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Biomedical subjects

A C Roth

Publications and source records attributed to A C Roth.

At least 37 records · Page 2Linked to original sources

Skin allograft rejection and hyperbaric oxygen treatment in immune-histoincompatible mice.

The effect of hyperbaric oxygen (HBO) as an immunosuppressive agent was evaluated by using a highly immunogenic skin allograft mouse model. Immune-histoincompatible female C57BL/6 and BALB/c mice (N = 30) were randomly assigned to three groups receiving no treatment (control group), low dose HBO treatment (two treatments once a week), and intermediate HBO treatment (two treatments 3 times/wk) 1 wk before and 2 wk after transplantation of a 1.5 x 2 cm full thickness skin allograft from the back. Rejection was observed a Day 7 and was completed 14 days after surgery in controls. Low dose and intermediate HBO treatment delayed skin allograft rejection, which was histologically confirmed.

Animals↗

Morphologic analysis of the microcirculation during reperfusion of ischemic skeletal muscle and the effect of hyperbaric oxygen.

The morphologic events in the microcirculation that lead to reperfusion injury of ischemic skeletal muscle remain incompletely understood. The purpose of this experiment was to evaluate leukocyte endothelial adherence characteristics and dynamic changes in microvessel caliber during reperfusion of an in vivo skeletal muscle ischemia preparation. In addition, the effect of hyperbaric oxygen treatment on these microcirculatory changes also was studied. An intravital microscopy preparation of a transilluminated gracilis muscle in 27 rats was used to observe a total of 101 arterioles and 63 venules (13 to 73 microns diameter). Baseline hemodynamics were videotaped for 30 minutes following muscle isolation. The animals were divided into six groups: (1) sham, no ischemia, (2) 4 hours of global ischemia only, (3) no ischemia plus hyperbaric oxygen (one 2.5 ATA/1 hour of treatment with 100% oxygen), (4) 4 hours of ischemia plus hyperbaric oxygen during ischemia, (5) 4 hours of ischemia plus hyperbaric oxygen immediately on reperfusion, and (6) 4 hours of ischemia plus hyperbaric oxygen 1 hour after reperfusion. Changes in arteriolar and venular diameters at specific times during 3 hours of reperfusion were recorded, and the number of adherent and slow-rolling leukocytes in 100-microns venular segments were counted and compared with baseline measurements. The proximity of arterioles to venules was classified as adjacent (< 15 microns) or distant (> 15 microns). No significant changes in leukocyte endothelial adherence or arteriolar diameter were noted in group 1 sham or group 3 nonischemic hyperbaric oxygen-treated rats when compared with baseline measurements. A significant increase in adherent leukocytes was observed in group 2 ischemic venules (+14.9 +/- 2.5) within 5 minutes of reperfusion, which was maintained for 3 hours. Reperfusion measurements of arteriolar diameter in group 2 ischemic muscle preparations demonstrated an initial vasodilation that was followed at 1 hour by a progressive and severe vasoconstriction (-46.9 +/- 11.3 percent at 3 hours) in arterioles adjacent to venules that was not seen in distant arterioles. The increase in adherent leukocytes seen in group 2 ischemic venules was significantly reduced by hyperbaric oxygen treatment given during ischemia (group 4) or up to 1 hour during reperfusion (groups 5 and 6). In addition, the progressive ischemic arteriolar vasoconstriction was inhibited in all groups (4, 5, and 6) treated with hyperbaric oxygen.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The effect of hyperbaric oxygen on reperfusion of ischemic axial skin flaps: a laser Doppler analysis.

This study evaluates the microvascular reperfusion of ischemic skin flaps with and without acute hyperbaric oxygen (HBO) treatment. Thirty-two axial pattern epigastric skin flaps (3 x 6 cm) in male Wistar rats were subjected to 8 hours of global ischemia by pedicle clamp occlusion. The rats were divided into the following control and two experimental groups: Control (n = 12) with ischemia, no HBO; Group 1 (n = 11) with HBO treatment (three 1.75-hour dives, 2.5 absolute atm, 100% O2) during ischemia; and Group 2 (n = 9) with HBO treatment (two 1.75-hour dives) immediately after ischemia. Laser Doppler flows were recorded in two distal standardized flap locations at 0.5, 2, 4, and 18 hours after reperfusion in control rats and Group 1 rats and at 18 hours only in Group 2 rats, using a Med-Pacific 6000 laser Doppler unit. Mean distal flap laser Doppler flows (mV) were Control: 0.5 hours = 23.2 +/- 11.9, 2 hours = 52.8 +/- 27.3, 4 hours = 53.6 +/- 32.1, 18 hours = 40.2 +/- 36.2; Group 1: 0.5 hours = 71.8 +/- 30.9 (p less than 0.05 vs. control), 2 hours = 74.3 +/- 27.3, 4 hours = 67.4 +/- 20.6, 18 hours = 79.1 +/- 40.3 (p less than 0.05 vs. control); and Group 2: 18 hours = 90.3 +/- 47.9 (p less than 0.05 vs. control). It is concluded that acute HBO treatment of ischemic rat skin flaps improves distal microvascular perfusion as measured by laser Doppler flowmetry. This effect is observed for HBO treatment given either during or immediately after prolonged global ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intermittent prophylactic treatment of recurrent vaginal candidiasis by postmenstrual application of a 500 mg clotrimazole vaginal tablet.

