Non-invasive flow estimation in an implantable rotary blood pump: a study considering non-pulsatile and pulsatile flows.

Non-invasive estimation of flow was investigated in an implantable rotary blood pump (iRBP) with a hydrodynamic bearing. The effects of non-pulsatile and pulsatile flows were studied using in vitro mock loops, and acute (N = 3) and chronic (N = 6) ovine experiments. Using the non-pulsatile and pulsatile mock loops an average flow estimation algorithm was derived from root mean square (RMS) pump impeller speed and RMS input power. These algorithms were programmed into the iRBP controller for subsequent validation in vivo. In the acute experiments, venous return and systemic vascular resistance were adjusted through pharmacological intervention and exsanguination to produce an average range of pump flows from 0.0 to 2.6 l min(-1). Over this range the RMS estimation error was 88 +/- 12 ml, with a linear correlation slope of 0.992 +/- 0.006 (R2 = 0.986 +/- 0.004). In the chronic experiments, animals were monitored daily for up to three months and an average range of flows from 2.8 to 4.8 l min(-1) recorded. A linear correlation between the estimated and measured pump flows yielded a slope of 1.005 +/- 0.006 (R2 = 0.966 +/- 0.004). The RMS estimation error was 120 +/- 11 ml. Using this algorithm it is possible to effectively estimate flow in a rotary blood pump without implanting additional invasive sensors.

Fluid dynamics of a textured blood-contacting surface.

This study examined the fluid dynamics of a textured blood-contacting surface using a computational fluid-dynamic modeling technique. The texture consisted of a regular array of microfibers of length 50 or 100 microm, spaced 100 microm apart, projecting perpendicularly to the surface. The results showed that the surface texture served as a flow-retarding solid boundary for a laminar viscous flow, resulting in a lowered wall shear stress on the hase-plane surface. However, the maximum wall shear stress on the fibers was much higher than the shear stress on the nontextured phase plane. At all fractions of fiber height down past 10 microm, the permeability of the textured region greatly exceeded the analytically predictable permeability of an equivalent array of infinite-height fihers. The lowered suiface shear stress appears to explain in part the enhanced deposition of formed blood elements on the textured surface.

Acute cellular interaction with textured surfaces in blood contact.

Textured blood-contacting surfaces can promote the formation of a blood-compatible pseudo-neointima. We hypothesized that by controlling the surface texturing, the pseudo-neointima thickness could be controlled. The hypothesis was tested experimentally by fabricating the polyurethane textured surfaces with three different fiber lengths, and exposing them simultaneously to the flowing blood in an ovine ex vivo carotid-jugular series shunt for periods up to 4 h. The textured surface consisted of regularly spaced tapered micro-fibers of defined length on a smooth base-plane surface. Because of the simple surface topography, detailed computational fluid-dynamic modeling of the surface could be obtained as a parallel study. Experimental results showed that white cell was the predominant cell type deposited on the textured surfaces, whereas macroscopic thrombus formation occurred only in one of nine blood-contacting experiments. White cell density on the textured base-plane surface was subsequently quantified by image-analyzing the electron micrographs of blood-contacted textured surfaces. The statistical analysis of cell densities on individual textured surfaces showed effects of wall shear stress on the textured base plane (which was obtained from the fluid-dynamic modeling), the longitudinal position of the test section in the series shunt, and blood-contact time.

VentrAssist hydrodynamically suspended, open, centrifugal blood pump.

A novel design is presented for an implantable centrifugal blood pump in which hydrodynamic forces acting on tapered edges of thick blades are used to suspend the impeller. The pump has no shaft, seals, or "spiders" and has clean flow lines with no stagnant zones. At 5 L/min and 100 mm Hg differential pressure, the measured hemolysis was in the range NIH 0.002-.005 g/100 L and the system efficiency was 19%.

Computer simulation of trabecular remodeling using a simplified structural model.

A simplified three-dimensional simulation of trabecular bone remodeling has been developed. The model utilizes 441 planar structural units to represent approximately 50 mm3 of initial bone volume with 199 basic multicellular units (BMUs). The simulation takes into account trabecular perforation in the structural model. The cases of male bone remodeling with no menopause and female bone remodeling with menopause are examined from the period of simulated age 25-80 years. Menopause is arbitrarily started at age 45 and extends for 7.5 years. Zero-, first-, and second-order BMU activation responses are employed to examine how the bone would be affected by the method of increase of BMU activation during menopause. At age 80, the female bone remodeling simulation produced a bone volume loss of approximately 49% for all three activation responses. This compared to a 38% bone volume loss for the case of no menopause. For the menopause simulations, an average of about 40% of the total bone loss was due to perforation.

