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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS1994

Microencapsulation of anti-tumor, antibiotic and thrombolytic drugs in microgravity

Encapsulation of cytotoxic or labile drugs enables targeted delivery and sustained release kinetics that are not available with intravenous injection. A new liquid-liquid diffusion process has been developed for forming unique microcapsules that contain both aqueous and hydrocarbon soluble drugs. Microgravity experiments, on sounding rockets (1989-92) and Shuttle missions STS-52 (1992) and STS-56 (1993) using an automated Materials Dispersion Apparatus, produced multi-lamellar microcapsules containing both Cis-platinum (anti-tumor drug) and iodinated poppy seed oil (a radiocontrast medium), surrounded by a polyglyceride skin. Microcapsules formed with amoxicillin (antibiotic) or urokinase (a clot dissolving enzyme), co-encapsulated with IPO, are still intact after two years. Microcapsules were formed with the drug so concentrated that crystals formed inside. Multi-layered microspheres, with both hydrophobic drug compartments, can enable diffusion of complementary drugs from the same microcapsule, e.g. antibiotics and immuno-stimulants to treat resistant infections or multiple fibrinolytic drugs to dissolve emboli. Co-encapsulation of enough radio-contrast medium enables oncologists to monitor the delivery of anti-tumor microcapsules to target tumors using computerized tomography and radiography that would track the distribution of microcapsules after release from the intra-arterial catheter. These microcapsules could have important applications in chemotheraphy of certain liver, kidney, brain and other tumors.

Morrison, Dennis R.↗
NASA NTRS1989

Vascular Responsiveness in Adrenalectomized Rats with Corticosterone Replacement

To determine under resting, unstressed conditions the circulating glucocorticoid concentrations that best maintain sensitivity of the vascular smooth muscle and baroreceptor responses to vasoactive agents, rats with vascular cannulas were sham-adrenalectomized (sham) or adrenalectomized (ADRX) and provided with four levels of corticosterone replacement (-100 mg fused pellets of corticosterone: cholesterol 0, 20, 40, and 80% implanted subcutaneously at the time of adrenal surgery). Changes in vascular and baroreflex responses were determined after intravenous injection of varying doses of phenylephrine and nitroglycerin with measurement of arterial blood pressure and heart rate in the conscious, chronically cannulated rats. Vascular sensitivity was decreased, and resting arterial blood pressure tended to be decreased in the adrenalectomized rats; both were restored to normal with levels of corticosterone (40%), which also maintained body weight gain, thymus weight, and plasma corticosteroid binding globulin concentrations at normal values. The baroreflex curve generated from the sham group was different from the curves generated from the ADRX+O, 20, and 40% groups, but not different from that of the ADRX+80% group, suggesting that the baroreflex is maintained by higher levels of corticosterone than are necessary for the maintenance of the other variables. These data demonstrate that physiological levels of corticosterone (40% pellet) restore vascular responsiveness, body weight, thymus weight, and transcortin levels to normal in ADRX rats, whereas higher levels (80% pellet) are necessary for restoration of the baroreflex.