The therapeutic efficacy of intermittent, monthly, postmenstrual prophylaxis with a single 500 mg clotrimazole vaginal tablet (n = 33) was compared with placebo tablets (n = 29) in 62 woman (age 28.1, SD 7.2 years) with recurrent vulvovaginal candidiasis. The number of episodes of acute vulvovaginal candidiasis experienced during the year prior to inclusion was 6.3, SD 1.9. The cumulative recurrence frequency after 6 months intermittent prophylaxis with clotrimazole (30.3%) was lower (p less than 0.001) than that recorded for the women who received placebo (79.3%). After an additional 6 months observation period without treatment there was no significant difference in the cumulative recurrence frequency between the groups (clotrimazole 84.9%; placebo 86.2%). The vagina was recolonised with Candida albicans in 70% of the women after 6 months prophylactic treatment with clotrimazole and in 86% of the women who had received placebo. Thus, this study has demonstrated that postmenstrual prophylactic treatment with a single 500 mg clotrimazole vaginal tablet, applied monthly, prevents recurrence of symptoms, although it does not eliminate yeasts from the vagina.

Administration, Intravaginal↗

Effects of intravenous terbutaline on maternal circulation and fetal heart activity.

The effects of terbutaline on maternal circulation and fetal heart activity were studied in 15 healthy pregnant women admitted for external cephalic version. The two-step infusion of terbutaline (5-10 micrograms/min) resulted in increases in maternal heart rate (p less than 0.001), cardiac output (p less than 0.001), systolic arterial pressure (p less than 0.001) and pulse pressure (p less than 0.001), while diastolic arterial pressure (p less than 0.001) and total peripheral vascular resistance (p less than 0.001) were reduced. Mean arterial pressure was unchanged after the infusion. Fetal heart activity assessed by cardiotocography showed a gradual increase in baseline fetal heart rate (p less than 0.01) and an increased percentage acceleration time (p less than 0.05). Fetal movements also increased during the infusion (p less than 0.05). The terbutaline infusion had a positive inotropic effect and produced decreased systemic vascular resistance in the pregnant woman, and placental transfer of the drug resulted in increased fetal heart activity. The potential influence of the drug-induced changes in maternal hemodynamics on utero-placental perfusion require further investigation.

Adult↗

[Tissue protection by elimination of oxygen free radicals in the post-ischemic reperfusion phase].

Prolonged ischemia decreases the chances for a successful pedicled or free tissue transfer as well as for major limb replantation. Skeletal muscle is especially sensitive to periods of prolonged ischemia and reperfusion. It is now hypothesized that tissue injury occurs during reperfusion due to the formation of toxic oxygen-free radicals. A replantation model, using the rabbit hind limb tibialis anterior muscle, was developed, to assess muscle function and histological appearance following ischemic intervals of five and eight hours. Muscle strength five weeks after injury was used as a functional measurement of tissue damage. The effects of the superoxide free radical scavenger superoxide dismutase (SOD), the hydroxide radical scavenger dimethylsulfoxide (DMSO) and the xanthine-oxidase inhibitor allopurinol (ALLO), administered systemically just before reperfusion, were studied.

Allopurinol↗

The effect of acute hyperbaric oxygen therapy on axial pattern skin flap survival when administered during and after total ischemia.

The effect of hyperbaric oxygen (HBO) on axial pattern skin flap survival in male Wistar rats, when administered during and immediately following prolonged total flap ischemia, was evaluated. Eighty-one 3 x 6 cm rectangular epigastric skin flaps were elevated, and the inferior epigastric pedicle of each flap occluded for 8 hr. The animals were divided into a control and three other experimental groups: Control (n = 27) -8 hr flap ischemia, no HBO; Group (n = 21) - HBO therapy (100 percent O2--three 1.75 hr dives at 2.5 atm) during ischemia; Group 2 (n = 21) - HBO therapy (two 1.75 hr dives) following ischemia; Group 3 (n = 12) - HBO treatment during ischemia but with the flap contained in a metal-coated Mylar bag to prevent oxygen diffusion. The percentage of flap necrosis was calculated on postoperative day 6. Mean flap necrosis for controls was 28 percent (+/- 21 S.D.), while HBO treatment during ischemia or during reperfusion significantly reduced this necrosis to 9 percent (+/- 11) and 12 percent (+/- 14), respectively (p less than 0.01). The percentage of necrosis for Group 3, with the local with the local effect of HBO on the flap blocked by the diffusion barrier, was 5 percent (+/- 7), also significantly better than the controls (p less than 0.0005) but no different from the other two experimental groups. HBO treatment increases the percentage of axial pattern skin flap survival when administered during or immediately following total flap ischemia. The improved flap survival appears to be a systemic and not a local effect.

