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PubMed1996

Analysis of cerebral blood flow autoregulation in neonates.

The dynamic response of cerebral autoregulation to spontaneous changes in arterial blood pressure (ABP) is described by the relationship between cerebral blood flow velocity (CBFV) and resistance-area product (RAP). CBFV was measured with Doppler ultrasound in the middle cerebral artery and ABP with an intra-arterial catheter in 66 neonates. Spontaneous changes in mean ABP were automatically detected and the maximum derivative was used to synchronize the coherent averaging of corresponding CBFV and RAP transients. These were classified into two groups corresponding to intact (group A) or impaired (group B) autoregulation. The cross correlation between RAP and CBFV indicates a significant relationship with a time delay of 5 s for group A. The frequency response of RAP was estimated by the cross spectra with CBFV. Groups A and B present a similar amplitude spectra but the phase spectra of group A lags that of group B. The impulse responses of the two groups are also markedly different and were used to simulate the velocity response to a 5% step change in ABP. Impulse responses were also obtained for four different levels of pCO2 showing that hypercapnia leads to an impulse response similar to that of group B (impaired autoregulation). This method can be used to extend the usual dichotomic classification adopted in clinical studies of autoregulation.

Blood Flow Velocity↗

PubMed2004

Engineering of quorum-sensing systems for improved production of alkaline protease by Bacillus subtilis.

AIM: Engineering of Rap-Phr quorum-sensing systems of Bacillus subtilis and subsequent evaluation of the transcription of the aprE gene, encoding a major extracellular alkaline protease. METHODS AND RESULTS: Addition of synthetic Phr pentapeptides to the growth medium, or overproduction of pre-Phr peptides, slightly improved the transcription of the aprE gene in B. subtilis. Disruption of certain rap genes similarly improved the transcription of the aprE gene. The production of extracellular proteolytic enzymes was increased when the rapA mutation was combined with a degU32 (Hy) mutation for hyper-secretion. CONCLUSIONS: Certain Rap-Phr systems of B. subtilis seem to suppress extracellular AprE production. Although this may be an important feature under natural conditions, repression of AprE production by these systems is not desirable under fermentation conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: Although the levels of aprE transcriptional increase in this study are moderate, engineering of Rap-Phr systems may be used to improve the yield of Bacillus strains that are used for the production of the extracellular protease AprE, or Bacillus strains that use of the aprE promoter for the production of a heterologous protein.

Bacillus subtilis↗

PubMed1993

Supraventricular tachycardia, right atrial pressure, atrial natriuretic peptide and polyuria--a necessary sequence?

The release of atrial natriuretic peptide (ANP) may be stimulated by tachycardia and the evidence from human studies suggests that this is mediated by a rise in atrial pressure. However, animal experiments suggest that tachycardia can by itself increase ANP levels without increasing right atrial pressure (RAP). We report here the case of a healthy volunteer who had supraventricular tachycardia (SVT) whilst participating in a study evaluating the relationship between changes in RAP and changes in ANP. The ANP levels rose following the SVT but there was no rise in RAP, suggesting that heart rate can modulate ANP levels without changes in RAP as has been shown in animal experiments.

Adult↗

PubMed1993

Tumour necrosis factor and interleukin-6 production induced by components associated with merozoite proteins of Plasmodium falciparum.

P. falciparum merozoite antigens, merozoite surface protein-1 (MSP-1) and rhoptry associated protein-1 (RAP-1), were shown to be liberated into the supernatant of in vitro parasite cultures and to be included in the endotoxin-like exoantigen complex, previously designated Ag7. Material affinity purified from culture supernatants, using immobilized monoclonal antibodies specific for RAP-1 or MSP-1, stimulated normal human mononuclear cells to produce TNF and IL-6 in vitro. However, stimulation of TNF was absent, and that of IL-6 was reduced, when the antigens were purified from detergent extracts of infected erythrocytes. These results indicate that the RAP-1 and MSP-1 proteins themselves do not stimulate the production of TNF. Instead, other components associating with these exoantigens may be responsible for the TNF production. Mouse antisera blocking TNF production stimulated by P. yoelii exoantigens also blocked TNF production stimulated by material affinity purified from P. falciparum culture supernatants using RAP-1 specific monoclonal antibody, indicating the conserved structure of the TNF inducing component.

