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Biomedical subjects

M M Berger

Publications and source records attributed to M M Berger.

At least 19 recordsLinked to original sources
PubMed2006

ESPEN Guidelines on Enteral Nutrition: Intensive care.

Enteral nutrition (EN) via tube feeding is, today, the preferred way of feeding the critically ill patient and an important means of counteracting for the catabolic state induced by severe diseases. These guidelines are intended to give evidence-based recommendations for the use of EN in patients who have a complicated course during their ICU stay, focusing particularly on those who develop a severe inflammatory response, i.e. patients who have failure of at least one organ during their ICU stay. These guidelines were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1985. They were discussed and accepted in a consensus conference. EN should be given to all ICU patients who are not expected to be taking a full oral diet within three days. It should have begun during the first 24h using a standard high-protein formula. During the acute and initial phases of critical illness an exogenous energy supply in excess of 20-25 kcal/kg BW/day should be avoided, whereas, during recovery, the aim should be to provide values of 25-30 total kcal/kg BW/day. Supplementary parenteral nutrition remains a reserve tool and should be given only to those patients who do not reach their target nutrient intake on EN alone. There is no general indication for immune-modulating formulae in patients with severe illness or sepsis and an APACHE II Score >15. Glutamine should be supplemented in patients suffering from burns or trauma.

APACHE↗
PubMed2005

[Perioperative evaluation of lung function].

Respiratory diseases contribute significantly to perioperative morbidity and mortality. Severe pulmonary complications usually emerge postoperatively. To minimise pulmonary risk, the perioperative evaluation of lung function is of major significance, allowing the identification of patient and surgery-related risk factors. In particular, the significance of the intraoperative assessment of lung function has gained in importance over the last few years. The following article describes the possibilities and frontiers of the perioperative assessment of lung function, and focuses especially on the significance of preoperative pulmonary function tests and the intraoperative interpretation of respiratory pressure, flow, and volume loops.

Blood Gas Analysis↗
PubMed2005

Safety and intestinal tolerance of high-dose enteral antioxidants and glutamine peptides after upper gastrointestinal surgery.

OBJECTIVE: Safety and intestinal tolerance of an early high-dose enteral administration of antioxidative vitamins, trace elements, and glutamine dipeptides. DESIGN: open intervention trial. SETTING: Two university teaching hospitals. PATIENTS: A total of 14 patients requiring jejunal feeding (64+/-14 y). INTERVENTION: A measure of 500 ml/day Intestamin (FreseniusKabi: 250 kcal/1.050 kJ, 300 microg selenium, 20 mg zinc, 400 mug chromium, 1500 mg vitamin C, 500 mg vitamin E, 10 mg beta-carotene, 30 g glutamine) for 5 days beginning 6 h after surgery. Parenteral/enteral nutrition was provided to achieve energy target (25 kcal/kg/day). ASSESSMENTS: Intestinal complaints, plasma nutrients, and glutathione. RESULTS: Only minor signs of nausea, hiccups, flatulence (3/14). Plasma micronutrients (except beta-carotene) postoperatively decreased and increased to normal on day 5. Extracellular glutamine remained low (preop: 520+/-94; d1: 357+/-67; d5: 389+/-79 micromol/l); total glutathione decreased (d1: 9.4+/-3.8; d5: 3.6+/-2.5 micromol/l). CONCLUSION: Study feed is well tolerated and metabolically safe representing a valuable tool for targeted pharmaconutrient supply.

Antioxidants↗
PubMed2004

Failure to detect enterovirus in the spinal cord of ALS patients using a sensitive RT-PCR method.

OBJECTIVE: To assess the association of enteroviruses (EV) with ALS by applying a sensitive seminested reverse transcription (RT) PCR protocol to the detection of enteroviral RNA in a blinded set of archived tissues from ALS and control cases. METHODS: The specimen set consisted of 24 frozen spinal cord samples from ALS cases, 17 frozen spinal cord samples from negative control (non-ALS) cases, and 5 frozen spinal cord positive control samples. The positive controls were two human spinal cord samples spiked with poliovirus (PV) and three spinal cords from PV-infected transgenic mice. A sensitive, EV-specific, seminested RT-PCR assay was used to detect EV genome in RNA extracted from the specimens and controls. RESULTS: The assay detected EV RNA in a 10(-5) dilution of infected mouse tissue. EV RNA was not detected in the ALS specimens or in specimens from control cases, despite the presence of amplifiable RNA as assessed by amplification with control primers, whereas all of the positive control specimens yielded the expected PV amplification product. CONCLUSION: The reported association between EV infection and ALS was not confirmed by testing this set of specimens with these sensitive methods.

