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Biomedical subjects

H D Battarbee

Publications and source records attributed to H D Battarbee.

At least 19 recordsLinked to original sources
PubMed2000

Duration of the hemodynamic effects of N(G)-nitro-L-arginine methyl ester in vivo.

The objective of this study was to quantify the duration of the hemodynamic activity of N(G)-nitro-l-arginine methyl ester (l-NAME) in a variety of different tissues following a single bolus injection of this nitric oxide synthase inhibitor to healthy rats. l-NAME (15 micromol x kg(-1)) was injected (ip) into rats to produce maximal inhibition of endothelial cell NOS. Animals were subsequently anesthetized and blood flow was quantified using the radioactive microsphere/reference organ technique. At 1 h following a single bolus injection of l-NAME blood flow was reduced to the entire gastrointestinal tract, pancreas, and liver. Three hours following l-NAME administration, blood flow to the stomach and upper small intestine had returned to pretreatment levels; however, blood flow to the jejunum, ileal-jejunal junction, and colon remained significantly reduced. Splenic blood flow was significantly reduced and hepatic arterial blood flow was further reduced at this time as well. After 6 h following l-NAME administration, blood flow in all organs had completely recovered to control levels. Although cardiac index and total peripheral resistance had also returned to preinjection values at this time, mean arterial pressure remained elevated at 6 h posttreatment. Blood flow to the brain, lungs, and psoas muscle were unaffected by l-NAME administration at any time point. Taken together, these data demonstrate a differential regulation of vascular tone by NO in different vascular beds and, depending upon the organ system in question, the vasoactive activity of l-NAME may last from 3 to 6 h following a single bolus injection of this NOS inhibitor.

Animals↗
PubMed2000

Cardiac excitation-contraction coupling in the portal hypertensive rat.

Basal contractility and responses to beta-adrenoceptor activation are compromised in hearts from rats with chronic portal vein stenosis. Here we report the effect of partial ligation of the portal vein on myocardial G protein expression, beta-adrenoceptor-G protein coupling, and excitation-contraction coupling (ECC). Contractility (dT/dt) was reduced 30-50% in right and left ventricles, but the rate of relaxation (-dT/dt) was unaffected. Isoproterenol-induced positive inotropism was diminished, but there was no difference in ED(50). The concentration-dependent increase in -dT/dt was unaffected. G(s)alpha and G(i)alpha expression, cholera toxin- and pertussis toxin-induced ADP-ribosylation, and formation of the agonist-receptor-G(s) complex were unaffected by portal vein stenosis. Of the components of ECC examined, the caffeine-sensitive sarcoplasmic reticulum Ca(2+) pool was reduced 35%, although the Ca(2+) uptake and release processes were unchanged; the apparent density of L-type Ca(2+) channels decreased 60% with no change in affinity; the dihydropyridine Ca(2+) channel agonist BAY K 8644 produced relative changes in dT/dt that were similar in both groups, suggesting normal function in the remaining Ca(2+) channels; and Na(+)/Ca(2+) exchange was reduced 50% in the portal vein stenosis group. These data suggest that the effect of portal vein stenosis on the myocardium is the result of alterations to ECC.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1999

Role of glutaraldehyde in calcification of porcine aortic valve fibroblasts.

Glutaraldehyde-treated porcine aortic valve xenografts frequently fail due to calcification. Calcification in the prostheses begins intracellularly. In a previous study, various types of cell injury to canine valvular fibroblasts, including glutaraldehyde treatment, led to calcification. An influx of extracellular Ca2+ into the phosphate-rich cytosol was theorized to be the mechanism of calcification. To test the Ca2+ influx theory, cytosolic Ca2+ and Pi concentrations were assessed in glutaraldehyde-treated porcine aortic valve fibroblasts, and their relationship to a subsequent calcification was studied. Glutaraldehyde caused an immediate and sustained massive cytosolic Ca2+ increase that was dose dependent and a several-fold increase in Pi. Calcification of cells followed within a week. The earliest calcification was observed in blebs formed on glutaraldehyde-treated cells. Live control cells or cells fixed with glutaraldehyde in Ca2+-free solution did not calcify under the same conditions. Concomitant increases in Ca2+ and Pi in glutaraldehyde-treated cells appear to underlie the mechanism of calcification, and the presence of extracellular Ca2+ during glutaraldehyde fixation promotes calcification.

