Tedd A. Brandon

Calcium alginate gel: A biocompatible and mechanically stable polymer for endovascular embolization

The development and optimization of calcium alginate for potential use in endovascular occlusion was investigated by testing its in vitro and in vivo mechanical stability and biocompatibility. The compressive resistance, rheology, and polymer yield of reacted alginate, and the polymer viscosity of unreacted alginate, were assessed. Biocompatibility was tested by injecting calcium alginate into the kidney capsule of rats. The reactivity of alginates with various structures and levels of purity were compared visually and histologically. Results suggest that calcium alginate is a biocompatible and mechanically stable gel for endovascular applications. Purified alginates exhibited compressive strength of 22 kPa and above at 40% compression, with no significant loss in elasticity. Purified alginate strength was significantly higher than that of crude alginates (p < 0.08). Purified alginates also exhibited significantly lower tissue reaction than crude alginates (p < 0.05). Of the alginates tested, purified high guluronic acid alginates (PHG) exhibited optimal strength and polymer yield, increased biocompatibility, and decreased viscosity. Clinical embolization treatments may be improved with the development of stable and biocompatible polymers such as calcium alginate. Possible uses of improved endovascular polymers include treating arteriovenous malformations (AVMs), aneurysms, blood flow to tumors, and vascular hemorrhaging.

Thermoelectric enzyme sensor for measuring blood glucose

A new calorimetric sensor has been developed which employs a thin-film thermopile in association with an immobilized enzyme. The thermopile detects the minute temperature rise that occurs when a specific chemical substrate is catalyzed by the enzyme. A prototype sensor is described which generates an equivalent proportional voltage response to glucose concentrations present in either buffer solution or blood. These sensors have remained useful for up to 18 days when operated intermittently for measuring glucose in buffer solutions, or for up to 4 days when operated continuously. When implanted inside cardiovascular shunts on anesthetized dogs, the sensors responded appropriately to changes in the blood glucose concentration.

In vivo evaluation of injectable thermosensitive polymer with time-dependent LCST

The focus of this study was to examine the biocompatibility, time-dependent LCST, and bioerodable properties of a copolymer system composed of NIPAAm, dimethyl-gamma-butyrolactone (DMBL), and acrylic acid (AAc). Sprague Dawley rats were subcutaneously injected with 25 wt % solutions of poly(NIPAAm-co-DMBL-co-AAc). At predetermined times, animals were sacrificed and polymer implants were recovered for characterization via 1H-NMR. In addition, polymer-contacting tissue sections were harvested and processed for histology. The biocompatibility of the implants was assessed by counting the number of fibroblasts and leukocytes present at the tissue-implant interface. The LCST data obtained from the in vivo implants was shown to agree with that of in vitro findings. Implant mass was shown to decrease after 4 days, indicating accelerated diffusion rates with increased implant swelling, hydrolytic degradation was confirmed with 1H-NMR measurements. The cellular presence at the copolymer implant-tissue interface was shown to return to that of normal tissue 30 days postimplantation, which suggests a normal wound healing response.

The lack of transplacental movement of the cyanide antidote thiosulfate in gravid ewes

UNLABELLED A previous study reported that the co-infusion of IV sodium thiosulfate (STS) with sodium nitroprusside (SNP) to near-term gravid ewes prevented both maternal and fetal cyanide toxicity. We questioned whether maternally administered STS crossed the ovine placenta to enhance fetal transulfuration of cyanide, or whether the fetus was dependent on maternal detoxification of cyanide after diffusion of cyanide into the maternal circulation. Ten anesthetized, near-term gravid ewes underwent hysterotomies with delivery of fetal heads for venous catheterization. Five control ewes received IV isotonic sodium chloride solution, whereas five experimental ewes received IV STS (50 mg/kg over 15 min). Serial plasma thiosulfate concentrations in ewes and fetuses were measured over 135 min. Areas under the time-plasma thiosulfate concentration curves were calculated for experimental and control ewes at 2758+/-197 and 508+/-74 min x mg(-1) x L(-1), respectively (P < 0.008). Mean areas under the curve for experimental and control fetuses were 236+/-34 and 265+/-23 min x mg(-1) x L(-1), respectively (P > 0.5). Maternally administered STS may prevent fetal cyanide poisoning from SNP administration without relying on STS crossing the placenta into the fetal circulation. Fetal cyanide may cross down a concentration gradient from fetal to maternal circulation, to be transulfurated to thiocyanate in maternal tissues. IMPLICATIONS We evaluated the mechanism of action of sodium thiosulfide (STS) in sodium nitroprusside-induced cyanide toxicity in the ewe. Fetal cyanide poisoning is alleviated by maternal administration of STS, although this cyanide antidote apparently does not cross the placenta.