Animals↗

PubMed1987

Recurrent abdominal pain in childhood. Relationship to psychological adjustment of children and families: a preliminary study.

The study investigated the prevalence of emotional and behavioural problems in children with recurrent abdominal pain (RAP), the sensitivity of RAP children to a painful stimulus, and the attitudes shown by RAP mothers to issues of health and illness. Three groups of children were compared including two groups with RAP, one in which an organic cause for the pain was found, and one where no organic cause was identified. The third group consisted of pain-free children from the general community. No consistent patterns of differences was identified between the groups on the measures used. Possible reasons for the findings are discussed and recommendations made for further research in this area.

Abdomen↗

PubMed1995

An in vitro evaluation of venous cannula in a simulated partial (femoro-femoral) cardiopulmonary bypass circuit.

We designed a study to evaluate three factors (siphon gradient [PH], the right atrial pressure [RAP], and the inferior vena caval flow [IVCF]) to be optimized to maximize the venous drainage flow (DF) during partial cardiopulmonary bypass using eight venous cannulas of three different types and an original model circuit. The relationship between venous DF and the three factors is indicated by the multiple regression equation DF2 = alpha PH + beta RAP + gamma IVCF2 + C, where alpha, beta, and gamma are regression estimates and C is a constant. Multiple regression analysis results showed that DF was positively correlated with PH and RAP and negatively correlated with IVCF. A long cannula with 12 side holes and 60 cm long was considered to be useful to yield the optimal venous drainage flow under the condition of maintenance of the flow balance (DF and ICVF) and the pressure balance (RAP and IVCP) at the zero point. Moreover, this model may allow extensive research in flow dynamics of venous cannula without involving human subjects.

Atrial Function↗

PubMed1995

Modulation of the arterial coronary blood flow by asynchronous activation with ventricular pacing.

UNLABELLED: This study aims to test the assumptions that: (1) coronary arterial flow is attenuated in an early activated region by ventricular pacing; (2) asynchronous mechanical activation caused by ventricular pacing under controlled perfusion pressure and intact coronary tone is associated with reduced coronary flow compared to atrial pacing; and (3) abolishment of vascular tone under controlled perfusion pressure diminishes the expected difference in blood flow between atrial and ventricular pacing. Blood flow velocity (BFV) in the left anterior descending (LAD) and the left circumflex arteries (CFX) and a wall thickening index were measured in 14 open-chest dogs under normal conditions, and constant perfusion pressure. Four pacing sites were used: right atrium (RAp), mid-right ventricle (RVp), mid-left ventricle (LVp), and left ventricular apex (Apexp). Pacing modes were either sequential ventriculoatrial (VA) (protocol A, n = 7), or sequential atrioventricular (AV) (protocol B, n = 7), with a shorter AV difference (30 msec) than normal. RESULTS: BFV was decreased in the LAD during RVp and Apexp pacing by 9.7%-12.9% versus RAp and by 11.6%-14.6% versus LVp (P < 0.05). No BFV variations were observed in the CFX. Flow velocity conductance (FVC = mean blood flow velocity divided by the mean aortic pressure) was higher by 16%-28% in the CFX for the three ventricular pacing sites versus the atrial pacing, and higher by 14.1% +/- 6.1% only in LVp versus RAp pacing in the LAD (P < 0.05). Wall thickening index reduced during ventricular pacing in all three ventricular sites by 50%-64% (P < 0.05) compared to atrial pacing. Under constant perfusion pressure, LAD blood flow decreased with ventricular pacing as compared to right atrial pacing; this was particularly pronounced during the diastolic phase (16.6%-45.5%, P < 0.02). Normalized oscillatory flow amplitude (OFAn) was reduced in RVp pacing compared to RAp and LVp pacing (16.2 +/- 3.5 and 21.7% +/- 4.1%, respectively, P < 0.03). The variations in blood flow and OFAn disappeared with adenosine-mediated maximum vasodilatation. SUMMARY: (1) Mean and phasic flows are reduced in the early activated LAD region by ventricular pacing (RVp, Apexp). (2) Under controlled perfusion pressure and intact vascular tone, ventricular pacing compromises blood flow compared with atrial pacing. (3) This effect disappears when vascular tone is eliminated by intracoronary injection of adenosine, suggesting that the coronary autoregulation is responsible for some of the effects.