5' Untranslated Regions↗
PubMed2002

Deformation-induced endothelin B receptor-mediated smooth muscle cell apoptosis is matrix-dependent.

To maintain normal blood flow, pressure overload in both arteries and veins requires a structural adaptation of the vessel wall (remodelling) that involves smooth muscle cell (SMC) hypertrophy and/or hyperplasia. Due to its potent vasoconstrictor and growth-promoting effects, endothelin-1 (ET-1) is a likely candidate to initiate and/or promote remodelling in blood vessels exposed to a chronic increase in blood pressure. To test this hypothesis, isolated segments of the rabbit carotid artery and jugular vein were perfused at different levels of intraluminal pressure. In both types of segments, pressure overload (160 and 20 mmHg, respectively) resulted in an increase in endothelial prepro-ET-1 and SMC endothelin B receptor (ETB-R) expression. Moreover, in pressurised segments from the carotid artery an ETB-R antagonist-sensitive increase in SMC apoptosis in the media was observed, while in the vein medial SMC started to proliferate. Isolated SMC from these rabbit blood vessels as well as from the aorta and vena cava of the rat, when cultured on a collagen or laminin matrix, uniformly revealed an ETB-R-mediated increase in apoptosis upon exposure to mechanical deformation plus exogenous ET-1 (10 nmol/L). However, when grown on a fibronectin matrix, the cultured SMC did not respond with an increase in apoptosis under otherwise identical experimental conditions. These findings suggest that deformation-induced activation of the endothelin system in the vessel wall not only plays a crucial role in remodelling, but that the structural components of the vessel wall, in particular the cell-matrix interaction, determine how SMC respond phenotypically to these changes in gene expression.

Animals↗
PubMed2002

Fractional hepatic de novo lipogenesis in healthy subjects during near-continuous oral nutrition and bed rest: a comparison with published data in artificially fed, critically ill patients.

BACKGROUND AND AIMS: In critically ill patients, fractional hepatic de novo lipogenesis increases in proportion to carbohydrate administration during isoenergetic nutrition. In this study, we sought to determine whether this increase may be the consequence of continuous enteral nutrition and bed rest. We, therefore, measured fractional hepatic de novo lipogenesis in a group of 12 healthy subjects during near-continuous oral feeding (hourly isoenergetic meals with a liquid formula containing 55% carbohydrate). In eight subjects, near-continuous enteral nutrition and bed rest were applied over a 10 h period. In the other four subjects, it was extended to 34 h. Fractional hepatic de novo lipogenesis was measured by infusing(13) C-labeled acetate and monitoring VLDL-(13)C palmitate enrichment with mass isotopomer distribution analysis. Fractional hepatic de novo lipogenesis was 3.2% (range 1.5-7.5%) in the eight subjects after 10 h of near continuous nutrition and 1.6% (range 1.3-2.0%) in the four subjects after 34 h of near-continuous nutrition and bed rest. This indicates that continuous nutrition and physical inactivity do not increase hepatic de novo lipogenesis. Fractional hepatic de novo lipogenesis previously reported in critically ill patients under similar nutritional conditions (9.3%) (range 5.3-15.8%) was markedly higher than in healthy subjects (P<0.001). These data from healthy subjects indicate that fractional hepatic de novo lipogenesis is increased in critically ill patients.

Adult↗
PubMed2001

Influence of selenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial.

OBJECTIVE: To investigate whether early selenium (Se) supplementation can modify the post-traumatic alterations of thyroid hormone metabolism, since the first week after trauma is characterised by low plasma Se and negative Se balances. DESIGN: Prospective, placebo-controlled randomised supplementation trial. SETTING: Surgical ICU in a tertiary university hospital. PATIENTS: Thirty-one critically ill trauma patients aged 42 +/- 16 years (mean +/- SD), with severe multiple injury (Injury Severity Score 30 +/- 7). INTERVENTION: Supplementation during the first 5 days after injury with either Se or placebo. The selenium group was further randomised to receive daily 500 microg Se, with or without 150 mg alpha-tocopherol (AT) and 13 mg zinc supplements. The placebo group received the vehicle. Circulating Se, AT, zinc, and thyroid hormones were determined on D0 (= day 0, admission), D1, D2, D5, D10, and D20. RESULTS: Plasma Se, low on D0, normalised from D1 in the selenium group; total T4 and T3 increased more and faster after D2 (P = 0.04 and 0.08), reverse T3 rising less between D0 and D2 (P = 0.05). CONCLUSIONS: Selenium supplements increased the circulating Se levels. Supplementation was associated with modest changes in thyroid hormones, with an earlier normalisation of T4 and reverse T3 plasma levels. The addition of AT and zinc did not produce any additional change.

