Biomedical subjects

H Lu

Publications and source records attributed to H Lu.

At least 289 records · Page 16Linked to original sources

PubMed1997

Defective cell migration in an ovarian cancer cell line is associated with impaired urokinase-induced tyrosine phosphorylation.

The urokinase receptor (u-PAR), a protein anchored to cell membrane by a glycosyl phosphatidylinositol, plays a central role in cancer cell invasion and metastasis by binding urokinase plasminogen activator (u-PA), thereby facilitating plasminogen activation. Plasmin can promote cell migration either directly or by activating metalloproteinases that degrade some of the components of the extra cellular matrix. However, the IGR-OV1-Adria cell line contains the u-PAR but does not migrate even in the presence of exogenous u-PA, although the parental IGR-OV1 cell line migrates normally in the presence of u-PA. We therefore investigated the role of cell signalling for u-PA induced cell locomotion. We show that cell migration induced by u-PA-u-PAR complex is always associated with tyrosine kinase activation for the following reasons: (1) the blockade of the u-PAR by a chimeric molecule (albumin-ATF) inhibits not only the u-PA-induced cell migration, but also the signalling in IGR-OV1 line; (2) the binding of u-PA to u-PAR on non-migrating IGR-OV1-Adria cells was not associated with tyrosine kinase activation; (3) the inhibition of tyrosine kinase also blocked cell migration of IGR-OV1. Therefore tyrosine kinase activation seems to be essential for the u-PA-induced cell locomotion possibly by the formation of a complex u-PAR-u-PA with a protein whose transmembrane domain can ensure cell signalling. Thus, IGR-OV1 and IGR-OV1-Adria cell lines represent a good model for the analysis of the mechanism of u-PA-u-PAR-induced cell locomotion.

Blotting, Western↗

PubMed1997

The in vivo time course for elimination of adrenalectomy-induced apoptotic profiles from the granule cell layer of the rat hippocampus.

Although apoptotic cellular degeneration has been reported to be extremely rapid with the use of in vitro models, the time needed to clear apoptotic neurons in the in vivo brain is unknown. In this study we used a simple morphological approach to solve this problem. Four days after adrenalectomy (ADX), all of the operated rats morphologically displayed hippocampal granule cell apoptosis that was prevented completely by corticosterone replacement immediately after ADX. Therefore, we intravenously injected the rats with corticosterone 4 d after ADX and subsequently maintained them on corticosterone replacement in saline drinking water. This corticosterone replacement could protect healthy granule cells promptly and continuously against hormone-deficient apoptosis, because the normal glucocorticoid receptor immunoreactivity within the granule cell nuclei, which disappeared after ADX, was identified 1 hr after corticosterone replacement was started, and this effect persisted for several days. However, this corticosterone treatment could not prevent the irreversible apoptosis of the already degenerated granule cells at various stages of the same progressive apoptotic process. Then we successively traced the disappearance of apoptotic granule cells throughout the hippocampus at different time points by Nissl and silver staining. Given that the apoptotic cells at the earliest stage of the degenerating process when the ADX rats received corticosterone injection were the last to disappear, the period from corticosterone injection until the disappearance of the last degenerating debris of apoptotic cells was taken to represent the time course for elimination of apoptotic neurons in vivo. We discovered that the elimination of apoptotic granule cells took 72 hr.

Adrenalectomy↗

PubMed1997

Specific cleavage of the large subunit of replication factor C in apoptosis is mediated by CPP32-like protease.

Recent evidence suggests that the growing family of cysteine proteases related to the interleukin-1beta-converting enzyme (ICE) is of central importance in mediating apoptosis. Proteolytic cleavage of a small group of cellular substrates by these enzymes in association with the onset of apoptosis has been reported. In the present study, we searched a protein data base for potential death substrates possessing the CPP32 cleavage site, DEVD, and identified several candidates including RFC140, the large subunit of replication factor C, which we subsequently demonstrated to be specifically cleaved in a variety of cell types undergoing apoptosis in response to different cytotoxic agents, whereas no degradation is observed in a cell line resistant to etoposide-induced apoptosis. The abrogation of RFC140 cleavage in apoptotic extracts by Ac-DEVD-CHO, a potent inhibitor of CPP32, together with the finding that a CPP32 consensus cleavage sequence, DEVD, exists in RFC140, suggests that CPP32 or a close relative is responsible for RFC140 degradation in apoptosis.

