Spillover Rate Research Articles

Cooperative R&D with product market competition

A simple model RJV is presented to examine the private and social incentives for cooperative R&D in the presence of product market competition. The key assumption to our analysis was that the spillover rate increases with cooperation in R&D and total industry profit decreases as the spillover rate increases due to intensified post-innovation competition. This leads to a negative impact of cooperative R&D, introducing a trade-off in the model. It is shown that private firms prefer a cooperative R&D to non-cooperative R&D competition when spillover rates are high and that the private incentive for cooperative R&D is less than the social incentive.

The Effect of Calcination on H2 Spillover in Pt/MoO3

Abstract The effect of catalyst preparation on the morphology of Pt/MoO 3 and the kinetics of hydrogen spillover have been qualitatively investigated in this first of two works. The morphology of the materials has been characterized by transmission electron microscopy and selective chemisorption, and the chemical state of Pt and the presence of chlorine have been determined with XPS and EDXS. The kinetics of hydrogen spillover in Pt/MoO 3 catalysts as a function of calcination temperature has been recorded with isothermal and temperature programmed reduction experiments. As the calcination temperature of the Pt/MoO 3 samples was increased, the initial rate of reduction (hydrogen uptake) increased and the temperature of initial reduction decreased. Characterization indicates that as calcination temperature is increased, overlayers of MoO 3 on Pt are produced, but additionally the Cl content associated with the Pt phase diminishes. The roles of overlayers and residual chlorine are postulated as follows: overlayers improve the degree of contact of MoO 3 with Pt crystallites, giving hydrogen access to more MoO 3 particles and increasing total H 2 uptake. On the other hand, the intrinsic rate of H 2 spillover from Pt particles into the bulk of MoO 3 appears to be controlled by the amount of residual Cl. When the Pt phase is well dispersed in a series of samples differing only by calcination temperature, it appears that the enhanced H 2 spillover rate stems not from a promotion due to MoO 3 overlayers, but by a lessening of spillover inhibition caused by chlorine.

Cooperative R&D and vertical product differentiation

A partial equilibrium model with vertical product differentiation, Coumot competition and quality determined by R&D expenses is analysed. Cooperative agreements on R&D entail higher levels of R&D, quality, output and welfare than at the non-cooperative equilibrium, under well denned conditions on spillover rates. This confirms, in a new setting, a well-known outcome of models with cost reducing R&D. Further, cooperation in R&D allows a larger number of firms to operate in the industry than in the non-cooperative case. Via a reduction in prices, a new source of social gains from cooperative research is identified.

Spillover rate from Pd to AI 20 3

To measure the rate of spillover on Pd/Al[sub 2]O[sub 3], the authors used interrupted TPR and isotope exchange before a complete TPR experiment. In this approach, [sup 12]CO was adsorbed at 300 K and the catalyst temperature was then raised in H[sub 2] flow to facilitate spillover. The heating ramp was interrupted before a significant amount of CH[sub 4] formed, and the sample was quickly cooled to 300 K. Then the catalyst was exposed to [sup 13]CO to displace any [sup 12]CO that remained on the Pd surface. At room temperature, gas phase CO readily exchanges with adsorbed CO on Pd. The authors also observed previously that gas phase CO does not exchange with CH[sub 3]O on Al[sub 2]O[sub 3] of Ni/Al[sub 2]O[sub 3]. Thus, any [sup 12]CO remaining on the catalyst after exchange was assumed to be present as [sup 12]CH[sub 3]O on the Al[sub 2]O[sub 3] surface. The amount of [sup 12]CH[sub 4] that formed during the subsequent TPR was thus a measure of how much [sup 12]CO had spilled over to the Al[sub 2]O[sub 3] since all the adsorbed [sup 12]CH[sub 3]O was hydrogenated to [sup 12]CH[sub 4]. A series of TRP experiments with different interruption temperaturesmore » yielded a TPR spectrum for spillover and an estimate of the activaiton energy for spillover.« less

The autonomic nervous system and cardiac arrhythmias.