Animals↗
PubMed1999

Cardiac impairment and nitric oxide synthase activity in the chronic portal vein-stenosed rat.

Decreased cardiac contractility and beta-adrenergic responses have been observed in the chronic portal vein-stenosed (PVS) rat. Because nitric oxide (NO) may be increased in PVS and has been recognized as a negative inotropic agent, we investigated the induction of NO synthase (NOS2) and/or changes in constitutive NOS (NOS3) as factors in the cardiac dysfunction of the PVS rat. Ten to twelve days after portal vein stenosis or sham operation, cardiac function was evaluated in paced left ventricular papillary muscles (LVPM) and right ventricular strips (RV). To determine if NO modulation of contractile function was altered in PVS, we examined the increase in developed tension produced by the effect of Nomega-nitro-L-arginine (L-NNA) on the myocardial force-frequency relationship. Cardiac tissue NOS2 and NOS3 activities were assayed, Western blot analyses of NOS2 and NOS3 expression were performed, and circulating nitrate-nitrite (NOX) levels (an indicator of in vivo NOS activity) were assayed. Basal LVPM and RV contractile indexes were significantly reduced in PVS (30-50%), without a change in the relaxation rate. No between-group differences in the cardiac NOS2 or NOS3 enzymatic activities of PVS and sham-operated (SO) rats were observed. Western blots revealed no cardiac NOS2 expression in either SO or PVS rats. In contrast, NOS3 was expressed in both SO and PVS rats, but there was no quantitative difference in expression between the two groups. Changes in the cardiac force-frequency relationship (staircase effect) after L-NNA were consistent with NOS3 modulation of contractile function in both SO and PVS rats, but there was no between-group difference in the modulation. Circulating NOX concentrations did not differ between SO and PVS rats. In conclusion, protein expression data, enzymatic assays, end-product assays, and functional data indicate that between-group differences in NOS2 and NOS3 activity are not responsible for the cardiac impairment that has been observed in the chronic PVS rat.

Animals↗
PubMed1996

Superior mesenteric artery blood flow and indomethacin-induced intestinal injury and inflammation.

Intestinal injury caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased mucosal permeability, microvascular injury, focal intravascular thrombus formation, fibrin deposition, and neutrophil infiltration. Ulcerations and adhesions are also prominent feature of this injury. Although NSAID-induced inhibition of prostaglandin formation has been suggested to produce ischemic injury and inflammation, no studies have directly assessed intestinal blood flow in experimental NSAID-induced enteropathy. This study tested the hypothesis that indomethacin-induced small bowel injury and inflammation result from intestinal ischemia. With the use of pulsed Doppler flowmetry, superior mesenteric artery blood flow was continuously monitored in conscious rats after doses of indomethacin known to promote acute and then chronic small bowel inflammation (7.5 mg/kg, 2 sc doses spaced 24 h apart). After 72 h, rats were anesthetized and a section of small bowel was removed for histology and intestinal myeloperoxidase activity measurements. Mean arterial blood pressure was not affected until 32 h after indomethacin, when it decreased 20% (P < 0.05) to P < 0.01). Sustained blood flow changes first occurred at 20 h, when an increase of 15% (P < 0.01) was observed, whereas flow resistance decreased. Flow resistance continued to decrease for the remainder of the 72-h period, and there was an accompanying blood flow increase to +40% (P < 0.05 to P < 0.01). Intestinal ulcers developed in 86% of indomethacin-treated rats. Adhesions, dilation, and thickening of the distal jejunum and proximal ileum were observed in most indomethacin-treated rats. Histological grading of intestinal injury yielded scores of 7.1 +/- 1.2 and zero for indomethacin-treated and vehicle-injected rats, respectively (P < 0.01). Myeloperoxidase activity was greater in indomethacin-treated rats (6.7 +/- 1.9 vs. 1.8 +/- 0.3 U/cm, P < 0.05). These results suggest that indomethacin-induced enteropathy is associated with an increase, not a decrease, in superior mesenteric artery blood flow. Therefore, ischemia dose not appear to be a mechanism by which subcutaneous indomethacin administration produces small intestinal injury and inflammation.