Animals↗

PubMed1997

LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice.

To better define the specific function of Mac-1 (CD11b) versus LFA-1 (CD11a) and the other CD11 integrins in vivo, we have disrupted murine CD11b by targeted homologous recombination in embryonic stem cells and generated mice which are homozygous for a mutation in CD11b. A null mutation was confirmed by Southern blotting, RNase protection assay, immunohistochemistry, and flow cytometry. Neutrophils isolated from mice deficient in Mac-1 were defective in adherence to keyhole limpet hemocyanin-coated glass, iC3b-mediated phagocytosis, and homotypic aggregation. When challenged by thioglycollate intraperitoneally, Mac-1-deficient mice had similar levels of neutrophil accumulation in the peritoneal cavity at 1, 2, and 4 h. Treatment with mAb to LFA-1 blocked 78% of neutrophil accumulation in Mac-1-deficient mice and 58% in wild-type mice. Neutrophil emigration into the peritoneal cavity 16 h after the implantation of fibrinogen-coated disks was not reduced in Mac-1-deficient mice whereas neutrophil adhesion to the fibrinogen-coated disks was reduced by > 90%. Neutrophils from Mac-1-deficient mice also showed reduced degranulation. Our results demonstrate that Mac-1 plays a critical role in mediating binding of neutrophils to fibrinogen and neutrophil degranulation, but is not necessary for effective neutrophil emigration, which is more dependent upon LFA-1.

Animals↗

PubMed1997

A new method for straightening DNA molecules for optical restriction mapping.

We have developed an improved method of straightening DNA molecules for use in optical restriction mapping. The DNA was straightened on 3-aminopropyltriethoxysilane-coated glass slides using surface tension generated by a moving meniscus. In our method the meniscus motion was controlled mechanically, which provides advantages of speed and uniformity of the straightened molecules. Variation in the affinity of the silanized surfaces for DNA was compensated by precoating the slide with single-stranded non-target blocking DNA. A small amount of MgCl2 added to the DNA suspension increased the DNA-surface affinity and was necessary for efficient restriction enzyme digestion of the straightened surface-bound DNA. By adjusting the amounts of blocking DNA and MgCl2, we prepared slides that contained many straight parallel DNA molecules. Straightened lambda phage DNA (48 kb) bound to a slide surface was digested by EcoRI restriction endonuclease, and the resulting restriction fragments were imaged by fluorescence microscopy using a CCD camera. The observed fragment lengths showed excellent agreement with their predicted lengths.

Bacteriophage lambda↗

PubMed1997

Skeletal muscle ventricles, left ventricular apex-to-aorta configuration. 1 to 11 weeks in circulation.

BACKGROUND: Skeletal muscle ventricles (SMVs) have been used in animals in a variety of configurations to provide circulatory assistance. Long-term survival and function have been demonstrated. Our laboratory recently obtained promising short-term hemodynamic data in a left ventricular apex-to-aorta model. METHODS AND RESULTS: SMVs were constructed from the left latissimus dorsi muscle in five adult mongrel dogs. After a 3-week period of vascular delay and 5 to 7 weeks of electrical conditioning, valved conduits were used to connect the left ventricular apex to the SMV and the SMV to the descending aorta. The SMV was then stimulated to contract during cardiac diastole. Initial measurements showed a significant increase in the mean femoral diastolic pressure (62 +/- 6 versus 51 +/- 5 mm Hg, P < .05). There was also a decrease in the left ventricular tension-time index (11.5 +/- 2.5 versus 14.6 +/- 2.1 mm Hg.s, P < .05), indicating a decrease in the work requirement of the left ventricle. During SMV stimulation, the majority of flow (65%) was through the SMV circuit and was associated with reversal of flow in the proximal descending thoracic aorta. The longest-surviving animal survived 76 days, at which time pressure augmentation was still seen (mean femoral diastolic pressure, 63 +/- 0.9 versus 50 +/- 1.2 mm Hg, P < .05). CONCLUSIONS: Survival beyond the acute setting is possible with this model. Diastolic pressure augmentation can be effectively maintained over time.

Animals↗

PubMed1997

Acceleration of the folding of hen lysozyme by trifluoroethanol.

