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Biomedical subjects

R F Tuma

Publications and source records attributed to R F Tuma.

At least 37 records · Page 2Linked to original sources

Age-related alterations in the arterial microvasculature of skeletal muscle.

This study investigated the possibility that the aging process results in alterations in the structure and/or functional reactivity of the microvessels that could contribute to increased resistance to blood flow in working skeletal muscle. Initially, latex casts were made of the cremaster muscle microvasculature in adult (12 mo) and senescent (24 mo) male Fischer 344 rats. Although the average diameter was not different between age groups, segmental length (distance between adjacent branches) increased significantly (3rd order) during aging. Additionally, in vivo experiments were performed to determine the response of the vessels to the topical application of norepinephrine and adenosine. There was no increase in vasoconstriction produced by norepinephrine; however, the vasodilation in response to adenosine declined dramatically (1st and 2nd order) with advancing age. It can be concluded that the increase in skeletal muscle vascular resistance during contraction in aged male rats could be explained by morphological changes and/or the diminished vasodilation elicited by adenosine.

Adenosine↗

Effect of ultrasound on regional cerebral blood flow in neonatal rats.

By employing a laser-Doppler flowmeter, an investigation was performed to determine whether ultrasound causes a change in regional cerebral blood flow (rCBF). rCBF in neonatal rats (age: 2-6 days postgestation) was measured before, during, and after exposure of both cerebral hemispheres to continuous-wave ultrasound (1.0 MHz) at an intensity of 2.0 W/cm2 (SATA) for a period of 5 min. After 3 min of ultrasound treatment, there was a statistically significant augmentation in rCBF (p less than 0.05) with rCBF increasing by a factor of 2.7 +/- 0.4 (mean +/- SEM) after 5 min of ultrasound. This response was demonstrated to be a transient effect, because rCBF returned to its original value 4-6 min after termination of the ultrasound treatment.

Animals↗

Influence of nitrous oxide administration and discontinuation thereof on blood flow in cerebral cortex, cerebellum and brain stem in the rat.

The effect of nitrous oxide on blood flow in the cerebral cortex, the cerebellum and the brain stem was evaluated in a rat model. Catheters were surgically implanted in advance to avoid influence from other anaesthetics. The animals were housed in a plastic tube where they were allowed to breathe spontaneously. Blood flow was determined with a microsphere technique. Animals were exposed to nitrous oxide, 75-80%, for 45 min and blood flow was measured after 15 and 45 min exposure and was compared to values obtained during room air breathing. In one animal group, nitrous oxide was administered for 45 min and blood flows were measured after 5 and 30 min withdrawal of the gas. Results showed that all animals had significant hyperventilation. In three groups CO2 had to be added to inspiratory gases to normalize arterial blood gases. This was interpreted as caused by stressful experimental conditions, not blunted by the nitrous oxide. Cortical blood flow values in the control situation were also higher than obtained in other animal studies. Despite this, nitrous oxide showed a significant vasodilation in the cerebral cortex and the brain stem at 15 min exposure. At discontinuation of nitrous oxide administration, blood flow values had decreased at 5 min.

Animals↗

Leukocyte involvement in cerebral ischemia and reperfusion injury.

Leukocytes have been postulated to contribute to cerebral ischemia and reperfusion injury. The present study implies that leukocytes have a deleterious effect in the brain following ischemia. We compared the alteration of cortical electrical activity following transient, incomplete cerebral ischemia in control and leukopenic rats by monitoring somatosensory evoked potentials and electroencephalographic activity. There was complete cessation of electroencephalographic activity, and the cortical peak of the evoked potential was abolished during ischemia in the control animals. However, when the animals were rendered leukopenic, there was maintenance of electroencephalographic activity with reduced amplitude and preservation of the cortical peak of the evoked response during the ischemic period. This indicates that when the animals are made leukopenic, even under ischemic conditions, the neurophysiologic functioning is still maintained to a certain extent.

Animals↗

Inhibition of platelet hemostatic plug formation by trigramin, a novel RGD-peptide.

