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Biomedical subjects

B Klitzman

Publications and source records attributed to B Klitzman.

69 records · Page 4Linked to original sources
PubMed1989

The effect of nicotinamide on microvascular density and thermal injury in rats.

The effects of nicotinamide on the microvasculature and wound healing were examined in rats subjected to thermal injury. Rats (250 g) were treated with 50 mg nicotinamide intraperitoneally twice daily for 21 days and then heart and brain biopsies were taken. Skin biopsies were removed from sites in and adjacent to the injury throughout the course of healing. Tissues were stained for alkaline phosphatase and capillary length density was determined by morphometric analysis. Significant increases were observed in the heart, brain, and dermal tissue of treated animals compared to controls. Capillary density in the injured skin was significantly greater when compared to the injured skin of saline-treated controls. The injuries of the rats that were treated systemically with nicotinamide healed significantly faster than saline-treated as determined by planimetric evaluation of the granulation bed and eschar.

Animals↗
PubMed1989

Hydrostatic pressure reduces thrombogenicity of polytetrafluoroethylene vascular grafts.

A prime factor in the thrombogenicity of synthetic materials in contact with blood is the blood-gas interface. Small pockets of gas, known as gas nuclei, are trapped within surface interstices. The resulting blood-gas interface denatures plasma proteins and activates clotting factors and platelets. Expanded polytetrafluoroethylene (ePTFE) vascular prostheses 1 mm in internal diameter were placed in saline under 6,000 psig hydrostatic pressure for 2 h in an attempt to dissolve all gas nuclei (i.e., to denucleate). Carotid-carotid bypasses were performed in rats using 280-mm lengths of ePTFE. All 10 control grafts lost patency in 5 min, whereas the 14 denucleated grafts had a median patency duration of 300 min (P less than 0.01). In 15-mm-long rat femoral artery interpositional ePTFE grafts, 90% of controls thrombosed within 10 min, whereas only 7% of denucleated grafts thrombosed over the duration of the 7-day observation period (P less than 0.001). Denucleation also resulted in a significant reduction (P less than 0.02) in 111In-labeled platelet adhesion to 36% of control. Scanning electron microscopy confirmed the reduced accumulation of platelets on denucleated grafts. These data suggest that the removal of trapped air with hydrostatic pressure significantly reduces the thrombogenicity of ePTFE microvascular prostheses and may have application to other clinical (catheters, valves, tubing, etc.) or experimental (micropipettes, electrodes, etc.) materials that interface with blood.

Animals↗
PubMed1988

Decreased thrombogenicity of vascular prostheses following gas denucleation by hydrostatic pressure.

The high rate of thrombosis of 1.0-mm polytetrafluoroethylene (PTFE) grafts has limited their use in microvascular surgery. One possible reason for this is the blood-gas interface due to entrapped air in the interstices. The present study examines the effect on patency rates of elimination of this blood-gas interface by high pressurization. Comparing pressurized and nonpressurized grafts in the same animals showed a patency rate of 100 percent at 7 days for treated grafts, while the control (nonpressurized) grafts had all clotted by 1 hour. The implications for microvascular surgery as well as vascular surgery in general are discussed.

Animals↗
PubMed1987

Routine clinical use of laser Doppler flowmeter to monitor free tissue transfer: preliminary results.

Preliminary results indicate that a new laser Doppler flowmeter is more easily understood by nursing personnel than other laser Doppler units currently available. This monitor has demonstrated its capability in identifying and predicting tissue ischemia before clinically determined failure. Further evaluation of the device is warranted to define its use more clearly in the clinical setting.

Animals↗
PubMed1987

Increased survival of skin flaps by scavengers of superoxide radical.

Elevation of rat abdominal skin flaps, followed by ligation and division of the left inferior neurovascular pedicle, resulted in only a 40% survival of the area normally perfused by the ligated artery and vein. Superoxide dismutase (SOD) (EC 1.15.1.1) administered i.v. (20,000 U/kg) 30 min before flap elevation increased survival to 52%. SOD derivatized with polyethylene glycol, which increases circulating half-life, was more effective, increasing survival to 80%. This protective effect resulted from the catalytic activity of the derivatized enzyme because inactivation by treatment with H2O2 eliminated its effect on skin flap survival. An equimolar mixture of Desferal and MnCl2, which catalyzes the dismutation of O2- in vitro, improved survival to 72%. Desferal-Fe3+, which lacks in vitro SOD activity, or Mn2+ alone did not affect the survival of skin flaps, but Desferal alone was nearly as effective as the Desferal-Mn2+ mixture. This effect of Desferal may result from acquisition of and subsequent removal of iron in vivo. These results support the view that the superoxide radical or a product derived from it plays a role in limiting the survival of island skin flaps.

