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C J Hartley

Publications and source records attributed to C J Hartley.

At least 19 recordsLinked to original sources
PubMed2005

Kelp fly virus: a novel group of insect picorna-like viruses as defined by genome sequence analysis and a distinctive virion structure.

The complete genomic sequence of kelp fly virus (KFV), originally isolated from the kelp fly, Chaetocoelopa sydneyensis, has been determined. Analyses of its genomic and structural organization and phylogeny show that it belongs to a hitherto undescribed group within the picorna-like virus superfamily. The single-stranded genomic RNA of KFV is 11,035 nucleotides in length and contains a single large open reading frame encoding a polypeptide of 3,436 amino acids with 5' and 3' untranslated regions of 384 and 343 nucleotides, respectively. The predicted amino acid sequence of the polypeptide shows that it has three regions. The N-terminal region contains sequences homologous to the baculoviral inhibitor of apoptosis repeat domain, an inhibitor of apoptosis commonly found in animals and in viruses with double-stranded DNA genomes. The second region contains at least two capsid proteins. The third region has three sequence motifs characteristic of replicase proteins of many plant and animal viruses, including a helicase, a 3C chymotrypsin-like protease, and an RNA-dependent RNA polymerase. Phylogenetic analysis of the replicase motifs shows that KFV forms a distinct and distant taxon within the picorna-like virus superfamily. Cryoelectron microscopy and image reconstruction of KFV to a resolution of 15 A reveals an icosahedral structure, with each of its 12 fivefold vertices forming a turret from the otherwise smooth surface of the 20-A-thick capsid. The architecture of the KFV capsid is unique among the members of the picornavirus superfamily for which structures have previously been determined.

Amino Acid Sequence↗
PubMed2002

Role of propofol and its solvent, intralipid, in nitric oxide-induced peripheral vasodilatation in dogs.

BACKGROUND: The commercial propofol preparation in an intralipid solution causes marked vasodilatation. Both propofol and its solvent seem to stimulate the nitric oxide (NO) pathway. The role of intralipid in cardiac and regional haemodynamic changes induced by propofol and their respective interactions with the NO pathway was assessed. METHODS: Dogs were instrumented to record arterial pressure, heart rate, cardiac output, dP/dt (the first derivative of left ventricular pressure) and vertebral, carotid, coronary, mesenteric, hepatic, portal and renal blood flows. Experimental groups were as follows. Group 1 (control; n = 11): N-methyl-L-arginine (L-NMA) 20 mg kg-1 i.v.; Group 2 (n = 8): propofol (10 mg ml-1) 4 mg kg-1 i.v. bolus followed by 0.6 mg kg-1 min-1; Group 3 (n = 6): intralipid 0.25 ml kg-1 bolus followed by 0.06 ml kg-1 min-1. After 60 min, L-NMA was injected in Groups 2 and 3. RESULTS: Propofol induced increases in heart rate, coronary and carotid blood flows, and decreases in systemic vascular resistance and dP/dt. Intralipid increased renal blood flow, carotid vascular resistance and mesenteric vascular resistance. In the presence of intralipid, L-NMA-induced pressor response and systemic, carotid and renal vasoconstriction were more pronounced than in control dogs. CONCLUSIONS: Except for the coronary and carotid circulations, intralipid modulates the NO pathway in cardiac and regional blood flow.

Anesthetics, Intravenous↗
PubMed2001

Over-production of hydantoinase and N-carbamoylamino acid amidohydrolase enzymes by regulatory mutants of Agrobacterium tumefaciens.

