Inducing Muscle Heat Shock Protein 70 Improves Insulin Sensitivity and Muscular Performance in Aged Mice.

Heat shock proteins (HSPs) are molecular chaperones with roles in longevity and muscular preservation. We aimed to show elevating HSP70 improves indices of health span. Aged C57/BL6 mice acclimated to a western diet were randomized into: geranylgeranylacetone (GGA)-treated (100 mg/kg/d), biweekly heat therapy (HT), or control. The GGA and HT are well-known pharmacological and environmental inducers of HSP70, respectively. Assessments before and after 8 weeks of treatment included glycemic endpoints, body composition, and muscular endurance, power, and perfusion. An HT mice had more than threefold, and GGA mice had a twofold greater HSP70 compared with control. Despite comparable body compositions, both treatment groups had significantly better insulin sensitivity and insulin signaling capacity. Compared with baseline, HT mice ran 23% longer than at study start, which was significantly more than GGA or control. Hanging ability (muscular endurance) also tended to be best preserved in HT mice. Muscle power, contractile force, capillary perfusion, and innervation were not different. Heat treatment has a clear benefit on muscular endurance, whereas HT and GGA both improved insulin sensitivity. Different effects may relate to muscle HSP70 levels. An HSP induction could be a promising approach for improving health span in the aged mice.

Benefits of standardizing the treatment of arrhythmias in the sheep (Ovis aries) model of chronic heart failure after myocardial infarction.

Large animal models of heart failure are essential in preclinical device testing. In sheep, catheter-based coil embolization of the left anterior descending and diagonal artery provides a minimally invasive and reproducible model of myocardial infarction (MI). Although widely used, this model has historically been plagued with a 30% mortality rate, both in the literature and in our own experience. Our study endeavored to decrease the mortality rate by targeting the most common cause of death, intractable arrhythmias, during creation of the ovine MI model. To this end, we evaluated 2 methods of managing perioperative antiarrhythmic therapy and cardiopulmonary resuscitation during model creation. The first group of sheep was managed at the discretion of the individual operator, whereas the second group was treated according to a standardized protocol that included mandatory pretreatment with amiodarone. Sheep experiencing life-threatening arrhythmias, most commonly ventricular fibrillation, were either resuscitated according to operator-driven instructions or the standardized protocol. By comparing these 2 treatment groups, we have shown that using a standardized protocol is advantageous in reducing mortality associated with the ovine MI model. Since implementing the standardized protocol, our laboratory has lowered the expected mortality rate to 10% during catheter-based induction of ovine MI and has greatly reduced the number of animals required for study needs. In addition, the standardized protocol has proven beneficial in training new staff members. By implementing this standardized method of model management, the outcomes of model creation have been optimized.

In vivo intravascular ultrasound analysis of the absorption rate of the Angio-Seal vascular closure device in the porcine femoral artery.

AIMS: Device-based arterial closure is currently used to achieve haemostasis following percutaneous intervention. Little is known about the in vivo patterns of device absorption. We aimed to characterise the absorption dynamics following implantation of the Angio-Seal VIP closure device (AVCD) (St. Jude Medical, St. Paul, MN, USA) by using serial intravascular ultrasound (IVUS) and histology. METHODS AND RESULTS: Eleven AVCD were implanted following 6 Fr femoral arterial sheath in six pigs. Using carotid access, angiograms and IVUS were performed at baseline, 3, 5, 7, 14, 30 and 42 days following deployment. At termination, arteries were processed for histology at 14 (n=3), 30(n=4) and 42 days (n=4). By IVUS, following implantation the intravascular component (IC) area remained unchanged up to 14 days and decreased by 50% at 30 days and 95% by 42 days. By histology, there was a progressive decline in the IC area at 14 days and decrease by 30% at 30 days and 77% by 42 days. Histology demonstrated almost complete absorption of the IC and no signs of severe chronic granulomatous inflammation. CONCLUSIONS: IVUS serial imaging demonstrated almost complete absorption of the IC by 42 days in normal porcine femoral arteries. There was no evidence of severe chronic granulomatous vascular inflammation demonstrated by histology.