Animals↗

PubMed1994

Depressed concentrations of oxytocin and cortisol in children with recurrent abdominal pain of non-organic origin.

The purpose of the present study was to measure plasma concentrations of oxytocin, cortisol and prolactin in children with recurrent abdominal pain of non-organic origin (RAP). Forty children with RAP and 34 controls, matched for age and sex, participated in the study. A blood sample was collected after an overnight fast in association with clinical examinations. Oxytocin, cortisol and prolactin levels were determined by radioimmunoassay (RIA). Oxytocin and cortisol concentrations in the children with RAP were found to be significantly reduced compared with those of the controls (approximately 24 versus 63 pmol/l for oxytocin and 160 versus 300 nmol/l for cortisol, respectively). The low oxytocin and cortisol levels persisted at a second examination 3 months later. No significant differences in the prolactin levels were observed between RAP and controls.

Abdominal Pain↗

PubMed1999

Detection of equine antibodies to babesia caballi by recombinant B. caballi rhoptry-associated protein 1 in a competitive-inhibition enzyme-linked immunosorbent assay.

A competitive-inhibition enzyme-linked immunosorbent assay (cELISA) was developed for detection of equine antibodies specific for Babesia caballi. The assay used recombinant B. caballi rhoptry-associated protein 1 (RAP-1) and monoclonal antibody (MAb) 79/17.18.5, which is reactive with a peptide epitope of a native 60-kDa B. caballi antigen. The gene encoding the recombinant antigen was sequenced, and database analysis revealed that the gene product is a rhoptry-associated protein. Cloning and expression of a truncated copy of the gene demonstrated that MAb 79/17.18.5 reacts with the C-terminal repeat region of the protein. The cELISA was used to evaluate 302 equine serum samples previously tested for antibodies to B. caballi by a standardized complement fixation test (CFT). The results of cELISA and CFT were 73% concordant. Seventy-two of the 77 serum samples with discordant results were CFT negative and cELISA positive. Further evaluation of the serum samples with discordant results by indirect immunofluorescence assay (IFA) demonstrated that at a serum dilution of 1:200, 48 of the CFT-negative and cELISA-positive serum samples contained antibodies reactive with B. caballi RAP-1. Four of five CFT-positive and cELISA-negative serum samples contained antibodies reactive with B. caballi when they were tested by IFA. These data indicate that following infection with B. caballi, horses consistently produce antibody to the RAP-1 epitope defined by MAb 79/17.18.5, and when used in the cELISA format, recombinant RAP-1 is a useful antigen for the serologic detection of anti-B. caballi antibodies.

Amino Acid Sequence↗

PubMed1975

Long-term prognosis in children with recurrent abdominal pain.

The present study is a follow-up of 34 cases admitted to a paediatric department with recurrent abdominal pain (RAP) in 1942 and 1943. 45 persons without a history of RAP were selected at random and included as controls. Using a questionnaire, there was a higher incidence of gastrointestinal symptoms among persons with a history of RAP during childhood than among controls (P less than 0.05). 18 of the original 34 cases who still had symptoms were re-examined; 11 had a clinical picture consistent with a diagnosis of irritable colon, 5 had a picture compatible with both irritable colon and peptic ulcer/gastritis, and 2 had duodenal ulcer. Abdominal pains occurred no more frequently among children of parents who had had RAP during childhood than among children of parents without such a history. However, there was a higher incidence of abdominal pain among children of parents who were complaining of abdominal discomfort at the time of the investigation than among children whose parents were without such symptoms (P less than 0.005).