Darlington, Daniel N.↗
NASA NTRS1999

Evaluation of Factors Affecting Powdered Drug Reconstitution in Microgravity

Owing to the high cost of transporting mass into space, and the small volume available for equipment in the Space Shuttle Orbiter and the International Space Station, refrigeration space is extremely limited. For this reason, there exists strong motivation for transporting certain drugs in powdered form so that they do not require refrigeration. When needed, the powdered drug will be mixed with saline to obtain a liquid form that may be injected intravenously. While this is a relatively simple task in a 1-G environment, there are some difficulties that may be encountered in 0-G. In non-accelerated spaceflight, gravitational and inertial forces are eliminated allowing other smaller forces, such as capillary forces and surface tension, to dominate the behavior of fluids. For instance, water slowly ejected from a straw will tend to form a sphere, while fluid in a container will tend to wet the inside surface forming a highly rounded meniscus. Initial attempts at mixing powdered drugs with saline in microgravity have shown a tendency toward forming foamy emulsions instead of the desired homogeneous solution. The predominance of adhesive forces between the drug particles and the interface tensions at the gas/liquid and solid/liquid interfaces drastically reduce the rate of deaggregation of the drug powder and also reduce the rate of absorption of saline by the powder mass. In addition, the capillary forces cause the saline to wet the inside of the container, thus trapping air bubbles within the liquid. The rate of dissolution of a powder drug is directly proportional to the amount of surface area of the solid that is exposed to liquid solvent. The surface area of drug that is in contact with the liquid is greatly reduced in microgravity and, as a result, the dissolution rate is reduced as well. The KC-135 research described here was aimed at evaluating the extent to which it is possible to perform drug reconstitution in the weightlessness of parabolic flight using standard pharmacological supplies. The experiment included a parametric assessment of possible factors affecting the reconstitution process. The specific questions that we wished to answer were: (1) Is it possible to reconstitute powdered drugs in weightlessness using standard pharmacological equipment? (2) What are the differences between drug reconstitution in a 1-G and a 0-G environment? (3) What techniques of mixing the drug powder and diluent are more successful? (4) What physical and chemical factors play a role in determining the success of mixing and dissolution? (5) Is it necessary to employ crewmember and equipment restraints during the reconstitution process?

Schaffner, Grant↗
NASA NTRS2001

Stimulated single fiber electromyography in the mouse: techniques and normative data

As the number of new transgenic mouse models of human neuromuscular disease continues to increase, the development of sophisticated electrophysiologic techniques for assessing the peripheral nervous system in these models has become important. Neuromuscular junction (NMJ) dysfunction, in particular, is often not detectable by morphologic or other techniques. To enable sensitive testing of murine NMJ function, we developed and tested a method for stimulated single fiber electromyography (S-SFEMG) in the gastrocnemius muscles of anesthetized mice. Jitter was assessed by measuring the mean consecutive latency difference (MCD) of single fiber responses to sciatic nerve stimulation at 2 HZ. Mean MCD values in normothermic mice were in the range of 6-8 micros for different strains, with no MCD values exceeding 25 micros. Reduced core temperature (to 29 degrees--30 degrees C) resulted in increased jitter, whereas intubation and mechanical ventilation of mice did not alter these values. Intraperitoneal and intravenous injection of vecuronium, however, resulted in progressively increased jitter followed by blocking in continuously monitored fibers. These observations validate the utility of S-SFEMG in mice as an index of NMJ function under a variety of physiologic conditions, and suggest that a high safety factor for neuromuscular transmission exists at mouse NMJs. Copyright 2001 John Wiley & Sons, Inc.

Non-NASA Center↗
NASA NTRS1998

Mechanisms underlying very-low-frequency RR-interval oscillations in humans

BACKGROUND: Survival of post-myocardial infarction patients is related inversely to their levels of very-low-frequency (0.003 to 0.03 Hz) RR-interval variability. The physiological basis for such oscillations is unclear. In our study, we used blocking drugs to evaluate potential contributions of sympathetic and vagal mechanisms and the renin-angiotensin-aldosterone system to very-low-frequency RR-interval variability in 10 young healthy subjects. METHODS AND RESULTS: We recorded RR intervals and arterial pressures during three separate sessions, with the patient in supine and 40 degree upright tilt positions, during 20-minute frequency (0.25 Hz) and tidal volume-controlled breathing after intravenous injections: saline (control), atenolol (0.2 mg/kg, beta-adrenergic blockade), atropine sulfate (0.04 mg/kg, parasympathetic blockade), atenolol and atropine (complete autonomic blockade), and enalaprilat (0.02 mg/kg, ACE blockade). We integrated fast Fourier transform RR-interval spectral power at very low (0.003 to 0.03 Hz), low (0.05 to 0. 15 Hz), and respiratory (0.2 to 0.3 Hz) frequencies. Beta-adrenergic blockade had no significant effect on very-low- or low-frequency RR-interval power but increased respiratory frequency power 2-fold. ACE blockade had no significant effect on low or respiratory frequency RR-interval power but modestly (approximately 21%) increased very-low-frequency power in the supine (but not upright tilt) position (P<0.05). The most profound effects were exerted by parasympathetic blockade: Atropine, given alone or with atenolol, abolished nearly all RR-interval variability and decreased very-low-frequency variability by 92%. CONCLUSIONS: Although very-low-frequency heart period rhythms are influenced by the renin-angiotensin-aldosterone system, as low and respiratory frequency RR-interval rhythms, they depend primarily on the presence of parasympathetic outflow. Therefore the prognostic value of very-low-frequency heart period oscillations may derive from the fundamental importance of parasympathetic mechanisms in cardiovascular health.