While the hydantoin-hydrolysing enzymes from Agrobacterium strains are used as biocatalysts in the commercial production of D-p-hydroxyphenylglycine, they are now mostly produced in heterologous hosts such as Escherichia coli. This is due to the fact that the activity of these enzymes in the native strains is tightly regulated by growth conditions. Hydantoinase and N-carbamoylamino acid amidohydrolase (NCAAH) activities are induced when cells are grown in the presence of hydantoin or an hydantoin analogue, and in complete medium, enzyme activity can be detected only in early stationary growth phase. In this study, the ability of Agrobacterium tumefaciens RU-OR cells to produce active enzymes was found to be dependent upon the choice of nitrogen source and the presence of inducer, 2-thiouracil, in the growth medium. Growth with (NH4)2SO4 as the nitrogen source repressed the production of both enzymes (nitrogen repression) and also resulted in a rapid, but reversible loss of hydantoinase activity in induced cells (ammonia shock). Mutant strains with inducer-independent production of the enzymes and/or altered response to nitrogen control were isolated. Of greatest importance for industrial application was strain RU-ORPN1F9, in which hydantoinase and NCAAH enzyme activity was inducer-independent and no longer sensitive to nitrogen repression or ammonia shock. Such mutants offer the potential for native enzyme production levels equivalent to those achieved by current heterologous expression systems.

Agrobacterium tumefaciens↗
PubMed2001

Measurement of cardiac function in conscious rats.

The goal of this study was to establish that 1. blood velocity profile in the rat aorta is parabolic, and 2. measure of left ventricular thickening fraction can be used in rats. Spontaneously hypertensive and normotensive Wistar Kyoto rats were instrumented with a 20-MHz pulsed Doppler flow probe around the thoracic aorta and a 20-MHz pulsed Doppler thickening probe on the left ventricle. Doppler frequency shifts were measured throughout the entire aorta diameter, and individual blood velocity profiles were constructed. It was demonstrated that blood velocity in the ascending aorta of rats is laminar; therefore, cardiac output can be measured using the pulsed Doppler method. In Wistar Kyoto rats, left ventricular thickening fraction was 24 +/- 1% and 25 +/- 1%, 2 and 3 weeks following surgery. In spontaneously hypertensive rats, left ventricular thickening fraction was 22 +/- 2%. Halothane depressed left ventricular thickening fraction, whereas isoproterenol increased left ventricular thickening fraction in conscious rats. Thus, pulsed Doppler technique is a valuable tool for evaluating cardiovascular function in conscious rats.

Analysis of Variance↗
PubMed2001

Role of heparin and nitric oxide in the cardiac and regional hemodynamic properties of protamine in conscious chronically instrumented dogs.

BACKGROUND: Because protamine is administered to reverse heparin, a drug that might itself affect the pharmacologic properties of protamine, this study was designed to assess the properties of protamine alone and in the presence of heparin in conscious dogs. METHODS: Twelve dogs were instrumented to continuously record cardiac and regional hemodynamics. On separate occasions, a dose of protamine (0.5, 1, 3, 5, and 8 mg/kg) was randomly administered either alone or in the presence of heparin (ratio 100 IU/mg). Heparin (300 IU/kg) and protamine (3 mg/kg) were administered in the presence of N-methyl-L-arginine, a specific nitric oxide synthase inhibitor. Identical experiments were performed with protamine (8 mg/kg) in the absence of heparin on a separate occasion. RESULTS: Protamine alone produced limited cardiac and regional changes. In the presence of heparin, protamine produced hypotension at 3, 5, and 8 mg/kg, vasodilatation at 3 and 5 mg/kg, and a more pronounced dose-dependent increase in pulmonary pressure at 3, 5, and 8 mg/kg. Simultaneously, transient carotid vasodilatation at 3 and 5 mg/kg, coronary and hepatic vasodilatation at 3, 5, and 8 mg/kg, as well as a decrease in vertebral vascular resistance were recorded at 1, 3, and 8 mg/kg. Protamine produced an immediate increase followed by a secondary decrease in renal vascular resistance. Protamine-induced secondary pulmonary pressor effects were attenuated. In the presence of heparin, nitric oxide synthase blockade selectively attenuated protamine-induced immediate hypotension, systemic vasodilatation, and coronary, mesenteric, and hepatic vasodilations as well as the decrease in portal blood flow and accentuated the renal vasoconstriction. CONCLUSIONS: The presence of heparin accentuated the decrease in cardiac function induced by protamine as well as its effects on regional circulation. The data provide evidence that the nitric oxide pathway is involved in the systemic and selective regional heparin-protamine-mediated vasodilatation in conscious dogs.

