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Biomedical subjects

S U Sys

Publications and source records attributed to S U Sys.

At least 19 recordsLinked to original sources

Thromboembolic events after aortic valve replacement in elderly patients with a Carpentier-Edwards Perimount pericardial bioprosthesis.

OBJECTIVES: Thromboembolic events after aortic valve replacement with a bioprosthesis were the most frequently occurring complications in elderly patients. Whether this was valve related or dependent on other factors needed further exploration. METHODS: Five hundred patients with a median age of 73 years were followed retrospectively after aortic valve replacement with a pericardial prosthesis for occurrence of thromboembolism. Of these, 348 also underwent coronary artery bypass grafting. Twenty-five factors were investigated for their potential effect by using univariate and multivariate analysis. RESULTS: Univariate analysis revealed 6 significant factors: preoperative endocarditis (P =.0001), preoperative cerebrovascular accident (P =.002), use of postoperative warfarin sodium (Coumadin, DuPont Merck; P =.006), arterial hypertension (P =.023), size of valve prosthesis of 27 mm or larger (P =.023), and hospital thromboembolism (P =.040). There was a trend toward increased fatal thromboembolism in patients without medication. With a multivariate analysis, 4 factors remained significant: preoperative cerebrovascular accident (risk ratio, 4.8; P =.0016), warfarin sodium (risk ratio, 3.0; P =.0028), preoperative endocarditis (risk ratio, 5.6; P =.006), and hospital thromboembolism (risk ratio, 6.1; P =.016). Hypertension had a borderline effect. Age, sex, diabetes, 4 coronary artery factors, 3 other valvular factors, atrial fibrillation, and carotid artery disease had no significant effect. CONCLUSIONS: Some emboli seemed triggered by the valve prosthesis. A proper anticoagulant protocol but also a treatment of hypertension is important in the prevention of thromboembolism after aortic valve replacement with a bioprosthesis. We did not find a significant role of atrial fibrillation and carotid artery disease.

Aged↗

Role of age, gender and association of CABG on long-term results after aortic valve replacement with a Carpentier-Edwards bioprosthesis in the elderly.

AIM: The problem of postoperative sudden death and the effect of age, gender and association of coronary artery bypass grafting were studied after implantation of a bioprosthetic valve in aortic position. METHODS DESIGN: retrospective investigation during 13 year. SETTING: general hospital. PATIENTS: 500 mostly symptomatic patients who received this bioprosthesis had a follow-up of 2,022 patient-year for 499 patients. INTERVENTION: aortic valve replacement with a Carpentier-Edwards pericardial prosthesis. MEASURES: hospital complications and mortality, long-term mortality with focus on sudden death and its risk factors, valve related complications and other cardiac events. RESULTS: Within the hospital: atrial fibrillation was the most frequent complication, for which only gender had an effect (p=0.014). The most occurring valve related complications were thrombo-embolic events. Mortality was adversely affected by male gender (p=0.040). Long-term results: thrombo-embolic events were the most important valve related complications. These events and haemorrhage, endocarditis and reoperation rate were not affected by the association of a CABG. Univariate analysis in patients over 73 showed that the need for CABG significantly increased global mortality (p=0.0001), occurrence of cardiac fatality (p=0.0003) and congestive heart failure (p=0.0036). Non-valve related factors seemed most responsible for postoperative sudden death. CONCLUSION: Age, male gender and the association of a CABG remain important determinants for postoperative survival, but not for the occurrence of valve related complications. Sudden death seems not always related to the valve prosthesis, but is as such classified by convention.

Age Distribution↗

Increased coronary perfusion augments cardiac contractility in the rat through stretch-activated ion channels.