Animals↗
PubMed1987

Reduced cell death in skin flaps in rats treated with difluoromethylornithine.

The beneficial effects of alpha-difluoromethylornithine (DFMO) were assessed in a model of peripheral ischemia. DFMO is an irreversible inhibitor of ornithine decarboxylase (ODC), the initial enzyme in the production of polyamines. A 7 x 7 cm rat abdominal skin flap was surgically raised based on two inferior epigastric nerve, artery, and vein pedicles. One of the pedicles was then ligated and the skin was sutured back in place. Necrosis of skin was assessed 2 and 7 days after surgery. The rats were divided into four groups: control, DFMO, DFMO + polyamines, and polyamines alone. DFMO was administered in drinking water at 0.2%. Polyamines (putrescine, spermidine, and spermine) were each administered by daily i.p. injection at a dose of 10 mg/kg. The percentage of necrosis of the area of skin at risk in controls was 65 +/- 2% (mean +/- SEM). Necrosis was significantly reduced with DFMO (19 +/- 1%), with DFMO plus polyamines (37 +/- 3%), or with polyamines alone (41 +/- 2%). Protein synthesis and ornithine decarboxylase activity in the skin were both significantly decreased by DFMO. These studies demonstrate that DFMO protects skin from ischemic damage at least in part through actions on polyamine metabolism.

Animals↗
PubMed1985

Measurement of erythrocyte velocity by use of a periodic differential detector.

An optical velocimeter employing a linear array of photodiodes has been developed and utilized for measuring erythrocyte velocities in the microcirculation. A magnified image of a microvessel is projected and aligned on a one-dimensional array of photodiodes. Photocurrent from odd-ordered diodes is summed, photocurrent from even-ordered diodes is summed, and a signal proportional to the difference between these two currents is produced by a differential amplifier. The center frequency of the output signal of the differential amplifier is proportional to the erythrocyte velocity. After lowpass filtering the output of the differential amplifier, a signal proportional to its frequency and therefore velocity is produced by a frequency-voltage converter. In vitro calibration with a moving dried smear of erythrocytes illustrated a linear relation between the output of the frequency-voltage converter and erythrocyte velocity for a wide range of velocities and magnifications. The system produces a stable zero output at zero velocity and had an estimated frequency response of greater than 40 Hz in vivo. Volumetric flow rates computed from velocity and diameter measurements at arteriolar bifurcations in the rat cremaster muscle were consistent with mass conservation.

Animals↗
PubMed1983

Oxygen transport in resting and contracting hamster cremaster muscles: experimental and theoretical microvascular studies.

Intravital microscopy of the superfused cremaster muscle was used to measure the density, diameter, length, hematocrit, red cell velocity, and red cell flux in capillaries of the pentobarbital-anesthetized hamster. Oxygen microelectrodes were used to measure oxygen tension (Po2) at a position 75-100 micrometers deep in the muscle between the venous ends of capillaries and, very importantly, at the superfusate-muscle interface. These parameters were measured in resting and contracting muscles and under three values of superfusate Po2: low (8mm Hg), medium (40 mm Hg), and high (75 mm Hg). These data were complete enough to be useful input parameters in a recently developed mathematical model of oxygen transport in exposed tissue (A. S. Popel, 1981, Math. Biosci. 55, 231-246). The model indicated that with high superfusate Po2, oxygen was supplied to the resting muscle almost exclusively from the superfusate because of the vasoconstriction and reduced blood flow. Oxygen consumption of the resting muscle was estimated to be 0.4 ml O2/100 ml tissue X min, assuming muscle oxygen consumption was uniform and independent of Po2 above 1 mm Hg. The estimated rise in oxygen consumption with exercise was four to eight times resting muscle values, which agrees with previously published data. Also, the model predicted an inlet capillary Po2 of 27 mm Hg with a low superfusate Po2, which is consistent with the few available direct measurements. The model emphasized that with measurement of the Po2 at the superfusate-tissue interface, the complex O2 transport effects of the superfusate can be accurately characterized. Measurement of this and other parameters of the model leads to a potentially useful prediction of the Po2 distribution within tissues under a variety of conditions.

Animals↗
PubMed1982

Capillary network geometry and red cell distribution in hamster cremaster muscle.

