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C Wagner-Mann

Publications and source records attributed to C Wagner-Mann.

9 recordsLinked to original sources

Multiple effects of ryanodine on intracellular free Ca2+ in smooth muscle cells from bovine and porcine coronary artery: modulation of sarcoplasmic reticulum function.

1. The effects of ryanodine and caffeine on intracellular free Ca2+ concentration ([Ca2+]i) were studied by use of fura-2 microfluorometry in single smooth muscle cells freshly dispersed from bovine and porcine coronary artery. 2. Bovine and porcine cells demonstrated similar sensitivities to 10 min of exposure to ryanodine in physiological salt solution (PSS), as determined by comparable dose-dependent decreases in the subsequent [Ca2+]i transient induced by 5 mM caffeine. 3. Ryanodine (10 microM) caused a significant increase in [Ca2+]i to a plateau level 27 +/- 3% and 38 +/- 4% above baseline [Ca2+]i (baseline [Ca2+]i = [Ca2+]i at 0 min) in porcine and bovine cells, respectively, when bathed in PSS. In bovine cells the time required to reach 1/2 the plateau level was only 3 min versus 6 min for porcine cells. 4. The ryanodine-induced plateau increase in [Ca2+]i was 35 +/- 5% above baseline for bovine cells bathed in 0 Ca PSS (PSS including 10 microM EGTA with no added Ca2+), but only 7 +/- 3% above baseline in porcine cells during 10 min exposure to 10 microM ryanodine. In bovine cells [Ca2+]i showed proportional increases when extracellular Ca2+ was increased from the normal 2 mM Ca2+ PSS to 5 and 10 mM. 5. Cells pretreated with caffeine in 0 Ca PSS, which depleted the caffeine-sensitive sarcoplasmic reticulum Ca2+ store, showed no increase in [Ca2+]i when challenged with 10 microM ryanodine. The ryanodine-associated increase in [Ca2+]i, which was sustained in 0 Ca PSS during the 10 min ryanodine exposure in cells not pretreated with caffeine, suggests that ryanodine releases Ca2+ from the sarcoplasmic reticulum, but also inhibits Ca2+ efflux.6. Intracellular free Ba2+ ([Ba24],) was measured with fura-2 microfluorometry to define further the Ca2" efflux pathway inhibited by ryanodine; specifically, Ba2+ is not transported by the Ca2" pump, but will substitute for Ca2" in Na+-Ca24 exchange. In porcine cells pretreated with caffeine in 0 Ca PSS to deplete the caffeine-sensitive sarcoplasmic reticulum Ca2+ store, depolarization with 80 mM K4 in 2 mM external Ba24 caused a 100 +/- 6% increase in fura-2 fluorescence ([Ba2+]j). During the 17.5 min 0 Ca PSS recovery from depolarization, exposure to 10 microM ryanodine inhibited the removal of [Ba24]i by 69 + 3% when compared with control (0 Ca PSS without ryanodine).7. It was concluded that in bovine and porcine smooth muscle cells: (a) ryanodine (> 10 microM) releases Ca24 from the sarcoplasmic reticulum; (b) ryanodine ( 10O microM) decreases Ca24 efflux, probably by inhibition of Na+-Ca2+ exchange; (c) the sarcoplasmic reticulum Ca24 store may be larger in bovine than in porcine smooth muscle cells; thus, porcine cells have a relatively greater reliance on Ca24 influx to increase [Ca2+]i.

Animals

Comparison of intranasal and intratracheal oxygen administration in healthy awake dogs.