Animals↗
PubMed2001

Comparison of cardiac and regional hemodynamic responses to N-methyl-L-arginine and aminoguanidine infusions in conscious pigs.

The aim of this study was to elucidate cardiac and regional hemodynamics using a nonspecific inhibitor of the constitutive and inducible nitric oxide synthase (NOS), N-methyl-L-arginine (L-NMA), and a specific inhibitor of the inducible NOS, aminoguanidine, in conscious pigs. Animals were divided into two groups. After hemodynamics were stabilized, animals in group 1 (n = 5) received an infusion of L-NMA at 300 microg/kg per min, i.v., over 60 min, and group 2 (n = 5) received an infusion of aminoguanidine, infused at 1 mg/kg per min over 60 min. Hemodynamic parameters including arterial blood pressure, heart rate, cardiac output, dP/dt, and carotid, coronary, hepatic, portal, mesenteric, and renal blood flows were continuously recorded before and 5, 15, 30, 45, 60, and 120 min after L-NMA infusion or aminoguanidine infusion, or both. The L-NMA vasopressor response (20%) was associated with a significant increase in systemic vascular resistance (45%). Carotid, hepatic, and renal vascular resistance increased significantly by 95%, 110%, and 20%, respectively, at 60 min after L-NMA infusion. Finally, heart rate, cardiac output, dP/dt, and portal and mesenteric blood flows remained unchanged after L-NMA infusion. In contrast, aminoguanidine infused at 1 mg/kg per min over 60 min did not change systemic arterial blood pressure or regional blood flow in conscious pigs. Furthermore, aminoguanidine had no effect on acetylcholine vasodilator effects. In conclusion, the lack of pressor effects and of agonist-stimulated NO production induced by aminoguanidine suggests that aminoguanidine is a weak inhibitor of the constitutive NOS. Compared with L-NMA, the selectivity of aminoguanidine may decrease possible side effects that could occur as a result of inhibition of constitutive NOS.

Acetylcholine↗
PubMed2001

Evaluation of cardiovascular parameters of a selenium-based antihypertensive using pulsed Doppler ultrasound.

The pharmacology of selenium is of much interest because selenium deficiency has been linked to cardiovascular diseases, cancer, and arthritis, and selenoenzymes are critical cellular antioxidants. We have previously reported that phenyl-2-aminoethylselenide (PAESe) and its derivatives represent a novel class of selenium-based antihypertensive agents that exhibit unique biochemical and pharmacologic properties. We now report on experiments designed to probe the hemodynamic mechanism of action of these compounds in spontaneously hypertensive rats (SHR). A noninvasive pulsed Doppler ultrasound probe was used to measure peak blood flow velocity in the aortic arch from the right second intercostal space. PAESe was found to increase peak aortic blood flow velocity (+44%), heart rate (+16%), and blood flow acceleration (+105%), while decreasing left ventricular ejection time (LVET) (-37%) concomitant with a decrease in mean arterial pressure (-54%). These results were compared with the known vasodilator hydralazine, which had similar effects on mean arterial pressure (MAP) and peak velocity but caused an increase in LVET (+42%) and a decrease in heart rate (-18%). Taken together, our results suggest that PAESe decreases blood pressure via a decrease in peripheral resistance, which overcomes the initial increase in heart rate and acceleration to give a net decrease in MAP.

Animals↗
PubMed2001

Stem cell plasticity in muscle and bone marrow.

