Drug elution form porous ceramic components for threshold reduction in pacemaker applications

Abstract

Heart pacemakers are used widely in the community. They are being designed to incorporate an increasing number of functions. In addition, there is a general desire to make them smaller and more comfortable to wear. Thus there exists a need to improve the energy efficiency of stimulation, to ensure that the battery will last 5-10 years. As for all implants, when the electrode of the pacemaker lead comes in contact with tissue, the body responds with a local inflammatory reaction and the formation of a fibrous capsule (scar tissue) which makes the electrode/tissue interface less favourable for energy transfer to the cardiac muscle. Manufacturers of cardiac pacemakers have been investigating ways of improving the operating efficiency of the pacemaker by reducing the inflammation. The most effective approach was shown to be the delivery of a small amount of an anti-inflammatory steroid (dexamethasone sodium phosphate, (DSP)) close to the electrode/tissue interface (1,2). Composite electrode tips have been developed, based on this new concept, in which the electrode is combined with a polymeric collar containing the DSP. The collar is positioned immediately adjacent to the electrode. Testing in sheep has shown that composite electrode tips with drug eluting collars lower the stimulation threshold voltage by nearly 50 %, and effectively eliminate the peak in stimulation threshold voltage that is observed for electrode tips without drug eluting collars approximately two weeks after implantation. (Stimulation threshold voltage is the voltage amplitude of pacing pulse required for the implanted pacemaker to take over from the "natural" pacemaker of the heart). Stimulation thresholds for drug-eluting composite electrode tips remained low and stable for up to eighteen months duration. The concept thus showed excellent potential for a substantial reduction in the stimulation energy required. However, the silicone collars used were found to be dimensionally unstable (swelling of up to 20 % can occur). Therefore it was decided to investigate the use of collars made of a very stable material, namely the biocompatible, bio-inert ceramic aluminium oxide. One of the aims of the current work was to develop cost effective methods for producing the minute collars, i.e. without machining. One collar has the shape of a truncated cone, nominal major diameter 2.0 mm, minor diameter 1.75 mm, height 0.6 mm, with a cylindrical axial hole of O.92mrn diameter. Another collar, used in a different type of lead, has major and minor outside diameters of 2.9 and 2.7 mm respectively, an inside diameter of 2.4 mm and a height of 2.25 mm. This very thin-walled truncated cone is referred to as a ’sleeve’. Another aim was to develop methods for fabricating porous ceramic materials, with tightly controlled volume fractions of several pore sizes and shapes, to serve various applications, e.g. tissue ingrowth for improved electrode fixation, and drug elution. Yet another aim was to infuse collars made of such materials with DSP (and sleeves with a related drug, dexamethasone acetate, DA) and to assess their performance. This paper reports the results obtained.