The refolding of a partially structured state of hen lysozyme formed in 60% (v/v) 2,2,2-trifluoroethanol (TFE) has been studied using hydrogen exchange pulse labelling monitored by 2D 1H NMR, and by stopped flow fluorescence and CD measurements. The results are compared with similar studies of the refolding of the protein denatured in 6 M guanidine hydrochloride (GuHCl). Two conclusions have emerged from these studies. First, provided that the refolding conditions are identical, the two denatured states fold with very similar kinetics, despite the fact the extensive secondary structure is present in the TFE-denatured state but not in the protein denatured in 6 M GuHCl. This arises because of the rapid equilibration of structure in the species formed in the initial stage of folding. Second, whilst addition of GuHCl to the refolding buffer decreases the rate of folding, low concentrations of TFE increase the rate of folding. The result is consistent with slow steps in the refolding of lysozyme being associated primarily with the reorganisation of hydrophobic interactions rather than of hydrogen bonded structure.

Animals↗

PubMed1997

Neutrophil CD18-dependent arrest on intercellular adhesion molecule 1 (ICAM-1) in shear flow can be activated through L-selectin.

Neutrophil emigration through endothelial cells under shear flow involves several adhesion processes including cell rolling, arrest, and transmigration. Rolling is mediated by selectins, while arrest and transmigration both require activated CD18 integrins. One mode of CD18 activation is via selectins expressed on neutrophils and endothelial cells. We have recently reported that cross-linking of L-selectin (CD62L) resulted in the rapid activation of CD18-dependent adhesion. In the current study, we examine whether binding of E-selectin (CD62E) and L-selectin can activate neutrophil CD18-dependent adhesion under shear flow. Human ICAM-1 (CD54) and E-selectin were co-transfected into L cells. Neutrophil capture, rolling, and arrest on these monolayers were quantitated in a parallel plate flow chamber at a wall shear stress of 2.0 dyne/cm2. Under these conditions, E-selectin supported cell capture and rolling on the monolayer, but did not trigger CD18-mediated cell arrest within 200 microm of rolling. However, when neutrophils were treated with anti-L-selectin mAb and cross-linked with a secondary mAb, approximately 50% of the cells arrested within 54 microm. Cell arrest was also observed in response to IL-8 stimulation. A subthreshold level of IL-8 in combination with L-selectin cross-linking potentiated the level of cell arrest due to either stimulus alone. The transition to cell arrest involved both LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18). Blocking either subunit alone failed to reduce arrest, while blocking both molecules with mAbs reduced the number to baseline levels. These data support the conclusion that L-selectin, but not E-selectin, can signal the transition from neutrophil rolling to cell arrest under shear flow.

Adult↗

PubMed1997

Changes of phosphatidylcholine-specific phospholipase C in hepatocarcinogenesis and in the proliferation and differentiation of rat liver cancer cells.

The biological significance of phosphatidylcholine-specific phospholipase C (PC-PLC) in hepatocarcinogenesis and the proliferation and differentiation of rat liver cancer cells was investigated. The Ca2+-dependent activities of PC-PLC gradually increased during N-nitrosodiethylamine (DEN)-induced hepatocarcinogenesis and peaked at weeks 18-20 when the tumour formed. There was a close relationship between Ca2+-dependent PC-PLC activities and cellular DNA content, membranous gamma-glutamyltranspeptidase (gamma-GT), and tyrosine protein kinase. In contrast, Ca2+-independent PC-PLC activities decreased during hepatocarcinogenesis. Similarly, when CBRH-7919 rat liver cancer cells were treated with phorbol 12-myristate 13-acetate, a proliferation stimulator of the cells, gamma-GT and Ca2+-dependent activities of PC-PLC and the expression of alpha-fetoprotein increased significantly. However, when these cells were induced by retinoic acid to differentiate, Ca2+-dependent PC-PLC and gamma-GT activities decreased significantly, together with alpha-fetoprotein expression. There was a close relationship between Ca2+-dependent PC-PLC and gamma-GT activities during differentiation as there was during proliferation. We suppose that Ca2+-dependent PC-PLC is involved in rat hepatocarcinogenesis induced by DEN and that it plays an important role in the phorbol ester-induced proliferation or retinoic acid-induced differentiation of liver cancer cells.