Performance of a Hydrogel Composite Pericardial Substitute After Long-term Implant Studies

A novel composite patch has been tested as a pericardial substitute to reduce adhesion formation after cardiac surgery. The patch consists of poly 2-hydroxyethyl methacrylate (pHEMA) hydrogel reinforced with a polyethylene terephthalate (PET) mesh. The hydrogel-PET composite pericardial patches were implanted in canines for 6, 9, and 12 months. Upon termination, adhesion formation and epicardial reaction to the implant were rated. No adhesions formed between the patch and the native pericardium or epicardium. A thin fibrous layer on the epicardium progressively developed where the patch contacted the heart. The coronary anatomy remained visible. Histologically, the response to the implant was fibrous in nature. No significant signs of cellular inflammation were found. The gross appearance of the retrieved patches was nearly identical to that of preimplant patches. Mechanical tests showed no significant changes (alpha = 0.05) in patch strength or stiffness. Hydrogel water content initially increased during implantation. The thickness of the patch did not change significantly (alpha = 0.05) throughout the study. Scanning electron microscopy (SEM) revealed unequal layers of hydrogel on either side of the PET mesh and cracks in the hydrogel surfaces of retrieved patches. Both SEM and light microscopic observation of the patches showed traces of calcification in patches in the 9 and 12 month studies.

Rapid switching between transverse electrode pairs within a biphasic shock lowers implantable defibrillator thresholds

In order to minimize energy requirements and prolong the lifetime of implantable cardioverter-defibrillators (ICDs), it is necessary to optimize the delivered waveform without compromising defibrillation efficacy. Four electrodes were implanted on, in, and near the heart of nine pigs, Results indicate that by rapidly switching between sequential electrode pairs within each phase of a single biphasic shock 2, 4, or 8 times, significantly lower energies are needed for defibrillation.

Progressive pressure expansion in skeletal muscle ventricle conditioning.

Skeletal muscle ventricle (SMV) conditioning typically results in reduced muscle performance. This study investigated the effects of progressive SMV resting pressure expansion and dynamic muscle training on SMV pumping capability. SMVs were formed from latissimus dorsi muscle in five goats. Three experimental SMVs were conditioned against a compliant pneumatic implant system. SMV resting pressure was progressively increased as the SMV adapted to each increment. Resting pressure rose from 40 to 100-120 mmHg over an 8 week period of time. Two control SMVs were conditioned against a non expanded incompressible implant. Both experimental and control SMVs were electrically burst stimulated for at least 6 weeks after an initial 2 week vascular delay interval. Results demonstrate that 1) experimental SMVs increased in volume; 2) SMV passive and active (evoked isovolumetric pressure) pressure-volume curves adapted to the increasing or static resting volume; and 3) two of three experimental SMVs generated greater stroke volumes than control SMVs across a range of counterpulsation pressures and electrical stimulation parameters. Progressive pressure expansion using a compliant implant system improved final SMV pumping performance and merits further investigation.

Circumferential switching between multiple electrode pairs within a biphasic shock lowers implantable defibrillator thresholds

In order to maximize the efficiency of implantable cardioverter-defibrillators (ICDs) it is important to optimize the waveform and electrode placement so as to minimize the energy necessary for successful defibrillation. We placed six electrodes in, near, and on pig hearts in order to explore the efficacy of dividing a biphasic waveform into a series of pulses delivered to four quadrants of the heart so as to more evenly distribute current. Each phase of the waveform was split into four or eight pulses. It was found that dividing the shock into pulses and distributing current around the heart reduced the average voltage and energy required for defibrillation.

Selective electrical stimulation of latissimus dorsi muscle

In this paper we describe a novel electrical stimulation approach that can potentially increase the efficiency with which skeletal muscle can be used to provide power for cardiac assistance. Results are presented from acute animal studies in which a nerve cuff electrode array is used to selectively stimulate the three functionally distinct regions of the latissimus dorsi muscle.

Hemodynamic responses to 6 degree head-down rest in dogs: effect of aerobic conditioning.

The -6 degree head-down position is used in humans to produce fluid shifts that resemble those occurring in microgravity. Alternative animal models of microgravity may be helpful for extensive exploration of this unique condition. The dog may be a viable candidate. Sixteen dogs were assigned to one of three conditions: anesthetized open chest, anesthetized closed chest, and awake. Dogs in groups 1 (N = 6) and 2 (N = 6) were divided into an exercise or a sedentary treatment, and dogs in group 3 (N = 4) served as their own controls. Following instrumentation the dogs were put in the head-down position for 1 h. Measurements included right atrial pressure, heart rate, and mean arterial pressure for all groups, left ventricular pressure and LV dp/dt for group 1, and cardiac output and iliac flow for group 2. Right atrial pressure increased for all groups. Heart rate demonstrated non-significant changes over time or group. Significant differences were noted for mean arterial pressure, left ventricular pressure and LV dp/dt for exercise condition in response to HDR. It appears that -6 degrees of head-down rest produces similar cardiovascular responses in dogs as those observed in humans and that exercise has a minor effect on those responses.