Adult↗
PubMed2001

Early metabolic and splanchnic responses to enteral nutrition in postoperative cardiac surgery patients with circulatory compromise.

OBJECTIVES: To assess the hemodynamic and metabolic adaptations to enteral nutrition (EN) in patients with hemodynamic compromise. DESIGN AND SETTING: Prospective study in a university hospital surgical ICU, comparing baseline (fasted) with continuous EN condition. PATIENTS: Nine patients requiring hemodynamic support by catecholamines (dobutamine and/or norepinephrine) 1 day after cardiac surgery under cardiopulmonary bypass. INTERVENTION: Isoenergetic EN via a postpyloric tube while catecholamine treatment remained constant. Baseline (fasted) condition was compared to continuous EN condition. MEASUREMENTS AND MAIN RESULTS: Cardiac index (CI), mean arterial pressure (MAP), pulmonary and wedge pressures, indocyanine green (ICG) clearance, gastric tonometry, plasma glucose and insulin, and glucose turnover (6,62H2-glucose infusion) were determined repetitively every 60 min during 2 h of baseline fasting condition and 3 h of EN. During EN CI increased (from 2.9 +/- 0.5 to 3.3 +/- 0.5 l min-1 m-2), MAP decreased transiently (from 78 +/- 7 to 70 +/- 11 mmHg), ICG clearance increased (from 527 +/- 396 to 690 +/- 548 ml/min), and gastric tonometry remained unchanged, while there were increases in glucose (158 +/- 23 to 216 +/- 62 mg/dl), insulin (29 +/- 23 to 181 +/- 200 mU/l), and glucose rate of appearance (2.4 +/- 0.2 to 3.3 +/- 0.2 mg min-1 kg-1). CONCLUSIONS: The introduction of EN in these postoperative patients increased CI and splanchnic blood flow, while the metabolic response indicated that nutrients were utilized. These preliminary results suggest that the hemodynamic response to early EN may be adequate after cardiac surgery even in patients requiring inotropes.

Adaptation, Physiological↗
PubMed2001

Resuscitation, anaesthesia and analgesia of the burned patient.

Burns resuscitation has evolved over the past few decades towards more evidence-based management. It has been shown that patients with major burns (i.e. involving more than 30% of the body surface) benefit from invasive monitoring, and physiological variable targeted resuscitation using vasoactive agents for cardiovascular support. The invasive approach results in a reduction of mortality rates. Since the introduction of the Parkland formula in 1968, there has been a trend towards the administration of fluid resuscitation far in excess of the volume predicted with this formula. This has led to an increase in complication rates, with more pulmonary oedema, and the appearance of abdominal compartment syndrome. Hypertonic saline solutions, whether with dextran or not, have shown no advantage over the classic Ringer's lactate solution. The colloid controversy has reached burns resuscitation, with the demonstration that the liberal use of albumin is associated with higher mortality rates. Fresh frozen plasma should only be used for specific coagulation disorders. On the other hand, artificial colloids, particularly gelatine, remain a useful tool in patients with major burns and haemodynamic instability, particularly, and can be given as early as 6 h after injury. Considering the actual evidence, using inotropes and vasopressors to reach supranormal haemodynamic endpoints seems preferable to delivering unrestricted amounts of fluid.

Journal Article↗
PubMed2000

Detection and cellular localization of enterovirus RNA sequences in spinal cord of patients with ALS.