Animals↗

PubMed1997

Replication of a Gonad-Specific Insect Virus in TN-368 Cells in Culture

A newly discovered, nonoccluded, insect virus, known as gonad-specific virus (GSV) was found to replicate in Trichoplusia ni (TN-368) tissue culture cells. Light-microscope observations indicated that 90% of the infected cells showed cytopathic effects by 2 days postinoculation. Electron-microscopic observations revealed the productive replication of this nonoccluded virus with enveloped virus particles clearly visible in the nucleus of infected cells. These particles had approximately the same size and shape reported for GSV recovered from the in vivo host, Helicoverpa zea (corn earworm). Southern blot analysis indicated that the EcoRI restriction enzyme profiles of viral DNA from GSV-infected TN-368 were nearly identical to that of viral DNA from insects. Inoculation of healthy female, H. zea adults with cell-culture-derived virus yielded progeny moths with the same symptoms as insects inoculated with GSV propagated in vivo. These studies clearly demonstrate the ability of GSV to replicate in TN-368 cells in culture.

Journal Article↗

PubMed1997

[Ketamine racemate and S-(+)-ketamine. Cerebrovascular effects and neuroprotection following focal ischemia].

The phencyclidine derivative ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist with the thalamo-neocortical projection system as the primary site of action. Racemic ketamine consists of the enantiomers S(+)-ketamine and R(-)-ketamine. Racemic ketamine has never been considered an adequate anaesthetic agent in neurosurgical patients since it produces regionally specific stimulation of cerebral metabolism (CMRO2) and increases cerebral blood flow (CBF) and intracranial pressure (ICP). However, recent experiments suggest that both tracemic ketamine and S(+)-ketamine may reduce infarct size in animal models of incomplete cerebral ischaemia and brain injury. This experimental protective effect appears to be related to decreases in Ca++ influx and maintenance of brain tissue magnesium levels due to NMDA and quisqualate receptor blockade by ketamine. Studies in dogs have shown that racemic ketamine (2.0 mg/kg) increases CBF in the presence of the cerebral vasodilator N2O. In contrast, studies in rats without background anaesthesia showed increases in CBF after racemic ketamine (100 mg/kg i.p.). This suggests that the cerebrovascular effects of racemic ketamine are related to the pre-existing cerebrovascular tone induced by background anaesthetics. Cerebrovascular CO2 reactivity was maintained regardless of the baseline cerebrovascular resistance. There are several mechanisms by which racemic ketamine may increase CBF. It induces dose-dependent respiratory depression with consequent mild hypercapnia in spontaneously ventilating subjects. This produces vasodilation due to the intact cerebrovascular CO2 reactivity. Racemic ketamine also induces regional neuroexcitation, which leads to stimulation of cerebral glucose consumption in the limbic, extrapyramidal, auditory, and sensory-motor systems. This regional neuroexcitation with increased CMRO2 produces increases in CBF that can be blocked by infusion of barbiturates or benzodiazepines. However, increases in CBF with racemic ketamine (1 mg/kg) may also occur during normocapnia and without changes in CMRO2. This effect is related to some additional direct cerebral vasodilating potency of racemic ketamine based on a mechanism involving blockade of Ca++ channels. The effects of racemic ketamine on CBF autoregulation have not been investigated systematically. However, studies in rats have shown that CBF autoregulation was maintained with low- and high-dose S(+)-ketamine. Infusion of racemic ketamine alters intracranial volume and ICP. Studies in spontaneously ventilating pigs with and without intracranial hypertension have shown that racemic ketamine (0.5-5.0 mg/kg) produces increases in PaCO2 and ICP. In contrast, identical experiments with mechanical ventilation and controlled PaCO2 showed no changes in ICP following racemic ketamine infusion. This implies that increases in ICP are related to inadequate ventilation with consecutive hypercapnia and increases in intracranial blood volume. However, mechanical ventilation may not be sufficient to control ICP following racemic ketamine. Experiments in mechanically ventilated dogs indicate that racemic ketamine (2 mg/kg) increases cerebral blood volume and ICP even in the presence of normoventilation, a response that is reversible by hyperventilation or the administration of diazepam. Studies in patients have shown that racemic ketamine (2.0 mg/kg) reduces CBF in the presence of cerebral vasodilators like halothane or N2O. In contrast, studies in unanaesthetised humans showed increases in CBF after racemic ketamine (2-3 mg/kg). This observation is consistent with animal studies and suggests that the cerebrovascular effects of racemic ketamine are related to the pre-existing cerebrovascular tone induced by background anaesthetics. Studies in humans with and without intracranial pathology confirm the data from animal experiments. (ABSTRACT TRUNCATED)

Animals↗

PubMed1997

Clinical assessment of prolonged myocardial preservation for patients with a severely dilated heart.