Vascular geometry and red cell distribution were examined in 133 capillaries by means of intravital microscopy in the cremaster muscle of the pentobarbital-anesthetized hamster. Significant correlations (P less than 0.01) were found between diameter and flow, length and resistance, red cell transit time and flow, and red cell flux and hematocrit. Most unexpected was the lack of correlation (P greater than 0.2) between flow and resistance, length, or hematocrit. In addition, we analyzed the relation between blood flow and red cell flux at capillary bifurcations. The red blood cells had a slight (7%), but significant (P less than 0.025), tendency to enter the branch having either higher flow, red cell velocity, or pseudoshear rate (velocity/diameter). The net effect of the preferential red cell flow was to reduce mean capillary hematocrit from 13.7% prior to the bifurcation to 13.3% in the two branches. Finally, increasing the oxygen level of the superfusate above the muscle caused vasoconstriction and an increased heterogeneity of capillary red cell flux and hematocrit, decreasing the capacity for oxygen transport to the tissue.

Animals↗
PubMed1982

Augmented tissue oxygen supply during striated muscle contraction in the hamster. Relative contributions of capillary recruitment, functional dilation, and reduced tissue PO2.

To investigate the relative contributions of alterations in blood flow, capillary density, and tissue PO2 to elevated oxygen delivery in working muscle, we conducted experiments on the suffused hamster cremaster muscle, using in vivo microscopic techniques. Muscle PO2 was measured during striated muscle twitch contraction at 1 Hz. Tissue oxygenation was changed by using suffusion solutions equilibrated with 0%, 5%, 10%, 21%, or 50% oxygen. Contraction caused an increase in capillary density (capillary recruitment), whose magnitude was related to the equilibration gas and, thus, to the suffusate PO2. Capillary recruitment first increased as the oxygen content was raised, peaked with 10% oxygen, and then diminished with higher oxygen content. Arteriolar functional dilation was also observed; when oxygen was raised above 21%, dilation was decreased. The data suggest that oxygen supply is increased primarily by arteriolar conductance changes with low suffusion solution oxygen (0% to 5%), and by capillary recruitment and increased PO2 gradients above 10% oxygen. When vasomotor tone was increased by addition of norepinephrine to the suffusion medium, the changes observed were similar to those observed when oxygen was increased. Therefore, we propose that the altered microvascular responses during vasoconstriction are a function of vascular tone rather than the levels of tissue PO2. A model is proposed which may partially explain the relations among vascular tone, functional dilation, and capillary recruitment. Our data also suggest that tissue PO2 may not be precisely regulated about a narrowly defined set point in this striated muscle but that, instead, tissue PO2 is a dependent variable controlled by the integrated effects of capillary recruitment, functional vasodilation, and altered metabolism.

Animals↗
PubMed1979

Microvascular hematocrit and red cell flow in resting and contracting striated muscle.

Microvascular hematocrit and its possible relation to oxygen supply were systematically examined. We studied the red cell volume fraction (hematocrit) in arterial blood and in capillaries under a variety of circumstances. Control capillary hematocrit averaged 10.4 +/- 2.0% (SE) and arteriolar (14.2 micrometer ID) hematocrit averaged 13.9 +/- 1.2% in cremaster muscles of pentobarbital-anesthetized hamsters. Carotid artery hematocrit was 53.2 +/- 0.6%. The low microvessel hematocrit could not be entirely explained by a high red cell flux through arteriovenous channels other than capillaries (shunting). Hematocrit was not only low at rest, but varied with physiological stimuli. A 1-Hz muscle contraction increased capillary hematocrit to 18.5 +/- 2.4%, and maximal vasodilation induced a rise to 39.3 +/- 9.5%. The quantitative relations between capillary red cell flux, arterial hematocrit, and total blood flow could be explained by a two-element model of microvascular blood flow that incorporated a relatively slow-moving plasma layer (1.2 micrometer). Such a model would generate a low microvessel hematocrit and might reduce the diffusion capacity of individual capillaries, but would not reduce time-averaged red cell flux or alter steady-state vascular oxygen supply.

Animals↗
PubMed1978

Interrelations between contracting striated muscle and precapillary microvessels.

Arterioles and capillaries in the hamster cremaster muscle were observed during electrical stimulation of striated muscle fibers in order to characterize the microcirculatory basis of functional hyperemia. When contraction was restricted to single muscle fibers, responses were variable and frequently transient. Stimulation of either small bundles of muscle fibers or the entire cremaster muscle resulted in reproducible responses typified by: 1) a latency period, 2) an early, often transient phase of dilation, and 3) a second, slower phase of dilation. The latency varied inversely with contraction frequency, and the magnitude of the dilation varied directly with contraction frequency over the range 1--8/s. With stimulation of single fibers and small groups of fibers, arteriolar vasodilation was highly localized to regions of the arterioles that were in close apposition to the stimulated fibers. The number of capillaries with red blood cell flow increased during contraction, and the increase was graded with contraction frequency. The changes observed suggest that the vascular response during functional hyperemia is a two-part process and that the control processes are influenced by contraction frequency.

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