Non-NASA Center↗
NASA NTRS1994

Noradrenergic lesioning with an anti-dopamine beta-hydroxylase immunotoxin

Sympathectomy has been achieved by a variety of methods but each has its limitations. These include lack of tissue specificity, incomplete lesioning, and the age range of susceptibility to the lesioning. To circumvent these drawbacks, an immunotoxin was constructed using a monoclonal antibody against the noradrenergic specific enzyme dopamine beta-hydroxylase (D beta H) coupled via a disulfide bond to saporin, a ribosomal inactivating protein. Three days after intravenous injection of the anti-D beta H immunotoxin (50 micrograms) into adult Sprague-Dawley rats, 66% of neurons in the superior cervical ganglia were chromatolytic. Superior cervical ganglia neurons were poisoned in 1 day old and 1 week old (86% of neurons) neonatal rats following subcutaneous injection of 3.75 and 15 micrograms, respectively. The anti-D beta H immunotoxin will be a useful tool in the study of the peripheral noradrenergic system in adult and neonatal animals.

Non-NASA Center↗
NASA NTRS2011

Method for Impeding Degradation of Porous Silicon Structures

This invention relates to surface modification of porosified silicon (pSi) structures with poly(alkylene) glycols for the purpose of controlled degradation of the silicon matrix and tailored release of encapsulated substances for biomedical applications. The pSi structures are currently used in diverse biomedical applications including bio-molecular screening, optical bio-sensoring, and drug delivery by means of injectable/orally administered carriers and implantable devices. The size of the pores and the surface chemistry of the pSi structure can be controlled during the microfabrication process and thereafter. A fine regulation of the degradation kinetics of mesoporous silicon structures is of fundamental importance. Polyethylene glycols (PEGs) represent the major category of surface modifying agents used in classical drug delivery systems and in pharmaceutical dosage forms. PEGylation enables avoidance of RES uptake, thus prolonging circulation time of intravenously injectable nanovectors. PEG molecules demonstrate little toxicity and immunogenicity, and are cleared from the body through the urine (molecular weight, MW less than 30 kDa) or in the feces (MW greater than 30kDa). The invention focuses on the possibility of finely tuning the degradation kinetics of the pSi nanovectors and other structures through surface conjugation of PEGs with various backbone lengths/MWs. To prove the concept, pSi nanovectors were covalently conjugated to seven PEGs with MW from 245 to 5,000 Da and their degradation kinetics in physiologically relevant media (phosphate buffer saline, PBS pH7.4, and fetal bovine serum) was assessed by the elemental analysis of the Si using inductive coupled plasma atomic emission spectroscopy (ICP-AES). The conjugation of the PEG with lowest MW to the nanovectors surface did not induce any change in the degradation kinetics in serum, but inhibited degradation and consequently the release of orthosilicic acid into buffer. When PEGs with the longer chains were evaluated, Si mass loss from the nanovectors was slowed down, and the PEGylated structures were almost fully degraded within 18 24 hours in serum and within 48 hours in PBS. The most dramatic effect was observed for high MW PEGs 3,400 and 5,000 Da, which prominently inhibited the degradation of the systems, with complete degradation achieved only after four days. For these PEGs, during the early stages of the degradation, there was a lag period of little or no Si mass loss from the nanovector. The obtained profiles were in agreement with the erosion of the nanovector surface as observed by scanning electron microscopy.

