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Biomedical subjects

D R Gross

Publications and source records attributed to D R Gross.

At least 19 recordsLinked to original sources

N omega-nitro-L-arginine blocks the second phase but not the first phase of the endothelium-dependent relaxations induced by substance P in isolated rings of pig carotid artery.

Endothelium-dependent relaxations can be evoked by a variety of stimuli, among them substance P (SP), which is found in sensory nerve fibers supplying the adventitia-media junction of most muscular arteries. This study determined the role of endothelium-derived nitric oxide as a mediator of endothelium-dependent relaxations to SP in isolated rings of the pig carotid artery suspended in organ chambers for isometric tension recording. SP (10(-12)-10(-7) M) caused concentration-dependent relaxations of arteries precontracted with norepinephrine (10(-7) M). The relaxations were characterized by a partially transient relaxation (phase 1) and a sustained relaxation of the artery (phase 2). The inhibitor of nitric oxide formation, N omega-nitro-L-arginine (L-NNA) methyl ester caused a gradual increase in tension, the phase I response at 3 x 10(-10) to 3 x 10(-7) M SP was shifted to the right, but the maximal relaxation was comparable in the presence of L-NNA. However, the sustained relaxation after addition of substance P (phase II) was lost and tension in the presence of L-NNA returned to a level above that induced by L-NNA and norepinephrine (10(-9) M). These results suggest that the endothelium-dependent relaxations to SP, particularly the prolonged relaxation (phase II), are due to de novo synthesis of nitric oxide and hence fully abolished by a specific inhibitor.

Animals

Evaluation of hypercholesterol diet-induced changes in viscoelastic properties of carotid circulation in pigs.

Measurements of pulsatile pressure and flow at the input of the left and right carotid arteries and a new lumped parameter model were used to quantify changes in the overall dynamic mechanical properties of the carotid circulation between five control diet-fed pigs and five pigs fed a hyperlipidemic diet for 16 wk. The model represents the portion of the circulation supplied by either the left or the right carotid artery and is characterized by five parameters: peripheral resistance (Rp), an overall inertance (L), and an overall frequency-dependent compliance constituted by a capacitor C (static compliance) in series with a Maxwell section, i.e., a capacitor Cd, in parallel with a resistor Rd. Rp was calculated as the ratio between mean pressure (P) and mean flow (Q). The other four parameters were estimated by fitting measured to model predicted flows. The average static compliance was reduced by 40% (P = 0.01) between normal (P = 62.0 +/- 4.3 mmHg) and hyperlipidemic diet-fed pigs (P = 62.7 +/- 4.7 mmHg). A significant reduction in the overall cross-sectional area was inferred from a 53% increase (P = 0.05) in L, whereas resistance vessel tone was unchanged as judged from estimates of Rp. No signs of occlusive disease were found in any of the animals.

Animals

Three-dimensional tissue deformation in subcutaneous tissues overlying bony prominences may help to explain external load transfer to the interstitium.

Anesthetized, carefully positioned, female, weanling, white-haired pigs were used to test the hypothesis that (1) interface pressure, the pressure between the skin and an external load, can be used to predict the interstitial fluid pressure over the wings of ilia and the last dorsal spinous process and (2) three-dimensional tissue deformation of the interstitium under the load could partially explain how the external load is transferred at that site. When a 4 or 8 kg load was distributed over the hips of the pigs, the interface pressures over the ilia were approximately 145 and 207 cm H2O, respectively. Approximately 28% of this pressure was transferred to the tissue, resulting in an increase in interstitial fluid pressure of approximately 39 cm H2O for the 4 kg load and 60 cm H2O for the 8 kg load. However, over the spinous process, about 42-43% of the load was transferred to the interstitium. Subcutaneous tissue marker movement occurred along the gamma and theta spherical coordinate but no significant tissue marker movement along the phi coordinate. The latter indicates no significant twisting of the tissue while the former demonstrates three-dimensional shearing. There were also indications of tissue creep since the markers continued to move with constant loading.

Animals

Systemic autoregulation counteracts the carotid baroreflex.