The role of stretch-activated ion channels (SACs) in coronary perfusion-induced increase in cardiac contractility was investigated in isolated isometrically contracting perfused papillary muscles from Wistar rats. A brief increase in perfusion pressure (3-4 s, perfusion pulse, n = 7), 10 repetitive perfusion pulses (n = 4), or a sustained increase in perfusion pressure (150-200 s, perfusion step, n = 7) increase developed force by 2.7 +/- 1.1, 7.7 +/- 2.2, and 8.3 +/- 2.5 mN/mm(2) (means +/- SE, P < 0.05), respectively. The increase in developed force after a perfusion pulse is transient, whereas developed force during a perfusion step remains increased by 5.1 +/- 2.5 mN/mm(2) (P < 0.05) in the steady state. Inhibition of SACs by addition of gadolinium (10 micromol/l) or streptomycin (40 and 100 micromol/l) blunts the perfusion-induced increase in developed force. Incubation with 100 micromol/l N(omega)-nitro-L-arginine [nitric oxide (NO) synthase inhibition], 10 micromol/l sodium nitroprusside (NO donation) and 0.1 micromol/l verapamil (L-type Ca(2+) channel blockade) are without effect on the perfusion-induced increase of developed force. We conclude that brief, repetitive, or sustained increases in coronary perfusion augment cardiac contractility through activation of stretch-activated ion channels, whereas endothelial NO release and L-type Ca(2+) channels are not involved.

Animals↗

Activation of cardiac endothelium as a compensatory component in endotoxin-induced cardiomyopathy: role of endothelin, prostaglandins, and nitric oxide.

BACKGROUND: In view of growing evidence of an important endothelial paracrine regulation of cardiac function, the present study investigated the role of cardiac endothelium-derived endothelin-1 (ET-1), prostaglandins, and nitric oxide (NO) during endotoxin-induced cardiomyopathy in rabbits. METHODS AND RESULTS: Immunohistochemical studies showed a marked transient coinduction of the inducible isoforms of NO synthase (NOS-2) and cyclooxygenase (COX-2) in endocardial endothelium and coronary arteriolar endothelium of hearts 12 hours after intravenous administration of lipopolysaccharide (LPS+12h); staining for both isoforms was much weaker 24 hours later (LPS+36h). Nitrotyrosine localization was similar to that of NOS-2, suggesting a NOS-2-related endothelial formation of peroxynitrite in septic hearts. Contractile performance of papillary muscles was depressed in both LPS-treated groups. In the LPS+12h group, however, isometric twitches were significantly prolonged (482+/-14 versus 420+/-14 ms in the saline-treated group, P<0.005). This twitch prolongation was completely reversed by simultaneous administration of BQ-123 and indomethacin to block endogenous ET-1 and prostaglandins, respectively. In addition, in the LPS+12h group, myocardial inotropic responsiveness to exogenous ET-1 was enhanced (P<0.01). CONCLUSIONS: Cardiac endothelial activation and myocardial sensitization to endothelium-derived mediators may be part of an adaptive response in the early (12 hours) stages of septic cardiomyopathy.

Animals↗

Distribution and role of Na(+)/K(+) ATPase in endocardial endothelium.

OBJECTIVE: In mammalian cardiomyocytes, alpha isoforms of Na(+)/K(+) ATPase have specific localisation and function, but their role in endocardial endothelium is unknown. METHODS: Different alpha isoforms in endocardial endothelium and cardiomyocytes of rabbit were investigated by measuring contractile parameters of papillary muscles, by RT-PCR, by Western blots and by immunocytochemistry. RESULTS: Inhibition of Na(+)/K(+) ATPase by decreasing external K(+) from 5.0 to 0.5 mmol/l caused biphasic inotropic effects. The maximal negative inotropic effect at external K(+) of 2.5 mmol/l was significantly larger in +EE muscles (with intact endocardial endothelium) than in -EE muscles (with endocardial endothelium removed) (-22.5+/-2.4% versus -5.9+/-4.0%, n=7, P<0.05). Further decrease of K(+) to 0.5 mmol/l caused endothelium-independent positive inotropy (27.8+/-11.8% for +EE versus 18.6+/-11.3% for -EE, n=7, P>0.05). Inhibition of Na(+)/K(+) ATPase either by dihydro-ouabain (10(-9) to 10(-4) mol/l, n=4) or by K(+) decrease following inhibition of Na(+)-H(+) exchanger by dimethyl-amiloride (50 micromol/l, n=6) caused endothelium-independent positive inotropic effects only. RT-PCR and Western Blot demonstrated alpha(1) and alpha(2) Na-K-ATPase isoforms in cardiomyocytes, but only alpha(1) in cultured endocardial endothelial cells. Immunohistochemistry showed that alpha(1) in endocardial endothelium was predominantly present at the luminal side of the cell (n=7) and that alpha(1) and alpha(2) displayed different localisation in cardiomyocytes. CONCLUSIONS: These results suggested that negative and positive inotropic effects of Na(+)/K(+) ATPase inhibition in +EE muscles could be attributed to inhibition of endocardial endothelial alpha(1) and muscle alpha(2) isoform, respectively. Accordingly, the endocardial endothelial alpha(1) isoform of Na(+)/K(+) ATPase may contribute to blood-heart barrier properties of this endothelium and may control cardiac performance via endothelial Na(+)/H(+) exchange.