Disturbed autonomic nervous 'balance' of the sympathetic nervous and vagal outflows to the heart potentiates the experimental development of ventricular arrhythmias in laboratory animals. For some time the best evidence for the occurrence of a similar phenomenon in humans was provided by the long QT interval syndrome, sufferers of which are very prone to develop serious ventricular arrhythmias and in whom evidence exists of abnormal anatomy and function of the cardiac sympathetic nerves. Recently the case for disturbed autonomic function causing clinical arrhythmias has become more broadly based. Reduced baroreflex sensitivity after myocardial infarction, and low heart rate variability, both of which rest largely on vagal underactivity, have been shown to be associated with substantially increased risk of subsequent sudden death. A second observation is that patients having recovered from unexpected ventricular tachycardia or ventricular fibrillation have markedly increased cardiac sympathetic activity compared with appropriate reference groups, based on measurements of the rate of spillover of the sympathetic neurotransmitter, noradrenaline, from the heart to plasma. These clinical findings support a role for cardiac autonomic dysfunction, specifically sympathetic activation and vagal withdrawal, in arrhythmogenesis. These observations are timely, given the recent demonstration that most conventional anti-arrythmics are of little benefit in preventing sudden death. A reappraisal of the anti-arrhythmic activity of beta-adrenergic blocking drugs, and evaluation of potential benefits of other pharmacological and non-pharmacological means of favourably altering cardiac autonomic function is now needed.

Increased norepinephrine spillover into the jugular veins in essential hypertension.

In essential hypertension sympathetic nerve firing is commonly increased. A central nervous system origin has been presumed but not tested directly. To estimate cerebral norepinephrine release in essential hypertension, spillover of norepinephrine into the cerebrovascular circulation was measured by isotope dilution, with high internal jugular venous sampling. Norepinephrine was released into the cerebrovascular circulation in both hypertensive patients and healthy volunteers and was present after administration of the ganglion blocker trimethaphan and in patients with sympathetic nervous failure, indicating that brain neurons and not cerebrovascular sympathetic nerves were the probable source. Although differing among hypertensive patients, norepinephrine spillover on average was higher in the hypertensive patients (153 +/- 41 pmol/min) than in healthy subjects (59 +/- 12 pmol/min; p less than 0.05), and was elevated in six of 17 patients, in whom the accompanying whole body norepinephrine spillover rate was higher than in the remaining 11 patients (p less than 0.01). To test for a possible link between brain norepinephrine release and human sympathetic nervous function, the effect of the tricyclic antidepressant desipramine (0.3 mg/kg i.v.) on both brain and whole body norepinephrine spillover was measured in healthy volunteers. Desipramine lowered the cerebrovascular spillover of norepinephrine, its precursor dihydroxyphenylalanine, and its metabolite dihydroxyphenylglycol by 50-80% and produced a mean fall of 35% in whole body norepinephrine spillover. One interpretation of these results is that human sympathetic nerve firing is dependent on norepinephrine release within the brain and that increased cerebral norepinephrine release may possibly be present in some patients with essential hypertension, underlying their higher sympathetic nerve firing rates.

Effect of desipramine on norepinephrine metabolism in humans: interaction with aging

To determine whether differences in neuronal reuptake contribute to age-related changes of sympathetic nervous system activity, we compared norepinephrine (NE) release and metabolism during [3H]NE infusion and decay in six young (age 19-26 yr) and seven older (age 61-73 yr) healthy nonobese subjects. Subjects were studied on a control day and on a separate day after desipramine (DMI; 125 mg orally), a neuronal reuptake blocker. Compartmental analysis of plasma NE specific activity was used to determine several NE kinetic parameters. Plasma NE levels and NE spillover rates were higher in the elderly. Although plasma NE was unaffected by DMI in both age groups, both the metabolic clearance rate of NE from plasma and the rate of NE spillover into plasma fell in young and older groups during DMI. Furthermore, DMI dramatically lowered the mass of NE in the extravascular compartment and the rate of NE entry into the extravascular compartment. Thus neuronal uptake blockade has major effects on NE release as well as NE metabolism in humans. However, age-related differences in NE kinetics cannot be explained by differences in neuronal uptake.