OBJECTIVE: To investigate the possible association of persistent enterovirus (EV) infection with the development of ALS. BACKGROUND: Although ALS is a clinically well-defined motor neuron disease, little is known about the etiology and pathogenesis of the sporadic cases. Among the different causes that have been hypothesized, conflicting results have been reported about the possible role of persistent enteroviral infection. METHODS: Reverse transcriptase-PCR (RT-PCR) and direct RT in situ PCR (RT-IS-PCR) were performed in formaldehyde-fixed spinal cord samples of 17 patients with confirmed ALS and 29 control subjects with no history of motor neuron disease. When obtained, PCR products were sequenced subsequently. RESULTS: Using direct RT-IS-PCR, EV nucleic acid sequences were detected in 15 (88.3%) of 17 patients with ALS compared to 1 (3.4%) of 29 control subjects. PCR products were located in neuronal cell bodies of the anterior horns of the spinal cord. The RT-PCR products obtained in 13 of the 17 patients with ALS showed between 94% and 86% homology with echovirus 7 sequences. CONCLUSION: The 88.3% rate of detection of enterovirus (EV) nucleic acids in the neuronal cell bodies within the gray matter of the spinal cord of patients with ALS strongly suggests association between persistent EV RNA and ALS. Further work is required to confirm that the persisting EV sequences we detected are somehow involved in the development of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Impact of a bicarbonated saline solution on early resuscitation after major burns.

OBJECTIVE: The study aimed at assessing the impact of the introduction of a bicarbonated saline solution on total fluid load, weight gain and acid base status during acute burn resuscitation. DESIGN: Based on a retrospective patient record review. SETTING: Burn care centre of a surgical ICU in a tertiary university hospital. PATIENTS: Two groups of adult patients (20/20), with thermal burns of 25% or more body surface area were studied. INTERVENTION: Modification of the resuscitation fluid composition from lactated Ringer's solution (LR: Na 132 mmol/l, Cl 112 mmol/l, 263 mosm/l), to bicarbonated 0.9% saline (BS: Na 180 mmol/l, Cl 154 mmol/l, 340 mosm/l) METHODS: Age, weight, burn size and depth, inhalation injury, fluid intakes over 48 h post-injury, plasma sodium, chloride, creatinine, albumin levels, blood gases and ventilation support were recorded. RESULTS: The demographic characteristics of the patients (41 +/- 16 years) in the two groups were not different, with severe burns involving 44 +/- 17% body surface area. While the total fluid volumes administered did not differ, BS was associated with lower plasma pH, base excess and bicarbonate levels for 24 h and with hyperchloraemia. Clinical evolution did not differ. CONCLUSIONS: Using bicarbonated saline solution for resuscitation causes a transient hyperchloraemic dilutional acidosis compared with LR, and has no other detectable clinical impact over the first 10 days after severe burn injury.

Adult↗
PubMed2000

Intestinal absorption in patients after cardiac surgery.

OBJECTIVES: We designed this study to assess intestinal absorption in patients with adequate or altered hemodynamic status after cardiac surgery and to test clinical tolerance to early enteral nutrition. DESIGN: Prospective, descriptive study. SETTING: Surgical intensive unit in a university teaching hospital. PATIENTS: Cardiac surgery patients, age 64+/-10 yrs (mean +/-SD) were subdivided into two groups according to hemodynamic status: group I, 16 patients with adequate hemodynamic status; group II, 23 patients with hemodynamic failure. These groups were compared with healthy controls (group III, n = 6). INTERVENTIONS: Paracetamol pharmacokinetic study on days 1 and 3 with nasogastric or postpyloric paracetamol administration. Early postpyloric or conventional gastric nutrition in group II. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations were measured on days 1 and 3, and area under the curve (AUC) was calculated. Absorption was strongly reduced on day 1 in all patients after gastric administration (lower peak paracetamol and AUC), but normal after postpyloric delivery. Duration of anesthesia and of circulatory bypass did not affect paracetamol absorption. On day 3, AUC was close to normal in case of hemodynamic failure. Peak absorption on day 1 was negatively correlated with opiate dose (r2 = 0.176, p = .008). Hypocaloric enteral nutrition was well tolerated. CONCLUSIONS: The close-to-normal AUC, during low cardiac output, despite lower peak paracetamol, shows absorption was not suppressed, only delayed, because of decreased pyloric motility. The decrease on day 1 can be attributed to opiates, known to alter pyloric function and to slow down the intestinal transit.

APACHE↗
PubMed2000

Segmental bioelectrical impedance analysis to assess perioperative fluid changes.

