The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes

Objective: The purpose of this study was to investigate the properties of the slow component of the delayed rectifier potassium current (I-Ks) in myocytes isolated from undiseased human left ventricles. Methods: The whole-cell configuration of the patch-clamp technique was applied in 58 left ventricular myocytes from 15 hearts at 37 degreesC. Nisoldipine (1 muM) was used to block inward calcium current (I-Ca) and E-4031 (1-5 muM) was applied to inhibit the rapid component of the delayed rectifier potassium current (I-Ks). Results: In 31 myocytes an E-4031 insensitive, but L-735,821 and chromanol 293B sensitive, tail current was identified which was attributed to the slow component of I-K (I-Ks). Activation of I-Ks was slow (tau = 903 +/- 101 ms at 50 mV, n = 24), but deactivation of the current was relatively rapid ( tau =122.4 +/- 11.7 ms at -40 mV, n = 19). The activation of I-Ks was voltage independent but its deactivation showed clear voltage dependence. The deactivation was faster at negative voltages (about 100 ms at -50 mV) and slower at depolarized potentials (about 300 ms at 0 mV). In six cells, the reversal potential was -81.6 +/- 2.8 mV on an average which is close to the K+ equilibrium potential suggesting K+ as the main charge carrier. Conclusion: In undiseased human ventricular myocytes, I-Ks exhibits slow activation and fast deactivation kinetics. Therefore, in humans I-Ks differs from that reported in guinea pig, and it best resembles I-Ks described in dog and rabbit ventricular myocytes

Adjunctive role of manual lymph drainage in the healing of venous ulcers: A comparative pilot study

Compression therapy plays a pivotal role in the treatment of venous leg ulcers and clinical observations include lymph stasis as contributing to the maintenance of chronic wounds. This finding raises the question whether further improvement in lymph circulation with manual lymph drainage (MLD) as a part of complex decongestive physiotherapy (CDP) can improve ulcer healing. We examined whether CDP improves healing of venous leg ulcers and compared the efficacy of CDP with that of multilayered compression with short-stretch bandages. Eight patients (mean age: 64.8 years, mean ulcer area: 23.07 cm2, duration of ulcers: 25.37 months) were treated with a 5-day-course of CDP and 9 patients (mean age: 70.77 years, mean ulcer area: 21.47 cm2, duration of ulcers: 15.8 months) were included in a 10-day-course of CDP. Control goup consisted of 9 patients (mean age: 56.33 years, mean ulcer area: 13.87 cm2, duration of ulcers: 6.11 months) receiving multilayered compression. Wound surface measurement was carried out on days 5 and 10 and ulcer area reduction rate was calculated as area (initial)-area (final)/time unit. There was no statistical difference between the 5-daycourse of CDP and compression of the same duration regarding ulcer healing (t=-1.62, df=15, p= 0.125). A 10-day-course of CDP significantly increased ulcer healing compared to compression of the same duration (t=-2.42, df=16, p= 0.039). Our preliminary results suggest that MLD as a part of CDP supports healing of venous leg ulcers

The cellular electrophysiologic effect of a new amiodarone like antiarrhythmic drug GYKI 16638 in undiseased human ventricular muscle: comparison with sotalol and mexiletine

The cellular electrophysiologic effect of GYKI 16638, a new antiarrhythmic compound was studied and compared with that of sotalol and mexiletine in undiseased human right ventricular muscle preparation by applying the conventional microelectrode technique. GYKI 16638 (5 muM), at stimulation cycle length of 1000 ms, lengthened action potential duration (APD(90)) from 338.9 +/- 28.6 ms to 385.4 +/- 24 ms (n = 9, p < 0.05). This APID lengthening effect, unlike that of sotalol (30 muM), was rate-independent. GYKI 16638, contrary to sotalol and like mexiletine (10 muM), exerted a use-dependent depression of the maximal rate of depolarization (V-max) which amounted to 36.4 +/- 11.7 % at cycle length of 400 ms (n = 5, p < 0.05) and was characterised with an offset kinetical time constant of 298.6 +/- 70.2 ms. It was concluded that GYKI 16638 in human ventricular muscle shows combined Class IB and Class III antiarrhythmic properties, resembling the electrophysiological manifestation seen after chronic amiodarone treatment

Diagnosis and treatment of primary lymphedema consensus document of the international union of phlebology (IUP)-2013

Primary lymphedema can be managed effectively as a form of chronic lymphedema by a sequenced and targeted treatment and management program based around a combination of Decongestive Lymphatic Therapy (DLT) with compression therapy, when the latter is desired as an adjunct to DLT. Treatment in the maintenance phase should include compression garments, self-management, including self-massage, meticulous personal hygiene and skin care, in addition to lymphtransport-promoting excercises and activities, and, if desired, pneumatic compression therapy applied in the home. When conservative treatment fails, or gives sub-optimal outcomes, the management of primary lymphedema can be improved, where appropriate, with the proper addition of surgical interventions, either reconstructive or ablative. These two surgical therapies can be more effective when fully integrated with manual lymphatic drainage (MLD)-based DLT postoperatively. Compliance with a long-term commitment to MLD/DLT and particularly compression postoperatively is a critical factor in determining the success of any new treatment strategy involving either reconstructive or palliative surgery. The future of management of primary lymphedema has never been brighter with the new prospect of gene-and perhaps stem-cell oriented management