Recent discoveries have demonstrated the extraordinary plasticity of tissue-derived stem cells, raising fundamental questions about cell lineage relationships and suggesting the potential for novel cell-based therapies. We have examined this phenomenon in a potential reciprocal relationship between stem cells derived from the skeletal muscle and from the bone marrow. We have discovered that cells derived from the skeletal muscle of adult mice contain a remarkable capacity for hematopoietic differentiation. Cells prepared from muscle by enzymatic digestion and 5 day in vitro culture were harvested and introduced into each of six lethally irradiated recipients together with distinguishable whole bone marrow cells. Six and twelve weeks later, all recipients showed high-level engraftment of muscle-derived cells representing all major adult blood lineages. The mean total contribution of muscle cell progeny to peripheral blood was 56%, indicating that the cultured muscle cells generated approximately 10- to 14-fold more hematopoietic activity than whole bone marrow. Although the identity of the muscle-derived hematopoietic stem cells is still unknown, they may be identical to muscle satellite cells, some of which lack myogenic regulators and could respond to hematopoietic signals. We have also found that stem cells in the bone marrow can contribute to cardiac muscle repair and neovascularization after ischemic injury. We transplanted highly purified bone marrow stem cells into lethally irradiated mice that subsequently were rendered ischemic by coronary artery occlusion and reperfusion. The engrafted stem cells or their progeny differentiated into cardiomyocytes and endothelial cells and contributed to the formation of functional tissue.

Age Factors↗
PubMed2001

Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells.

Myocyte loss in the ischemically injured mammalian heart often leads to irreversible deficits in cardiac function. To identify a source of stem cells capable of restoring damaged cardiac tissue, we transplanted highly enriched hematopoietic stem cells, the so-called side population (SP) cells, into lethally irradiated mice subsequently rendered ischemic by coronary artery occlusion for 60 minutes followed by reperfusion. The engrafted SP cells (CD34(-)/low, c-Kit(+), Sca-1(+)) or their progeny migrated into ischemic cardiac muscle and blood vessels, differentiated to cardiomyocytes and endothelial cells, and contributed to the formation of functional tissue. SP cells were purified from Rosa26 transgenic mice, which express lacZ widely. Donor-derived cardiomyocytes were found primarily in the peri-infarct region at a prevalence of around 0.02% and were identified by expression of lacZ and alpha-actinin, and lack of expression of CD45. Donor-derived endothelial cells were identified by expression of lacZ and Flt-1, an endothelial marker shown to be absent on SP cells. Endothelial engraftment was found at a prevalence of around 3.3%, primarily in small vessels adjacent to the infarct. Our results demonstrate the cardiomyogenic potential of hematopoietic stem cells and suggest a therapeutic strategy that eventually could benefit patients with myocardial infarction.

Animals↗
PubMed2000

Myocardial blood flow and myocardial uptake of (201)Tl and (99m)Tc-sestamibi during coronary vasodilation induced by CGS-21680, a selective adenosine A(2A) receptor agonist.

BACKGROUND: We investigated the hemodynamic and coronary vasodilatory effects of CGS-21680, a potent selective adenosine A(2A) agonist, as well as its potential use as a new stress modality in combination with perfusion scintigraphy. METHODS AND RESULTS: A stenosis of the left anterior descending coronary artery (LAD) was produced in dogs to reduce the reactive hyperemic response to <20%. Adenosine and CGS-21680 were then separately infused to maximize left circumflex coronary artery (LCx) flow velocity. (201)Tl (0.5 mCi) and (99m)Tc-sestamibi (5 mCi) were injected at the maximal dose of CGS-21680. Heart rate decreased with adenosine but increased during CGS-21680 infusion (P<0.005). The decrease in systolic blood pressure was more prominent with adenosine than with CGS-21680 (P<0.005). In the control LCx zone, maximal myocardial blood flow (MBF) (measured by radioactive microspheres) increased 3.1-fold during adenosine infusion (P<0.005) and 3.8-fold during CGS-21680 infusion (P<0.005). In the stenotic LAD zone, MBF did not change significantly. During adenosine and CGS-21680 infusion, stenosis/control zone MBF ratios were comparable (0.32+/-0.11 versus 0.27+/-0.10, P=NS), and transmural (201)Tl and (99m)Tc-sestamibi count-activity ratios (0.48+/-0.11 and 0.51+/-0.09, respectively) were also comparable (P=NS). Myocardial scintigraphy uncovered perfusion defects in all dogs. CONCLUSIONS: CGS-21680 elicits coronary vasodilation comparable to that of adenosine and produces profound heterogeneity of MBF and of (201)Tl and (99m)Tc-sestamibi myocardial uptake, rendering it a promising agent for pharmacological myocardial perfusion imaging.

