MICE: a potential histopathological pitfall.
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Aged↗
Biomedical subjects
S Saleh
Publications and source records attributed to S Saleh.
The value of frozen section Pipelle endometrial biopsy as an outpatient procedure in the diagnosis of ectopic pregnancy.
This is a prospective study evaluating 28 patients who were suspected to have ectopic pregnancy. Frozen section Pipelle endometrial biopsy was performed as an outpatient procedure to look for the presence of chorionic villi in the specimen. The sensitivity of the frozen section endometrial biopsy in detecting the presence of chorionic villi was 13.3% and the specificity was 100%. The positive predictive value was 100% and the negative predictive value was 50%. We concluded that frozen section endometrial biopsy was not helpful in predicting intrauterine gestational process; therefore, it has a limited application in patients suspected to have ectopic pregnancy.
Ambulatory Surgical Procedures↗
Human neutrophil gene expression profiling following xenogeneic encounter with porcine aortic endothelial cells: the occult role of neutrophils in xenograft rejection revealed.
The role of innate immune cells in the recognition and activation of xenogeneic endothelium has always been considered secondary to the initial insult of xenoreactive natural antibodies (XNA) and complement. It was argued, however, that innate immune cells are capable of recognizing and activating xenogeneic endothelium in the absence XNA and complement. Here, we show that porcine aortic endothelial cells (PAECs) activate human neutrophils directly. This contact-dependent activation causes a transient calcium rise leading to increased reactive oxygen metabolite (ROM) production. Neutrophil gene-expression profiling using an adenylate uridylate-rich element-based microarray revealed a dramatic change in the neutrophil gene profiles upon exposure to PAECs. The PAEC-dependent neutrophil transcriptional activity was further confirmed by real-time polymerase chain reaction, which revealed a rapid increase in the mRNA message of a number of inflammatory cytokines. The activation of human neutrophils by PAECs was independent of galactose alpha1,3-galactose (Galalpha1,3-gal) structures, as inclusion of saturating concentrations of anti-Galalpha1,3-gal l antibodies had no significant effect. Furthermore, this activation was inhibited in the presence of the calcium chelator 1,2-bis(O-aminophenyl-ethane-ethane)-N,N,N',N'-tetraacetic acid-acetoxymethyl ester and the ROM inhibitor diphelylene iodonium. Our data illustrate the direct activation of innate immune cells by PAECs in the absence of XNA and complement and suggest alternative recognition sites between PAECs and human innate immune cells.
Animals↗
Immobilization of rolling NK cells on platelet-borne P-selectin under flow by proinflammatory stimuli, interleukin-12, and leukotriene B4.
Recruitment of leukocytes from bloodstream to extrahematic sites is tightly regulated by a variety of adhesion molecules that are expressed on the leukocytes and the vessel walls. In this manuscript, we describe the interactions between natural killer (NK) cells and activated, autologous platelets under physiologic flow. We found that surface-adherent human platelets are capable of recruiting human NK cells from flow and that this recruitment is characterized by an initial tethering followed by a rolling phase. Both phases were dependent on the adhesion molecule P-selectin and its counter-ligand on the NK cells (P-selectin glycoprotein ligand 1). Activation of rolling NK cells with inflammatory mediators commonly found in atherosclerotic plaques (interleukin-12 and leukotriene B4) causes immediate cessation of the rolling process and conversion to stationary adhesion. Blocking antibodies to the adhesion molecules membrane-activated complex-1 and leukocyte function antigen-1 inhibited this conversion. Our data suggest that platelets deposited at sites of vascular injury may provide an alternative substrate to endothelial cells for initial recruitment of NK cells to the vessel wall. This may result in extravasation of the NK cells if the appropriate chemotactic signal is applied. These data implicate the P-selectin and integrin family of adhesion molecules in the recruitment of NK cells to atherosclerotic sites.
Antibodies↗
Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia/reperfusion in rats.