A novel textured surface for blood-contact.

Blood-contacting surface modifications aimed at reduction of thromboembolic complications have included the texturing of surfaces so as to promote the formation of a stable pseudo-neointima. A technique has been developed whereby a textured surface consisting of regularly spaced micro-fibres was produced on a smooth base plane. Polyurethane vascular patches with and without the textured luminal surface were fabricated and implanted bilaterally in ovine carotid arteries for 1- and 3-week implantation periods (n = 6 per period). One of 6 arteries with textured patches in the 1-week group was occluded. All other arteries were patent. At 1 week, all patent textured patches had adherent thrombus covering the entire patch surface. By 3 weeks, the thrombus had organised to form a stable pseudo-neointima. Non-textured patches at 1 week had only partial surface coverage of thrombus. At 3 weeks, 4 of 6 non-textured patches had significant red thrombus in the lumen. At 3 weeks, there was also evidence of cellular migration from artery onto both textured and non-textured patches. These findings suggest that the major role of the textured surface was as a promoter of a stabilised thrombus base onto which subsequent cellular migration and tissue healing occurred more rapidly than onto a smooth polyurethane surface.

Dysgerminoma in an Arabian filly.

A yearling Arabian filly was referred to the Veterinary Medical Teaching Hospital with a history of weight loss, profound anemia, and peritoneal effusion. At necropsy, a large, soft, mottled tan and red neoplastic mass was at the pelvic inlet replacing the left ovary. Additional tumor nodules of various sizes were disseminated throughout the mesentery, diaphragm, and serosal surfaces of the abdominal viscera. Histologically, the neoplasm had sheets of large round to polygonal cells separated into lobules by fibrous connective tissue with multifocal areas of necrosis. Tumor cells stained strongly for alkaline phosphatase. Immunohistochemically, tumor cells expressed vimentin and were negative for cytokeratin. Ultrastructurally, the neoplastic cells had a characteristic nucleolus with an elaborate reticular nucleolonema in an irregular configuration. This is the first in-depth detailed report of this very rare germ cell tumor of the ovary in horses.

Pathogenesis of vitamin (A and D)-induced premature growth-plate closure in calves.

The pathogenesis of vitamin A-induced premature growth-plate closure was investigated in calves. A progressive increase in the severity of growth-plate lesions with time and a progressive increase in the extent of growth-plate involvement was observed. There was initial loss of metachromasia from the growth plate in a region that formed a narrow horizontal band of cartilage composed of the epiphyseal growth zone and a strip of reserve-zone cartilage. Immunostaining revealed there was loss of aggrecan, decorin, and biglycan from this region; however, it was doubtful that the regional loss of proteoglycan was a major contributing factor in the pathogenesis of premature growth-plate closure. This is because this region was the vestige of cartilage that remained when growth-plate closure was almost complete. The major alteration was premature mineralization of columnar cartilage and subsequent endochondral ossification. This caused the depth of the columnar zone to be reduced. Columnar-zone cartilage cells appeared immature where the matrix became mineralized and lacked the morphology of hypertrophic chondrocytes. The depth of the reserve-cartilage zone also was reduced as matrix mineralization of the columnar zone progressed, and further reduction in columnar cartilage depth occurred. Eventually, there was matrix mineralization within the adjacent reserve cartilage. The distribution of reaction product after immunostaining with antibodies to the following proteins was described during normal endochondral ossification: aggrecan, decorin, biglycan, versican, type I collagen propeptide, type I collagen, type II collagen, osteopontin, osteocalcin, osteonectin, bone sialoprotein, and alkaline phosphatase. Biglycan, type I collagen propeptide, type I collagen, osteopontin, osteocalcin, osteonectin, bone sialoprotein, and alkaline phosphatase were localized within the cytoplasm or surrounding matrix of hypertrophic chondrocytes. In vitamin-treated calves, these same proteins were found in regions undergoing premature matrix mineralization even though the chondrocytes did not have a hypertrophic morphology. Therefore, vitamin treatment did not cause just a selective expression, but it caused expression of a large number of matrix proteins normally associated with the hypertrophic chondrocyte phenotype. Finally, completely mineralized columnar and reserve cartilage were removed by a modeling/remodeling process similar to that seen in the metaphysis.

Osteosarcoma following total hip arthroplasty in a dog.