Animals↗

Experimental evaluation of oxygen free radical scavengers in the prevention of reperfusion injury to skeletal muscle.

A prolonged preoperative ischemic interval decreases the chances for successful replantation of an amputated limb. Skeletal muscle is especially sensitive to periods of prolonged ischemia. It is now hypothesized that significant tissue injury occurs during reperfusion, when oxygen-rich blood contacts anaerobic metabolites forming toxic oxygen free radicals. A replantation model, using the rabbit hind limb tibialis anterior muscle, was developed to assess muscle function and histological appearance following ischemic intervals of five and eight hours. Muscle strength five weeks after injury was used as a functional measurement of tissue damage. The effects of the superoxide free radical scavenger superoxide dismutase (SOD) and the hydroxyl radical scavenger dimethylsulfoxide (DMSO), administered systemically just before reperfusion, were studied. Muscle treated with SOD following five hours of ischemia had essentially normal strength and histological appearance; however, there was no protective effect after eight hours. DMSO treatment had no beneficial effects after five hours of ischemia, but after eight hours DMSO-treated muscle had significantly better function than untreated muscle. Histological examination confirmed the functional results. Clinical treatment of ischemic limbs with free radical scavengers before revascularization may aid in avoiding reperfusion injury and may improve survival and later muscle function.

Animals↗

Carbon dioxide exchange across the walls of arterioles: implication for the location of the medullary chemoreceptors.

The location of the medullary chemoreceptors is not conclusively established. The original experiments, which were believed to suggest a shallow surface location in the ventrolateral medulla, have been questioned because substances, particularly CO2, applied on the surface of the medulla could diffuse into small arterioles. Because the whole tissue blood flow is supplied by surface arterioles, they could transport substances from the surface into the tissue to the respiratory centers. We studied simple transport equations describing movement of CO2 in arterioles bathed by rapidly flowing cerebrospinal fluid (CSF) and arterioles in tissue perfused by capillaries. Substantial exchange of CO2 could occur across the arteriole wall for all expected sizes of vessels when the partial pressure of CO2 at the outside wall was determined by CSF. When an arteriole is surrounded by tissue, only vessels with inside diameters (ID) less than or equal to 50 micron will exchange substantial amounts of CO2 but the smallest arterioles may be nearly in equilibrium with the tissue. The CO2 gradient in tissue around the arteriole will extend approximately 1 mm. Our simple theoretical description of CO2 transport in arterioles predicts substantial exchange in precapillary vessels. CO2 picked up by the smallest surface arterioles when the medulla is perfused at a high rate with CSF will not stay in the blood past the putative depth of the chemoreceptors. In arterioles greater than 30 micron, however, the CO2 could be carried to the respiratory centers.

Arterioles↗

Nitrite-induced iron deficiency in the neonatal rat.

Neonatal rats from dams receiving 2 or 3 g NaNO2/liter in the drinking water through -gestation and lactation suffered severe microcytic anemia as well as growth retardation and high mortality. Lipemia, fatty liver damage, decreased erythropoiesis of spleen and bone marrow, and reduced plasma and tissue iron levels were noted in affected pups. These effects were all consistent with and characteristic of iron deficiency. Experiments presented here were designed to show that the maternally mediated toxicity of nitrite is actually an iron deficiency syndrome in the pups caused by inadequate iron transfer from dam to pup. It was found that administration of exogenous iron supplement to pups of treated mothers reversed the anemia and other effects of nitrite toxicity noted both in previous studies and in unsupplemented littermates. Mothers of affected pups were themselves anemic. Finally, we fully documented severe iron deficiency in pups of nitrite-treated mothers and showed that these mothers produced milk of reduced iron content. It appears then that nitrite-consuming dams have a reduced capacity to transfer iron to their pups. The nitrite-associated toxicities in the pups are actually a result of an iron deficiency.

Anemia↗

Evaluation of the developmental toxicity of sodium nitrite in Long-Evans rats.