Ischaemia/reperfusion (I/R) induced gastric lesion, is known to be linked with free radical (FR) formation. Therefore, this model was used to assess the antioxidant effects of Nigella sativa oil (N.O) and thymoquinone (TQ) on gastric mucosal redox state and gastric lesions, 1 and 24 h after reperfusion. Male Wistar rats were subjected to I/R and were injected with either N.O (2.5 and 5 ml/kg, p.o) or TQ (5, 20, 50 and 100 mg/kg, p.o). The results showed that I/R elevated the levels of lipid peroxide (LPX) and lactate dehydrogenase (LDH), while decreased those of reduced glutathione (GSH) and superoxide dismutase (SOD). These biochemical changes were accompanied by an increase in the formation of gastric lesions, which was reduced by either treatment. N.O tended to normalize the level of LDH, GSH and SOD. However, its effect to restore LPX was only seen 24 h after reperfusion. Moreover, the aforementioned parameters were nearly reinstated by TQ. On the other hand, high doses of TQ (50 and 100 mg/kg) severely reduced the GSH content, 1 h after reperfusion. These results indicate that both N.O and TQ possess gastroprotective effect against gastric lesions which may be related to the conservation of the gastric mucosal redox state.
Animals↗
The effect of Nigella sativa oil against the liver damage induced by Schistosoma mansoni infection in mice.
It has been reported that Nigella sativa oil possesses anticestode and antinematode actions. Besides, it produced a hepatoprotective effect in some models of liver toxicity. Therefore, our aim in this work was to study the effect of the Nigella oil (N.O) on Schistosomiasis mansoni infected mice. The oil was given in two dose levels (2.5 and 5 ml/kg, orally for two weeks) either alone or in combination with praziquantel (PZQ), the drug of choice for the treatment of schistosomiasis. Three aspects of drug action were investigated, the effect on Schistosomiasis mansoni infection, the effect on liver functions, and on redox state. The parasitological investigation included worm distribution, oogram pattern and ova count. Furthermore, liver granuloma diameters were measured. The biochemical parameters were the serum level of L-alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), albumin (Alb) and total protein. Moreover, to assess the antioxidant capability of the Nigella oil, four parameters were studied, viz., liver lipid peroxide (LPD) and reduced glutathione (GSH) contents and the activity of the defence enzyme superoxide dismutase (SOD) and lactate dehydrogenase (LDH). When the oil was given alone, it reduced the number of S. mansoni worms in the liver and decreased the total number of ova deposited in both the liver and the intestine. Furthermore, it increased the number of dead ova in the intestinal wall and reduced the granuloma diameters markedly. When N.O was administered in combination with PZQ, the most prominent effect was a further lowering in the dead ova number over that produced by PZQ alone. Concerning the biochemical parameters, infection of mice with S. mansoni produced a pronounced elevation in the serum activity of ALT, GGT, with a slight increase in AP level. However, it tended to reduce serum albumin level. These changes were accompanied with an alteration in the liver contents of LPD and GSH along with a significant decline in the activity of the cytosolic SOD and LDH. Administration of Nigella sativa oil succeeded partially to correct the previous changes in ALT, GGT, AP activity, as well as the Alb content in serum. However, it failed in the liver to restore either LPD and GSH content or LDH and SOD activities to normal level. These results suggest that Nigella sativa oil may play a role against the alterations caused by S. mansoni infection, an effect which may be induced partly by improving the immunological host system and to some extent with its antioxidant effect.
Analysis of Variance↗
Cross-reactivities between date palm (Phoenix dactylifera L.) polypeptides and foods implicated in the oral allergy syndrome.
BACKGROUND: Date fruit and pollen antigens share a number of cross-reactive epitopes. Date pollen has been shown to cross-react with antigens from Artemisia, cultivated rye (Secale cereale), Timothy grass (Phleum pratense), Sydney golden wattle (Acacia longifolia) and Bermuda grass (Cynodon dactylon) pollen. The present study was carried out to examine any cross-reactivities between date palm polypeptides and antigens of some common foods and vegetables that have been implicated in the oral allergy syndrome (OAS). Because most of such cross-reactivities in other allergens are attributable to the presence of carbohydrate chains and profilin, their role was also investigated. METHODS: Fresh extracts of 20 common fruits and vegetables were prepared. Putative date profilins were isolated by affinity chromatography using a poly L-proline column. Date fruit extracts were digested by various endoglycosidases and the immunoglobulin (Ig)E binding of the postdigest products was assessed in immunoblots. Rabbit antisera to whole date fruit extracts, Timothy grass profilin and putative date profilins, as well as human sera from date sensitive individuals were used in immunoblotting, ELISA and in inhibition experiments. RESULTS: IgG, ELISA and immunoblot results with the different rabbit antisera and date-sensitive atopic sera showed several antigenic cross-reactivities and similar cross-reactivities were seen with birch, date and timothy grass profilins. IgE, ELISA and immunoblot experiments with pooled date sensitive human sera showed a range of cross-reactivities with some food extracts. A number of the IgE cross-reactivities could be inhibited after preabsorption of pooled sera with date extracts. Sixty-six percent of individual date hypersensitive human sera bound IgE in putative date fruit profilin and their pooled sera bound IgE in birch pollen profilin. IgE-binding of the endoglycosidase digested date fruit extracts to atopic serum pool was restricted to only a very low molecular weight band of 6.5-8 kDa. CONCLUSION: These results indicate that date palm polypeptides share cross-reactive IgG and IgE epitopes with a number of foods implicated in the oral allergy syndrome, bind to birch and Timothy grass profilins and bind IgE through glycosyl residues. The clinical relevance of these cross-reactivities needs to be further elucidated.