BACKGROUND: The purpose of this study was to compare the myocardial protective effect of histidine-tryptophan-potassium and glucose-insulin-potassium cardioplegic solutions in patients with a dilated heart (left ventricular diastolic diameter > 55 mm, left ventricular systolic diameter > 45 mm) associated with prolonged cross-clamp time (longer than 200 minutes). METHODS: We selected 20 patients with dilated hearts due to severe aortic regurgitation. Glucose-insulin-potassium cardioplegia was used in 11 patients and histidine-tryptophan-potassium cardioplegia was used in 9 patients. RESULTS: After operation, the cardiac index was significantly increased in the histidine-tryptophan-potassium group (p < 0.05). Postoperative percent fractional shortening was 13.4% +/- 3.1% in the glucose-insulin-potassium group and 23.6% +/- 2.6% in the histidine-tryptophan-potassium group (p < 0.05). Creatine kinase levels were significantly lower in the histidine-tryptophan-potassium group than that in the glucose-insulin-potassium group (p < 0.05). The incidence of ventricular arrhythmia (higher than Lown's grade 2) was lower in the histidine-tryptophan-potassium group. CONCLUSIONS: These data support the superiority of the histidine-tryptophan-potassium method over the glucose-insulin-potassium method for protection of the dilated heart during prolonged ischemia in open heart operations.

Aortic Valve Insufficiency↗

PubMed1997

Blood pressure responses to exercise as predictors of blood pressure level after 5 years.

There is considerable disagreement in the literature on the clinical usefulness of exercise testing as a tool for prediction of future hypertension. Much of the discrepancy between various reports is attributable to the difficulties of blood pressure (BP) measurement during exercise. Therefore, we investigated whether accurate intraarterial BP measurement will increase the predictive power of exercise testing. The BP responses to dynamic and isometric exercise were evaluated in 97 healthy, unmedicated men, of whom 34 were normotensive (NT), 29 borderline (BHT), and 34 mildly hypertensive (HT) using three criteria: 1) achieved BP during the test, 2) the change of the BP from baseline to exercise, and 3) the group was divided into high responders (HIGH, n = 19, systolic BP > or = 220 and diastolic BP > or = 105 mm Hg) and normal responders (n = 60). Five years later the BP was reassessed by casual measurements and noninvasive ambulatory 24-h monitoring (NAMB) in 79 (81%; 27 NT, 24 BHT, and 28 HT) subjects. The achieved isometric BP correlated well with the follow-up BP (casual systolic BP r = 0.43, diastolic BP r = 0.45, and NAMB systolic BP r = 0.44, diastolic BP r = 0.58, P < .001). However, achieved dynamic BP showed a poorer relationship to future BP (r range, 0.09 to 31, P = NS to P < .01). Because the intraarterial preexercise sitting BP also correlated well with follow-up BP (r range, 0.33 to 0.48, P < .01 to P < .001), and the r values were close to those of achieved isometric BP we used multiple regressions (including all resting and exercise BP values as independent variables) to evaluate the contributions of the baseline and exercise values for prediction of the follow-up BP. The baseline value explained 12% to 23% (from casual diastolic BP to NAMB diastolic BP, systolic BP values) of future BP variance, whereas achieved isometric BP ranged an additional 1% to 11% (from casual systolic BP to NAMB diastolic BP) of variance. In general, BP change from baseline with stressors did not correlate with follow-up measurements. In the high responder group the achieved dynamic BP did not correlate significantly with the follow-up BP, whereas the achieved isometric diastolic BP did correlate (casual diastolic BP r = 0.56, P < .05, NAMB systolic BP and diastolic BP r = 0.52, P < .05). Both groups had similar future BP levels. In conclusion, even with very accurate BP readings the reactivity to dynamic exercise is a weak predictor of future BP, and does not improve the prediction compared to resting BP values. Intraarterial BP response to isometric exercise marginally improves the prediction of future BP levels.

Adult↗

PubMed1997

Does orthostatic testing have any role in the evaluation of the young subject with mild hypertension?: an insight from the HARVEST study.