The interaction between autoregulation and baroregulation and its effect on the gains of the short-term pressure regulatory system was studied by performing both open- and closed-loop experiments in the same five anesthetized, vagotomized dogs, and by analyzing the data making use of a new model. With carotid pressure constant (no baroregulation) the pressure-flow data were convex to the flow axis, thus indicating the presence of autoregulation. When baroregulation was present the data were convex to the pressure axis. Our model was able to fit the data as measured in both cases. From the fitting procedure the zero-flow pressure intercept Pzf, the autoregulation resistance gain Gra, and the baroregulation resistance gain Grb were estimated. Pzf was about 20 mmHg in three dogs and about zero in the other two. Average values of Gra and Grb were 13.0 +/- 3.5 mmHg min2/L2 and 0.83 +/- 0.25 min/L, respectively. The two curves which fitted the data points collected in the presence and in the absence of baroreflex intersected at a point (Qo, Po) generally different from the control point. We determined the open-loop gain, Goc = GrbQo, about the point (Qo, Po). The averaged value was 2.23 +/- 0.84. When autoregulation was neglected, the resistance gain Grb and the open-loop gain Goc obtained from the same closed-loop method were underestimated (0.32 +/- 0.15 min/L and 0.88 +/- 0.48, respectively). In the open-loop preparation the carotid sinuses were isolated and the aortic (P) versus carotid (Pca) pressure data were collected. A third-order polynomial was fitted to these data.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Geometry and pump function in cardiac ventricular hypertrophy.

Ventricular pump function can be quantified by the inverse relation between pressure and output, i.e., the pump function graph, which is obtained by varying arterial load without changing end-diastolic volume, inotropic state and heart rate. The ratio of pressure and output, i.e., the peripheral resistance, can be represented in the same graph by a line through the origin. The 2 pressure-output relations intersect in the working point, i.e., the pressure and flow at the prevailing steady state. In normal, anesthetized cats the ventricle appears to be matched to the arterial load in the sense that the working point is found at the optimal power, i.e., the optimal value of the product of pressure and output along the pump function graph. To maintain this matching criterion during pressure overload, the ventricular volume has to remain the same while thickening of the wall takes place: concentric hypertrophy. With volume overload, matching would be preserved with eccentric hypertrophy. Because volume and pressure overloads typically lead to eccentric and concentric hypertrophy, respectively, the matching criterion may be a valuable predictor of the geometric changes found with changes in load. This idea was further investigated experimentally by determining the position of the working point in the perinephritic cat that had 1 kidney removed and the other wrapped in cellophane for 15 to 26 weeks. The working point was no longer found at the optimal power, indicating that either matching was permanently comprised or that the ventricle was still trying to restore matching.

Animals

On-line pressure estimation for a left heart assist device.

Long term measurement of blood pressures is essential for control of circulatory systems with artificial hearts or circulatory assist devices. Efforts to obtain reliable continuous direct measurements of blood pressures, however, have not been successful. This paper describes an on-line pressure estimation technique for use with a portable pneumatically driven left heart assist device. The on-line maximum likelihood algorithms are used for the estimation with the technique based on the use of physical models of the components of the driver and blood pump system. This technique estimates the inlet and outlet pressures of the blood pump. The directly measured driving air pressure and piston position of the pneumatic actuator are used for the estimation. In vitro and in vivo experiments were made to test the use of the on-line estimation technique. The results show successful linear correlations between the actual pressures and their estimates. This technique offers the following advantages: accurate pressure information for on-line control, accessibility to the transducers for recalibration, and noninvasive location of the transducers.

Algorithms

Short-term systemic autoregulation.

We studied total systemic autoregulation in closed-chest, chloralose-anesthetized dogs. Cardiac out-put (previously implanted electromagnetic flow probe on ascending aorta) and aortic pressure were varied by reducing venous return using a balloon catheter in the vena cava. Compensatory action of the baroreflex was prevented by bilateral vagotomy and isolation of both carotid sinuses. To avoid high vessel tone carotid sinus pressure was set at the original baseline value using a pressurized blood reservoir. With each balloon inflation aortic flow and aortic pressure decreased and stabilized in about 1 min. Pressure and flow were allowed to return to base-line values after each balloon inflation in an attempt to minimize the activation of slower regulatory mechanisms. The steady-state pressure-flow relations could be fitted with a sigmoidal curve. The mean quality (0 less than Q less than 1) of autoregulation in eight dogs was 0.41 +/- 0.08 (SD). Autoregulation was found in the pressure range from 42 to 140 mmHg. The early appearance of total systemic autoregulation suggests that, in the intact animal, it may counteract baroreflex control.

Animals

Segmental volume distensibility of the canine thoracic aorta in vivo.