Allergens↗
The exocyclic 1,N2-deoxyguanosine pyrimidopurinone M1G is a chemically stable DNA adduct when placed opposite a two-base deletion in the (CpG)3 frameshift hotspot of the Salmonella typhimurium hisD3052 gene.
The pyrimidopurinone adduct M1G [3-(2'-deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-a]-purin-10(3H)-one], formed in DNA upon exposure to malondialdehyde or base propenals, was incorporated into 5'-d(ATCGCMCGGCATG)-3'-5'-d(CATGCCGCGAT)-3', where M = M1G. This duplex contained a two-nucleotide bulge in the modified strand, and was named the M1G-2BD oligodeoxynucleotide. It provided a model for -2 bp strand slippage deletions associated with the (CpG)3-iterated repeat hotspot for frameshift mutations from the Salmonella typhimurium hisD3052 gene. M1G was chemically stable in the M1G-2BD duplex at neutral pH. The two-base bulge in the M1G-2BD oligodeoxynucleotide was localized and consisted of M1G and the 3'-neighbor deoxycytosine. The intrahelical orientation of M1G was established from a combination of NOE and chemical shift data. M1G was in the anti conformation about the glycosyl bond. The 3'-neighbor deoxycytosine appeared to be extruded toward the major groove. In contrast, when M1G was placed into the corresponding fully complementary (CpG)3-iterated repeat duplex at neutral pH, spontaneous and quantitative ring-opening to N(2)-(3-oxo-1-propenyl)-dG (the OPG adduct) was facilitated [Mao, H., Reddy, G. R., Marnett, L. J., and Stone, M. P. (1999) Biochemistry 38, 13491-13501]. The structure of the M1G-2BD duplex suggested that the bulged sequence lacked a cytosine amino group properly positioned to facilitate opening of M1G and supports the notion that proper positioning of deoxycytosine complementary to M1G is necessary to promote ring-opening of the exocyclic adduct in duplex DNA. The structure of the M1G-2BD duplex was similar to that of the structural analogue 1,N(2)-propanodeoxyguanosine (PdG) in the corresponding PdG-2BD duplex [Weisenseel, J. P., Moe, J. G., Reddy, G. R., Marnett, L. J., and Stone, M. P. (1995) Biochemistry 34, 50-64]. The fixed position of the bulged bases in both instances suggests that these exocyclic adducts do not facilitate transient bulge migration.
Alcohol Oxidoreductases↗
Synthesis and evaluation of novel aldose reductase inhibitors: Effects on lens protein kinase Cgamma.
PURPOSE: To synthesize novel aldose reductase inhibitors (ARI) that will normalize losses in protein kinase Cgamma (PKCgamma) observed during diabetes and galactosemia. METHODS: ARI were synthesized as tricyclic pyrones 1-6 (HAR-1 through HAR-6) from 3-methyl-1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran and (5aS,7S)-7-isopropenyl-3-methyl-1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran and were tested by inhibition of aldose reductase enzyme activity in vitro and by inhibition of polyol formation in lens epithelial cells in culture. Identified compounds were further tested in galactosemic rat lens in vivo for (a) normalized PKCgamma levels by Western blot, (b) reduction of phosphorylation of the gap junction protein Cx46 by analyses of co-immunoprecipitated proteins, and (c) by normalization of gap junction activity as measured by dye transfer. RESULTS: HAR-1 (1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran-3-acetic acid) was identified as an ARI with IC50 for aldose reductase inhibition at 2 nM. Polyol accumulation in lens epithelial cells was reduced by 80% at 10 microM. Rats fed 40% galactose for 9 days had an 80% reduction in PKCgamma levels which were normalized by HAR-1 at 100 mg/kg/day, fed orally. Phosphorylation of Cx46 was increased by 50% and this was normalized in HAR-1 treated rats (6 day treatment). Gap junction activity of galactosemic rats was reduced by 55% and this was normalized by HAR-1 in six day-treated rats. CONCLUSIONS: HAR-1 is a novel ARI which normalized losses of PKCgamma, changes in Cx46 phosphorylation, and gap junction activity.