The aim of the study was to assess the clinical significance of the blood pressure (BP) reaction to standing in 1029 stage I hypertensives. Office BP was measured six times in the supine position and six times after 2 min of standing. All subjects underwent 24-h ambulatory BP monitoring, and measurements of 24-h urinary epinephrine and norepinephrine excretion. Echocardiography was performed in 636 patients. With use of mixture analysis we could single out a population with abnormal diastolic BP response to standing (hyperreactors, n = 95). These subjects had a diastolic BP increase from lying to standing of >11 mm Hg. The other subjects were defined as normoreactors (n = 934). Office systolic BP was similar in the two groups. Diastolic BP was lower (91 +/- 6 mm Hg v 95 +/- 5 mm Hg, P < .0001) and heart rate was higher in the hyperreactors (77 +/- 10 beats/min v 75 +/- 9 beats/min, P = .004). After adjusting for age, gender, and smoking habits the statistical significance did not change. Adjusted 24-h systolic BP (P = .02) and diastolic BP (P = .02) were higher in the hyperreactors than in the normoreactors. Hyperreactors were characterized by higher cardiac index (3.2 +/- 0.8 L/min/m2 v 3.0 +/- 0.7 L/min/m2, P = .008 for adjusted values), lower total peripheral resistance (1420 +/- 330 dyne/sec/cm(-5) v 1600 +/- 380 dyne/sec/cm(-5), P = .003), and higher urinary norepinephrine output (114.9 +/- 80.3 microg/24 h v 90.6 +/- 78.5 microg/24 h, P = .03). Dimensional echocardiographic data and albumin excretion rate did not differ between the two groups. In conclusion, mixture analysis allowed us to identify a population of young mild hypertensives with exaggerated BP response to standing. Hyperreactors were characterized by higher whole-day BP and by a hyperkinetic hemodynamic pattern as a result of increased sympathetic tone.

Adolescent↗

PubMed1997

Home blood pressure as a predictor of future blood pressure stability in borderline hypertension. The Tecumseh Study.

We evaluated time-related blood pressure trends in the Tecumseh study participants, none of whom received antihypertensive treatment. At baseline the blood pressures were measured in the field clinic and by self measurement at home (twice daily for 7 days). After a mean of 3.2 +/- 0.42 years, the clinic and home pressure readings were repeated. Nine hundred forty-six subjects had clinic and home blood pressure readings at baseline. Of these 735 (380 men, 355 women; average age, 32 years) also completed the second examination. Blood pressure, morphometric data, and biochemical measures at the first examination were used as predictors of future clinic blood pressures. Five hundred ninety-six subjects were normotensive on both examinations (81%). Of 79 subjects (10.7%) with clinic hypertension (> 140 mg Hg systolic or 90 mm Hg diastolic) at baseline, 38 remained hypertensive ("sustained hypertension") and 41 became normotensive ("transient hypertension") after 3 years. Another 60 normotensives at baseline (10.4%) became hypertensive on second examination ("de novo hypertensives"; incidence; 8.1%). The home blood pressure readings on both examinations were reproducible. The three hypertensive groups had elevated home blood pressure, were overweight, had dyslipidemia, and higher insulin values. Only the home blood pressure proved predictive of subsequent blood pressure trends. A home blood pressure of 128 and 83 mm Hg or higher detected "sustained" hypertension with a 48% sensitivity and 93% specificity. Readings of 120 and 80 mm Hg or lower predicted future normotension with a 45% sensitivity and a 91% specificity. We conclude that self determination of the blood pressure at home is useful in the management of borderline hypertension. An algorithm for the management of these patients is proposed.

Adolescent↗

PubMed1997

[Effect of S-(+)-ketamine on autoregulation of cerebral blood flow].