Intranasal (IN) and intratracheal (IT) oxygen administration techniques were compared by measuring inspired oxygen concentrations (FIO2) and partial pressures of arterial oxygen (PaO2) in 5 healthy dogs at various IN (50, 100, 150, and 200 ml/kg of body weight/min) and IT (10, 25, 50, 100, 150, 200, and 250 ml/kg/min) oxygen flow rates. Intratracheal administration of oxygen permitted lower oxygen flow rates than IN administration. Each IT oxygen flow rate produced significantly higher FIO2 and PaO2 than the corresponding IN flow rate. An IT oxygen flow rate of 25 ml/kg/min produced FIO2 and PaO2 values equivalent to those produced by an IN oxygen flow rate of 50 ml/kg/min. An IT oxygen flow rate of 50 ml/kg/min produced FIO2 and PaO2 values equivalent to those produced by IN oxygen flow rates of 100 and 150 ml/kg/min. All IT oxygen flow rates greater than or equal to 100 ml/kg/min produced FIO2 and PaO2 values that were greater than FIO2 and PaO2 values produced by IN oxygen flow rates of 200 ml/kg/min. The lowest flow rates studied (50 ml/kg/min, IN, and 10 ml/kg/min, IT) produced PaO2 capable of maintaining 97% hemoglobin saturation, which should be adequate for most clinical situations. Arterial blood gas analysis and FIO2 measurements are necessary to accurately guide oxygen flow adjustments to achieve the desired PaO2 and to prevent oxygen toxicity produced by excessive FIO2.

Administration, Intranasal

Primary action of endothelin on Ca release in bovine coronary artery smooth muscle cells.

Intracellular free Ca concentrations (Cai) were determined by fura-2 microfluorometry in single freshly dispersed cells to differentiate endothelin (ET)-induced Ca release from Ca influx through voltage-gated Ca channels (VGCC). In physiological solution ET (10(-8) M) significantly (P less than 0.05) increased Cai 23 +/- 3% (+/- SE) above baseline; this increase was not significantly attenuated by 2 x 10(-4) M lanthanum, a blocker of VGCC, or Ca-free solution. When the sarcoplasmic reticulum was depleted of Ca by prolonged treatment with 5 x 10(-3) M caffeine, depolarization with 80 mM K (80K; or 30K) plus ET did not increase Cai above that induced by 80K (or 30K) in caffeine alone. In contrast, 10(-6) M BAY K 8644, instead of ET in the protocol, significantly (P less than 0.05) increased Cai above that induced by 80K (or 30K). ET released Ca from the caffeine-sensitive internal store but was not rapid and transient like caffeine-induced release, which elicited a peak Cai increase in less than 1 min; instead, release was more gradual and prolonged with Cai peaking in greater than 2 min, thus resembling the response to 10(-5) M ryanodine. With two ET exposures, either a transient nonrepeatable increase in Cai or a delayed, but sustained, increase in Cai resulted, similar to the response to ryanodine. These data indicate that in freshly dispersed bovine cells the predominant mechanism by which ET increases Cai is release of Ca from the sarcoplasmic reticulum; if any increase in L-type voltage-gated Ca influx occurred, it was minimal and matched by efflux.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Endothelin mediates Ca influx and release in porcine coronary smooth muscle cells.

Endothelin (ET)-induced changes in intracellular free Ca (Cai) in freshly dispersed coronary artery smooth muscle cells were determined using fura-2 microfluorometry to differentiate the action of ET on Ca influx vs. release from internal stores. Comparison was made with caffeine (CAF)-induced Ca release from the sarcoplasmic reticulum (SR) to determine whether ET acts on the same Ca store. In physiological external solution, ET (5 x 10(-8) M) induced a rapid (within 90 s), transient (less than 2.5-min duration) 70% increase in Cai above baseline (n = 20). Pretreatment with diltiazem (10(-4) M; n = 10) did not change the amplitude or shape of the ET-induced Cai transient. In Ca-free solution, ET elicited a Cai response similar in duration but smaller (P less than 0.05) in peak magnitude (31% increase; n = 7). CAF (5 x 10(-3) M) also elicited a rapid (less than 60 s), transient 82% increase in Cai (n = 7). In the continued presence of CAF, ET caused no change in Cai. In contrast, ET elicited a transient 69% increase in Cai (n = 8), and in the continued presence of ET, CAF caused a 24% increase in Cai. Ryanodine (5 x 10(-5) M) suppressed the subsequent ET-induced Cai transient. These data on porcine cells suggest ET induces a rapid release of Ca from a CAF- and ryanodine-sensitive store and causes rapid influx of Ca, which is different from bovine smooth muscle cells. The return of Cai to baseline values in the continued presence of ET suggests the ET-sensitive store is depleted and increased Ca efflux matches Ca influx.