Acetates↗
Ca(2+)-dependent production of reactive oxygen metabolites by human neutrophils in response to fluorinated propranolol analogues.
Fluorinated analogues of propranolol, namely trifluoroethyl propranolol (F3), pentafluoropropyl propranolol (F5), and heptafluorobutyl propranolol (F7), were found to induce reactive oxygen metabolite (ROM) production in human neutrophils in a dose-dependent manner. Preincubation of neutrophils with the calcium chelator BAPTA-AM or the tyrosine kinase inhibitor genistein inhibited this ROM production. Direct measurements of intracellular calcium revealed that these analogues caused a transient increase in intracellular calcium. In addition, these fluorinated analogues of propranolol caused a transient increase in actin polymerization. The effects of these compounds were found to be dependent upon the degree of fluorination of the parent compound. Propranolol, on the other hand, had no direct effect on ROM, calcium, or actin polymerization when added alone to neutrophils, although it did modify responses of cells to various stimuli. Whereas ROM production induced by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine was enhanced in a dose-dependent manner, the response to the particulate stimulus, latex beads, was abolished.
Actins↗
Structure of the malondialdehyde deoxyguanosine adduct M1G when placed opposite a two-base deletion in the (CpG)3 frameshift hotspot of the Salmonella typhimurium hisD3052 gene.
Malondialdehyde (MDA) is a toxic and mutagenic metabolite produced by lipid peroxidation, and prostaglandin biosynthesis. MDA induces frameshift mutations in tester strains of Salmonella typhimurium. It reacts with DNA, and at physiological pH the major adduct is a pyrimidopurinone formed by reaction with guanine: M1G [3-(2'-deoxy-beta-D-erythropentofuranosyl)pyrimido[1,2-alpha]-purin-10(3H)-one]. When site-specifically incorporated into a duplex oligodeoxynucleotide containing a frameshift-prone (CG)3 repeat derived from the Salmonella typhimurium hisd3052 gene, spontaneous opening of M1G to the N2-(3-oxo-1-propenyl)-dG species occurred. In this work d(ATCGCMCGGCATG), (M=M1G) was annealed to d(CATGCCGCGAT) to model the putative strand slippage intermediate which would precede a two base deletion in the (CG)3 iterated repeat. 1H NMR studies indicate that in contrast to the duplex DNA structure, M1G remains intact. A single bulge conformation exists. M1G and its 3'-neighbor cytosine are unpaired. The M1G is intrahelical and stacked, whereas the unpaired cytosine is poorly stacked and appears to be extrahelical.
Base Pairing↗
Dimensional stability and weight changes of tissue conditioners.
The dimensional stability of tissue conditioners characterizes the ability of the materials to yield accurate functional impressions of oral mucosa. This study evaluated the linear dimensional changes with time of six tissue conditioners (COE Comfort, FITT, GC Soft-Liner, Hydro-Cast, SR-Ivoseal and Visco-Gel) using a travelling microscope, and relationship between these changes and weight changes. The absorption and solubility of these materials were also determined. The percentage changes in dimension and weight in water storage were measured at 2 (baseline), 8 and 24 h, and 2, 4, 7, 14 and 21 days after specimen preparation. All materials except SR-Ivoseal exhibited shrinkage and weight loss during water storage, whilst SR-Ivoseal exhibited expansion and an increase in weight. The percentage solubility for all materials except SR-Ivoseal was higher than the percentage absorption. A positive linear relationship was found between the percentage changes in linear dimension and those in weight (r=0.797 - 0.986, P < 0.05). Water absorption and solubility of the materials were found to be associated with dimensional changes. The results suggest that the period recommended for forming functional impressions would be 24 h after insertion in the mouth. In addition, it is important to select tissue conditioners suitable for functional impressions because of the wide ranges of dimensional stability among the materials.
Absorption↗
Inhibition of endotoxin-induced vascular hyporeactivity by 4-amino-tetrahydrobiopterin.