PURPOSE: The present study investigates the effects of S-(+)-ketamine on cerebral blood flow (CBF) autoregulation in rats. METHODS: Following IRB approval, 24 nonfasted male Sprague-Dawley rats were anesthetised with isoflurane, intubated and mechanically ventilated. Catheters were inserted into the right femoral artery, both femoral veins, and into the right jugular vein for drug administration, measurement of mean arterial blood pressure (MAP), and blood sampling. Cortical cerebral blood flow was measured using laser-Doppler-flowmetry (PF 403, Perimed). At the end of surgery isoflurane was discontinued and all animals were randomly assigned to one of the following anaesthetic treatments. In group 1 (n = 8, control), anaesthesia was maintained using fentanyl (10 micrograms/kg i.v. bolus, followed by 25 micrograms/kg/h i.v.) and N2O/O2 (FiO2: 0.3). In group 2 (n = 8) and group 3 (n = 8) animals received 0.5 mg/kg/min S-(+)-ketamine i.v. or 1.0 mg/kg/min S-(+)-ketamine i.v. and O2/air (FiO2: 0.3), respectively. CBF was tested by graded haemorrhage. Arterial blood gases, arterial pH, and pericranial temperature were controlled over time. RESULTS: CBF autoregulation was maintained under low and high doses of S-(+)-ketamine compared to fentanyl/N2O-anaesthetised controls. However, low-dose S-(+)-ketamine shifted the autoregulatory curve towards higher MAP values. CONCLUSIONS: The present study indicates that autoregulatory cerebrovascular dilation is preserved with low and high doses of S-(+)-ketamine. Differences in the lower limit of CBF autoregulation may be consistent with an increased sympathetic tone induced by low doses of S-(+)-ketamine.

Anesthetics, Dissociative↗

PubMed1997

Gender differences in the relationship between left ventricular size and ambulatory blood pressure in borderline hypertension. The HARVEST Study.

AIM: To assess whether the are gender differences in cardiac adaptation to raised blood pressure levels in young subjects with borderline to mild hypertension. METHODS AND RESULTS: In 499 18-45-year-old stage I hypertensive subjects (377 men and 122 women) with a mean age of 33 +/- 9 years and office blood pressure of 146 +/- 11/ 94 +/- 6 mmHg, ambulatory blood pressure monitoring in duplicate, echocardiography and 24-h urinary catecholamines measurement were performed. RESULTS: The whole group was divided into quartiles of increasing daytime blood pressure and differences in left ventricular echocardiographic data were analysed in the two sexes separately. In men no left ventricular parameter differed across the quartiles, while in women left ventricular mass, posterior wall thickness and interventricular septum thickness showed a clear tendency to increase with increasing levels of systolic blood pressure. In multiple regression analysis, daytime systolic blood pressure explained only a small fraction of the variance in left ventricular parameters in men, while in women daytime systolic blood pressure was a main determinant of left ventricular mass and posterior wall and septal thicknesses. Body weight explained most of the variance in all dimensional parameters in men. In women weight was an important predictor of left ventricular mass and diameter, but was unrelated to left ventricular posterior wall and septal thicknesses. CONCLUSIONS: Daytime systolic blood pressure is the most important predictor of left ventricular mass and geometry in pre-menopausal women with stage I hypertension, while in men left ventricular dimensional indices are chiefly explained by body weight.

Adolescent↗

PubMed1997

Smoking is associated with higher cardiovascular risk in young women than in men: the Tecumseh Blood Pressure Study.

BACKGROUND: Tobacco smoking is associated with a higher prevalence of atherosclerosis and respiratory disease. OBJECTIVE: To investigate differences between hemodynamic and biochemical findings in smokers and nonsmokers in the two sexes separately in the Tecumseh population. METHODS: We studied 851 subjects. They were divided according to smoking habits into group 1, nonsmokers (258 men and 234 women); and group 2, smokers (185 men and 174 women). RESULTS: Unpaired Student's t-tests and nonparametric tests were performed to determine the between-group P-values. Only hematocrit differed significantly between smokers and nonsmokers in both sexes (43.9 +/- 0.2 and 44.6 +/- 9.3%, P < 0.05 in men; 39.2 +/- 0.3 and 40.3 +/- 0.3%, P = 0.007 in women, respectively in nonsmokers and smokers). Triglycerides (80.6 +/- 3.8 and 99.6 +/- 4.3 mg/dl, P < 0.001), left ventricular mass index (95.4 +/- 1.9 and 100.0 +/- 1.2 g/m2, P = 0.008), and posterior wall thickness (9.5 +/- 0.1 and 9.71 +/- 0.01 mm, P = 0.044) were elevated and high-density lipoproteins were decreased (48.7 +/- 0.8 and 44.5 +/- 0.9 mg/dl, P < 0.01) only in women smokers. After adjustment for home systolic blood pressure and body mass index the differences in women remained significant except for posterior wall thickness. CONCLUSION: Tobacco smoking is deleterious to both sexes but it appears to be particularly harmful to women. Our data can, in part, explain why the relative risk of myocardial infarction is higher in women than it is in men.

Adolescent↗