Animals

Platelet function testing in the pony.

Platelet isolation techniques and platelet function were evaluated in 35 adult ponies. Platelet recovery from whole blood was consistent and the preparation of platelet rich plasma was facilitated by an enhanced erythrocyte sedimentation rate. All platelet samples aggregated in response to 10 microM ADP. However, concentrations of ADP as high as 100 microM did not elicit significant 14C-serotonin release. Collagen induced irreversible platelet aggregation and 14C-serotonin release in all samples. The threshold dose for collagen in most ponies was 1.5 micrograms. Arachidonic acid (500 microM) failed to induce irreversible platelet aggregation or 14C-serotonin release in any of the samples evaluated. Pony platelets were nonresponsive to epinephrine (5.5 microM).

Adenosine Diphosphate

Thermal and heart rate response to ultrasonic exposure in the second and third trimester dog fetus.

A total of 39 fetuses from five pregnant dogs were used in this study. Following pentobarbital anesthesia of the dams the gravid uterus was exposed and partially exteriorized. Fetal and maternal electrocardiograms were recorded, along with fetal abdominal temperatures, during ultrasound exposures of 3.4 MHz and 2, 4, 6, 8 or 12 W/cm2 (continuous wave), spatial average intensities, for 6 minutes. Baseline fetal abdominal temperatures were 35.2 +/- 1.5 (SD) degrees C. Baseline fetal heart rates were 176.8 +/- 4.3 (SD) beats per minute. These studies indicate that the product of intensity and time of exposure, under the conditions of these experiments, is directly related to increases in fetal abdominal temperature and fetal heart rate.

Animals

Pharmacodynamics and pharmacokinetics of orally administered bishydroxycoumarin in the goat.

Eight goats, 2 nontreated controls and 6 treated, were used to study the pharmacodynamics and pharmacokinetics of bishydroxycoumarin. In 5 of the 6 treated goats, there was a significant relationship between prothrombin times and drug concentrations. Activated clotting times did not change with time in either the controls or the treated goats. Five of 6 treated goats reached a plateau of drug concentration after 24 to 36 hours. Lag times for onset of pharmacologic effect ranged from 12 to 24 hours. The one goat (No. 3) that did not respond in concert with the other 5 was extremely nervous and became anorectic during the period of indoor confinement.

Animals

A comparison of standard femoral head and neck excision and femoral head and neck excision using a biceps femoris muscle flap in the dog.

Sixteen normal 20 to 30 kg dogs had standard femoral head and neck excision (8 dogs) or femoral head and neck excision with interposition of a biceps muscle flap (8 dogs). Lameness lessened at week 6, and did not differ between groups; neither group returned to a completely normal gait. Weightbearing decreased on the operated pelvic limb compared to controls (forceplate analysis). Weightbearing force of the muscle flap dogs was significantly less at weeks 6 and 16 than that of the standard femoral head and neck excision dogs. The operated limb of both groups was shortened; shortening was significantly greater for the muscle flap group. Hip extension was limited in both groups. Both groups had decreased (more acute) hip, stifle, and hock angles measured in standing position. Thigh muscle atrophy was more pronounced in the muscle flap group at week 6. More soft tissue was interposed in the muscle flap group at necropsy compared to the group with standard femoral head and neck excision, but the difference was not statistically significant. Skeletal muscle fibers were present in the interposed fibrous connective tissue of the muscle flap group, and the healed surfaces were smoother than those of the standard femoral head and neck excision group.

Animals