The 4-amino analogue of tetrahydrobiopterin (4-ABH(4)) is a potent pterin-site inhibitor of nitric oxide synthases (NOS). Although 4-ABH(4) does not exhibit selectivity between purified NOS isoforms, a pronounced selectivity of the drug towards inducible NOS (iNOS) is apparent in intact cells. This work was carried out to investigate the potential iNOS selectivity of 4-ABH(4) in isolated pig pulmonary and coronary arteries. Endothelium-dependent relaxations of pig pulmonary and coronary artery strips to bradykinin or calcium ionophore A23187 were inhibited by 4-ABH(4) in a concentration-dependent manner. Half-maximal inhibition was observed at 60 - 65 microM (pulmonary artery) and 200 - 250 microM 4-ABH(4) (coronary artery). Pig coronary artery strips precontracted with 0.1 microM 9, 11-dideoxy-9, 11-methanoepoxy-prosta-glandin F(2alpha) (U46619) showed a time-dependent relaxation (monitored for up to 18 h) upon incubation with 1 microg ml(-1) lipopolysaccharide (LPS). Addition of 10 microM 4-ABH(4) 1 h after LPS led to a pronounced inhibition of the LPS-triggered relaxation, whereas the pterin antagonist had no effect when given> or =4 h after LPS. Incubation of pulmonary and coronary artery strips with 1 microg ml(-1) LPS attenuated contractile responses to norepinephrine (1 microM) and U46619 (0.1 microM). This hyporeactivity of the blood vessels to vasoconstrictor agents was inhibited by 4-ABH(4) in a concentration-dependent manner [IC(50)=17.5+/-5.9 microM (pulmonary artery) and 20.7+/-3 microM (coronary artery)]. The effect of 0.1 mM 4-ABH(4) was antagonized by coincubation with 0.1 mM sepiapterin, which is known to supply intracellular BH(4) via a salvage pathway. These results demonstrate that 4-ABH(4) is a fairly selective inhibitor of iNOS in an in vitro model of endotoxaemia, suggesting that this drug and/or related pterin-site NOS inhibitors may be useful to increase blood pressure in severe infections associated with a loss of vascular responsiveness to constrictor agents caused by endotoxin-triggered iNOS induction in the vasculature.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Reproductive outcome after abdominal myomectomy.
This is a retrospective study to evaluate the reproductive outcome after abdominal myomectomy. Seventy myomectomies were performed at the Jordan University Hospital over a 10-year period. Fifty-five percent of these patients were infertile at the time of surgery. The most common indication for the myomectomy was a combination of infertility and menorrhagia (34.2%). A successful pregnancy was recorded in 53.8% of those who attempted pregnancy after the operation.
Journal Article↗
Nosocomial infections in the intensive care units at a university hospital in a developing country: comparison with National Nosocomial Infections Surveillance intensive care unit rates.
OBJECTIVE: As a measure of the quality of care provided to patients in the intensive care unit, comparison of nosocomial infection rates with those of the National Nosocomial Infection surveillance was completed during a 3-year observation period. DESIGN: The study design was a prospective study during 3 years between 1993 and 1995. During that period, patients at the medical/surgical and neurosurgical intensive care units and the high-risk nursery were surveyed for nosocomial infections. Device use, bloodstream infection, urinary tract infection, and ventilator-associated pneumonia nosocomial infection rates were calculated and compared with the National Nosocomial Infection Surveillance published rates for the same period. SETTING: The study setting was the medical/surgical intensive care unit, the neurosurgical intensive care unit, and the high-risk nursery at the Jordan University Hospital. RESULTS: Overall infection rates were 17.2 per 100 patients in the medical/surgical intensive care unit, 14.2 to 18.5 per 100 patients in the neurosurgical intensive care unit, and 13.4 to 73.5 per 100 patients in the high-risk nursery. When compared with the weight of the infants, these rates were 61.9 to 94 per 100 in infants weighing <1500 g, 26 to 30.8 per 100 patients in infants weighing >1500 g to 2500 g, and 11.7 to 14.4 per 100 in infants weighing >2500 g. Whereas device use was moderate, bloodstream infection and ventilator-associated pneumonia rates were >90th percentile for National Nosocomial Infection Surveillance in the high-risk nursery, and urinary tract infection was >90th percentile in the medical/surgical and neurosurgical intensive care units. Nosocomial infections at the intensive care units in developing countries need further investigation and control.
Adolescent↗
Evidence for IL-12-activated Ca2+ and tyrosine signaling pathways in human neutrophils.