Trigramin, a cysteine rich, RGD (Arg-Gly-Asp)-containing peptide from Trimeresurus gramineus snake venom (Mr 7,500) has been previously reported to inhibit fibrinogen binding to ADP-activated platelets and platelet aggregation (disassociation constant 10(-8) M). The present study demonstrates that the infusion of trigramin (17-212 micrograms/100 g body wt) significantly prolonged the bleeding time of severed mesenteric arteries in hamsters (anesthetized with 65 mg/kg pentobarbital), whereas the infusion of RGDS (Arg-Gly-Asp-Ser, 0.45-1.0 mg/100 g body wt) failed to increase the bleeding time in this model. The bleeding time immediately returned to normal after cessation of trigramin infusion. The pattern of the disappearance of 125I-labeled trigramin from the circulation fit a two-compartment model with the half-life for the fast component between 0.7 and 2.0 min and with the half-life for the slow component between 31 and 105 min. It appeared that the kidney and liver are major routes of elimination of trigramin from the circulation. The ability of trigramin to prolong bleeding time, as well as its rapid disappearance from the circulation, indicates that this peptide may be a useful compound to transiently prevent the ability of platelets to form thromboemboli without impairing their long-term hemostatic function.

Animals↗

Investigation of the source of the blue field entoptic phenomenon.

The cellular source of the blue field entoptic phenomenon was investigated in two microvascular preparations using video-microscopy with lighting conditions similar to those under which the entoptic phenomenon is visualized within the human eye. In the wing of the hibernating bat, microvascular flow was simultaneously videotaped under transmission illumination at 430 nm and under unfiltered illumination. In the rat cremaster alternating observations were made using transmission illumination at 430 nm and epi-illumination fluorescence microscopy with leukocytes rendered fluorescent by intravenous Quinacrine. In both preparations, low magnification video-microscopy using 430 nm illumination produced a field of particles, which were brighter than the background, flowing within a network of dark vessels. The appearance of the particles and their movement simulated the blue field entoptic particle motion. Under higher magnification, the particles appeared brighter than the plasma gaps between red blood cells and were demonstrated to be leukocytes by morphology, by specific staining and by typical behavioral movement. The particles were observed in terminal arteriols capillaries, and post-capillary venules where they were not obscured by red blood cells. The results of this study of two microvascular preparations strongly suggest that in the human eye the blue field entoptic phenomenon is produced by leukocytes flowing within the macular retinal microvasculature.

Animals↗

Preservation of skeletal muscle hyperemic response to contraction with aging in female rats.

In a previous investigation (Irion et al., 1987), a significant age-related decline in skeletal muscle blood flow during intermittent tetanic contractions was observed in male Fischer 344 rats. This decline in the hyperemic response to muscle contraction was accompanied by an increased fatigability of skeletal muscle of senescent male rats. In the present investigation, anesthetized female adult and senescent Fischer 344 rats were instrumented for stimulation of the plantar flexor muscles in situ, and blood flow measurement by the tracer microsphere technique. After determination of optimum length and maximum tetanic force, muscles were stimulated to contract at the rate of 120 tetani/min. No significant differences could be observed between adult and senescent females in skeletal muscle fatigability or blood flow. The only significant differences observed between senescent and younger females were a decrease in splenic blood flow and an increase in body weight. In contrast to male rats of the same age, no impairment of skeletal muscle blood flow or change in fatigability could be detected in senescent female rats.

Aging↗

The effect of intravenous lidoflazine on whole blood-induced basilar artery contraction. An in vivo study.

Lidoflazine, a piperazine derivative of known selectivity for vascular smooth muscle, was evaluated as a possible agent for prophylaxis of cerebral vascular contraction induced by subarachnoid perfusion with whole blood. Previous studies from this laboratory have indicated its efficacy in preventing basilar artery contraction induced by serotonin. The animals treated with a subarachnoid perfusion of whole blood had a mean 30% reduction in vessel diameter over the control value. Groups that were treated with 0.5 mg/kg of lidoflazine and 1.0 mg/kg of lidoflazine and then perfused with whole blood in the subarachnoid space had reductions in control diameter of 2.8% and 6.8%, respectively. One group treated with 2.0 mg/kg of lidoflazine and then perfused with whole blood actually had an increase in diameter of 6.8% over the control value. Lidoflazine, when administered intravenously at a slow rate, will not adversely lower systemic blood pressure and can prevent the contraction of cerebral vessels when the stimulus for contraction is whole blood within the subarachnoid space.