Vilentchouk, Biana Godin↗
NASA NTRS2012

Improved Whole-Blood-Staining Device

Dramatic improvements have been made in NASA s Whole Blood Staining Device (WBSD) since it was last described in "Whole-Blood-Staining Device," NASA Tech Briefs, Vol. 23, No. 10 (October 1999), page 64. The new system has a longer shelf life, a simpler and more effective operational procedure, improved interface with instrumentation, and shorter processing time. More specifically, the improvements have targeted bag and locking clip materials, sampling ports, and air pocket prevention. The WBSD stains whole blood collected during spaceflight for subsequent flow cytometric analysis. In short, the main device stains white blood cells by use of monoclonal antibodies conjugated to various fluorochromes, followed by lysing and fixing of the cells by use of a commercial reagent that has been diluted according to NASA safety standards. This system is compact, robust, and does not require electric power, precise mixing, or precise incubation times. Figure 1 depicts the present improved version for staining applications, which is a poly(tetrafluoroethylene) bag with a Luer-lock port and plastic locking clips. An InterLink (or equivalent) intravenous- injection port screws into the Luer-lock port. The inflatable/collapsible nature of the bag facilitates loading and helps to minimize the amount of air trapped in the fully loaded bag. Some additional uses have been identified for the device beyond whole blood staining. The WBSD has been configured for functional assays that require culture of live cells by housing sterile culture media, mitogens, and fixatives prior to use [Figure 2(a)]. Simple injection of whole blood allows cell-stimulation culture to be performed in reduced gravity conditions, and product stabilization prior to storage, while protecting astronauts from liquid biohazardous materials. Also, the improved WBSD has reconstituted powdered injectable antibiotics by mixing them with diluent liquids [Figure 2(b)]. Although such mixing can readily be performed on Earth by shaking in glass vials, it cannot readily be performed this way in outer space without entraining air bubbles. The present device can be preloaded with the powder and diluent(s) in separate compartments. The powder and diluent( s) can be mixed, without introducing air bubbles, by removing the clip(s), then shaking. This use of the device could also be advantageous in terrestrial applications because it maintains the isolation of the constituents until the time of use.

Sams, Clarence F.↗
NASA NTRS1992

Changes in left ventricular function as determined by the multi-wire gamma camera at near presyncopal levels of lower body negative pressure

At presyncopal levels of lower body negative pressure (LBNP), we have frequently observed electrocardiographic responses that may be due to changes in cardiac position and/or shape, but could be indicative of altered myocardial function. To further investigate this, we evaluated cardiac function using a nuclear imaging technique in 21 healthy subjects (17 men and 4 women) after 30 minutes of supine rest and near the end of a presyncopal-limited LBNP exposure (LBNP averaged 65 plus or minus 3 mmHg at injection). Cardiac first pass images were obtained with a Multi-Wire Gamma Camera following an intravenous bolus injection of 30-50 millicurries of Tantalum-178. Manual blood pressures and electrocardiograms were obtained throughout the 3 minute graded LBNP protocol. Between rest and injection during LBNP, heart rate increased (P less than 0.01) from 67 plus or minus 3 beats per minute to 99 plus or minus beats per minute, systolic blood pressure decreased (P less than 0.01) from 110 plus or minus 3 mmHg to 107 plus or minus 3 mmHg and left ventricular ejection fraction (EF) decreased (P less than 0.01) from 0.57 plus or minus 0.02 to 0.48 plus or minus 0.02. During LBNP, ST segment depression of at least 0.5 mm occurred in 7 subjects. Subjects with ST depression had greater reductions (P = 0.05) in EF than subjects without ST depression (0.15 plus or minus 0.07 versus 0.005 plus or minus 0.03), but also tolerated greater levels (P less than 0.05) of negative pressure (88 plus or minus mmHg versus 69 plus or minus 5 mmHg). There was a significant relationship between presyncopal LBNP level and EF (R(exp 2) = 0.50, P less than 0.05). Our findings suggest there may be a decrease in systolic myocardial function at high levels of LBNP.

Pintner, R.↗
NASA NTRS2000

Effect of hyperosmotic solutions on salt excretion and thirst in rats

We investigated urinary changes and thirst induced by infusion of hyperosmotic solutions in freely moving rats. Intracarotid infusions of 0.3 M NaCl (4 ml/20 min, split between both internal carotid arteries) caused a larger increase in excretion of Na(+) and K(+) than intravenous infusions, indicating that cephalic sensors were involved in the response to intracarotid infusions. Intravenous and intracarotid infusions of hyperosmotic glycerol or urea (300 mM in 150 mM NaCl) had little or no effect, suggesting the sensors were outside the blood-brain barrier (BBB). Intracarotid infusion of hypertonic mannitol (300 mM in 150 mM NaCl) was more effective than intravenous infusion, suggesting that cell volume rather than Na(+) concentration of the blood was critical. Similarly, intracarotid infusion (2 ml/20 min, split between both sides), but not intravenous infusion of hypertonic NaCl or mannitol caused thirst. Hyperosmotic glycerol, infused intravenously or into the carotid arteries, did not cause thirst. We conclude that both thirst and electrolyte excretion depend on a cell volume sensor that is located in the head, but outside the BBB.