Abdomen↗

PubMed1978

Precipitating antibodies to cellular antigens in Sjögren's syndrome, rheumatoid arthritis, and other organ and nonorgan-specific autoimmune diseases.

The prevalence of three precipitating antibodies, anti-SS-A anti-SS-B, and rheumatoid arthritis precipitin (RAP), reacting with an extract of the human lymphoid cell line Wil2, was studied in the sicca syndrome, Sjögren's syndrome with rheumatoid arthritis, rheumatoid arthritis, various seronegative spondyloarthritides, and organ and nonorgan-specific autoimmune disease. Anti-SS-A and snti-SS-B occurred most frequently in the sera of patients with the sicca syndrome whereas RAP occurred most frequently in seropositive rheumatoid arthritis sera. However, the data did not support previous studies where patients with sicca syndrome had a high incidence of anti-SS-A and/or -SS-B antibodies but had a low frequency of RAP, and patients with Sjögren's syndrome in association with rheumatoid arthritis had a high incidence of RAP but a low incidence of anti-SS-A and/or -SS-B. Instead the three antibodies were present in both forms of Sjögren's syndrome. This suggested a difference in the diseases in the UK compared to the USA, or that these antibodies do not have the more subtle diagnostic specificity that was originally suggested.

Aged↗

PubMed1984

Control of right atrial pressure at constant cardiac output suppresses volume natriuresis in anesthetized rats.

The blood volume of anesthetized rats was expanded acutely by 33% with donor blood while a caval snare was gradually tightened so that right atrial pressure (RAP) was prevented from rising (n = 6). In control experiments (n = 5) an aortic snare was used to hold mean arterial blood pressure near the values found in the experimental series. However, RAP was allowed to change freely and increased by 1.6 +/- 0.4 mmHg (1 mmHg = 133.322 Pa) during volume expansion. When the two groups were compared, there were no significant differences between their mean arterial blood pressures (near 110 mmHg) or in their cardiac outputs (near 0.25 mL X min-1 X g body weight-1). There were, however, significant differences between their renal responses to the volume load. When RAP was free to change, the rate of volume excretion (V) increased to 30 +/- 15 (SEM) microL X min-1 X g kidney weight-1 (KW) from its control value of 3.49 +/- 0.31 and the rate of sodium excretion (UNaV) increased to 3.59 +/- 0.20 muequiv X min-1 X g KW-1 from its preinfusion value of 0.42 +/- 0.10. When RAP was not allowed to increase during volume loading, V and UNaV did not change from their respective preinfusion values (2.99 +/- 0.46 microL X min-1 X g KW-1 and 0.35 +/- 0.10 muequiv X min-1 X g KW-1). The results imply that during acute blood volume expansion increased central vascular pressure is a prerequisite for the homeostasis of body water and salt.

Anesthesia↗

PubMed2004

Left atrial dilatation resulting from chronic mitral regurgitation decreases spatiotemporal organization of atrial fibrillation in left atrium.

Atrial conduction properties have been shown to differ among animal atrial fibrillation (AF) models of rapid atrial pacing (RAP), chronic mitral regurgitation (MR), and control. We hypothesized that these conduction differences would continue with the onset of AF, which would affect AF spatiotemporal organization, resulting in model-specific characteristics of AF. With frequency domain analysis of electrograms acquired from high-density optical mapping, AF from the right (RA) and left (LA) atrium in animals with RAP and MR were compared with control animals. At follow-up, the hearts were excised and perfused, and optical action potentials were recorded from a 2 x 2-cm area each of the RA and LA free wall with a 16 x 16 photodiode array. AF was induced with extra stimuli, several 2.4-s AF episodes were recorded in each dog, and a fast Fourier transform was calculated. The dominant frequency (DF) was determined, and the organization (organization index, OI) was calculated as the ratio of the area under the dominant peak and its harmonics to the total area of the spectrum. All possible pairs of electrograms for each episode were cross-correlated. LA AF in the chronic MR model showed an increase in the highest DF, the number of DF domains, and in frequency gradient compared with AF in control or RAP models. In addition, there was a decrease in OI and in the correlation coefficients in the LA of the MR model. These results suggest that the AF substrate in the MR model may be different from that of control or RAP models.