OBJECTIVES: Perioperative fluid accumulation determination is a challenge for the clinician. Bioelectrical impedance analysis (BIA) is a noninvasive method based on the electrical properties of tissues, which can assess body fluid compartments. The study aimed at assessing their changes in three types of surgery (thoracic, abdominal, and intracranial) requiring various regimens of fluid administration. DESIGN: Prospective descriptive trial. PATIENTS: A total of 26 patients scheduled for elective surgery were separated into three groups according to site of surgery: thoracic (n = 8), abdominal aortic (n = 8), and brain surgery (n = 10). SETTING: University teaching hospital. INTERVENTION: None. MEASUREMENTS: Whole body, segmental (arm, trunk, and legs) BIA at multiple frequency (0.5, 50, 100 kHz) was used to assess perioperative fluid accumulation after surgery. The fluid balances were calculated from the charts. RESULTS: The patients were aged 62+/-4 yrs. Fluid balances were 4.8+/-1.0 L, 4.1+/-0.5 L, and 1.9+/-0.3 L, respectively, in the three groups. In trunk surgery patients, fluid accumulation was detected as a drop in impedance in the operated area at all frequencies. In the operated area, there was an expansion of both intra- and extracellular compartments. A reduction in high frequencies' impedance in the legs was only detected after aortic surgery. Fluid accumulation and trunk impedance changes were strongly correlated. Neurosurgery only induced minor body fluid changes. CONCLUSIONS: Segmental BIA is able to detect and localize perioperative fluid accumulation. It may become a bedside tool to quantify and to localize fluid accumulation.

Abdomen↗
PubMed2000

Effects of cardiogenic shock on lactate and glucose metabolism after heart surgery.

BACKGROUND: Hyperlactatemia is a prominent feature of cardiogenic shock. It can be attributed to increased tissue production of lactate related to dysoxia and to impaired utilization of lactate caused by liver and tissue underperfusion. The aim of this prospective observational study was to determine the relative importance of these mechanisms during cardiogenic shock. PATIENTS: Two groups of subjects were compared: seven cardiac surgery patients with postoperative cardiogenic shock and seven healthy volunteers. METHODS: Lactate metabolism was assessed by using two independent methods: a) a pharmacokinetic approach based on lactate plasma level decay after the infusion of 2.5 mmol x kg(-1) of sodium lactate; and b) an isotope dilution technique for which the transformation of [13C]lactate into [13C]glucose and 13CO2 was measured. Glucose turnover was determined using 6,62H2-glucose. RESULTS: All patients suffered from profound shock requiring high doses of inotropes and vasopressors. Mean arterial lactate amounted to 7.8 +/- 3.4 mmol x L(-1) and mean pH to 7.25 +/- 0.07. Lactate clearance was not different in the patients and controls (7.8 +/- 3.4 vs. 10.3 +/- 2.1 mL x kg(-1) x min(-1)). By contrast, lactate production was markedly enhanced in the patients (33.6 +/- 16.4 vs. 9.6 +/- 2.2 micromol x kg(-1) x min(-1); p < .01). Exogenous [13C]lactate oxidation was not different (107 +/- 37 vs. 103 +/- 4 mmol), and transformation of [13C]lactate into [13C]glucose was not different (20.0 +/- 13.7 vs. 15.2% +/- 6.0% of exogenous lactate). Endogenous glucose production was markedly increased in the patients (1.95 +/- 0.26 vs. 5.3 +/- 3.0 mg x kg(-1) x min(-1); p < .05 [10.8 +/- 1.4 vs. 29.4 +/- 16.7 micromol x kg(-1) x min(-1)]), whereas net carbohydrate oxidation was not different (1.7 +/- 0.5 vs. 1.3 +/- 0.3 mg x kg(-1) x min(-1) [9.4 +/- 2.8 vs. 7.2 +/- 1.7 micromol x kg(-1) x min(-1)]). CONCLUSIONS: Hyperlactatemia in early postoperative cardiogenic shock was mainly related to increased tissue lactate production, whereas alterations of lactate utilization played only a minor role. Patients had hyperglycemia and increased nonoxidative glucose disposal, suggesting that glucose-induced stimulation of tissue glucose uptake and glycolysis may contribute significantly to hyperlactatemia.

Acidosis, Lactic↗
PubMed2000

Pressure-induced upregulation of preproendothelin-1 and endothelin B receptor expression in rabbit jugular vein in situ : implications for vein graft failure?

