Chronic implantation

In addition to the loss of GAD staining (i.e. GABA) neurons and inhibitory symmetrical synapses around an alumina focus in primates (see above), studies with a chronically implanted cortical cup over a cobalt lesion (focus) in rats show an increased release of glutamate that is associated with spiking (Dodd and Bradford 1976). 

FIGURE 3. Amphetamine increases the firing rate of a substantia nigra pars reticulata neuron in the chronically implanted, behaving rat... 

The development of acute tolerance and dependence evoked in mice by morphine can be suppressed by pretreatment with NTI. Multiple administration of either NTI or 5 NTII before and during chronic implantation with morphine pellets also substantially inhibits the development of morphine tolerance and dependence. These results suggest the use of 8 antagonists to be useful for the prevention of opioid tolerance and physical dependence without compromising the antinociceptive potency of p opioid receptor agonists (Abdelhamid et al., 1991). 

Dymond AM, Kaechele LE, Jurist JM, et al. 1970. Brain tissue reactions to some chronically implanted metals. J Neurosurg 33 574-580. 

Ward WK, Wood MD, Casey HM, Quinn MJ, Federiuk IF. The effect of local subcutaneous delivery of vascular endothelial growth factor on the function of a chronically implanted amperometric glucose sensor. Diabetes Technology and Therapeutics 2004, 6, 137-145. 

Ward WK, Troupe JE. Assessment of chronically implanted subcutaneous glucose sensors in dogs the effect of surrounding fluid masses. American Society for Artificial Internal Organs 1999, 45, 555-561. 

Wisniewski N, Rajamand N, Adamsson U, Lins PE, Reichert WM, Klitzman B, Ungerstedt U. Analyte flux through chronically implanted subcutaneous polyamide... 

In acute and first chronic implantations in rabbits, the stimulator structures showed an excellent performance. Only minor foreign body reaction occurred. The fixation support structures are located apart from the stimulation site. By this, more choices are available to fix the structure to the retina. Possible ophthalmologic fixation methods include laser scar formation and retinal tacks without affecting the ganglionic structures directly under the stimulation elec-... 

Caldum channel antagonist activity was determined in isolated rabbit ear artery rings depolarized by a high K+ concentration [7]. The duration of action in vitro (Dw) was determined by means of wash-out experiments. Rabbit ear artery rings were contracted by a submaximal concentration of calcium, and incubated with the tested compounds for 60 min. Subsequently, they were washed with saline solution until the initial contraction was restored. Dw was defined as the time required by the tissue to recover the basal effect elicited by a submaximal concentration of calcium [8], Antihypertensive activity and Dw were determined in chronically implanted spontaneously hypertensive rats (SHR) [9]. 

Encainide has been reported to cause sinus node arrest in association with prolonged sinus node recovery time (19). It also raises the pacing threshold in patients with chronic implanted pacemakers (20), although this has not been reported to increase the failure rate of pacemakers. 

The FDA has made several modifications to the tests required by Part 1 of the ISO 10993 standard for the category of surface devices that permanently contact mucosal membranes. The ISO does not require acute, subchronic, or chronic implantation tests as does FDA. FDA requires irritation, systemic toxicity, acute, subchronic, and chronic tests for external communicating devices, tissue/bone/ dentin with prolonged and permanent contact. Device manufacturers are advised to consider tests to detect chemical components of device materials that may be pyrogenic. This matrix is a framework and not a checklist and it is stressed by the FDA that necessary safety testing will be decided on a case-by-case basis. 

A good correlation exists between the ability of a drug to counteract the increase of NA in rat brain caused by a monoamine oxidase inhibitor and the reduction of self-stimulation behavior of chronically-implanted rats.l ... 

Chronically Implanted Nenroelectric Interfaces (Recording Arrays)... 

A spinout from Donoghue s and Normann s research efforts. Cyberkinetics Neurotechnology Systems, Inc., has demonstrated in pilot studies human control of cursor movement using a 4 x 4 mm 96-channel intracortical microelectrode array chronically implanted into the primary motor cortex [57]. As of this writing, they have demonstrated the abflity to record over 6 months postimplantation. 

Spiegel, E.A. and H.T. Wycis, Chronic implantation of intracerebral electrodes in humans, in Electrical Stimulation of the Brain, D.E. Sheer, Ed. 1961, University of Texas Press Austin, TX, pp. 37-44. 

McCreery, D.B., Yuen, T.G., Agnew, W.F., and BuUara, L.A. A characterization of the effects on neuronal excitability due to prolonged microstimulation with chronically implanted microelectrodes. IEEE Trans. Biomed. Eng. 1997 44 931-939. 

Finally, a panel discussion was convened where the relative merits of the different approaches to visual prosthetics were debated. The session ended with a general consensus that visual prostheses are technically feasible and that chronically implanted devices and clinical testing are a necessary next step to assess efficacy. 

One final but important point that an investigator should realize is that animals which are chronically implanted with electrodes can be tested without interference from anesthetizing drugs or stressful restraint. 

Neural electrodes are often used for chronic implant applications that demand chemical and electrical stability of materials. Yamato et al. found that PPy has limited electrical response under cyclic voltammetry because of structural defects along the CP backbone... 

M.R. Abidian, L.G. Salas, A. Yazdan-Shahmorad, T.C. Marzullo, D.C. Martin, and D.R. Kipke. In-vivo evaluation of chronically implanted neural microelectrode arrays modified with poly (3,4-ethylenedioxythiophene) nanotubes. In Proceedings of the 3rd International IEEE EMBS Conference on Neural Engineering Kohala Coast, Hawaii, USA, 2007. 

The packaging of the pressure transducer is also a problem that needs to be addressed, especially when the transducer is in contact with blood for long periods of time. Not only must the package be biocompatible, but it also must allow the appropriate pressure to be transmitted from the biological fluid to the diaphragm. Thus, a material that is mechanically stable under corrosive and aqueous environments in the body is needed. Chronically implanted objects are usually coated with a fibrous capsule by the body as a part of the foreign body response, and this capsule can exert a force on the pressure sensor that will affect its baseline pressure. Thus, it is important to package pressure sensors with materials that will minimize this encapsulation. 

Maynard, E.M., Fernandez, E., Normann, R.A. A technique to prevent dural adhesions to chronically implanted microelectrode arrays. J. Neurosci. Methods 97, 93-101 (2000)... 

Bongiorni MG, DI Cori A, Zucchelli G et al (2010) A modified transvenous single mechanical dilatation technique to remove a chronically implanted active-fixation coronary sinus pacing lead. Pacing Clin Electrophysiol [Epub ahead of print]... 

Love CJ, Wilkoff BL, Byrd CL et al (2000) Recommendations for extraction of chronically implanted transvenous pacing and defibrillator leads indications, facilities, training. Pacing Clin Electrophysiol 23(4) 544-551... 

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