Previous investigations on the in vivo effects of chronic heat on tissue suggest a response where... more Previous investigations on the in vivo effects of chronic heat on tissue suggest a response whereby heated tissue temperatures decrease over time. This response occurred in conjunction with localized angiogenesis, which possibly contributed to the temperature decreases by increasing local perfusion and enhancing tissue heat transfer. Our own studies were the first to use a chronic heat source to heat tissue at initial interfacial temperatures between 40 degrees C and 46 degrees C. Initial temperatures above 45.3+/-2.2 degrees C caused necrosis of adjacent tissue. Through an adaptive response, the necrosis was removed by 7 weeks and replaced by a highly vascularized tissue capsule at 41.8+/-0.5 degrees C. The present study sought to characterize the spatial distribution, number of capillaries, and temperatures associated with this adaptive response. Heated and control muscle tissue sections were removed after 2, 4, and 7 weeks of heating at 0.08 W/cm2. Tissue layer thicknesses and capillary densities were measured and correlated with corresponding tissue temperatures. Necrosis was present adjacent to the heat source at 2 and 4 weeks; however by 7 weeks, a highly vascularized fibrous tissue capsule had replaced nearly all necrosis. Capillary densities, particularly near the heat source, were significantly greater at 7 weeks than at either 2 or 4 weeks. Capillary densities in heated tissue capillary fronts tripled from 2 to 7 weeks (106.4+/-14.3 caps/mm2 versus 39.1+/-18.5 caps/mm2). Furthermore, a mean temperature of 41.7+/-0.9 degrees C was measured in heated tissue capillary fronts at all durations, suggesting that this may be a threshold temperature for heat-induced angiogenesis or endothelial cell survival. These findings more completely characterize the perfusion component of the current mathematical model for heat transfer in tissue and will help to establish guidelines for the functional heat loss that an implantable, heat-producing device may allow.
: Pyridoxalated‐hemoglobin‐polyoxyethylene conjugate (PHP), which is made from out‐dated human re... more : Pyridoxalated‐hemoglobin‐polyoxyethylene conjugate (PHP), which is made from out‐dated human red blood cells by two major chemical modifications, namely pyridoxalation and conjugation with polyoxyethylene (POE), is currently under development as a physiological oxygen carrier. This study assessed the effects of PHP‐88 solution, which contains 8% (wt/vol) each of hemoglobin (Hb) and maltose, on renal function when it was infused 3 times every other day into the intact circulation of 8 dogs (5 dogs for the PHP group and 3 for the control group; 20 ml/kg for the first infusion, and 10 ml/kg each for the second and third infusions, at the rate of 2.5 ml/h/kg). Serial determinations of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out pre‐ and postinfusion for up to 3 months along with measurements of blood and urine analyses, urine output rate, fractional excretion of sodium (FES), and free water clearance (CH2O). The results showed that plasma colloid osmotic pressure (COP) elevated an average of 3.3 mm Hg (p = 0.0085), and GFR and RPF tended to increase by 13% (NS) and 38% (NS), respectively, immediately after the third infusion with PHP solution. Urine output rate increased during and after the infusion, and FES and CH2O also increased for 24 h after the infusion in both groups. Blood urea nitrogen, serum creatinine, and serum Na+ concentrations were not affected greatly by the infusions, but hematocrit was decreased by 8% in the PHP group, indicating approximately a 42% expansion of plasma volume. These changes were observed to return to their preinfusion levels by 1 week postinfusion. Renal histology of the PHP group obtained at 2 weeks postinfusion revealed vacuole formation in the proximal tubules which was not associated with any pathologic changes indicative of cell death or regeneration. In 4 out of 5 dogs at 3 months postinfusion (necropsy), the vacuoles were not present. Though urinary N‐acetyl β‐glucosaminidase (NAG) activity had significantly increased after infusion, it returned to the preinfusion level by 1 month postinfusion. No detrimental effect of vacuoles on the assessed renal tubular functions was confirmed in the present study. The result demonstrated that multiple infusions of PHP solutions were well tolerated in normal dogs, and the observed effects were conceived predominantly attributable to the physiological response of the kidneys to an oncotic load into the circulation, which produced plasma volume expansion.