Segments of the canine ascending aorta, upper descending thoracic aorta, and middle descending thoracic aorta were instrumented with ultrasonic dimension gauges and a cathetertip manometer simultaneously to measure changes in segment diameter, length, and intravascular pressure. Volume distensibility (EV) was calculated as the sum of circumferential extensibility (EC), longitudinal extensibility (EL), and high order extensibilities (EK) for each segment. The EC and EL were linear expressions that represented percentage volume changes per mmHg pulse pressure due to circumferential and longitudinal dimensional changes. The high order extensibilities (second and third order) accounted for the percentage volume changes per mmHg pulse pressure due to the interactions between circumferential and longitudinal dimensional changes. Mean(SEM) EV values from six dogs were 1.62(0.31), 0.84(0.08), and 0.62(0.08)% delta V/mmHg delta P for the ascending aorta, upper descending thoracic aorta, and middle descending thoracic aorta segments respectively. The EV, EL, and EK of the ascending aorta segment were significantly greater than those of the upper descending thoracic aorta and middle descending thoracic aorta segments, whereas EC was significantly less in the ascending aorta than in both the upper descending thoracic aorta and middle descending thoracic aorta segments. It is concluded that there are regional differences in aortic distensibility and its components in vivo. Longitudinal wall motion is an important determinant of these aortic mechanical properties.

Animals

Effects of eight weeks of physical conditioning on atherosclerotic plaque in swine.

Effects of individually prescribed exercise on the regression or interference with deposition of atherosclerotic plaque were studied. Twenty miniature swine allotted, by litter, to a control-diet group (groups CE and CS) and an atherogenic diet group (groups AE and AS). All pigs were subjected to injury (balloon catheter) of the aortic endothelium. They were fed for 8 weeks and after an initial graded exercise test was done, then each group was suballotted to an exercising group (groups CE and AE) or a sedentary group (groups CS and AS). Groups CE and AE (exercised) were given 8 weeks of training. Groups CS and AS (sedentary) were sham exercised during this period. A second graded exercise test was administered to the swine (all groups) before they were euthanatized. Aortas were analyzed for the percentage of area involved and for atherosclerotic plaque density. Samples of blood from the swine after they were fasted were obtained before the start of the project (base line) and once every 2 weeks thereafter. These were analyzed for triglycerides, high- and low-density lipoprotein, and total cholesterol concentration. Comparison of results of blood lipid analyses from weeks 1, 9, and 15 did not show significant differences within diet groups between exercise and sedentary. Significant differences at weeks 9 and 15 were observed between diet groups (ie, the pigs fed the atherosclerotic diet had higher blood lipids). Plaque formation was not found in the pigs fed the control diet (groups CE and CS). Plaque formation was evident in all pigs fed the atherosclerotic diet (groups AE and AS) with no significant differences between exercised and sedentary groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Haemolysis in vivo by therapeutic intensities of ultrasound.

Therapeutic intensities of MHz ultrasound directed at the upper abdominal area of rats in vivo resulted in damage to the circulating red blood cells. This damage was detected as free haemoglobin in the plasma as well as microspheres and spherocytic cell fragments which are characteristically produced when blood is heated to more than 49 degrees C. The magnitude of this effect increased with increasing frequency of the ultrasound and was dependent upon the time-averaged intensity, even when the ultrasound was delivered as bursts of high spatial peak intensities. Thermal lesions were found above 10 W/cm2 SP at 1 MHz and above 3 W/cm2 SP at 3.4 MHz. These results show that the observed blood cell damage is primarily a thermal effect which occurs as the blood perfuses anatomical structures which are being heated by the ultrasound beam.

Animals

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

Effects of naloxone in treating hemorrhagic shock in dogs with maintained baroreceptor responsiveness.

The efficacy of treating hemorrhagic shock with naloxone in conjunction with fluids, compared with fluid therapy alone, was studied. Previously instrumented dogs were anesthetized with 0.04 mg of fentanyl/kg + 2.2 mg of droperidol/kg and pentobarbital sodium (to effect). Blood was withdrawn from each animal to achieve and maintain a mean arterial blood pressure of 40 to 50 mm of Hg for the first 2 hours of the experiment (t = 0 to 120 minutes). At t = 120 minutes, IV fluid administration was begun (all dogs) and continued for 1 hour (lactated Ringer's solution at a dosage of 70 ml/kg/hr). Hypothermia was corrected. Control dogs were given no other treatment. Dogs in the naloxone plus fluids group were given an IV bolus of naloxone (1 mg/kg) at t = 120 minutes and 1 mg of naloxone/kg/hr in the fluids from t = 120 to t = 180 minutes. Treatment (either naloxone plus fluids or fluids alone) was stopped at t = 180 minutes, and measuring of response was continued for an additional hour (posttherapeutic period). Significant differences were not seen in mean arterial pressures, left ventricular peak systolic pressures, dP/dt max, time constant T (a measure of left ventricular elasticity), and mean pulmonary arterial pressures between the dogs given naloxone and fluid therapy and those given fluid therapy alone. All dogs in both groups survived the procedure.

