and environmental factors in osteoporosis

We hypothesized that environmental factors might affect the relationship between genetic predisposition and the risk of bone mineral density (BMD) loss. Cases were 114 Japanese women with a confirmed diagnosis of postmenopausal osteoporosis and controls were 171 general Japanese women. Genetic risk of SNPs in the estrogen receptors was analyzed by a case–control study. The interaction between gene and environmental factors for osteoporosis were assessed by a case‐only design. Significant increases in osteoporosis risk were observed with minor alleles of rs2077647 located in the first exon and rs2234693 located in the first intron of estrogen receptor α (ESRα). Haplotype CC at these risk SNPs was strongly associated with osteoporosis risk (odds ratio [OR] = 3.15, 95% confidence interval [CI] = 1.83–5.41). There was a statistically significant interaction between haplotype CC and alcohol drinking; moderate alcohol consumption decreased genetic risk of osteoporosis (OR = 0.22, 95%CI = 0.05–0.83). © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1529–1534, 2012     

Moyamoya syndrome associated with gamma knife surgery for cerebral arteriovenous malformation: case report

A 30-year-old female developed moyamoya syndrome after gamma knife surgery (GKS) for cerebral arteriovenous malformation (AVM), and was treated with bypass surgery. She suffered from flittering scotoma, right transient hemianopsia, and headache for 1 year. Cerebral angiography revealed a Spetzler-Martin grade III AVM located in the left occipital lobe. After staged embolization, GKS was performed with a minimum dose of 20 Gy to the periphery of the nidus at the 50% isodose level of the maximum target dose. Gradual nidus regression was achieved, and the clinical symptoms disappeared completely. However, at 30 months after GKS, the patient suffered transient ischemic attack. Cerebral angiography showed left middle cerebral artery occlusion with moyamoya vessels. The patient underwent direct and indirect bypass surgery. After surgery, the patient was free from ischemic symptoms. Chronic inflammation and long-term changes in expression of cytokines and growth factors after GKS may have triggered this case.     

Life-threatening veno-occlusive disease after living-related liver transplantation

Veno-occlusive disease (VOD) can develop in association with the administration of cytotoxic chemotherapeutic agents and irradiation. In solid-organ transplant settings, azathioprine has been implicated as a predisposing factor. VOD with fatal outcome occurred in a post liver-transplant recipient who had never been exposed to any agents that have the potential to induce VOD. At onset, the disease manifested clinically as gross ascites and progressive jaundice and was observed after clinically diagnosed acute graft rejection. The disease was confirmed by histologic examinations. Histologic studies of biopsy samples from this patient revealed that most small hepatic veins less than 300 microm in diameter were affected, exhibiting concentric intimal thickening with sparse inflammatory cells. A few of the hepatic veins exhibited active endotheliitis with occasional extension of inflammation to neighboring centrilobular areas. Despite intensified immunosuppression, the observed fibrous obliterative changes were irreversible. Although the cause of VOD in this patient is tentative, the damage to the endothelium, associated with acute rejection, is likely to be attributable. VOD deserves recognition as one of the causes for liver dysfunction and persistent ascites after liver transplantation.     

Left thoracotomy approach in reoperative off-pump coronary revascularization

Objective: Reoperative coronary bypass grafting is at high risk. Particularly in redo cases where the patent graft is running near the midline of the sternum, the graft may be exposed to injury by a median sternotomy and subsequent dissection. Whereas, off-pump bypass grafting from the left axillary artery or descending thoracic artery by a left thoracotomy approach is safe for preventing graft damage.Methods: From March 1998 to February 2002, we performed off-pump coronary artery bypass grafting by a left thoracotomy approach in 9 patients. The left axillary artery was used as the inflow vessel in 4 cases, and the descending thoracic, aorta in 5.Results: The radial artery was anastomosed proximally to the axillary artery in 4 cases and the descending thoracic aorta in one case. The saphenous vein graft was anastomosed, proximally to the descending thoracic aorta in 4 cases. Transdiaphragmatic minimally invasive bypass grafting for the right coronary artery was simultaneously performed in 3 cases. Postoperative cardiac events were ventricular arrhythmia in 6 cases and supraventricular arrhythmia in 3 cases. There was no damage to the patent grafts. Postoperative coronary angiography performed, in 8 cases revealed all the grafts to be patent without stenosis. Cardiac symptoms were not found after the operation in any of the cases.Conclusions: These procedures can prevent the injury to patent grafts caused by a median sternotomy, and will be one of the useful strategies for reoperative off-pump coronary artery bypass grafting.