Osteosarcoma involving the distal right femur was diagnosed in a nine-year-old female neutered Rottweiler seven years after total hip arthroplasty had been performed on that limb. The findings were consistent with a primary bone tumour and pathological fracture of the right femoral condyle with loosening of the orthopaedic implant and fracture of the polymethylmethacrylate at the distal aspect of the femoral component. Possible hypotheses to explain the association of osteosarcoma with total hip arthroplasty suggest that the neoplastic process was the result of some derangement of host tissue and the healing process or that the implants or their by-products were carcinogenic. Given the large number of total hip arthroplasties that are routinely performed in dogs, the development of a malignant lesion appears to be an extraordinary complication and may be completely coincidental.

Articular chondrocalcinosis of the humeral head in greyhounds.

Of 143 Greyhounds necropsied consecutively, 6 (4%) had chondrocalcinosis of the scapulohumeral joint; lesions were identified in 6 additional dogs. Lesions were seen exclusively in the humeral head, mainly in the plateau region. The lesions in the dogs of the initial group were unilateral, but 2 of the 6 additional dogs had bilateral lesions. Focal mineralization of articular cartilage appeared as a white raised nidus, sometimes surrounded by a translucent halo in the opaque cartilage. Circular, small translucent cartilage foci, with or without beginning mineralization, were adjacent to definitive chondrocalcinosis lesions. Chondrocyte necrosis and matrix degradation were considered to antedate appearance of matrical mineral granules; mineralization of the cartilage was considered a secondary process, but not necessarily an epiphenomenon. Scanning electron microscopy indicated that the chondrocalcinosis lesion was composed of deposits of irregularly fused stone material that, in scanning and transmission electron micrographs, was composed of irregular spheroids, 0.05 to 0.5 micron in diameter. The spheroids contained poorly formed needle-like crystals of apatite. Sparse transformation of the mineral phase into hydroxyapatite was considered to be attributable to a biological mechanism that inhibited phase transition. Cartilage degeneration and chondrocalcinosis of the plateau region of the humeral head appear to be unique lesions that develop in young Greyhounds. It is possible that these lesions are the result of the biomechanical stress of training and racing.

The significance of transient changes in trabecular bone remodeling activation.

After menopause, bone turnover is increased due to an increase in the activation of bone remodeling basic multicellular units (BMUs). The importance of changes in BMU activation to bone histomorphometry data and bone volume has not received adequate attention by many skeletal researchers. Therefore, the influence of BMU activation on the above parameters was modeled by way of computer simulation, and the results were compared to data from published post-menopausal bone loss studies. Using control theory concepts, the increase in BMU activation after menopause was modeled as a zero-, first-, or underdamped (oscillatory) second-order transient BMU activation response to the step input: the decline in estrogen. A computer simulation was developed to model the influence of these three transient BMU activation responses on quantitative histological surface parameters and bone volume. The transient BMU activation responses doubled the number of active BMUs. All three types of transient BMU activation responses produced a rapid 5% decline in bone volume due to increased remodeling space. Oscillations in bone volume and histologic surface parameters over time, similar in nature to those seen in studies of ovariectomized animals, were predicted by the simulation for the oscillatory activation response examined, underdamped second order. An oscillatory BMU activation response may explain some of the transient events during menopause. The increased coherence of BMUs created by such a response may increase the likelihood of trabecular perforations. the inherent nature of an oscillatory activation response may cause its detection to be overlooked and bone remodeling data to be misinterpreted.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxic effects of solanum malacoxylon on sheep bone.

Solanum malacoxylon (Sm), a calcinogenic plant that contains 1,25-(OH)2D3 glycoside, was administered orally to sheep. Fifty milligrams of air-dried leaves three times a week caused an increased volume density of cancellous bone within lumbar vertebrae and an increased trabecular thickness. There was little remodeling activity at the end of a 180-day treatment period, and few trabecular bone surfaces had tetracycline double labels at this time. Bone biopsies taken at the end of a 1-month treatment demonstrated increased extent of bone-forming surfaces and osteoid volume. Sm caused a mineralization defect that was transitory but resulted in unmineralized lines and foci in osteones. These remaining foci of unmineralized bone were associated with the deposition of acid mucopolysaccharide, and acid mucopolysaccharide accumulation could be identified on all bone envelopes in 30-day biopsy specimens. A similar hyperostosis in the metaphyses of rats was produced by parenteral administration of 1,25-(OH)2D3 for 10 days.

Toxic effects of Solanum malacoxylon on sheep bone.