Assessment of sympathetic cardiovascular influences in man: Haemodynamic and humoral markers versus microneurography

Evaluation of sympathetic cardiovascular influences has important physiological, pathophysiological and clinical implications. This paper reviews some of the methods employed to measure these influences in man, along with their advantages and disadvantages. The most useful methods appear to be the measurement of plasma noradrenaline (particularly when modified to calculate spillover rate of noradrenaline) and direct recording of sympathetic nerve traffic. With the former, despite the technological advances in measurement, certain methodological problems remain, such as the separation of noradrenaline secretion from clearance. With the latter technique peripheral muscle and skin sympathetic activity can be measured separately but the question of regional vascular variability has still to be resolved. A combination of these two methods may represent the ideal approach. This review considers the complex problems associated with attempts to precisely quantify sympathetic cardiovascular influences in man.

Evidence of a Selective Increase in Cardiac Sympathetic Activity in Patients with Sustained Ventricular Arrhythmias

Although enhanced efferent cardiac sympathetic nervous activity has been proposed as an important factor in the genesis of ventricular arrhythmias and sudden cardiac death, direct clinical evidence has been lacking. We measured the rates of total and cardiac norepinephrine spillover into the plasma, which reflect respectively overall and cardiac sympathetic nervous activity, in 12 patients who had recovered from a spontaneous, sustained episode of ventricular tachycardia or ventricular fibrillation outside the hospital 4 to 48 days earlier. The results were compared with those from three age-matched reference groups without a history of ventricular arrhythmias: 12 patients with coronary artery disease, 6 patients with chest pain but normal coronary arteries, and 12 healthy, normal subjects. The patients who had had ventricular arrhythmias had reduced left ventricular ejection fractions, as compared with the patients with coronary artery disease or chest pain (mean [+/- SE], 46 +/- 3 percent vs. 58 +/- 4 percent and 69 +/- 5 percent, respectively; P less than 0.003). The rates of total norepinephrine spillover into the plasma were similar in the three reference groups, but 80 percent higher in the patients with ventricular arrhythmias (P less than 0.005). The rate of cardiac norepinephrine spillover was 450 percent higher in these patients (176 +/- 39 pmol per minute, as compared with 32 +/- 8 pmol per minute in the normal subjects; P less than 0.001), a disproportionate increase relative to the increase in total spillover, which indicated selective activation of the cardiac sympathetic outflow. This increase in cardiac norepinephrine spillover was probably caused by a reduction in left ventricular function. These results suggest that in some patients major ventricular arrhythmias are associated with and perhaps caused by sustained and selective cardiac sympathetic activation. We speculate that depressed ventricular function was present before the ventricular arrhythmia occurred, and that this resulted in reflex cardiac sympathetic activation, which in turn contributed to the genesis of the arrhythmia.

Propranolol and atenolol inhibit norepinephrine spillover rate into plasma in conscious spontaneously hypertensive rats

