Gastric stimulation: influence of electrical parameters on gastric emptying in control and diabetic rats

BACKGROUND: The aim of this study was to test the effect of different pulse frequencies and amplitudes during gastric stimulation (GS) on gastric emptying in the rat. METHODS: GS was performed in 2 groups of laparotomized rats: healthy control animals, and rats with acute diabetes. The effects of four pulse frequencies (0.5, 1, 10, 20 Hz) and three pulse amplitudes (5, 20, 40 mA) were tested. The volumes emptied from the stomach after the oro-gastric instillation of a nutrient solution were compared to those obtained in animals without GS. Intragastric pH values were assessed under basal conditions and after GS. RESULTS: In both groups, GS increased emptied volumes compared to conditions without stimulation (p < 0.05) for pulse frequencies above 0.5 Hz. Increases in pulse frequencies accelerated gastric emptying (p < 0.01) with a plateau at around 10 Hz. The increase in pulse amplitudes resulted in larger emptied volumes only when the pulse frequency was 1 Hz (p < 0.04) while the opposite effect was observed at 20 Hz (p < 0.04). The most effective combinations to enhance gastric emptying compared to baseline conditions were 10 Hz with 5 or 20 mA. The overall effect of GS on gastric emptying compared to baseline conditions without stimulation, was greater in diabetic than in controls rats (p < 0.05). During stimulation, intragastric pH values were not different from basal conditions during fasting or after a meal in control and diabetic rats. CONCLUSIONS: Although both pulse frequency and amplitude should be considered during GS, frequency appears to be the most critical point. The possibility of increasing gastric emptying by electrical stimulation in diabetic rats suggests potential clinical applications for this method

A novel macroencapsulating immunoisolatory device: the preparation and properties of nanomat-reinforced amphiphilic co-networks deposited on perforated metal scaffold

This paper describes the design and preparation of the non-biological components (the hardware ) of a conceptually novel bioartificial pancreas (BAP) to correct diabetes. The key components of the hardware are (1) a thin (5-10 microm) semipermeable amphiphilic co-network (APCN) membrane [i.e., a membrane of cocontinuous poly(dimethyl acryl amide) (PDMAAm)/polydimethylsiloxane (PDMS) domains cross-linked by polymethylhydrosiloxane (PMHS)] expressly created for macroencapsulation and immunoisolation of a tissue graft; (2) an electrospun nanomat of PDMS-containing polyurethane to reinforce the water-swollen APCN membrane; and (3) a perforated hollow-ribbon nitinol scaffold to stiffen and provide geometric stability to the construct. The reinforcement of water-swollen hydrogels with an electrospun nanomat is a generally applicable new method for hydrogel reinforcement. Details of device design and preparation are discussed. The advantages and disadvantages of micro- and macro-immunoisolation are analyzed, and the requirements for the ideal immunoisolatory membrane are presented. Burst pressure, and glucose and insulin permeabilities of representative devices have been determined and the effect of device composition and wall thickness on these properties is discussed

A new bioartificial pancreas utilizing amphiphilic membranes for the immunoisolation of porcine islets: a pilot study in the canine

We have developed a replaceable bioartificial pancreas to treat diabetes utilizing a unique cocontinous amphiphilic conetwork membrane created for macroencapsulation and immunoisolation of porcine islet cells (PICs). The membrane is assembled from hydrophilic poly(N,N-dimethyl acrylamide) and hydrophobic/oxyphilic polydimethylsiloxane chains cross-linked with hydrophobic/oxyphilic polymethylhydrosiloxane chains. Our hypothesis is that this membrane allows the survival of xenotransplanted PICs in the absence of prevascularization or immunosuppression because of its extraordinarily high-oxygen permeability and small hydrophilic channel dimensions (3-4 nm). The key components are a 5-10 microm thick semipermeable amphiphilic conetwork membrane reinforced with an electrospun nanomat of polydimethylsiloxane-containing polyurethane, and a laser-perforated nitinol scaffold to provide geometric stability. Devices were loaded with PICs and tested for their ability to maintain islet viability without prevascularization, prevent rejection, and reverse hyperglycemia in three pancreatectomized dogs without immunosuppression. Tissue tolerance was good and there was no systemic toxicity. The bioartificial pancreas protected PICs from toxic environments in vitro and in vivo. Islets remained viable for up to 3 weeks without signs of rejection. Neovascularization was observed. Hyperglycemia was not reversed, most likely because of insufficient islet mass. Further studies to determine long-term islet viability and correction of hyperglycemia are warranted