Animals

Contribution of the lung to total body clearance of meperidine in the dog.

The potential role of the lung in the disposition of meperidine was examined in six conscious dogs instrumented for measurement of appropriate hemodynamic parameters. Following an intravenous bolus injection of 5 mg/kg, blood samples were collected simultaneously from cannulas placed in the left ventricle and the pulmonary artery, concurrent with the hemodynamic measurements. Pulmonary clearance, calculated from concentration differences between pulmonary arterial and left ventricular blood and pulmonary blood flow, averaged 12.1 +/- 3.70 mL/min/kg, accounting for 58 +/- 13% of the total clearance of the drug. These results help resolve differences between previously reported meperidine clearance in the dog and physiological blood flows and imply that the dog may be a poor model for this drug in humans where clearance is primarily hepatic.

Animals

Viscoelastic behavior of the thoracic aorta of dogs and rabbits.

Data are presented which demonstrate no correlation between atrial electrical activity and diameter changes in the descending thoracic aorta of dogs or rabbits. The experiments conducted included bypassing a segment of the descending thoracic aorta in dogs, and production of a variety of arrhythmias without the bypass in dogs and rabbits. We found no evidence of electrical stimulation-induced phasic activity as suggested by other authors.

Animals

Plasma volume and estimated liver plasma flow during hyperbaric and hyperoxic exposures in awake dogs.

Five different experiments were conducted to determine if estimated liver plasma flow and/or plasma volume were changed as a result of exposure to 2.8 atmospheres absolute (ATA) while breathing 100% oxygen or 6 ATA while breathing compressed air. The experiments were designed to separate the relative roles of the ambient pressure, the partial pressure of oxygen, the time of high oxygen exposure or some combination of these factors on any observed changes. We found that time was not a factor in the changes seen. Hyperbaria resulted in a decrease in estimated liver plasma flow at all pressures greater than 1 ATA. There was an apparent increase in plasma volume at 1.3 ATA and a return towards 1 ATA values at higher pressures. Hyperoxia resulted in a decrease in estimated liver plasma flow at 975 mm Hg but not at 912 mm Hg. The flow was then increased again at 2128 mm Hg. Plasma volume decreased significantly at 912 mm Hg returned to baseline (152 mm Hg) values at 975 mm Hg and then decreased again at 1054 and 2128 mm Hg PO2.

Animals

Hemodynamic effects of 10% dextrose and of dextran 70 on hemorrhagic shock during exposure to hyperbaric air and hyperbaric hyperoxia.

Six groups of six conditioned dogs each were instrumented with an electromagnetic flow-meter transducer around the pulmonary artery, and indwelling silastic cannulae in the pulmonary artery, the left ventricle, the ascending aorta, and the right atrium. After allowing a minimum of 5 d for recovery, the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA), breathing 100% oxygen (PO2 2128 mm Hg) and at 6 ATA breathing air (PO2 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. This required a rather constant 40 +/- 4.5 ml X kg-1 body weight of total blood removed. Three groups, one at each depth perturbation, were then given Dextran 70, the other three groups 10% dextrose. Fluids were administered at a constant rate until the mean aortic pressure rose to within 90% of its original 1 ATA baseline value. At this point, the infusion was stopped and the total amount of fluid administered was recorded. Hemodynamic parameters were measured or calculated for eight different time periods during each experiment. The amount of Dextran 70 required did not change with hyperbaric exposure but only half as much 10% dextrose was required at depth. Dextran 70 held the cardiovascular parameters constant for 30 min following administration but after 10% dextrose, cardiac output tended to decrease at 15 and 30 min posttreatment. There were no significant differences in the cardiovascular effects of hemorrhage between or among the dogs exposed to the three different environmental conditions.

Animals

An evaluation of plasma volume expanders in the treatment of decompression sickness.

Each of 29 goats was instrumented with an ultrasonic flowmeter transducer around the left common carotid artery and a silastic catheter in the anterior vena cava. Following recovery from the surgery the goats were subjected to a dive protocol designed to elicit symptoms of decompression sickness (DCS). The goats were returned to the surface and, following a 20-min observation period, were either left untreated (controls) or treated with one of five different plasma volume expanders. The plasma volume expanders were evaluated based on their ability to decrease the severity of DCS and the number of arterial bubbles that could be counted. Analysis of the results shows that all of the five plasma volume expanders used appeared to reduce the severity of the signs of DCS and to decrease the number of arterial bubbles detected but that these tendencies were not statistically significantly except for Mannitol and Dextran 40. Animals that did not develop arterial bubbles tended to respond better to fluid therapy than did those that did develop bubbles.

Animals