Radiotracer techniques capable of measuring norepinephrine clearance and spillover rate into plasma were used to test the hypothesis that the antihypertensive effects of propranolol and atenolol in conscious spontaneously hypertensive rats are associated with an inhibition of norepinephrine release from postganglionic sympathetic neurons. The 10%-15% fall in mean arterial pressure produced over 4 h by propranolol (1, 3.3 and 10 mg/kg, s.c.) and atenolol (1, 3.3 and 10 mg/kg, s.c.) was not dose-related, and only the largest dose of propranolol caused a significant bradycardia. Each dose of atenolol significantly lowered heart rate. The decrease in blood pressure caused by propranolol and atenolol was not related to the decrease in heart rate. Both propranolol and atenolol inhibited norepinephrine clearance by 12% to 16%. The 1 mg/kg doses of propranolol and atenolol significantly suppressed norepinephrine spillover rate by 21% and 32%, respectively, at 4 h postinjection. As the dose of propranolol was increased, the inhibition of norepinephrine spillover was reversed as plasma epinephrine concentration rose by 125%. The suppression of norepinephrine spillover rate caused by atenolol was more persistent but did diminish after the 10 mg/kg dose, when plasma epinephrine concentration was elevated by 55%. Both drugs suppressed plasma renin concentration, but the inhibition of norepinephrine spillover rate by propranolol and atenolol was not related to the fall in plasma renin concentration. By comparison, treatment with the adrenergic neuron blocking agent bretylium (5, 10, 20 and 40 mg/kg, s.c.) elicited a dose-related vasodepression with no change in heart rate or plasma renin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Norepinephrine spillover faithfully reflects renal sympathetic nerve activity in conscious rabbits

The relationship between directly recorded renal sympathetic nerve activity (RSNA) and simultaneous renal norepinephrine (NE) spillover rate across the kidney at rest and in response to changes in mean arterial pressure (MAP) was examined in six conscious rabbits. Integrated RSNA and renal NE spillover rate at rest were 5.1 +/- 1.1 microV/s and 20.8 +/- 3.0 ng/min, respectively. Sodium nitroprusside infusions at 10 and 20 microgram.kg-1.min-1 significantly increased RSNA by 42 +/- 14 and 84 +/- 14% and renal NE spillover rate 39 +/- 22 and 107 +/- 22% in response to falls in MAP of 15 +/- 2 and 21 +/- 2 mmHg (19 and 27%), respectively. During phenylephrine infusion at 8 micrograms.kg-1.min-1, RSNA and renal NE spillover rate significantly decreased by 65 +/- 14 and 67 +/- 16%, respectively, in response to a 15 +/- 2 mmHg (19%) rise in MAP. There was a highly significant positive correlation between changes in directly recorded RSNA and changes in renal NE spillover rate (r = 0.81, P less than 0.01). The ratio of renal to total NE spillover rate at rest was 0.44 +/- 0.06. This ratio was decreased during both sympathetic stimulation (0.30 +/- 0.04) and inhibition (0.26 +/- 0.06). This study indicates that the measurement of renal NE spillover rate is a useful reliable method for detecting the changes in RSNA and its relative contribution to overall sympathetic nerve activity in response to physiological stimuli in conscious rabbits.

Does regional norepinephrine spillover represent local sympathetic activity?

Regional spillover of norepinephrine (NE), based on isotope dilution and single-compartment steady-state kinetics, is considered one of the best parameters for estimating organ sympathetic activity. However, the effects of local changes in clearance of NE on the spillover have not yet been investigated. We studied local NE kinetics and clearance in the forearm of 10 healthy subjects using intra-arterial infusions of NE, tritiated NE, the neuronal uptake inhibitor desipramine, and tyramine, which competes with NE for the neuronal uptake carrier. Before and during complete blockade of neuronal uptake by desipramine the venous concentration-time curves for tritiated NE and for NE released by tyramine were biexponential, consistent with the presence of (at least) two compartments for circulating tritiated NE and for locally released NE. The time constants for tyramine-induced release of NE and, in the same subjects during desipramine infusion, for tritiated NE were almost equal at the same level of forearm blood flow. This argues against possible diffusion or transport differences for NE to and from the circulation and the synapse. The regional intrinsic clearance capacity (a measure of the maximal ability of an organ to irreversibly remove drug by all pathways in the absence of any flow limitations) for NE decreased in the forearm by 65% (p less than 0.01) during neuronal uptake blockade by desipramine; the forearm clearance decreased by 59% (p less than 0.001), whereas the spillover rate of NE increased from 33 +/- 5 to 63 +/- 11 pmol.min-1 (p less than 0.05). Nitroprusside-induced increments in blood flow increased the spillover of NE from 18 +/- 4 to 35 +/- 6 pmol.min-1 (p less than 0.01); the clearance of circulating NE also increased (by 58%, p less than 0.05), and the intrinsic clearance capacity remained unchanged. This demonstrates that regional spillover of NE is markedly influenced by local changes in clearance and flow. The new parameter plasma appearance rate of NE is proposed. Although also derived from isotope dilution, this parameter may better approximate the regional entry of NE into the blood pool than spillover. This is corroborated by the nonsignificant changes of plasma appearance rate of NE during our desipramine and nitroprusside infusions.