The cytokine IL-12 is proposed to play a bridging role between innate and adaptive immunity. Here we demonstrate that IL-12 binds specifically to human neutrophils. This binding leads to a transient increase in 1) intracellular free calcium due to its release from membrane-enclosed stores and its influx from extracellular medium, 2) actin polymerization, and 3) tyrosine phosphorylation. IL-12 treatment also leads to a concentration-dependent increase in reactive oxygen metabolite production. The effect of IL-12 is blocked by neutralizing Abs to IL-12. Inhibition of either calcium transient or tyrosine phosphorylation causes inhibition of reactive oxygen metabolite production. However, inhibition of actin polymerization enhances IL-12-induced oxidase activation. Our data suggest 1) a direct role for IL-12 in the activation of human neutrophils, and 2) a calcium-dependent signaling pathway for IL-12.
Actins↗
Activation of naive xenogeneic but not allogeneic endothelial cells by human naive neutrophils: a potential occult barrier to xenotransplantation.
Here we demonstrate that human neutrophils, the predominant circulating leukocytes in intimate contact with endothelial cells lining the vasculature, directly recognize xenogeneic endothelium independently of xenoreactive natural antibody and complement. A rapid and calcium-dependent activation of native (unstimulated) xenogenic endothelial cells by human neutrophils leads to 1) translocation of P-selectin from the Wiebel-Palade bodies to the surface of xenogeneic endothelial cells, 2) increased synthesis and expression of vascular cell adhesion molecule-1 on the xenogeneic endothelial cells, and 3) enhanced killing of the xenogeneic endothelium by natural killer cells. Our data directly implicate naive neutrophils as major early participants in xenograft recognition and endothelial activation independent of xenoreactive natural antibodies and complement.
Animals↗
Evidence for preserved cardiopulmonary baroreflex control of renal cortical blood flow in humans with advanced heart failure. A positron emission tomography study.
BACKGROUND: The effect of cardiopulmonary baroreflexes on the renal circulation in healthy humans and patients with heart failure is unknown because of the technical limitations of studying the renal circulation. Positron emission tomography (PET) imaging is a new method to measure renal cortical blood flow in humans that is precise, rapid, reproducible, and noninvasive. The purpose of this study was to compare the effect of acute cardiopulmonary baroreceptor unloading by phlebotomy on regional blood flow in healthy humans and humans with advanced heart failure. METHODS AND RESULTS: We compared renal cortical blood flow and forearm blood flow in 10 healthy volunteers and 8 patients with heart failure (left ventricular ejection fraction, 0.24 +/- 0.02) during cardiopulmonary baroreceptor unloading with phlebotomy (450 mL). The major findings of this study are: (1) At rest, renal cortical blood flow is markedly diminished in humans with heart failure compared with healthy humans (heart failure, 2.4 +/- 0.1 versus healthy, 4.3 +/- 0.2 mL.min-1.g-1, P < .001). (2) In healthy humans, during phlebotomy, forearm blood flow decreased substantially (basal, 3.3 +/- 0.4 versus phlebotomy, 2.6 +/- 0.3 mL.min-1.100 mL-1, P = .02) and renal cortical blood flow decreased slightly but significantly (basal, 4.3 +/- 0.2 versus phlebotomy, 4.0 +/- 0.3 mL.min-1.g-1, P = .01). (3) The small magnitude of reflex renal vasoconstriction is not explained by the inability of the renal circulation to vasoconstrict, since the cold pressor stimulus induced substantial decreases in renal cortical blood flow in healthy subjects (basal, 4.4 +/- 0.1 versus cold pressor, 3.7 +/- 0.1 mL.min-1.g-1, P = .003). (4) In humans with heart failure, during phlebotomy, forearm blood flow did not change (basal, 2.6 +/- 0.3 versus phlebotomy, 2.7 +/- 0.2 mL.min-1.100 mL-1, P = NS), but renal cortical blood flow decreased slightly but significantly (basal, 2.4 +/- 0.1 versus phlebotomy, 2.1 +/- 0.1 mL.min-1.g-1, P = .01). (5) The cold pressor stimulus induced substantial decreases in renal cortical blood flow in patients with heart failure (basal, 2.9 +/- 0.1 versus cold pressor, 2.3 +/- 0.1 mL.min-1.g-1, P = .008). Thus, in patients with heart failure, there is an abnormality in cardiopulmonary baroreflex control of the forearm circulation but not the renal circulation. CONCLUSIONS: This study demonstrates the power of PET imaging to study normal physiological and pathophysiological reflex control of the renal circulation in humans and describes the novel finding of selective dysfunction of cardiopulmonary baroreflex control of one vascular region but its preservation in another in patients with heart failure.
Adult↗