Animals↗
PubMed1995

Cardiac beta-adrenoceptor-effector coupling in portal vein-stenosed rats.

Cardiac beta-adrenergic signal transduction was examined in chronic portal vein-stenosed rats. Basal tension and maximum rate of tension development were significantly depressed in left ventricular papillary muscles (0.21 +/- 0.03 N/cm2 and 8.2 +/- 1.7 N.s-1.cm-2, respectively) compared with sham-operated controls (0.51 +/- 0.05 N/cm2 and 19.9 +/- 4.4 N.s-1.cm-2, respectively). The positive inotropic response to isoproterenol was also attenuated. Adenosine 3',5'-cyclic monophosphate formation was decreased significantly when GTP (-41.9%), isoproterenol with GTP (-45.3%), or guanosine 5'-O-(3-thiotriphosphate) (-52.4%) was used to stimulate adenylyl cyclase, but not when Mn2+ or forskolin was used. Beta-Adrenoceptor density (sham operated 24.6 +/- 2.0 fmol/mg; portal vein stenosed 26.4 +/- 2.1 fmol/mg) and the apparent dissociation constant (sham operated 0.26 +/- 0.04 nM; portal vein stenosed 0.29 +/- 0.04 nM) were unaffected. Portal venous hypertension did not alter beta-adrenergic receptor affinity for isoproterenol. However, it was necessary for isoproterenol to occupy three times the number of receptors in papillary muscles from stenosed animals to produce an equal increase in force generation. These data suggest that although portal vein stenosis does not alter cardiac beta-adrenoceptor density or affinity for ligands, transduction of the signal between the receptor and adenylyl cyclase is adversely influenced and may be responsible for the diminished responsiveness of beta-adrenoceptors in the myocardium.

Adenylyl Cyclases↗
PubMed1995

Vagal and sympathetic components of the heart rate reflex in chronic portal vein stenosis.

The effects of portal hypertension and portosystemic shunting on autonomic components of the heart rate (HR) baroreflex and on skeletal muscle blood flow changes were investigated using the chronic portal vein-stenosed rat. Phenylephrine- and sodium nitroprusside-induced changes in mean arterial pressure (MAP), HR, and skeletal muscle conductance (SMC) were assessed before and after muscarinic or beta-adrenoceptor blockade. Stenosed rats had lower MAP than sham-operated rats (90 +/- 3 vs. 81 +/- 2 mmHg, P < 0.05), and their portal pressure was higher (7.4 +/- 0.5 vs. 13.9 +/- 1.0 mmHg, P < 0.005). Phenylephrine pressor responses were reduced in stenosed animals, their associated bradycardic responses were enhanced [-1.912 +/- 0.109 vs. -1.427 +/- 0.148 beats per minute (bpm)/mmHg, P < 0.01], and their SMC responses were diminished. Methylatropine abolished bradycardic responses and enhanced pressor responses without affecting SMC. After propranolol, reflex bradycardic responses in stenosed rats were less than in shams (-0.492 +/- 0.085 vs. -0.738 +/- 0.058 bpm/mmHg, P < 0.01), and their pressor and SMC responses became indistinguishable from shams. In contrast, tachycardic responses to nitroprusside-induced hypotension before propranolol were impaired in stenosed rats (-1.492 +/- 0.114 vs. -2.225 +/- 0.347 bpm/mmHg, P < 0.05), and their SMC responses were reduced. Muscarinic blockade did not affect HR or SMC responses to hypotension in either stenosed or sham rats. beta-Adrenoceptor blockade, however, prevented hypotension-induced tachycardia, enhanced nitroprusside depressor responses, and eliminated the between-group differences in SMC responses. These studies indicate that increased gain of the parasympathetic limb of the cardiac baroreflex was responsible for attenuated pressor responses to phenylephrine in portal vein-stenosed animals and that beta-adrenoceptors contributed to skeletal muscle vascular hyporesponsiveness to phenylephrine in portal-vein stenosed animals. Altered beta-adrenoceptor function also appears to contribute to impaired chronotropic and skeletal muscle conductance responses to hypotension.