Animals↗

Age-related change in skeletal muscle blood flow in the rat.

Anesthetized adult and senescent male Fischer 344 rats were instrumented for stimulation of in situ plantar flexor muscles and blood flow measurement by the tracer microsphere technique. After determination of optimum length and maximum tetanic force, muscles were stimulated to contract at the rate of 120 tetani/min. Senescent rats displayed significantly lower muscle blood flow and greater muscle fatigue than younger rats. Infusion of a nonspecific vasodilator in resting anesthetized rats also revealed a significantly lower potential to increase muscle blood flow in the senescent rats. Lower muscle blood flow of senescent rats during muscle contractions might be responsible, at least in part, for decreased performance of muscles of senescent male rats.

Aging↗

Considerations in use of microspheres for flow measurements in anesthetized rat.

The results of single injections of different doses of microspheres (60,000, 100,000, and 375,000) demonstrated a significant reduction in measured heart and kidney blood flows as a function of the number of microspheres injected. Measured flow to other organs was unaffected by a single injection of these doses of microspheres. The injection of microspheres at a faster rate (0.8 ml/min microsphere injection; 1.0 ml/min flush) resulted in higher calculated heart flow when compared with the slow rate (0.2 ml/min microsphere injection; 0.25 ml/min flush). A significant decrease (approximately 21%) in measured blood flow to the right side of the brain that was observed in all the groups is due to the occlusion of the right carotid artery by the cannulation procedure. Intra-aortic injection of microspheres resulted in reduced measured brain blood flow when compared with intraventricular injections. Accurate and reliable heart and brain blood flows were not obtained with intra-aortic injection of microspheres. However, intra-aortic injection of microspheres does provide accurate and reliable flow measurements for more distal organs.

Anesthesia↗

The effects of nifedipine on regional vascular resistance and blood flow in the spontaneously hypertensive rat.

The purpose of the study was to compare the peripheral vascular effects of the calcium blocker nifedipine (NF) in normotensive Wistar Kyoto (WKY; n = 25) rats and spontaneously hypertensive rats (SHR; n = 28). Male eighteen week old animals were anesthetized with pentobarbital (50 mg/kg i.p.) and subjected to the radioactive microsphere technique for measurement of systemic and regional hemodynamics. While NF (30 micrograms/kg i.v. or 100 micrograms/kg i.v.) was effective in reducing resistance in all sampled vascular beds of SHR and WKY, it reduced renal vascular resistance to a greater extent in the SHR than in WKY (p less than 0.025). The data suggested a similar strain-specific effect in the SHR coronary, stomach and brain vasculatures (0.12 less than p less than 0.16). By contrast, high dose NF had a preferential effect on the skeletal muscle vasculature of WKY (p less than 0.025 for blood flow, p less than 0.16 for resistance). The findings support the premise that each calcium blocker has unique regional effects that differ between SHR and WKY.

Animals↗

Age-related changes in regional blood flow in the rat.

The purpose of this investigation was to characterize the changes in regional blood flow and central hemodynamic measures that occur in the rat as a result of the aging process. The isotope-labeled microsphere technique was used to measure cardiac output and regional blood flows in conscious and anesthetized adult (12 mo) and senescent (24 mo) Fischer 344 virgin female rats. No significant changes were observed in central hemodynamic measurements or regional blood flows in conscious rats with the exception of a 25% reduction in splenic blood flow. Pentobarbital anesthesia significantly reduced cardiac index and heart rate but elevated total peripheral resistance and mean arterial blood pressure. There was a decrease in blood flow to skeletal muscle, spleen, duodenum, stomach, and brain tissue samples and increased hepatic arterial blood flow in both age groups. The use of anesthesia caused a greater reduction in the cardiac index and brain blood flow in the senescent anesthetized rats than in the adult rats. Heart and kidney blood flows were decreased by anesthesia in the senescent rats but not in the adult rats. Skeletal muscle blood flow, however, was significantly greater in the senescent anesthetized rats than in the younger anesthetized animals. Although body weight and organ weights of the liver, spleen, kidneys, stomach, heart, and brain were significantly greater for the senescent rats, no differences could be demonstrated in tibial length or lean body mass.