A trileaflet valve, compression molded of Hexsyn rubber, was evaluated as a component in temporar... more A trileaflet valve, compression molded of Hexsyn rubber, was evaluated as a component in temporary blood pumps. A pair of valves was integrated into an LVAD which was tested in vitro and in vivo. The valve's hemodynamic performance was satisfactory and the blood compatibility was excellent in a three-week, in vivo experiment conducted to demonstrate performance in a short-term application. Hexsyn, which has excellent properties and produces high quality, complex components with ease of fabrication, offers a potential for low-cost blood pump valves.
ABSTRACTHuman dura mater valves of various sizes with rigid and flexible stents were tested in an... more ABSTRACTHuman dura mater valves of various sizes with rigid and flexible stents were tested in an in vitro pulsatile mock circulatory system. A 22‐mm flexible stent valve incorporating a new fabrication technique showed almost the same pressure gradient as a 28‐mm rigid stent valve. The backflow/stroke volume ratio was about 4% at a net flow of 10 L/min. One hundred and five rigid stent‐mounted dura mater valves were used in 51 pump implantations for up to 316 days. Collagen fiber degeneration began three months after implantation. Microscopic and macroscopic calcification of the valve tissue was seen in eight out of 105 valves, giving an overall incidence of 7.6%. The calcified degeneration was dystrophic in nature, not accompanied by cellular reactions, and was seen in the areas of the valve under stress. The degenerative changes were more severe in the left side than in the right side of the total artificial heart. These findings suggest that mechanical damage to the tissue plays an important role in the pathogenesis of calcification.
The Cleveland Clinic Foundation and Foster Miller Technologies have been working to develop next ... more The Cleveland Clinic Foundation and Foster Miller Technologies have been working to develop next generation pulsatile Total Artificial Hearts (TAH), and Ventricular Assist Devices (VAD) based on a common technology base. Both of our designs use the "MagScrew" actuator technology and "biolized" pusher plate blood pump technology. The result is compact, rugged pumps of high performance and biocompatibility. The TAH is now undergoing its pre-clinical readiness program, while the VAD is completing engineering development.
Previous investigations on the in vivo effects of chronic heat on tissue suggest a response where... more Previous investigations on the in vivo effects of chronic heat on tissue suggest a response whereby heated tissue temperatures decrease over time. This response occurred in conjunction with localized angiogenesis, which possibly contributed to the temperature decreases by increasing local perfusion and enhancing tissue heat transfer. Our own studies were the first to use a chronic heat source to heat tissue at initial interfacial temperatures between 40 degrees C and 46 degrees C. Initial temperatures above 45.3+/-2.2 degrees C caused necrosis of adjacent tissue. Through an adaptive response, the necrosis was removed by 7 weeks and replaced by a highly vascularized tissue capsule at 41.8+/-0.5 degrees C. The present study sought to characterize the spatial distribution, number of capillaries, and temperatures associated with this adaptive response. Heated and control muscle tissue sections were removed after 2, 4, and 7 weeks of heating at 0.08 W/cm2. Tissue layer thicknesses and capillary densities were measured and correlated with corresponding tissue temperatures. Necrosis was present adjacent to the heat source at 2 and 4 weeks; however by 7 weeks, a highly vascularized fibrous tissue capsule had replaced nearly all necrosis. Capillary densities, particularly near the heat source, were significantly greater at 7 weeks than at either 2 or 4 weeks. Capillary densities in heated tissue capillary fronts tripled from 2 to 7 weeks (106.4+/-14.3 caps/mm2 versus 39.1+/-18.5 caps/mm2). Furthermore, a mean temperature of 41.7+/-0.9 degrees C was measured in heated tissue capillary fronts at all durations, suggesting that this may be a threshold temperature for heat-induced angiogenesis or endothelial cell survival. These findings more completely characterize the perfusion component of the current mathematical model for heat transfer in tissue and will help to establish guidelines for the functional heat loss that an implantable, heat-producing device may allow.