Adenosine↗
PubMed2000

Effects of N-methyl-L-arginine on cardiac and regional blood flow in a dog endotoxin shock model.

PURPOSE: Indirect evidence suggests a decrease in organ perfusion as a result of nitric oxide (NO) inhibition in endotoxic shock. Cardiac and regional hemodynamic responses to N-methyl-L-arginine (L-NMA), a nonspecific inhibitor of constitutive and inducible nitric oxide synthase (NOS), were assessed in nine conscious dogs subjected to endotoxin. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was titrated to a maximum of 200 microg/kg, IV, over 45 minutes. L-NMA was given in a dose of 20 mg/kg, IV. Hemodynamic parameters were recorded for 6 hours following L-NMA administration. RESULTS: LPS induced significant decreases in mean arterial blood pressure (MAP), cardiac output (CO), first derivative of left ventricular pressure (dP/dt), coronary blood flow, carotid blood flow, mesenteric blood flow, renal blood flow, and a significant hepatic vasodilation. L-NMA fully reversed the effects of LPS on MAP, heart rate, dP/dt, coronary and carotid blood flow, and reversed mesenteric blood flow and hepatic blood flow at 1 and 3 hours, respectively. L-NMA partially overcame the LPS-induced decrease in renal blood flow at 30 minutes and 1 hour. Except for mesenteric and carotid circulation, L-NMA did not change regional vascular resistance. CONCLUSIONS: It is likely that constitutive NOS is implicated in immediate cardiac, carotid, mesenteric, and renal vascular changes, whereas inducible NOS accounted for delayed responses in hepatic and coronary circulation.

Animals↗
PubMed2000

Hemodynamic changes in apolipoprotein E-knockout mice.

Apolipoprotein E-knockout (ApoE-KO) mice develop advanced atherosclerotic lesions by 1 yr of age and have been well characterized pathologically and morphologically, but little is known regarding their cardiovascular physiology and hemodynamics. We used noninvasive Doppler ultrasound to measure aortic and mitral blood velocity and aortic pulse-wave velocity in 13-mo-old ApoE-KO and wild-type (WT) mice anesthetized with isoflurane. In other mice from the same colony, we measured systolic blood pressure, body weight, heart weight, cholesterol, and hematocrit. Heart rate and blood pressure were comparable (P = not significant) between ApoE-KO and WT mice, but significant decreases (P < 0.001) were found in body weight (-22%) and hematocrit (-11%), and significant increases were found in heart weight (+23%), aortic velocity (+60%), mitral velocity (+81%) (all P < 0.001), and pulse-wave velocity (+13%, P < 0.05). We also found inflections in the aortic arch velocity signal consistent with enhanced peripheral wave reflection. Thus ApoE-KO mice have phenotypic alterations in indexes of peripheral vascular resistance and compliance and significantly elevated cardiac outflow velocities and heart weight-to-body weight ratios.

Animals↗
PubMed1999

Myocardial infarction and remodeling in mice: effect of reperfusion.

