Progressive age-associated activation of JNK associates with conduction disruption in the aged atrium.

Connexin43 (Cx43) is critical for maintaining electrical conduction across atrial muscle. During progressive aging cardiac conduction slows and becomes susceptible to disruption, predisposing to arrhythmias. Changes in Cx43 protein expression, or its phosphorylation status, can instigate changes in the conduction of the cardiac action potential. Our study investigated whether increased levels of activated c-jun N-terminal kinase (JNK) is the mechanism responsible for the decline of Cx43 protein and intercellular communication during progressive aging. We examined right atrial muscle from guinea pigs between 1 day and 38 months of age. The area of the intercalated disc increased with age concurrent with a 75% decline in total C43 protein expression and spatial re-organisation of the remaining protein. An age-dependent increase in activated-JNK correlated with a rise in phosphorylated Cx43. The data also correlated with slowing of the action potential conduction velocity across the right atria from 0.38±0.01 m/s at 1 month of age to 0.30±0.01 m/s at 38 months of age. The JNK activator anisomycin increased levels of activated JNK in myocytes and reduced Cx43 protein expression paralleling the aging effect The JNK inhibitor SP600125, was found to eradicate almost all trace of Cx43 protein from the intercalating discs. We conclude that in vivo activation of JNK increases with age leading to the loss of Cx43 protein from atrial myocytes. This progressive loss results in impaired conduction and is likely to contribute to the increasing risk of atrial arrhythmias with advancing age

Proximal Medial Gastrocnemius Release in the Treatment of Recalcitrant Plantar Fasciitis

Background: Isolated gastrocnemius contracture has been implicated as the cause of a number of foot and ankle conditions. Plantar fasciitis (PF) is one such condition that can be secondary to altered foot biomechanics as a result of gastrocnemius contracture. In this paper, we report our results with an isolated release of the proximal medial head of gastrocnemius for recalcitrant PF. Methods: We prospectively followed a consecutive series of 21 heels in 17 patients following a Proximal Medial Gastrocnemius Release (PMGR). PF was diagnosed clinically and confirmed radiologically in all cases. To be included, at least 1 year of conservative treatment must have been tried and an isolated gastrocnemius contracture confirmed clinically using Silfverskiold's test preoperatively. Outcome measures included a 5-point Likert scale as well as subjective and objective calf weakness assessments. Final followup was on average 24 (range, 8 to 36) months after the surgery. Results: Seventeen of the 21 heels (81%) reported total or significant pain relief following the surgery and none reported worsening of their symptoms. The majority did not have subjective or objective evidence of calf weakness. There were no ‘major’ complications and only one case that suffered a ‘minor’ complication. Conclusion: We believe a PMGR is a simple way of treating a patient with PF who has failed to respond to conservative management. In our series, the results were favorable, the recovery fast and the morbidity low. Level of Evidence: IV, Retrospective Case Series </jats:p

Wide-pulse, high-frequency, low-intensity neuromuscular electrical stimulation has potential for targeted strengthening of an intrinsic foot muscle: a feasibility study

Abstract Background Strengthening the intrinsic foot muscles is a poorly understood and largely overlooked area. In this study, we explore the feasibility of strengthening m. abductor hallucis (AH) with a specific paradigm of neuromuscular electrical stimulation; one which is low-intensity in nature and designed to interleave physiologically-relevant low frequency stimulation with high-frequencies to enhance effective current delivery to spinal motoneurones, and enable a proportion of force produced by the target muscle to be generated from a central origin. We use standard neurophysiological measurements to evaluate the acute (~ 30 min) peripheral and central adaptations in healthy individuals. Methods The AH in the dominant foot of nine healthy participants was stimulated with 24 × 15 s trains of square wave (1 ms), constant current (150% of motor threshold), alternating (20 Hz–100 Hz) neuromuscular electrical stimulation interspersed with 45 s rest. Prior to the intervention, peripheral variables were evoked from the AH compound muscle action potential (Mwave) and corresponding twitch force in response to supramaximal (130%) medial plantar nerve stimulation. Central variables were evoked from the motor evoked potential (MEP) in response to suprathreshold (150%) transcranial magnetic stimulation of the motor cortex corresponding to the AH pathway. Follow-up testing occurred immediately, and 30 min after the intervention. In addition, the force-time-integrals (FTI) from the 1st and 24th WPHF trains were analysed as an index of muscle fatigue. All variables except FTI (T-test) were entered for statistical analysis using a single factor repeated measures ANOVA with alpha set at 0.05. Results FTI was significantly lower at the end of the electrical intervention compared to that evoked by the first train (p < 0.01). Only significant peripheral nervous system adaptations were observed, consistent with the onset of low-frequency fatigue in the muscle. In most of these variables, the effects persisted for 30 min after the intervention. Conclusions An acute session of wide-pulse, high-frequency, low-intensity electrical stimulation delivered directly to abductor hallucis in healthy feet induces muscle fatigue via adaptations at the peripheral level of the neuromuscular system. Our findings would appear to represent the first step in muscle adaptation to training; therefore, there is potential for using WPHF for intrinsic foot muscle strengthening

Cadaveric experiments to evaluate pressure wave generated by radial shockwave treatment of plantar fasciitis

Background Shockwave treatment is increasingly used for plantar fasciitis and Achilles tendinopathy. To be effective it is believed that high pressure must be achieved in the tissues. We report on the first human cadaveric experiments to characterize pressure from radial shockwave therapy (rSWT) for plantar fasciitis. Methods The pressure from rSWT was measured in two cadaveric feet using a needle hydrophone. Maximal pressure and energy flux were calculated from the measurements. Results The pressure persisted longer than supposed, for up to 400 μs. The peak negative pressure was up to two Mega Pascal. The predicted energy in the tissue strongly depended on the time interval used in calculations. Conclusions The measured pressure may be sufficiently high to cause cavitation in the tissue, which is one of the proposed healing mechanisms associated with rSWT. The results suggest that the energy is imparted to the tissues for much longer than previously thought

Cadaveric experiments to evaluate pressure wave generated by radial shockwave treatment of plantar fasciitis

Background Shockwave treatment is increasingly used for plantar fasciitis and Achilles tendinopathy. To be effective it is believed that high pressure must be achieved in the tissues. We report on the first human cadaveric experiments to characterize pressure from radial shockwave therapy (rSWT) for plantar fasciitis. Methods The pressure from rSWT was measured in two cadaveric feet using a needle hydrophone. Maximal pressure and energy flux were calculated from the measurements. Results The pressure persisted longer than supposed, for up to 400 μs. The peak negative pressure was up to two Mega Pascal. The predicted energy in the tissue strongly depended on the time interval used in calculations. Conclusions The measured pressure may be sufficiently high to cause cavitation in the tissue, which is one of the proposed healing mechanisms associated with rSWT. The results suggest that the energy is imparted to the tissues for much longer than previously thought