NASA Discipline Regulatory Physiology↗
NASA NTRS2003

Basic and clinical immunology

Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

Review↗
NASA NTRS1998

N(N)-nicotinic blockade as an acute human model of autonomic failure

Pure autonomic failure has been conceptualized as deficient sympathetic and parasympathetic innervation. Several recent observations in chronic autonomic failure, however, cannot be explained simply by loss of autonomic innervation, at least according to our current understanding. To simulate acute autonomic failure, we blocked N(N)-nicotinic receptors with intravenous trimethaphan (6+/-0.4 mg/min) in 7 healthy subjects (4 men, 3 women, aged 32+/-3 years, 68+/-4 kg, 171+/-5 cm). N(N)-Nicotinic receptor blockade resulted in near-complete interruption of sympathetic and parasympathetic efferents as indicated by a battery of autonomic function tests. With trimethaphan, small postural changes from the horizontal were associated with significant blood pressure changes without compensatory changes in heart rate. Gastrointestinal motility, pupillary function, saliva production, and tearing were profoundly suppressed with trimethaphan. Plasma norepinephrine level decreased from 1.1+/-0.12 nmol/L (180+/-20 pg/mL) at baseline to 0.23+/-0.05 nmol/L (39+/-8 pg/mL) with trimethaphan (P<.001). There was a more than 16-fold increase in plasma vasopressin (P<.01) and no change in plasma renin activity. We conclude that blockade of N(N)-cholinergic receptors is useful to simulate the hemodynamic alterations of acute autonomic failure in humans. The loss of function with acute N(N)-cholinergic blockade is more complete than in most cases of chronic autonomic failure. This difference may be exploited to elucidate the contributions of acute denervation and chronic adaptation to the pathophysiology of autonomic failure. N(N)-Cholinergic blockade may also be applied to study human cardiovascular physiology and pharmacology in the absence of confounding baroreflexes.

Non-NASA Center↗
NASA NTRS2001

Left ventricular, systemic arterial, and baroreflex responses to ketamine and TEE in chronically instrumented monkeys

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

Non-NASA Center↗
NASA NTRS1999

Tachyphylaxis to PACAP-27 after inhibition of NO synthesis: a loss of adenylate cyclase activation

The vasodilator effects of pituitary adenylate cyclase activating polypeptide (PACAP-27) are subject to tachyphylaxis in rats treated with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). This study examined whether this tachyphylaxis is due to the loss of vasodilator potency of cAMP generated by activation of the G(s) protein-coupled PACAP receptors. Five successive treatments with PACAP-27 (2 nmol/kg iv) produced pronounced vasodilator responses in saline-treated rats that were not subject to tachyphylaxis. The first injection of PACAP-27 (2 nmol/kg iv) in L-NAME (50 micromol/kg iv)-treated rats produced vasodilator responses of similar magnitude to those in saline-treated rats, whereas four subsequent injections produced progressively and markedly smaller responses. The hemodynamic effects of the membrane-permeable cAMP analog 8-(4-chlorophenylthiol)-cAMP (8-CPT-cAMP; 5-15 micromol/kg iv) were similar in L-NAME-treated rats and in L-NAME-treated rats that had received the five injections of PACAP-27. In addition, five injections of 8-CPT-cAMP (10 micromol/kg iv) produced pronounced vasodilator responses in saline- and L-NAME-treated rats that were not subject to the development of tachyphylaxis. These results suggest that a loss of biological potency of cAMP is not responsible for tachyphylaxis to PACAP-27 in L-NAME-treated rats. This tachyphylaxis may be due to the inability of the G(s) protein-coupled PACAP receptor to activate adenylate cyclase.