Solanum malacoxylon (Sm), a calcinogenic plant that contains 1,25-(OH)2D3 glycoside, was administered orally to sheep. Fifty milligrams of air-dried leaves three times a week caused an increased volume density of cancellous bone within lumbar vertebrae and an increased trabecular thickness. There was little remodeling activity at the end of a 180-day treatment period, and few trabecular bone surfaces had tetracycline double labels at this time. Bone biopsies taken at the end of a 1-month treatment demonstrated increased extent of bone-forming surfaces and osteoid volume. Sm caused a mineralization defect that was transitory but resulted in unmineralized lines and foci in osteones. These remaining foci of unmineralized bone were associated with the deposition of acid mucopolysaccharide, and acid mucopolysaccharide accumulation could be identified on all bone envelopes in 30-day biopsy specimens. A similar hyperostosis in the metaphyses of rats was produced by parenteral administration of 1,25-(OH)2D3 for 10 days.

Pacing-induced dilated cardiomyopathy increases left-to-right ventricular systolic interaction.

BACKGROUND: The right ventricle (RV) receives part of its systolic pumping force from the left ventricle through systolic ventricular interaction. The purpose of this study was to determine the effects of dilated cardiomyopathy on left ventricular to right ventricular (LV-to-RV) systolic interaction. METHODS AND RESULTS: Studies were performed in six normal pigs and in six pigs in which dilated cardiomyopathy resulting in congestive heart failure (CHF) was produced with rapid ventricular pacing at 230 beats per minute for 1 week. In all pigs, we rapidly withdrew blood from the LV apex into a prosthetic ventricle in a single beat, which reduced LV systolic pressure without changing RV or LV end-diastolic pressure, and the resultant instantaneous changes in RV systolic pressure and pulmonary artery flow were determined. The LV-to-RV mean systolic interaction gain was calculated as the change from a normal beat to the instantaneous unloaded beat in mean RV systolic pressure divided by the change in mean LV systolic pressure. Mean systolic pressure gain was approximately 2 1/2 times greater (P < .05) in the CHF animals (0.103 +/- 0.018 mm Hg/mm Hg) than in the normal pigs (0.04- +/- 0.011 mm Hg/mm Hg). CONCLUSIONS: These data demonstrate that left-to-right ventricular systolic interaction is significantly greater in dilated cardiomyopathy compared with the normal heart, indicating that the contribution of the left ventricle to RV systolic pressure generation has increased. This is consistent with decreased elastance of the interventricular septum resulting in increased coupling between the ventricles.

Detecting right ventricular volume changes using the conductance catheter.

The purpose of this study was to assess the role of conductance catheter position within the right ventricle in obtaining adequate indications of phasic changes in ventricular volume. Possible applications of this technology are in rate responsive pacemakers and implantable defibrilators. The conductance catheter was placed in the right ventricle by cannulation of a jugular or femoral vein or a branch of the pulmonary artery. Position within the ventricle was documented from biplane fluoroscopy. Stroke volume was perturbed by: bolus injection of blood, vagal stimulation, venous infusion of methylcholine chloride, or isoprenaline. Four criteria were used to assess the quality of volume signals: (1) volume signal phase relative to the electrocardiogram; (2) magnitude parity of volume change from each electrode pair; (3) freedom from artifact; and (4) indication of stroke volume change during interventions. Greyhound dogs of either sex (n = 33), weight 20-32 kg. A total of 236 recordings from 14 distinct catheter positions were analyzed. Catheter positions originating from a femoral cannulation and one position from the pulmonary artery gave markedly superior volume transduction compared to those from the jugular route. Although right ventricular volume transduction was possible from all catheter trajectories, those resulting from the femoral approach were clearly superior. In the right ventricle, the inability to transduce a sufficient proportion of ventricular volume, in concert with the potential sensitivity of the catheter to atrial volume changes, may seriously limit the potential of the conductance technique in the applications envisaged.

Focal premature physeal closure (hyena disease) in calves.

Focal premature closure of long-bone physes was the cause of conformational abnormalities that affected about 1% of a herd of dairy replacement calves. Affected calves were noticed to "bunny hop" by 3 months of age, and by 6 months of age, they developed abnormal conformation characterized by short pelvic limbs. This condition resembled "hyena disease," which has been described in dairy calves in Europe and Japan. With the exception of the aforementioned abnormalities and femoropatellar joint distention, a group of 5 affected calves examined were clinically normal. At necropsy, focal to almost complete closure of physes was found in the humeri, tibias, and femurs. Cause was not established for the condition; however, it was discovered that the calves had been given supplemental vitamin A/D3 in amounts greater than 10 times those recommended.

