Reduced mitochondrial coupling in vivo alters cellular energetics in aged mouse skeletal muscle

The mitochondrial theory of ageing proposes that the accumulation of oxidative damage to mitochondria leads to mitochondrial dysfunction and tissue degeneration with age. However, no consensus has emerged regarding the effects of ageing on mitochondrial function, particularly for mitochondrial coupling (P/O). One of the main barriers to a better understanding of the effects of ageing on coupling has been the lack of in vivo approaches to measure P/O. We use optical and magnetic resonance spectroscopy to independently quantify mitochondrial ATP synthesis and O₂ uptake to determine in vivo P/O. Resting ATP demand (equal to ATP synthesis) was lower in the skeletal muscle of 30-month-old C57Bl/6 mice compared to 7-month-old controls (21.9 ± 1.5 versus 13.6 ± 1.7 nmol ATP (g tissue)⁻¹ s⁻¹, P = 0.01). In contrast, there was no difference in the resting rates of O₂ uptake between the groups (5.4 ± 0.6 versus 8.4 ± 1.6 nmol O₂ (g tissue)⁻¹ s⁻¹). These results indicate a nearly 50% reduction in the mitochondrial P/O in the aged animals (2.05 ± 0.07 versus 1.05 ± 0.36, P = 0.02). The higher resting ADP (30.8 ± 6.8 versus 58.0 ± 9.5 μmol g⁻¹, P = 0.05) and decreased energy charge (ATP/ADP) (274 ± 70 versus 84 ± 16, P = 0.03) in the aged mice is consistent with an impairment of oxidative ATP synthesis. Despite the reduced P/O, uncoupling protein 3 protein levels were not different in the muscles of the two groups. These results demonstrate reduced mitochondrial coupling in aged skeletal muscle that alters cellular metabolism and energetics.     

Diffusion‐weighted MRI monitoring of pancreatic cancer response to radiofrequency heat‐enhanced intratumor chemotherapy

The aim of this study was to evaluate the feasibility of using diffusion‐weighted MRI to monitor the early response of pancreatic cancers to radiofrequency heat (RFH)‐enhanced chemotherapy. Human pancreatic carcinoma cells (PANC‐1) in different groups and 24 mice with pancreatic cancer xenografts in four groups were treated with phosphate‐buffered saline (PBS) as a control, RFH at 42 °C, gemcitabine and gemcitabine plus RFH at 42 °C. One day before and 1, 7 and 14 days after treatment, diffusion‐weighted MRI and T₂‐weighted imaging were applied to monitor the apparent diffusion coefficients (ADCs) of tumors and tumor growth. MRI findings were correlated with the results of tumor apoptosis analysis. In the in vitro experiments, the quantitative viability assay showed lower relative cell viabilities for treatment with gemcitabine plus RFH at 42 °C relative to treatment with RFH only and gemcitabine only (37 ± 5% versus 65 ± 4% and 58 ± 8%, respectively, p < 0.05). In the in vivo experiments, the combination therapy resulted in smaller relative tumor volumes than RFH only and chemotherapy only (0.82 ± 0.17 versus 2.23 ± 0.90 and 1.64 ± 0.44, respectively, p = 0.003). In vivo, 14‐T MRI demonstrated a remarkable decrease in ADCs at day 1 and increased ADCs at days 7 and 14 in the combination therapy group. The apoptosis index in the combination therapy group was significantly higher than those in the chemotherapy‐only, RFH‐only and PBS treatment groups (37 ± 6% versus 20 ± 5%, 8 ± 2% and 3 ± 1%, respectively, p < 0.05). This study confirms that it is feasible to use MRI to monitor RFH‐enhanced chemotherapy in pancreatic cancers, which may present new options for the efficient treatment of pancreatic malignancies using MRI/RFH‐integrated local chemotherapy. Copyright © 2013 John Wiley & Sons, Ltd.     

Hemostatic efficacy of hydrophilic wound dressing after transradial catheterization

Here, we evaluate the efficacy of the Clo-Sur PAD nonwoven hydrophilic wound dressing (HWD) on hemostasis in an arterial-access site after transradial percutaneous coronary angiography compared with the RadiStop compression device (CD). Eighty patients who had undergone transradial coronary angiography with or without intravascular ultrasound were randomly assigned to the HWD or CD group. The time required to achieve hemostasis was measured, and the incidence of vascular complications was assessed. No significant differences in clinical and procedural characteristics were observed between the HWD group (n = 40) and the CD group (n = 40). A significant reduction in the time required to achieve hemostasis (58.7 +/- 32.6 minutes versus 131.3 +/- 59.1 minutes; p < 0.001) was associated with the use of HWD. The incidence of vascular complications was similar in both groups (5% for HWD versus 2.5% for CD; p = 0.500). No major complications, such as large hematoma or acute radial occlusion, occurred in the HWD group. In conclusion, HWD represents a safe alternative to the compression method. Hemostasis can be achieved more quickly using HWD, with no increase in access site complications, as compared to CD.     

Subintimal angioplasty of an aortoiliac occlusion: re-entry site created using a transseptal needle under intravascular ultrasound guidance.

PURPOSE: To report the use of a transseptal needle to cross the intimal flap in subintimal angioplasty of a flush aortoiliac occlusion via a retrograde approach. CASE REPORT: A 53-year-old man with claudication of the right lower limb and an angiographically documented right aortoiliac occlusion was treated with subintimal angioplasty via an ipsilateral retrograde approach. After puncture of the right common femoral artery, a 0.035-inch hydrophilic guidewire was advanced via the subintimal space toward the aortic true lumen, but the wire could not re-enter the true lumen. A transseptal needle was used to puncture the intimal flap under intravascular ultrasound (IVUS) guidance. Angioplasty/stenting was performed successfully, and the patient's symptoms were relieved. Computed tomography at 15 months revealed patent stents. CONCLUSION: The use of a transseptal needle to cross the intimal flap in total aortoiliac occlusions is technically feasible under IVUS guidance and enables successful angioplasty.     

Relationship between Angiographic Late Loss and 5-Year Clinical Outcome after Drug-Eluting Stent Implantation

Purpose

Currently, insufficient data exist to evaluate the relationship between angiographic late loss (LL) and long-term clinical outcome after drug-eluting stent (DES) implantation. In this study, we hypothesized that angiographic LL between 0.3 and 0.6 mm correlate with favorable long-term clinical outcomes.

Materials and Methods

Patients were enrolled in the present study if they had undergone both DES implantation in single coronary vessel and a subsequent follow-up angiogram (n=634). These individuals were then subdivided into three groups based on their relative angiographic LL: group I (angiographic LL <0.3 mm, n=378), group II (angiographic LL between 0.3 and 0.6 mm, n=124), and group III (angiographic LL >0.6 mm, n=134). During a 5-year follow-up period, all subjects were tracked for critical events, defined as any cause of death or myocardial infarction, which were then compared among the three groups.

Results

Mean follow-up duration was 63.0±10.0 months. Critical events occurred in 25 subjects in group I (6.6%), 5 in group II (4.0%), and 17 in group III (12.7%), (p=0.020; group I vs. group II, p=0.293; group II vs. group III, p=0.013). In a subsequent multivariate logistic regression analysis, chronic renal failure [odds ratio (OR)=3.29, 95% confidence interval (CI): 1.48-7.31, p=0.003] and long lesion length, defined as lesion length >28 mm (OR=1.88, 95% CI: 1.02-3.46, p=0.042) were independent predictors of long-term critical events.

Conclusion

This retrospective analysis fails to demonstrate that post-DES implantation angiographic LL between 0.3 and 0.6 mm is protective against future critical events.