Animals↗
PubMed1992

Cardiac performance in the portal vein-stenosed rat.

Patient studies and experimental models suggest that impaired cardiac function might contribute to the altered pressor responses and compromised reflex responses to hypotension observed in liver disease. To elucidate the role that portosystemic shunting plays in cardiac impairment, right atrial chronotropic and right ventricular inotropic responses to a beta-adrenoceptor agonist were compared using isolated cardiac tissues from sham-operated and chronic portal vein-stenosed rats. Maximal chronotropic responses of sinoatrial tissue from portal vein-stenosed rats to isoproterenol were reduced 18% (P less than 0.05) with no change in sensitivity [mean effective dose (ED50)]. Basal indexes of contraction were diminished 48% (P less than 0.0025) and 60% (P less than 0.0005) for developed tension and change in force over change in time (dF/dt), respectively, in ventricular tissue from portal vein-stenosed animals. In addition, the maximal response for isoproterenol-induced ventricular contraction was smaller in portal hypertensive animals (-44%, P less than 0.0005, and -52%, P less than 0.01 for developed tension and dF/dt, respectively), but no changes in isoproterenol ED50 values were found. These results indicate that portal venous hypertension with extensive portosystemic shunting leads to impairment of basal myocardial contraction and decreased chronotropic and inotropic responsiveness to beta-adrenoceptor agonists.

Animals↗
PubMed1992

Intestinal myoelectrical activity and transit time in chronic portal hypertension.

This study was designed to determine the effects of portal hypertension on intestinal myoelectrical activity and propulsion. In a single surgery, adult rats were implanted with a serosal electrode at each quarter of the small intestine, and portal hypertension was produced by calibrated constriction of the portal vein. To determine intestinal transit, portal vein-stenosed (PVS) and sham-operated animals were chronically implanted with a catheter in the proximal small intestine. Transit time was determined by measuring the progression of radioactive chromium along the bowel. Studies were conducted 6, 9, and 14 days after surgical preparation. Portal hypertension was associated with both transient and persistent changes in intestinal myoelectrical activity during the experimental period. Slow wave frequency was significantly reduced in the proximal small intestine on all test days and in the distal small intestine on day 14. Occurrence of the migrating myoelectric complex was reduced on days 6 and 9. Phase III amplitude was significantly reduced in the distal small intestine on all test days. Changes in intestinal myoelectrical activity in PVS animals were not associated with measurable changes in intestinal propulsion. The results suggest that both transient and persistent changes in intestinal myoelectrical activity occur during the 2-wk period after portal vein stenosis. The functional significance of the changes is unknown.

Action Potentials↗
PubMed1990

Responses to hypotension in conscious rats with chronic portal venous hypertension.

Heart rate, mean arterial pressure, and vascular conductance response to intravenous nitroprusside were compared in conscious, unrestrained portal vein-stenosed and sham-operated rats chronically instrumented for pulsed Doppler flowmetry. Ten to twelve days after portal vein stenosis, portal venous pressures were elevated and resting heart rates were greater. Portal vein-stenosed animals' depressor responses to nitroprusside were similar to those of sham-operated animals, despite a 41% reduction in their tachycardic response to arterial hypotension. Skeletal muscle vascular bed reflex responses to nitroprusside-induced hypotension were significantly attenuated in the portal vein-stenosed group, whereas their renal artery and superior mesenteric artery responses resembled that of the sham-operated group. After ganglionic blockade, tachycardic responses to hypotension were abolished, but portal vein-stenosed rats' heart rates remained greater than sham-operated rats. Comparisons of arterial pressure changes, renal artery, abdominal aorta, and superior mesenteric artery vascular conductance changes after ganglionic blockade revealed no differences in neurogenic vascular tone between groups. Ganglionic blockade enhanced nitroprusside depressor responses and increased vascular conductance responses to nitroprusside in both treatment groups while abolishing the between group difference in the skeletal muscle baroreflex response. These findings indicate that chronic prehepatic portal vein stenosis with portal venous hypertension results in reduced reflex tachycardic and skeletal muscle baroreflex responses to nitroprusside-induced hypotension.

Animals↗
PubMed1989

Pressor responses in conscious rats with chronic portal venous hypertension.