Animals↗

Agonists of the P2Y(AC)-receptor activate MAP kinase by a ras-independent pathway in rat C6 glioma.

We have previously shown that an ecto-NPPase modulates the ATP- and ADP-mediated P2Y(AC)-receptor activation in rat C6 glioma. In the present study, 2MeSADP and Ap(3)A induced no detectable PI turnover and were identified as specific agonists of the P2Y(AC)-receptor with EC(50) values of 250 +/- 37 pM and 1 +/- 0.5 microM, respectively. P2Y(AC)-receptor stimulation increased MAP kinase (ERK1/2) activation that returned to the basal level 4 h after stimulation and was correlated with a gradual desensitization of the P2Y(AC)-purinoceptor. The purinoceptor antagonists DIDS and RB2 blocked MAP kinase activation. An IP(3)-independent Ca(2+)-influx was observed after P2Y(AC)-receptor activation. Inhibition of this influx by Ca(2+)-chelation, did not affect MAP kinase activation. Pertussis toxin, toxin B, selective PKC-inhibitors and a specific MEK-inhibitor inhibited the 2MeSADP- and Ap(3)A-induced MAP kinase activation. In addition, transfection with dominant negative RhoA(Asn19) rendered C6 cells insensitive to P2Y(AC)-receptor-mediated MAP kinase activation whereas dominant negative ras was without effect. Immunoprecipitation experiments indicated a significant increase in the phosphorylation of raf-1 after P2Y(AC)-receptor activation. We may conclude that P2Y(AC)-purinoceptor agonists activate MAP kinase through a G(i)-RhoA-PKC-raf-MEK-dependent, but ras- and Ca(2+)-independent cascade.

Adenylyl Cyclases↗

Determinants of survival after aortic valve replacement as treatment for symptomatic aortic valve disease in the elderly.

BACKGROUND AND AIM OF THE STUDY: The effect of concurrent disease and cardiac comorbidity on survival after bioprosthetic valve replacement in elderly patients was assessed retrospectively. Risk factors were categorized as general, non-cardiac (age, diabetes, previously treated carcinoma) and cardiac (LVEF, three-vessel disease, previous CABG or valve replacement, and endocarditis). METHODS: A total of 400 elderly patients (median age 73 years; range: 71-76 years) was studied. Medical history included diabetes, previous CABG or aortic valve replacement (AVR), endocarditis and treatment of previous carcinoma. A left ventricular ejection fraction (LVEF) of <0.66 and presence of three-vessel disease were also investigated. Hospital deaths (and cause) were recorded; survival or date and cause of death after discharge were obtained by questionnaire. Kaplan-Meier univariate and Cox proportional hazards multivariate regression analyses were carried out. RESULTS: Mortality during follow up was 28.3%; hospital mortality was 3.8%. Univariate analysis showed five factors significantly to affect survival: LVEF, history of endocarditis, carcinoma, age and three-vessel disease. Fifteen of 38 patients with history of carcinoma died, 10 due to a malignancy. Of 76 patients with three-vessel disease, 26 died. A history of diabetes and previous CABG did not influence survival significantly. Four of eight patients with preoperative endocarditis died, all in hospital. Six of 11 patients died after redo-AVR, none before 36 months follow up. By Cox regression analysis, LVEF and histories of carcinoma and endocarditis remained significant. CONCLUSION: AVR should be performed before ventricular deterioration occurs. Previous CABG is not a contraindication for AVR. Endocarditis impaired survival. Long-term mortality after redo-AVR in this population was relatively high, but acceptable. AVR should also be performed in elderly patients with aortic valve disease. Since prognosis of symptomatic aortic valve disease is poor in the short term, AVR is indicated in patients treated for carcinoma.