Upregulation of endothelin-1 (ET-1) synthesis in venous bypass grafts in response to arterial levels of blood pressure may play a major role in graft failure. To investigate this hypothesis, isolated segments of the rabbit jugular vein were perfused at physiological (0 to 5 mm Hg) and nonphysiological (20 mm Hg) levels of intraluminal pressure. As judged by reverse transcription-polymerase chain reaction analysis (mRNA level), neither endothelin-converting enzyme nor endothelin A receptor expression appeared to be pressure sensitive. In contrast, there was a profound and time-dependent increase in endothelial prepro-ET-1 mRNA and intravascular ET-1 abundance (by ELISA) as well as in smooth muscle endothelin B receptor mRNA and functional protein (by superfusion bioassay) on raising the perfusion pressure from 5 to 20 mm Hg, but not from 0 to 5 mm Hg, for up to 12 hours. Video microscopy analysis revealed that the segments were distended by 75% at 5 mm Hg and near maximally at 20 mm Hg compared with the resting diameter at 0 to 1 mm Hg. Treatment of the segments with actinomycin D (1 micromol/L), the specific protein kinase C inhibitor, Ro 31-8220 (0.1 micromol/L), or the c-Src family-specific tyrosine kinase inhibitor, herbimycin A (0.1 micromol/L), demonstrated that the pressure-induced expression of these gene products occurs at the level of transcription and requires activation of protein kinase C, but not c-Src. In venous bypass grafts such deformation-induced changes in gene expression may contribute not only to acute graft failure through ET-1-induced vasospasm but also to endothelin A receptor- and/or endothelin B receptor-mediated smooth muscle cell hyperplasia and graft occlusion.

Animals↗
PubMed2000

Major reduction in plasma Lp(a) levels during sepsis and burns.

Plasma levels of lipoprotein(a) [Lp(a)], an atherogenic particle, vary widely between individuals and are highly genetically determined. Whether Lp(a) is a positive acute-phase reactant is debated. The present study was designed to evaluate the impact of major inflammatory responses on plasma Lp(a) levels. Plasma levels of C-reactive protein (CRP), low density lipoprotein cholesterol, Lp(a), and apolipoprotein(a) [apo(a)] fragments, as well as urinary apo(a), were measured serially in 9 patients admitted to the intensive care unit for sepsis and 4 patients with extensive burns. Sepsis and burns elicited a major increase in plasma CRP levels. In both conditions, plasma concentrations of Lp(a) declined abruptly and transiently in parallel with plasma low density lipoprotein cholesterol levels and closely mirrored plasma CRP levels. In 5 survivors, the nadir of plasma Lp(a) levels was 5- to 15-fold lower than levels 16 to 18 months after the study period. No change in plasma levels of apo(a) fragments or urinary apo(a) was noticed during the study period. Turnover studies in mice indicated that clearance of Lp(a) was retarded in lipopolysaccharide-treated animals. Taken together, these data demonstrate that Lp(a) behaves as a negative acute-phase reactant during major inflammatory response. Nongenetic factors have a major, acute, and unexpected impact on Lp(a) metabolism in burns and sepsis. Identification of these factors may provide new tools to lower elevated plasma Lp(a) levels.

Adult↗
PubMed2000

Elevated perfusion pressure upregulates endothelin-1 and endothelin B receptor expression in the rabbit carotid artery.

To investigate the hypothesis that high blood pressure activates the endothelin system in the vessel wall, isolated segments of the rabbit carotid artery were subjected to different levels of perfusion pressure. Both preproendothelin-1 (ppET-1) mRNA abundance and intravascular ET-1 peptide content were strongly upregulated on raising the intraluminal pressure from 90 to 160 mm Hg for 3 to 12 hours, and this increase in ppET-1 mRNA occurred predominantly in the endothelial cells. Endothelin-converting enzyme-1 and endothelin A receptor (ET(A)-R) expression were pressure-insensitive, whereas that of the ET(B)-R in the smooth muscle cells was also significantly enhanced. Both the pressure-induced increase in ppET-1 and ET(B)-R expression required RNA synthesis because they were abolished by actinomycin D. The nuclear signaling mechanisms involved therein, however, appeared to be different. Thus, the pressure-induced expression of ppET-1 and activation of CCAAT-enhancer binding proteins beta and delta were blocked by the tyrosine kinase inhibitor herbimycin A, whereas ET(B)-R expression and the nuclear translocation of activator protein-1 were abolished by the protein kinase C inhibitor Ro 31-8220. One consequence of these presumably deformation-induced changes in gene expression was an increased rate of apoptosis of the smooth muscle cells in the media that if transferable to the situation in human blood vessels may contribute to hypertension-induced arterial remodeling.

Animals↗