Effect of angiotensin-converting enzyme inhibition on renal norepinephrine spillover rate and baroreflex responses in conscious rabbits.

1. To evaluate the effects of angiotensin-converting enzyme (ACE) inhibition on sympathetic nerve activity, renal and total norepinephrine (NE) spillover rates were examined under control conditions and during enalaprilat infusion at rest and in response to sodium nitroprusside (SNP)-induced hypotension. 2. Resting renal and total NE spillover rate during enalaprilat infusion were similar to control values. 3. During SNP infusion at 10 micrograms/kg per min, renal NE spillover rate increased by 26% in enalaprilat-treated group and by 39% in controls, in response to falls in mean arterial pressure (MAP) of 25 and 19% respectively. 4. During sympathetic stimulation induced by SNP, total NE spillover rate was significantly increased in both groups, but the 50% (s.e.m. = 12) increase in the enalaprilat-treated group was less (P less than 0.05) than the 97% (s.e.m. = 16) change observed in controls. 5. Enalaprilat treatment resulted in a higher renal to total NE spillover ratio (P less than 0.05). The ratio fell in parallel in both groups during SNP-induced hypotension. 6. This study indicates that the sympathetic nervous system interacts dynamically with the renin-angiotensin system during hypotensive stimulation but this occurs predominantly at sites other than the kidney.

Effects of desipramine on sympathetic nerve firing and norepinephrine spillover to plasma in humans

In isolated organs, or when given in low dose intra-arterially, tricyclic antidepressant drugs are known to block reuptake of norepinephrine into sympathetic nerve varicosities, with a resultant increased norepinephrine washout. On the other hand, systemic administration of such drugs in humans reduces norepinephrine spillover to plasma. To clarify these seemingly contradictory findings, we have measured concurrently muscle sympathetic activity in the peroneal nerve (microneurography) and rates of norepinephrine spillover to plasma for the body as a whole and for the heart, the kidneys, and the forearm (radiotracer technique), both before and after intravenous infusion of desipramine, 0.5 mg/kg. Desipramine lowered the overflow of norepinephrine to plasma for the body as a whole and from the forearm and the kidneys (by 30-50%) but increased cardiac norepinephrine spillover by 25%. Both the number of sympathetic bursts per min in the peroneal nerve and their mean voltage amplitudes were markedly reduced after desipramine; total activity (bursts/min x mean burst amplitude) fell by approximately 90%. The effects of desipramine on norepinephrine spillover are explicable in terms of inhibition of central sympathetic outflow, balanced against the local blockade of transmitter reuptake. In most sites, the predominant effect is a reduction of norepinephrine overflow. For the heart, where reuptake is so important in transmitter disposition, the net effect is increased overflow.

Central sympathoinhibition and peripheral neuronal uptake blockade after desipramine in rabbits