Aging↗

Enhanced uptake of actinomycin D in the dog kidney by simultaneous injection of degradable starch microspheres into the renal artery.

Tritiated Actinomycin D and degradable starch microspheres were simultaneously injected into a renal artery in dogs. The spheres functioned to mechanically retard the washout of the drug from the kidney microcirculation. Degradation of the spheres by endogenous amylase resulted in the reestablishment of normal kidney blood flow within an hour after injection. Twenty-three per cent of the total amount of drug injected was retained in the kidney one hour after injection of the drug-sphere combination. When the same amount of the drug alone was selectively injected into a renal artery or given intravenously, 9% and 1.3% of the injected dose, respectively, was found in the kidney tissue one hour after injection. This procedure may be of benefit in the treatment of solid tumors, where the therapeutic ratio may be increased because of higher drug retention in the tumor tissue with a decreased availability of the drug for other sensitive tissues.

Animals↗

Blood flow in the rabbit tenuissimus muscle. Influence of preparative procedures for intravital microscopic observation.

The tenuissimus muscle in the rabbit and the cat is a suitable tissue for intravital microscopic investigation of skeletal muscle blood flow. In this study the influence of surgical procedures necessary for direct microscopic observation on the physiological state of the rabbit tenuissimus muscle was assessed by means of blood flow measurements. Mean resting blood flow was 2.8 +/0 0.8 (mean +2- S.D.) ml.min-1.100 g-1 in the left tenuissimus muscle when prepared for microscopic observation as determined by the radioactive microsphere method. This value was not significantly different from that in the intact unexposed muscle in the contralateral leg, 3.3 +/- 1.1. ml.min-1.100 g-1. Exposure of the muscle to atmospheric oxygen tension resulted in a reduction of blood flow to 0.7 +/- 0.4 ml.min-1.100 g -1, suggesting that local metabolic control mechanisms were active. The normal range of vascular control seemed to be maintained, as demonstrated by an increase in blood flow to 64.2 +/- 18.8 ml.min-1.100 g-1 during "maximal" vasodilation induced by topical application of PGE1. The tenuissimus muscle showed a marked sensitivity to mechanical stimulation. Slight stretching of the muscle, similar to what may occur during surgical preparation, resulted in an increase in blood flow to 17.5 +/- 5.7 ml.min-1.100 g-1. Flow values calculated from data obtained by direct microscopic measurements in the tenuissimus muscle agreed well with those obtained by the microsphere method.

Animals↗

Liquid ventilation: cardiovascular adjustments with secondary hyperlactatemia and acidosis.

Cardiovascular adjustments during liquid ventilation were investigated in seven cats. Cardiac output (CO) and regional blood flow were measured with radioactive microspheres during both spontaneous air breathing (control) and ventilation with fluorocarbon liquid, FC-80. CO was found to decrease 48% (P less than 0.05) during liquid breathing as compared to control. This decrease largely reflected a reduced stroke volume. Despite the decreased CO, mean arterial pressure remained unchanged, indicating a 48% increase (P less than 0.002) in total peripheral resistance (TPR). Secondary to the reduced CO and increased TPR, extensive redistribution of blood flow occurred during liquid ventilation. The arterial lactate concentration and lactate-to-pyruvate ratio (L/P) were significantly increased (P less than 0.02). Furthermore, the increase in L/P correlated with the decrease in CO (r = 0.70; P less than 0.01). In turn, the significant decrease in pH during liquid breathing was found to correlate with the increase in L/P (r = 0.85; P less than 0.001). These data clearly demonstrate signficant alterations in cardiovascular dynamics during liquid ventilation with secondary hyperlactatemia and acidosis.

Animals↗