Aged↗

Controlled auxotonic twitch in papillary muscle: a new computer-based control approach.

Based on new advancements in digital technology, we developed a PC- and DSP-based measurement and control system for isolated papillary muscle experiments. High flexibility was obtained through a three level control. Length or force was controlled real-time with a sample frequency of 5000 Hz. Muscle length and up to three segment lengths were measured simultaneously and each of these lengths could be chosen as feedback variable. Individual algorithms were implemented for different twitch types. Batches of twitches were organized in experiment protocols. The system included a new twitch type, namely a controlled auxotonic twitch. In this twitch, the muscle acted against a virtual ideal spring, giving a proportional change in developed force and shortening. The value of the virtual spring constant could be set on-line or defined in the experiment protocol. An increasing virtual spring constant represented a smooth transition from isotonic to isometric conditions.

Algorithms↗

Fetal biometry in different ethnic groups.

OBJECTIVE: The aim of this study was to determine whether differences in ultrasound-measured fetal biometry exist between pregnant woman of autochthonous Belgian origin and migrant women from Morocco and Turkey. METHOD: A prospective cross-sectional study was performed in which fetal biparietal diameter, head circumference, abdominal circumference and femur length were measured in pregnant women presenting between 18 and 40 weeks of gestation. Fetal weight was calculated using the formulae by Shepard and Hadlock. Only uncomplicated singleton pregnancies with a certain date of the last menstrual period, confirmed by early ultrasound, were included. The father of the child had to be of the same ethnic origin as the mother. Polynomial regression of the different measurements was performed for women of autochthonous Belgian origin and for migrant women from Morocco and from Turkey. RESULTS: Singleton fetuses numbering 524 were examined, including 369 Belgian, 78 Moroccan and 77 Turkish. Polynomial regression was performed for the three groups for the biparietal diameter, head circumference, abdominal circumference, femur length and estimated fetal weight. No significant difference between the three different ethnic groups could be demonstrated for the biparietal diameter (P = 0.39). There was a significant difference for the head circumference (P = 0.017), the abdominal circumference (P = 0.0015), the femur length (P = 0.0014) and the estimated fetal weight for both formulae (Shepard P = 0.047; Hadlock P = 0.0006). CONCLUSION: In this set of cross-sectional data no significant difference for ultrasound-measured fetal biparietal diameter between autochthonous Belgian women and migrant women from Morocco and from Turkey could be demonstrated. Differences do exist for the head circumference, the abdominal circumference, the femur length and the estimated fetal weight. The use of adapted charts of fetal size for pregnant women of Turkish or Moroccan origin should be considered.

Belgium↗

Fetal binocular distance: no differences between ethnic groups.

OBJECTIVE: The aim of this study was to detect if interethnic differences for fetal binocular distance exist between the autochthonous Belgian population and immigrants from Turkey or Morocco, and to evaluate the need for different reference charts by ethnicity. METHODS: A prospective cross-sectional study was performed. In 246 pregnant women who presented for routine prenatal ultrasound between 18 and 40 weeks of gestation age the binocular distance was measured. Polynomial regression was performed for the three ethnic groups. RESULTS: The population consisted of 171 autochthonous Belgian women, 31 women from Turkish origin and 44 women from Moroccan origin. A statistically significant difference for the fetal binocular distance was noted between the Moroccan versus the autochthonous Belgian and Turkish fetuses (F test, p = 0. 047). The order of magnitude of this statistical difference is extremely small and does not result in clinical relevance. CONCLUSION: A small, but statistically significant difference exists for the fetal binocular distance between fetuses of Moroccan origin versus those of autochthonous Belgian or Turkish origin. This difference is of no clinical importance and there is no need to adapt reference charts for ethnicity when studying these three groups.

Adult↗

Progressive deceleration in growth as an early sign of delayed puberty in boys.