Non-NASA Center↗
NASA NTRS1999

Effect of color coding and subtraction on the accuracy of contrast echocardiography

BACKGROUND: Contrast echocardiography may be used to assess myocardial perfusion. However, gray scale assessment of myocardial contrast echocardiography (MCE) is difficult because of variations in regional backscatter intensity, difficulties in distinguishing varying shades of gray, and artifacts or attenuation. We sought to determine whether the assessment of rest myocardial perfusion by MCE could be improved with subtraction and color coding. METHODS AND RESULTS: MCE was performed in 31 patients with previous myocardial infarction with a 2nd generation agent (NC100100, Nycomed AS), using harmonic triggered or continuous imaging and gain settings were kept constant throughout the study. Digitized images were post processed by subtraction of baseline from contrast data and colorized to reflect the intensity of myocardial contrast. Gray scale MCE alone, MCE images combined with baseline and subtracted colorized images were scored independently using a 16 segment model. The presence and severity of myocardial contrast abnormalities were compared with perfusion defined by rest MIBI-SPECT. Segments that were not visualized by continuous (17%) or triggered imaging (14%) after color processing were excluded from further analysis. The specificity of gray scale MCE alone (56%) or MCE combined with baseline 2D (47%) was significantly enhanced by subtraction and color coding (76%, p<0.001) of triggered images. The accuracy of the gray scale approaches (respectively 52% and 47%) was increased to 70% (p<0.001). Similarly, for continuous images, the specificity of gray scale MCE with and without baseline comparison was 23% and 42% respectively, compared with 60% after post processing (p<0.001). The accuracy of colorized images (59%) was also significantly greater than gray scale MCE (43% and 29%, p<0.001). The sensitivity of MCE for both acquisitions was not altered by subtraction. CONCLUSION: Post-processing with subtraction and color coding significantly improves the accuracy and specificity of MCE for detection of perfusion defects.

Multicenter Study↗
NASA NTRS1999

Periventricular anteroventral third ventricle lesions diminish the pressor response produced by systemic injection of the N-methyl-D-aspartate receptor antagonist MK-801

This study examined whether electrolytic ablation of the periventricular anteroventral third ventricle (AV3V) would affect the increases in mean arterial blood pressure (MAP) and heart rate (HR) in conscious rats produced by systemic injection of the centrally acting N-methyl-D-aspartate (NMDA) receptor ion-channel blocker, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (MK-801; 250 microgram/kg, i.v.). MK-801 produced a smaller increase in MAP in rats with AV3V lesions than in sham-lesion rats (+36+/-2% vs. +52+/-5%, respectively, P<0.05). In contrast, MK-801 produced similar increases in HR in the AV3V- and sham-lesion rats (+28+/-3% vs. +22+/-4%, respectively, P>0.05). These findings demonstrate that the MK-801-induced pressor response is dependent upon the integrity of the AV3V region, whereas the MK-801-induced tachycardia is not. Copyright 1999 Elsevier Science B.V.

NASA Discipline Regulatory Physiology↗
NASA NTRS1999

Role of the anterior region of the third ventricle in the cardiovascular responses produced by systemic injection of a nitric oxide synthase inhibitor

This study examined whether a prior electrolytic lesion of the tissue surrounding the anteroventral third ventricle (AV3V) would affect the increase in mean arterial blood pressure (MAP) and the fall in heart rate (HR) produced by systemic injection of the nitric oxide synthesis (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 25 micromol/kg, i.v.) in conscious rats. L-NAME produced a smaller increase in MAP in AV3V-lesion than in sham-lesion rats (+19+/-3 vs. +40+/-3 mmHg, respectively; P<0.05). In contrast, L-NAME produced similar falls in HR in the AV3V-lesion and sham-lesion rats (-103+/-15 vs. -97+/-8 bpm, respectively; P<0.05). These findings demonstrate that the L-NAME-induced pressor response is dependent upon the integrity of the AV3V region, whereas the L-NAME-induced bradycardia is not. Copyright 1999 Elsevier Science B. V.

Non-NASA Center↗
NASA NTRS1999

Human sympathetic and vagal baroreflex responses to sequential nitroprusside and phenylephrine

We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects' ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses.

NASA Discipline Cardiopulmonary↗