Heart rate, mean arterial pressure (MAP), and vascular conductance responses to graded phenylephrine (PE) infusions were compared in conscious, unrestrained portal vein-stenosed (PS), and sham-operated (SO) rats chronically instrumented for pulsed Doppler flowmetry. Ten days after stenosis, MAP was lower in PS than in SO, and PS heart rates were higher. Pressor sensitivity to PE was attenuated 70%, and bradycardic responses to increases in MAP were 47% greater in PS. Abdominal aorta vascular bed conductance sensitivity was reduced 84%, and renal artery sensitivity was reduced 29% in PS compared with SO, whereas the superior mesenteric artery conductance response was unaffected by portal vein stenosis. After ganglionic blockade, the heart rate of PS remained greater than that of SO, and comparisons of renal artery, abdominal aorta, and superior mesenteric artery vascular conductances revealed no significant differences in neurogenic vascular tone. Differences between PS and SO pressor responses were abolished by ganglionic blockade, as were differences in vascular bed conductance responses. These findings suggest that a greater bradycardic response and greater baroreflex-mediated withdrawal of sympathetic tone from skeletal muscle and renal vascular beds were responsible for the decreased pressor sensitivity observed in PS animals.

Animals↗
PubMed1987

The quantitative estimation of microvessels in microvascular networks.

A novel method is presented that greatly facilitates the determination of vessel segment number and density in both simple and complex microvascular networks. This approach was applied to microvascular networks represented by the Bra-Ket operator technique and accurately predicted the number of vessel segments in both tree-branched and loop-branched (arcade) networks. The method was then applied to the complex hexagonal array network described by Engelson et al. for gastrointestinal mucosa and accurately yielded an average vessel segment number of three around each hexagonal loop. This new method may be used for conveniently estimating tissue microvascular densities, such as vessel rarefaction or proliferation, and for the modelling of microvascular networks.

Animals↗
PubMed1987

Automated computation of relative flow resistance using a pulsed Doppler flowmeter.

Use of a pulsed Doppler flowmeter to assess changes in blood flow resistance often requires a laborious series of calculations, and full characterization of resistance changes frequently necessitates replotting of calculated data. To facilitate the interpretation of pulsed Doppler flowmetry data, a simple, inexpensive device was constructed that computes the signal ratio of mean arterial pressure (MAP) to directional pulsed Doppler outputs. With this device, relative flow resistance can be recorded and quantitatively assessed at a glance in three vascular beds in real time. This computer-like device was designed around the Burr-Brown DIV100HP integrated circuit. C741G OpAmps provide input buffering, zeroing, and ranging adjustments enabling the user to accurately follow resistance over a very broad range of changes without exceeding the device's operating limits. A LM339 quad comparator monitors the input of each DIV100 and indicates when operating limits are exceeded via a channel-specific LED indicator and an audible alarm. No significant attenuation of the input signals occurs over the range of direct current to 50 kHz, and the output is without significant phase shift. Comparisons with calculated changes in resistance derived from the MAP and pulsed Doppler flowmetry in unanesthetized, unrestrained rats confirmed that resistance changes can be measured with precision and accuracy.

Animals↗
PubMed1982

Effect of adrenalectomy on tyrosine hydroxylase activity.

Bilateral adrenalectomy produced a fall in blood pressure and an increase in tyrosine hydroxylase activity in the superior cervical ganglion in the rat. The fall in blood pressure and the increase in tyrosine hydroxylase activity in the superior cervical ganglion were prevented by giving the adrenalectomized animals 0.9% saline as their only drinking fluid. The increase in tyrosine hydroxylase activity was also prevented by decentralization (severing the preganglionic fiber) of the superior cervical ganglion. These results suggest that the induction of tyrosine hydroxylase activity results from a reflexly mediated increase in nerve impulse traffic that results from the adrenalectomy-induced fall in blood pressure. Further characterization of this response showed that the glucocorticoid, dexamethasone, did not cause a further induction of enzyme in adrenalectomized rats whereas, treatment with epinephrine as well as dexamethasone, did result in an augmentation of the enzyme activity above that seen in the already induced adrenalectomized animals.

Adrenalectomy↗