: Pyridoxalated‐hemoglobin‐polyoxyethylene conjugate (PHP), which is made from out‐dated human re... more : Pyridoxalated‐hemoglobin‐polyoxyethylene conjugate (PHP), which is made from out‐dated human red blood cells by two major chemical modifications, namely pyridoxalation and conjugation with polyoxyethylene (POE), is currently under development as a physiological oxygen carrier. This study assessed the effects of PHP‐88 solution, which contains 8% (wt/vol) each of hemoglobin (Hb) and maltose, on renal function when it was infused 3 times every other day into the intact circulation of 8 dogs (5 dogs for the PHP group and 3 for the control group; 20 ml/kg for the first infusion, and 10 ml/kg each for the second and third infusions, at the rate of 2.5 ml/h/kg). Serial determinations of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out pre‐ and postinfusion for up to 3 months along with measurements of blood and urine analyses, urine output rate, fractional excretion of sodium (FES), and free water clearance (CH2O). The results showed that plasma colloid osmotic pressure (COP) elevated an average of 3.3 mm Hg (p = 0.0085), and GFR and RPF tended to increase by 13% (NS) and 38% (NS), respectively, immediately after the third infusion with PHP solution. Urine output rate increased during and after the infusion, and FES and CH2O also increased for 24 h after the infusion in both groups. Blood urea nitrogen, serum creatinine, and serum Na+ concentrations were not affected greatly by the infusions, but hematocrit was decreased by 8% in the PHP group, indicating approximately a 42% expansion of plasma volume. These changes were observed to return to their preinfusion levels by 1 week postinfusion. Renal histology of the PHP group obtained at 2 weeks postinfusion revealed vacuole formation in the proximal tubules which was not associated with any pathologic changes indicative of cell death or regeneration. In 4 out of 5 dogs at 3 months postinfusion (necropsy), the vacuoles were not present. Though urinary N‐acetyl β‐glucosaminidase (NAG) activity had significantly increased after infusion, it returned to the preinfusion level by 1 month postinfusion. No detrimental effect of vacuoles on the assessed renal tubular functions was confirmed in the present study. The result demonstrated that multiple infusions of PHP solutions were well tolerated in normal dogs, and the observed effects were conceived predominantly attributable to the physiological response of the kidneys to an oncotic load into the circulation, which produced plasma volume expansion.
A trileaflet valve, compression molded of Hexsyn rubber, was evaluated as a component in temporar... more A trileaflet valve, compression molded of Hexsyn rubber, was evaluated as a component in temporary blood pumps. A pair of valves was integrated into an LVAD which was tested in vitro and in vivo. The valve's hemodynamic performance was satisfactory and the blood compatibility was excellent in a three-week, in vivo experiment conducted to demonstrate performance in a short-term application. Hexsyn, which has excellent properties and produces high quality, complex components with ease of fabrication, offers a potential for low-cost blood pump valves.
ABSTRACTHuman dura mater valves of various sizes with rigid and flexible stents were tested in an... more ABSTRACTHuman dura mater valves of various sizes with rigid and flexible stents were tested in an in vitro pulsatile mock circulatory system. A 22‐mm flexible stent valve incorporating a new fabrication technique showed almost the same pressure gradient as a 28‐mm rigid stent valve. The backflow/stroke volume ratio was about 4% at a net flow of 10 L/min. One hundred and five rigid stent‐mounted dura mater valves were used in 51 pump implantations for up to 316 days. Collagen fiber degeneration began three months after implantation. Microscopic and macroscopic calcification of the valve tissue was seen in eight out of 105 valves, giving an overall incidence of 7.6%. The calcified degeneration was dystrophic in nature, not accompanied by cellular reactions, and was seen in the areas of the valve under stress. The degenerative changes were more severe in the left side than in the right side of the total artificial heart. These findings suggest that mechanical damage to the tissue plays an important role in the pathogenesis of calcification.
The Cleveland Clinic Foundation and Foster Miller Technologies have been working to develop next ... more The Cleveland Clinic Foundation and Foster Miller Technologies have been working to develop next generation pulsatile Total Artificial Hearts (TAH), and Ventricular Assist Devices (VAD) based on a common technology base. Both of our designs use the "MagScrew" actuator technology and "biolized" pusher plate blood pump technology. The result is compact, rugged pumps of high performance and biocompatibility. The TAH is now undergoing its pre-clinical readiness program, while the VAD is completing engineering development.
Uploads