Peripheral- and central nervous system (CNS)-mediated effects of desipramine (Des) on sympathetic nerves and the contribution of alpha 2-adrenoceptors to these effects were studied in conscious rabbits. Blood pressure, renal sympathetic nerve activity (SNA), and norepinephrine (NE) reuptake and spillover into plasma were measured before and after intracisternal (ic) or intravenous (i.v.) administration of Des. In other animals, NE spillover responses to i.v. Des were examined before and after alpha 2-adrenoceptor blockade with i.v. idazoxan. Treatment with i.v. Des blocked neuronal reuptake and decreased renal SNA but did not alter blood pressure or NE spillover. Decreased NE release by sympathetic nerves after i.v. Des was reflected by a decrease in the combined rate of NE reuptake and spillover. Treatment with ic Des (at 1.7% of the i.v. dose) decreased blood pressure and renal SNA and produced equivalent falls in NE reuptake and spillover, indicating little peripheral effect of centrally administered Des on the efficiency of neuronal reuptake. Thus Des had two distinct actions: the drug blocked neuronal reuptake by direct actions on nerve endings and reduced SNA by actions within the CNS. After ic Des, decreased SNA produced parallel falls in NE reuptake, spillover, and blood pressure. After i.v. Des, blockade of neurotransmitter reuptake increased NE concentrations at sympathoeffector junctions offsetting the fall in SNA, so that there was little change in NE spillover or blood pressure. However, after alpha 2-adrenoceptor blockade with i.v. idazoxan, NE spillover increased in response to i.v. Des. Thus the Des-induced decrease in NE release was partly mediated by an action of raised intrasynaptic NE concentrations on inhibitory alpha 2-adrenoceptors.

Biochemical evidence of sympathetic hyperactivity in human hypertension.

Radiotracer measures of norepinephrine overflow to plasma are well suited for studying both human sympathetic nervous system responses to mental stress and sympathetic nervous pathophysiology in human hypertension. With an experimental laboratory stressor (cognitive challenge), we noted a preferential activation of the cardiac sympathetic outflow; however, in fainting reactions ("vasovagal syncope"), which occur infrequently during the course of central venous catheter placement under local anesthesia, the converse was seen--an almost total withdrawal of cardiac sympathetic activity. In primary human hypertension (particularly in younger patients), a differentiated activation of the sympathetic outflow to the heart and kidneys is present, based on measurements of norepinephrine spillover to plasma. It is uncertain whether this is attributable to behavioral factors and represents a component of the defense reaction. We previously reported overflow of norepinephrine into the cerebrovascular circulation (with high internal jugular venous sampling) in humans. Because this is resistant to ganglion blockade, brain neurons--not the cerebrovascular sympathetics--are the presumed source. In a preliminary study, we found higher rates of norepinephrine spillover into the cerebrovascular circulation in patients with essential hypertension than in healthy subjects, suggesting that an underlying increase in central nervous system norepinephrine turnover may be the basis for the increased sympathetic outflow.

Neuronal Re-Uptake of Noradrenaline by Sympathetic Nerves in Humans

1. Plasma concentrations of [3H]dihydroxyphenylglycol, the intraneuronal metabolite of noradrenaline, were examined during intravenous infusion of [3H]noradrenaline in 43 subjects, to assess the nature of its formation. Noradrenaline re-uptake by sympathetic nerves was estimated in 11 subjects from the effects of neuronal uptake blockade with desipramine on noradrenaline clearance and plasma concentrations of [3H]dihydroxyphenylglycol and endogenous dihydroxyphenylglycol. In seven subjects noradrenaline re-uptake and spillover into plasma were examined before and during mental arithmetic or handgrip exercise. 2. During infusion of [3H]noradrenaline, plasma [3H]dihydroxyphenylglycol increased progressively, indicating its formation from previously stored [3H]noradrenaline leaking from vesicles as well as from [3H]noradrenaline metabolism immediately after removal into sympathetic nerves. Thus, to estimate noradrenaline re-uptake, the amount of [3H]dihydroxyphenylglycol derived from [3H]noradrenaline metabolized immediately after removal into the sympathetic axoplasm must be isolated from that derived from [3H]noradrenaline sequestered into vesicles. 3. At rest in the supine position the rate of noradrenaline re-uptake was 474 +/- 122 pmol min-1 kg-1, 9.5-fold higher than the rate of spillover of noradrenaline into plasma (49.6 +/- 6.4 pmol min-1 kg-1). Noradrenaline re-uptake and spillover into plasma were both increased during mental arithmetic and isometric handgrip exercise.