Animals↗

PubMed2006

Structural atrial remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in canine models of structural and electrical atrial remodeling.

Several animal models of atrial fibrillation (AF) have been developed that demonstrate either atrial structural remodeling or atrial electrical remodeling, but the characteristics and spatiotemporal organization of the AF between the models have not been compared. Thirty-nine dogs were divided into five groups: rapid atrial pacing (RAP), chronic mitral regurgitation (MR), congestive heart failure (CHF), methylcholine (Meth), and control. Right and left atria (RA and LA, respectively) were simultaneously mapped during episodes of AF in each animal using high-density (240 electrodes) epicardial arrays. Multiple 30-s AF epochs were recorded in each dog. Fast Fourier transform was calculated every 1 s over a sliding 2-s window, and dominant frequency (DF) was determined. Stable, discrete, high-frequency areas were seen in none of the RAP or control dogs, four of nine MR dogs, four of six CHF dogs, and seven of nine Meth dogs in either the RA or LA or both. Average DFs in the Meth model were significantly greater than in all other models in both LA and RA except LA DFs in the RAP model. The RAP model was the only one with a consistent LA-to-RA DF gradient (9.5 +/- 0.2 vs. 8.3 +/- 0.3 Hz, P < 0.00005). The Meth model had a higher spatial and temporal variance of DFs and lower measured organization levels compared with the other AF models, and it was the only model to show a linear relationship between the highest DF and dispersion (R(2) = 0.86). These data indicate that structural remodeling of atria (models known to have predominantly altered conduction) leads to an AF characterized by a stable high-frequency area, whereas electrical remodeling of atria (models known to have predominantly shortened refractoriness without significant conduction abnormalities) leads to an AF characterized by multiple high-frequency areas and multiple wavelets.

Animals↗

PubMed1990

Chronic effects of a physiological dose of ANP on arterial pressure and renin release.

To determine the long-term effects of a physiological dose of atrial natriuretic peptide (ANP) on renin release, the renin response to reductions in renal arterial pressure (RAP) was studied during 1) control conditions and 2) acute and 3) chronic (5 days) intravenous infusion (5 ng.kg-1.min-1) of alpha-human ANP in conscious dogs maintained on a normal sodium intake. Renal perfusion pressure was servo controlled at reduced levels with an inflatable occluder placed around the abdominal aorta just above the renal arteries. Under control conditions, reducing RAP by 30 and 40 mmHg increased plasma renin activity (PRA) 4- to 5- and 9- to 10-fold, respectively. Acute ANP infusion had no significant effect on either basal levels of PRA or the PRA response to reduced RAP. During chronic ANP infusion there was a two- to threefold increment in plasma ANP concentration and approximately a twofold increase in urinary sodium excretion on day 1; however, there were no significant long-term changes in mean arterial pressure, basal PRA, or the levels of PRA achieved during reductions in RAP. These findings indicate that the changes in plasma ANP concentration that occur under normal physiological conditions do not appreciably alter either basal PRA or renin release in response to renal hypotension in conscious sodium-replete dogs studied under resting conditions.

Animals↗

PubMed1994

Influence of cardiac output distribution on cardiac filling pressure during rest and dynamic exercise in dogs.

