Biomedical subjects

D R Gross

Publications and source records attributed to D R Gross.

At least 37 records · Page 2Linked to original sources

PubMed1994

Early endotoxic shock results in enhanced vasodilator responses to nitroglycerin but unaltered responses to neuropeptides calcitonin gene-related peptide and substance P.

To determine the role that vasoactive neuropeptides, calcitonin gene-related peptide, and substance P play in tissue-blood flow regulation during early septic shock, we examined the responsiveness of arteries removed from pigs 3 h after administration of Escherichia coli lipopolysaccharide or saline vehicle. The carotid, cranial mesenteric, and left anterior descending coronary arteries were excised, and rings were cut from each vessel. Constrictor responses were obtained to cumulative doses of norepinephrine or potassium chloride. Rings were reconstricted and challenged with acetylcholine, substance P, calcitonin gene-related peptide, and nitroglycerin. Lipopolysaccharide significantly increased the cranial mesenteric artery's response to high concentrations of norepinephrine and the response to nitroglycerin in all vessels. This enhancement of responses to nitroglycerin suggests augmented smooth-muscle responsiveness to an exogenous source of nitric oxide, possibly associated with early depression of basal endothelial function. Depression of agonist-induced nitric oxide release may mask such enhancement with endothelial-dependent dilators and may enhance the response to adrenergic constrictors in some vascular beds.

Animals↗

PubMed1994

Instantaneous changes in arterial compliance reduce energetic load on left ventricle during systole.

We tested the hypothesis that arterial compliance changes during each cardiac cycle, and that these instantaneous changes are beneficial for energy conservation. Using an adaptive identification procedure, we were able to obtain an instantaneous impulse-response representation of the arterial system. By assuming a three-element windkessel model, we obtained the instantaneous compliance. The arterial compliance remained relatively constant during diastole but increased during systole. The calculated time trajectory was compared with an optimal compliance calculation based on minimum ventricular ejection energy criteria. The two compliance trajectories followed similar paths. We conclude that increases in arterial compliance during systole reduce the energy demands on the left ventricle.

Animals↗

PubMed1994

Elevations in circulating calcitonin gene-related peptide correlate with hemodynamic deterioration during endotoxic shock in pigs.

Calcitonin gene-related peptide (CGRP) is a potent vasodilatory neuropeptide, which may play a role in vascular dysfunction during septic shock. Sixteen pigs (25-50 kg) were anesthetized with ketamine and isoflurane in O2, and administered 100 micrograms/kg Escherichia coli lipopolysaccharide i.v. (LPS; n = 8) or saline vehicle (n = 8). Pigs were instrumented for hemodynamic determinations and blood sampling for CGRP assay (pg/ml) from the portal vein (PV) and the pulmonary (PA) and carotid (CA) arteries. Blood samples were collected into EDTA and aprotinin before (baseline) and at 60, 120, and 180 min after LPS administration. LPS caused significant deterioration in indices of hemodynamic function and a significant increase in plasma CGRP concentration at all sampling sites by 120 min (P < 0.01). No significant difference between sampling sites was recorded at any time. Plasma CGRP concentrations displayed significant negative correlations with mean arterial pressure, cardiac index, and left ventricular stroke work. These data confirm our previous findings of CGRP elevations in endotoxemic rats, and indicate that 1) LPS is a potent stimulus for the systemic release of CGRP, 2) increasing plasma CGRP concentrations temporally correlates with cardiovascular deterioration during LPS shock, and 3) there is little evidence that the portal circulation is a major source of circulating CGRP levels during LPS shock. Vasoactive neuropeptides, such as CGRP, may interact with other documented mediators of vascular dysfunction in the pathogenesis of septic shock.

Animals↗

PubMed1993

Scintigraphic evaluation of bacterial translocation during hemorrhagic shock.