OBJECTIVE: To describe the prepubertal growth pattern in boys with delayed puberty. METHODS: Growth curves for height and height velocity covering the age range 4-14 years were constructed on the basis of retrospectively obtained data in 85 boys with delayed puberty, who attained a normal final height. RESULTS: Between the age of 4 and 14 years the height in this cohort progressively deviated from the normal reference. At the age of 4 years, the height SDS was already significantly lower (median -0.8; p < 0.001) and progressively diminished during childhood, resulting in a median height SDS of -1.1 at the age of 12 years (p < 0.001). The median final height of this cohort (-0.4) was not different from their target height (-0.2). The degree of deceleration in growth during childhood was not determined by birth weight or birth height and did not influence final height. The decline of the height velocity with age in this group of boys with delayed puberty was significantly smaller (p < 0.001) than predicted by the model of Rikken and Wit. CONCLUSION: Late-maturing boys often show a prepubertal deceleration in growth that starts at an early age but that does not affect final height.

Adolescent↗

Fetal transverse cerebellar diameter in different ethnic groups.

AIMS: Transverse cerebellar diameter has been described as a tool to check for gestational age, but there are no available studies that attempt to determine differences in transverse cerebellar diameter between groups of different ethnic origin. The present study was undertaken to check for differences in ultrasound-measured transverse cerebellar diameter between pregnant women of autochthonous Belgian origin and migrant women from Morocco and Turkey. METHODS: A prospective cross-sectional study was performed. Patients were pregnant women presenting between 17 and 40 weeks of gestational age. Only uncomplicated singleton pregnancies with a known date of the last menstrual period confirmed by first trimester ultrasound were included. The father of the child had to be of the same ethnic origin as the mother. Polynomial regression was fitted for the three different ethnic groups. RESULTS: The transverse cerebellar diameter was obtained in 471 singleton fetuses, including 333 Belgian, 69 Moroccan and 69 Turkish. F-tests on the residual sums of squares of different fits demonstrated significant effects of ethnicity on the regression of the measurement versus gestational age (P < 0.00005). In a third order polynomial regression model the second order coefficient was significantly higher and the third order coefficient was significantly lower for the Moroccan group. CONCLUSION: The transverse cerebellar diameter is not independent of the ethnic origin of the patient. When using the transverse cerebellar diameter for the evaluation of fetal growth or for dating a pregnancy, care should be taken to rely on charts appropriate for the ethnic group, as demonstrated here for Moroccan fetuses.

Anthropometry↗

Improvement of endocardial and vascular endothelial function on myocardial performance by captopril treatment in postinfarct rat hearts.

Background-Endocardial (EE) and myocardial capillary vascular endothelial (myocap VE) cells have been shown to modulate the contractile characteristics of myocardium in a calcium-dependent manner. We evaluated the endothelial-myocardial interaction in the rat postinfarction myocardial infarction (MI) model and the effects of captopril. Methods and Results-Wistar rats were divided into 4 groups treated for 4 weeks: (1) control; (2) infarcted controls (left anterior coronary artery ligation); (3) infarcted+captopril 2 g/L in drinking water; and (4) infarct+captopril+triton intracoronary injection. Coronary VE function was evaluated by infusion of serotonin in Langendorff preparations (n=31), and the myocardial contractile characteristics were investigated by use of isolated papillary muscles (n=44). Cardiac mRNA for endothelial constitutive nitric oxide synthase (ecNOS) was measured, and its cellular location was evaluated by immunohistochemistry. Serotonin-induced increase in coronary flow was decreased in infarct controls compared with controls (4.6% versus 53.4%, P<0.01) but not in the 2 infarct+captopril groups. Intracoronary triton injection decreased serotonin-induced coronary flow in the infarct+captopril+triton group. All MI groups had decreased total tension in isolated papillary muscles. EE removal by triton immersion decreased total tension in all groups except for infarct controls (3.3 versus 3.2 g/mm(2)). Cardiac ecNOS mRNA decreased in the control infarct group but remained normal in the infarct+captopril group. Conclusions-Chronic postinfarction endothelium-induced coronary vasodilatation is impaired, and both EE and myocap VE dysfunction contribute to myocardial depression. Captopril use prevents these abnormalities and the reduction of cardiac ecNOS mRNA.

Angiotensin-Converting Enzyme Inhibitors↗

Nonuniformity of endothelial constitutive nitric oxide synthase distribution in cardiac endothelium.