Anatomic and functional changes after either a permanent left anterior descending coronary artery occlusion (PO) or 2 h of occlusion followed by reperfusion (OR) in C57BL/6 mice were examined and compared with those in sham-operated mice. Both interventions generated infarcts comprising 30% of the left ventricle (LV) measured at 24 h and equivalent suppression of LV ejection velocity and filling velocity measured by Doppler ultrasound at 1 wk. Serial follow-up revealed that the ventricular ejection velocity and filling velocity returned to the levels of the sham-operated controls in the OR group at 2 wk and remained there; in contrast, PO animals continued to display suppression of both systolic and diastolic function. In contrast, ejection fractions of PO and OR animals were depressed equivalently (50% from sham-operated controls). Anatomic reconstruction of serial cross sections revealed that the percentage of the LV endocardial area overlying the ventricular scar (expansion ratio) was significantly larger in the PO group vs. the OR group (18 +/- 1.7% vs. 12 +/- 0.9%, P < 0.05). The septum that was never involved in the infarction had a significantly (P < 0.002) increased mass in PO animals (22.5 +/- 1.08 mg) vs. OR (17.8 +/- 1.10 mg) or sham control (14.8 +/- 0.99 mg) animals. Regression analysis demonstrated that the extent of septal hypertrophy correlated with LV expansion ratio. Thus late reperfusion appears to reduce the degree of infarct expansion even under circumstances in which it no longer can alter infarct size. We suggest that reperfusion promoted more effective ventricular repair, less infarct expansion, and significant recovery or preservation of ventricular function.

Animals↗
PubMed1998

Both positive and negative portal venous and hepatic arterial glucose gradients stimulate hepatic glucose uptake after the same amount of glucose is infused into the splanchnic bed in conscious dogs.

We studied the effects of both positive and negative portal venous and hepatic arterial glucose gradients on hepatic glucose uptake after the same amount of glucose was administered into the portal vein and/or hepatic artery. Studies were performed on eight unrestrained conscious dogs with catheters in the portal vein, hepatic vein, gastroduodenal artery, superior mesenteric vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Glucose was infused as follows: protocol 1, 55.6 micromol/kg/min into the portal vein for the first 90 minutes; protocol 2, 27.8 micromol/kg/min into both the portal vein and hepatic artery for the next 90 minutes; and protocol 3, 55.6 micromol/kg/min into the hepatic artery for the last 90 minutes. The portal venous and hepatic arterial plasma glucose gradient was 2.1+/-0.3, -3.0+/-0.5, and -7.1+/-0.6 mmol/L, the rate of hepatic glucose uptake divided by the administered glucose load was 46%+/-11%, 42%+/-10%, and 57%+/-8%, net hepatic glucose uptake was 25.4+/-5.9, 23.5+/-5.6, and 31.6+/-4.6 micromol/kg/min; and the fractional hepatic extraction of glucose was 10.7%+/-2.2%, 11.6%+/-2.5%, and 15.0%+/-2.1%, respectively (mean+/-SEM of three points at 60, 75, and 90 minutes in each protocol). The rate of hepatic glucose uptake divided by the administered glucose load, net hepatic glucose uptake, and fractional hepatic extraction of glucose did not change significantly despite the various portal venous and hepatic arterial glucose gradients. We also studied the effect of the same amount of intraportal glucose infusion for 240 minutes on net hepatic glucose uptake. From 60 to 240 minutes, net hepatic glucose uptake did not change significantly. In conclusion, the liver took up a large amount of glucose administered into the portal vein and/or hepatic artery, regardless of positive or negative portal venous and hepatic arterial glucose gradients. Augmentation of hepatic glucose uptake is not dependent on the signal of the positive or negative portal venous and hepatic arterial glucose gradient.

Animals↗
PubMed1997

The age-associated alterations in late diastolic function in mice are improved by caloric restriction.