We investigated the use of gamma scintigraphy to evaluate the temporal and spatial patterns of translocation of radiolabeled Escherichia coli from the porcine jejunum during and following hemorrhagic shock. Thirteen healthy mixed breed pigs (22-43 kg) were randomly allocated to two groups. Pigs were anesthetized with sodium pentobarital (30 mg/kg) and mechanically ventilated (100% O2). Each pig was instrumented for mean arterial pressure (MAP) and superior mesenteric artery (SMA) blood flow determination. A 25-cm loop of vascularly intact distal jejunum was isolated, and 10 mCi (10(11) cfu) of radiolabeled E. coli (99mTcO4-) was placed within the bowel segment. Consecutive 5-min scintigrams of the entire abdomen and thorax were collected for 6 hr. Pigs in the shock group (n = 7) were hemorrhaged such that MAP was maintained at 50-60 mm Hg for 5 hr. Pigs in the sham group (n = 6) were maintained without hemorrhage for 6 hr. The total radioactive counts in the translocation regions of the scintigram were plotted against time, and the slope of the regression lines was compared between groups. In the shock group, SMA blood flow decreased significantly (P < 0.05) during the hypotensive period but returned above baseline during reperfusion. The mean (+/- SD) slopes for translocation regression lines were 9.3 +/- 11.4 counts/min and 36.3 +/- 33.7 counts/min in the sham and shock groups, respectively (P < 0.05). Translocation was scintigraphically evident 50-100 min following induction of hemorrhage and did not require reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

PubMed1993

Effect of anti-lipid A monoclonal antibody (E5) on microcirculatory function during lipopolysaccharide shock.

Early septic shock is characterized by fever, increased cardiac output, decreased systemic vascular resistance, and dilation of higher-order arterioles in peripheral tissues, such as skeletal muscle. We used a rat model of low-dose lipopolysaccharide (LPS) "septic" shock to investigate the potential benefit of an anti-lipid A monoclonal antibody preparation (E5) on macro- and microcirculatory function. Twenty-five male Sprague-Dawley rats were anesthetized and instrumented for measurement of arterial pressure (AP), heart rate (HR), and cardiac output (CO). The left cremaster muscle of each rat was prepared for in vivo video microscopic examination of changes in third-order arteriolar (A3) diameter and erythrocyte velocity. Rats were randomly assigned to two groups: Group I (n = 13) received E5 vehicle and 200 micrograms/kg Escherichia coli LPS; Group II (n = 12) received 2 mg/kg E5 iv prior to LPS administration. All variables were recorded at 15-min intervals for 30 min prior to and 150 min following LPS. Microcirculatory recordings were restricted to those rats where arteriolar diameters were 20-40 microns and vessels displayed obvious vasomotion (n = 7/group). Infusion of LPS caused no significant change in AP, an increase in CO by 105 min, an increase in HR by 75 min, an increase in diameter by 75 min, and a decrease in velocity by 165 min (P < 0.01). Pretreatment with E5 inhibited the A3 vasodilation but did not affect the macrocirculatory changes. These data suggest a potential therapeutic role for E5 in ameliorating LPS-induced changes in skeletal muscle microcirculation.

Animals↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1988

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↗

PubMed1987

Platelet accumulation on an artificial surface in vivo: effect of intravascular hemolysis.

Studies of thromboembolic complications after implantation of cardiovascular prosthetic devices have suggested that there is a correlation between the occurrence of hemolysis and the way in which platelets respond to an artificial surface. To test this hypothesis, we investigated the effect of low-level hemolysis (involving approximately 1% of the circulating red blood cells [RBCs] per hour) on the number of platelets that accumulated on woven Dacron arterial grafts used to bypass the carotid artery in six dogs. Each dog was used in one control and one test procedure, which were performed in random order. In the test procedures, hemolyzed autologous erythrocytes were infused (1 ml/kg/hr) for 10 minutes before, and during, blood flow through the graft. In the control procedures, physiologic saline solution was substituted for the hemolysate. Autologous indium-111 labeled platelets were used to estimate the number of platelets present on the Dacron surface one hour after the initiation of blood flow through the graft. More platelets accumulated on the Dacron surface in the presence of the hemolysate than in the presence of the saline. The increase caused by hemolysis ranged from 2% to 96%, with a mean of 43.7% +/- 35.9% (standard deviation).

Journal Article↗

PubMed1987

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↗

PubMed1986

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↗

PubMed1986

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↗

PubMed1986

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↗