Formation and decomposition of methoxy species on a Ni/Al 2O 3 catalyst

Temperature-programmed reaction and desorption (TPR, TPD) were combined with isotope exchange to study the forward and reverse spillover of CO on a 5.1% Ni/Al 2O 3 catalyst. Carbon monoxide adsorbs nondissociatively on Ni at 300 K, but a fraction of adsorbed CO dissociates at 425 K. Carbon monoxide on Ni, in the presence of H 2 at elevated temperature, spills over to form CH 3O on Al 2O 3. This CH 3O can undergo reverse spillover to form both CO and carbon on Ni. For low CH 3O coverages, mostly carbon forms, but at higher CH 3O coverages, mostly CO forms on Ni. The reverse spillover is faster at higher temperatures, for longer times, and for higher CH 3O coverages. The rate of reverse spillover is comparable to the rate of CH 3O hydrogenation, and reverse spillover may be the limiting step in Ch 3O hydrogenation. The rate of carbon hydrogenation on Ni is significantly inhibited by the presence of CO adsorbed on Ni, perhaps because H 2 adsorption sites are blocked.

Pulmonary Clearance of Norepinephrine in Lambs

The lungs play an important role in the metabolism of vasoactive substances including endogenous amines. The role of pulmonary clearance of circulating norepinephrine has not been well defined in the young lamb (7-8 d of age). Using radiolabeled tracer norepinephrine in acutely instrumented lambs, we determined the in vivo pulmonary clearance and spillover rate of norepinephrine under baseline and hypoxic conditions. The fractional extraction of norepinephrine, the percent removed on a single pass through the pulmonary circulation, was 23 +/- 2%. The corresponding pulmonary clearance rate was 61 +/- 10 mL/kg/min and the net pulmonary norepinephrine removal rate was 0.41 +/- 0.14 nmol/kg/min. This clearance represented over 70% of whole body norepinephrine clearance. The spillover of synaptic norepinephrine was 0.22 +/- 0.13 nmol/kg/min. During hypoxia, animals showed significant increases in pulmonary artery pressure and resistance. Fractional extraction and norepinephrine decreased to 16 +/- 3%, p less than 0.005. Pulmonary clearance decreased to 31 +/- 7 mL/kg/min, and net pulmonary norepinephrine removal rate decreased to 0.27 +/- 0.07 nmol/kg/min. These results demonstrate that pulmonary clearance plays a significant role in norepinephrine clearance in 1-wk-old lambs. Alteration of norepinephrine clearance during physiologic states such as hypoxia may be important in the pathophysiology of altered pulmonary vascular resistance in newborn animals.

Spillover of CO and H 2 onto Al 2O 3 surfaces

Temperature-programmed reaction and desorption (TPR, TPD) for Al 2O 3 physically mixed with supported Ni catalysts show directly that one of the two CH 4 peaks observed previously for TPR (CO hydrogenation) on Ni/Al 2O 3 catalysts results from spillover of adsorbed species onto Al 2O 3 and is not due to adsorption on unreduced Ni sites. Temperature-programmed desorption from physical mixtures of Al 2O 3 and 19% Ni/Al 2O 3 indicates that the support-bound species is a HCO complex, and the stoichiometry is consistent with that of a CH 3O species. The concentration of CH 30 on Al 2O 3 is estimated to be approximately 1 μmol/m 2 A1203 (350 μmol/g A1203). Though CH 3O does not form on the SiO 2 support of Ni/SiO 2, it does form on physical mixtures of Ni/SiO 2 and Al 2O 3 that were prepared to provide good contact between particles. The rate of spillover appears to increase with the closer proximity between the support and the catalyst, higher Ni surface area, and better contact between the particles, but it also depends on the Al 2O 3 area available for transfer. The rate of CH 3O hydrogenation increases with Ni surface area. An unexplained loss in Ni surface area was observed with physical mixtures of Al 2O 3 and catalysts that were prepared by crushing the particles while wet.