Caloric restriction reduces the magnitude of many age-related changes in rodents. Cardiac function is altered with senescence in mice, rats, and healthy humans. We examined the effects of life-long caloric restriction on diastolic and systolic cardiac function in situ using Doppler techniques in ad libitum-fed 30- to 32-month-old (AL) and calorically restricted (CR) 32- to 35-month-old female B6D2-F1 hybrid mice. The heart weight to body weight ratio was similar in AL (5.74 +/- .24 mg/g) and CR (5.68 +/- .20 mg/g) mice. Two systolic functional parameters known to decrease with age in both humans and mice, peak aortic velocity and aortic acceleration, were unchanged by CR compared to AL. In contrast, diastolic function was altered by caloric restriction. Although left ventricular peak early filling velocity (E) was not different between CR and AL, peak atrial filling velocity (A) was 50% lower in CR compared to AL (p < .001). The ratio of early diastolic filling to atrial filling (E/A ratio) was 64% higher in the CR (2.74 +/- .31) than the AL (1.55 +/- .07; p = .004). The fraction of ventricular filling due to atrial systole, the atrial filling fraction, was also reduced in CR (.21 +/- .04) compared to AL (.36 +/- .02; p = .007). These changes occurred in CR without alteration in E deceleration time, which is consistent with improved diastolic function in CR. Through mechanisms that remain unknown, lifelong caloric restriction may prevent the age-related impairments in late diastolic function but does not alter the impairments in systolic or early diastolic cardiac function.

Aging↗
PubMed1997

Noninvasive determination of pulse-wave velocity in mice.

Some transgenic mice have abnormal vascular function, but arterial geometry and dynamics are difficult to evaluate. To examine whether ultrasonic velocimetry could be used to determine arterial pulse-wave velocity (PWV) in mice, a custom-made 20-MHz pulsed Doppler instrument was used to obtain blood flow velocity signals from the aortic arch and the abdominal aorta 4 cm downstream. The upstroke (foot) of the velocity wave was timed at each site with respect to the R wave of the electrocardiogram, and PWV was calculated by dividing the separation distance by the difference in R-foot times. Doppler determinations were compared with invasive tonometry, and PWV was altered pharmacologically. It was found that the upstrokes of pressure (by tonometry) and velocity were coincident (+/-1 ms) and that PWV could be calculated by either method on exposed vessels. With the use of Doppler methods, pulse transit time was determined noninvasively with +/-1-ms resolution in 140 of 142 attempts in 82 mice. The calculated PWV in mice ranged from 220 to 850 cm/s with vasodilating anesthetics producing the low values and vasoconstricting agents producing the higher values. Thus PWV can be determined noninvasively in mice, is similar to that in other mammals, and responds as expected to vasoactive agents.

Animals↗
PubMed1997

The effect of somatostatin analogue on glucose homeostasis in conscious dogs.

Our aim was to clarify the effect of a somatostatin analogue (octreotide) on glucose flux in conscious dogs. We monitored the effects with catheters in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery before and after oral glucose administration. A significant increase of portal vein plasma flow after oral glucose was completely suppressed by both 4 and 1 micrograms/kg octreotide. All doses of octreotide (4, 1 and 0.1 microgram/kg) suppressed the glucose-induced increment of arterial glucose by dose response. Only 4 micrograms/kg of octreotide slightly but significantly suppressed hepatic glucose output. Marked suppression and delayed glucose absorption by the intestine was observed after 4 micrograms/kg of octreotide. One and 0.1 microgram/kg octreotide also suppressed glucose absorption without delayed absorption. Total amounts of absorbed glucose during 3h after oral glucose were 24 +/- 11% with 4 micrograms/kg of octreotide, 37 +/- 16% with 1 microgram/kg of octreotide, and 48 +/- 8% with 0.1 microgram/ kg of octreotide, all of which were significantly less than that of the control (73 +/- 8%). Using 4 micrograms/kg of octreotide treatment, the liver took up only 5 +/- 4% of the absorbed glucose, while the liver took up 35 +/- 6% and 43 +/- 9% of the absorbed glucose with 1 and 0.1 microgram/kg of octreotide. These latter values were similar to that of the control value of 34 +/- 4%. In conclusion, we found that octreotide administered before oral glucose had a remarkable stabilizing effect on postprandial glycemic surges. Both the direct inhibitory effect of octreotide on portal vein plasma flow and impaired glucose absorption would contribute to this decreased postprandial hyperglycemia, while its suppressive effect on other hormones, such as insulin and glucagon, did not seem to influence the reduction of hyperglycemia.

Animals↗