Sodium nitrite administered in the drinking water to Long-Evans rats during pregnancy and lactation severely affected erythropoietic development, growth, and mortality in their offspring. Pregnant rats were maintained throughout gestation on 0.5, 1, 2, or 3 g NaNO2/liter. There were no significant differences between treated and control litters at birth. Thereafter, pups of treated dams on 2 and 3 g NaNO2/liter gained less weight, progressively became severely anemic, and began to die by the third week postpartum. By the second week postpartum, hemoglobin levels, RBC counts, and mean corpuscular volumes of these pups were all drastically reduced compared to controls. Blood smears showed marked anisocytosis and hypochromasia. Gross chylous serum lipemia and fatty liver degeneration were noted. Histopathology demonstrated cytoplasmic vacuolization of centrilobular hepatocytes and decreased hematopoiesis in bone marrow and spleen. Administration of 1 g NaNO2/liter resulted in hematological effects but did not affect growth or mortality. NaNO2 (0.5 g/liter) was at or near the no observed effect level. Cross-fostering indicated that treatment during the lactational period was more instrumental in producing lesions than treatment during the gestational period. The data presented are consistent with the lactational induction of severe iron deficiency in the neonate.

Animals↗

The effects of transmural transport in the microcirculation: a two gas species model.

Diffusion of oxygen and carbon dioxide across the walls of noncapillary vessels in the microcirculation has been suggested by several studies. The formulation and steady-state solutions to a nine-compartment mathematical model of the microcirculation of skeletal muscle with transmural gas diffusion in all vessels are presented. The simultaneous transport of oxygen and carbon dioxide between arterioles, capillaries, and venules, and connective and muscle tissue at rest and exercise are described. Special attention is paid to the interactions of these gases in blood. This model predicts a longitudinal intravascular gradient in oxygen tension from large to small vessel with the tension at the precapillary vessels relatively insensitive to changes in the input tension. At rest, there is significant small arteriolar oxygen flux. However, during exercise, the precapillary transmural flux of oxygen is only a small fraction of the total metabolic demand. The model predicts large noncapillary fluxes of carbon dioxide, and also that tissue PCO2 is dependent on input tensions. The model also predicts that Bohr shifts due to either changes in input PCO2 or increased precapillary PCO2 due to increased metabolism may cause physiologically significant changes in precapillary PO2. Countercurrent shunting was predicted by the model to be significant only for carbon dioxide.

Animals↗

Electrode and cuvette for rapid continuous CO2 tension and pH measurement in blood.

An electrode and cuvette system has been developed for the continuous and rapid measurement of either blood CO2 tension or pH. The CO2 electrode consists of a 1.5-mm-diameter flat-tip glass pH electrode covered by a film of carbonic anhydrase solution, over which a 25-micron-thick dimethyl silicone membrane is attached. Porous ceramic filled with 20% polyacrylamide, equilibrated with a salt solution, serves as a salt bridge between a Ag-AgCl reference electrode and the pH electrode surface. The electrode is housed in a four-port cuvette assembly. Blood from a vessel of interest is delivered to the cuvette by means of an occlusive roller pump. The cuvette maintains the electrode and blood at a constant temperature and directs a continuous jet of blood against the electrode surface. The cuvette also allows for easy and frequent calibration of the electrode with either gas or liquid standards. The 90% response time of the CO2 electrode is 3.0 s for liquids and 1.3 s for gases. Removal of the dimethyl silicone membrane and carbonic anhydrase film yields a pH electrode that can continuously measure blood pH with a 90% response time of 1.6 s.

Animals↗

Diffusional shunting in the canine myocardium.

A test for the existence of a diffusional shunt in the myocardium was performed in closed-chest, chloralose-anesthetized dogs. Coronary blood flow was varied from 0.21 to 1.17 ml/min per g with a roller pump via a stainless steel coronary perfusion cannula. Following intracoronary artery bolus indicator injection, the coronary sinus venous appearance times of hydrogen, plasma protein labeled with indocyanine green dye, and red blood cells labeled with 99mTc were measured. Venous appearance time was calculated, either as the time from injection until the indicator reached 5% of its peak venous concentration or the time from injection until 0.1% of the injected material arrived at the coronary sinus. At low coronary flow rates (0.4 sec dye appearance time) hydrogen appearance preceded by about 1 second the appearance of the intravascular 99mTc-labeled red blood cells and the dyed plasma, indicating that hydrogen traversed an extravascular shunt path from small arteries to veins. As flow was increased, this hydrogen precession was reduced, and at high flows detectable levels of hydrogen arrived in the coronary sinus after the intravascular indicators. The difference in appearance time between hydrogen and the intravascular indicators was related linearly to the dye appearance time (proportional to l/flow), as would be expected with diffusional shunting. These data indicate that there is arterial-venous shunting of hydrogen in the myocardium. Furthermore, diffusional shunting may be important in the delivery of oxygen to, or removal of carbon dioxide from, the heart.

Animals↗