The distribution of cardiac output (CO) between compliant and noncompliant organs is an important determinant of the slope of the relationship predicted between CO and right atrial pressure (RAP). However, curves relating CO to RAP at rest are shifted rightward (higher CO) and upward (higher RAP) by exercise with no change in slope, despite a large rise in the fraction of CO directed to noncompliant muscle vasculature, which is predicted to decrease the slope. We sought to test whether reductions in CO imposed during rest and exercise are accompanied by changes in its distribution that would favor constant slopes. Six dogs had atrioventricular block produced surgically and had blood flow transducers implanted on the ascending aorta and the terminal aorta. Total muscle blood flow (MBF) was estimated from terminal aortic flow by assuming that all of the increase in CO in mild dynamic exercise is directed to muscle. CO was reduced by lowering ventricular pacing rate at rest and during graded treadmill exercise (2 and 4 miles/h at 0% grade). Exercise increased the fraction of CO directed to muscle (MBF/CO) (P < 0.001). The effect of changes in CO on MBF/CO depended on exercise intensity (P < 0.01). At rest, MBF/CO fell from 0.53 to 0.45 when CO was reduced; this is expected to reduce the slope of the measured relationship between CO and RAP. During exercise at 2 miles/h, MBF/CO changed little when CO was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1981

Control of glomerular filtration rate by circulating angiotensin II.

Previous studies from our laboratory have provided evidence that the renin-angiotensin system plays an important role in controlling glomerular filtration rate (GFR) through an efferent arteriolar vasoconstrictor mechanism; however, the relative importance of circulating versus intrarenally formed angiotensin II (ANG II) in this control has not been determined. In the present study, the role of circulating ANG II in regulating GFR during reduced renal artery pressure (RAP) was examined in sodium-depleted dogs. After 90 min of infusion of the angiotensin-converting enzyme inhibitor SQ 14225, which presumably inhibited formation of both circulating and intrarenal ANG II, reduction of RAP to 81 +/- 2 mmHg resulted in marked decreases in GFR, filtration fraction (FF), and calculated efferent arteriolar resistance (RE), whereas renal blood flow (RBF) was maintained approximately 40% above initial control levels determined before SQ 14225 infusion. Replacement of circulating ANG II during SQ 14225 infusion, by intravenous infusion of ANG II at rates that decreased RBF to control levels, increased GFR, FF, and RE to levels not significantly different from control while RAP was maintained constant by aortic constriction. These observations suggest that circulating ANG II plays an important role in regulating RE and GFR during reductions in RAP. The importance of intrarenally formed ANG II in controlling GFR remains to be determined.

Angiotensin II↗

PubMed1988

Control of sodium excretion in NE-ACTH hypertension: role of pressure natriuresis.

The purpose of this study was to test the hypothesis that, in the presence of high circulating catecholamines, ACTH decreases renal excretory capability and that its natriuretic effects are caused by increased renal arterial pressure (RAP). In six conscious dogs, norepinephrine (NE, 0.4 micrograms.kg-1.min-1) alone for 5 days caused a small but significant rise in arterial pressure (AP) from 102 +/- 6 to 115 +/- 8 mmHg. An infusion of ACTH (600 micrograms/day) for 7 days, superimposed upon the NE, caused a further rise in AP to a plateau of 143 +/- 9 mmHg after 5 days while cumulative sodium balance fell to -149 +/- 41 meq by the 7th day. Cumulative water balance fell to -660 +/- 232 ml by the 3rd day and then increased slightly. In contrast, when ACTH infusion was repeated during NE infusion while RAP was prevented from increasing using a servo-controlled aortic occluder, cumulative sodium balance increased to 197 +/- 35 meq and AP rose from 108 +/- 5 to 168 +/- 5 mmHg after 7 days and did not plateau. Cumulative water balance rose to 2,325 +/- 445 ml. Thus, in dogs receiving a background infusion of NE, ACTH causes moderate hypertension and natriuresis. However, when RAP is not allowed to rise, ACTH is associated with sodium retention and severe systemic hypertension, suggesting that the natriuretic effects of ACTH are caused by increased RAP and that the natriuresis blunts the chronic hypertensive effects of ACTH.

Adrenocorticotropic Hormone↗