Optimal management of a ventricular assist system. Contribution of flow visualization studies.

The Novacor (Baxter Novacor, Oakland, CA) Left Ventricular Assist System (LVAS) incorporates a versatile microprocessor based controller that permits a variety of operating modes. These include internally triggered automatic synchronous counterpulsation, electrocardiogram triggered synchronous operation, and full to empty or fixed rate asynchronous operation. The aim of this pilot study was to determine the extent to which washing of the blood contacting surfaces of the pump may be optimized by suitable choice of operating mode. Visualization of flow fields adjacent to surfaces in confined areas requires small, neutrally buoyant tracer particles for feature extraction. A novel technique using fluorescent tracer particles (100 microns), an argon laser, and a low pass optical filter has been developed for this purpose. Particle motion was tracked from video images and calculations were made of velocity. Flow visualization was performed under conditions that simulated clinically observed hemodynamic conditions, typical of the immediate post-implant period. At a given LVAS output, fluid speed in the vicinity of the inflow valve tended to increase at higher LVAS beat rates (and consequently lower LVAS stroke volumes). This and future work may well be useful in selecting the optimum modes of LVAS operation as a function of the hemodynamic status of the patient.

Fluid mechanics of left ventricular assist system outflow housings.

Using the Novacor (Baxter Novacor, Oakland, CA) Left Ventricular Assist System (LVAS) as a test bed, phasic flow patterns were analyzed for three outflow valve housing designs: 1) a triple sinus; 2) an axisymmetric concentric sinus (CS); and 3) a modified triple sinus (MS). The 21 mm Carpentier-Edwards trileaflet pericardial heart valve prosthesis was used for all experiments done on the three housing designs. The LVAS was actuated by a laboratory model of the Novacor LVAS control console, and it was connected to a mock flow loop with an adjustable afterload system to provide physiologic pressures and flows (Pao, 120/80 mmHg; pump output [PO], 2-6 L/min). Laser illuminated flow visualization techniques were used to investigate the phasic flow patterns of the housings, and the visualization derived velocity was verified by laser Doppler velocimetry at several selected points in the field. Formation of vortices behind the leaflets during the LVAS ejection phase was observed in each of the housing designs. They were well organized, and they circulated with the greatest strength in MS. These vortices tended to lie in a plane parallel to the main flow axis, with the rotational velocity increasing with the stroke volume of the LVAS. In the CS and the MS housings, a circumferential flow that provided good washing of this region was observed behind the stents.

Isolated ventricular systolic interaction during transient reductions in left ventricular pressure.

The volume and pressure of one ventricle have been demonstrated to modulate the volume and pressure in the contralateral chamber during systole and diastole. To quantitate the isolated systolic effects of left ventricular (LV) pressure on right ventricular (RV) mechanics, we rapidly withdrew blood from the LV immediately after diastole via an apex cannula during a single cardiac cycle in eight open-chest, open-pericardium anesthetized pigs (45 kg) and studied the effects on the RV. Reductions in LV pressure of up to 75 mm Hg were achieved in midsystolic without changing LV or RV diastolic volume or pressure. Resultant changes in RV flow and pressure development during these single unloaded beats may therefore be considered to result from pure systolic interaction. The instantaneous left-to-right systolic pressure gain [G(t)] was determined as the ratio of RV pressure change to LV pressure change as a function of time during systole, and the mean LV-to-RV systolic pressure gain was determined as the ratio of changes in mean systolic RV pressure to changes in mean systolic LV pressure. During LV unloading, there was an average reduction of 62.6 +/- 12.3% in the mean systolic LV pressure, which resulted in decreases of 13.6 +/- 6.4% in mean RV systolic pressure, 17.9 +/- 10.4% in RV stroke volume, and 27.0 +/- 11.3% in RV stroke work. G(t) was found to vary significantly within systole, reaching a minimum of 0.042 +/- 0.014 mm Hg/mm Hg at normalized time 0.70 of the systolic duration and a maximum of 0.079 +/- 0.029 at the end of RV ejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Chondrosarcoma in a wild great white heron from southern Florida.

A typical chondrosarcoma is reported from the nictitating membrane of a great white heron (Ardea herodius occidentalis). This is the first report of a neoplasm in a free flying ciconiiform, and was the only one found in a survey of 957 carcasses from Florida.