Endocardial endothelium and endothelium of coronary vessels produce NO. Histochemical methods have suggested that coronary arterial endothelial cells contain more endothelial constitutive NO synthase (ecNOS) than does coronary venous endothelium. We have further investigated the distribution of ecNOS in cardiac endothelium using immunofluorescence and en face confocal microscopy of rat heart. In endocardial endothelium, confocal microscopy revealed distinct ecNOS labeling of peripheral cell borders, cytoplasmic labeling, and labeling of the Golgi complexes. Labeling of the cell borders and of the Golgi complexes was confirmed by double staining for ecNOS and for platelet and endothelial cell adhesion molecule or Golgi 58k protein, respectively. Cytoplasmic labeling was strongest in coronary arterial endothelium. The size of the ecNOS-labeled Golgi complexes decreased from coronary arterial endothelial cells (8.63 +/- 0.39 microm2, mean +/- SE of 5 rats) to endocardial endothelium (7.07 +/- 0.61 microm2) and to coronary venous endothelium (3.65 +/- 0.20 microm2). In addition, pixel intensity of ecNOS labeling was higher in arterial endothelial cells than in venous endothelial cells. Endothelium of myocardial capillaries also contained small ecNOS-labeled Golgi complexes. No correlation was observed between endothelial cell surface area and Golgi complex size. Caveolin-1 labeling was strongest in capillaries and did not coincide completely with ecNOS labeling in endocardial and venous endothelium. These results suggest that endocardial and coronary arterial endothelium in the rat have a higher synthetic activity and might express more ecNOS than is expressed by cardiac venous and capillary endothelium. The observed heterogeneity in ecNOS distribution might be related to the specific mechanochemical environment and function of each endothelial compartment.

Animals↗

Reappraisal of the multicellular preparation for the in vitro physiopharmacological evaluation of myocardial performance.

In order to evaluate myocardial performance, single cardiomyocytes suffer from technical problems and from the fact that some basic functional properties vanish when one moves down the hierarchic scale from multicellularity to single cells. The isolated papillary muscle has at present proven to be superior to the isolated intact cardiomyocyte. A large number of major intra- and extracellular features required to describe myocardial performance can be derived from analyzing twitch contraction and relaxation in the multicellular isolated papillary muscle. In addition, the present paper illustrates the possibility to differentiate between effects of inotropic interventions on activating Ca2+ and Ca2+ sensitivity in multicellular preparations, from a grid analysis of isometric twitches in a coordinate system of peak rate of force development (+dF/dt; reflecting the time pattern of twitch contraction) versus time to half relaxation (tHR; reflecting the time pattern of twitch relaxation). The abundance of information about myocardial performance that can be derived from the easily accessible multicellular preparation reflects its physiological kinship with the intact ventricle.

Animals↗

Cardiac endothelium and myocardial function.

Endocardial endothelium and vascular endothelium of myocardial capillaries share common features as modulators of cardiac performance, rhythmicity and growth. Growing evidence suggests differences between these two cardiac endothelial cell types with regard to developmental, morphological and functional properties. A major difference probably resides in the way and extent by which these endothelial cells perceive and transmit signals.

Animals↗

The addition of indomethacin to betamimetics for tocolysis: any benefit for the neonate?

OBJECTIVE: To study the influence on the neonate of indomethacin administered to the mother as an additional tocolytic. STUDY DESIGN: The neonatal outcome in 76 closely matched low birth weight infants was compared retrospectively: those whose mothers received indomethacin together with betamimetics formed the study group, those whose mothers received only betamimetics formed the control group. RESULTS: There was an increased incidence of respiratory distress syndrome (RDS) in the study group (97% versus 45%; P<0.001), an increased need for surfactant use (68% versus 26%; P<0.001) and increased ventilatory support, and an increased incidence of bronchopulmonary dysplasia (BPD) (47% versus 24%; P=0.03). Gestation could not be prolonged significantly by the addition of indomethacin. CONCLUSION: Indomethacin as an additional tocolytic agent was associated with an increased incidence of RDS, surfactant use and BPD but did not significantly prolong gestation.

Adrenergic beta-Agonists↗