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Biomedical subjects

R Maier

Publications and source records attributed to R Maier.

At least 37 records · Page 2Linked to original sources

Left ventricular architecture after valve replacement due to critical aortic stenosis: an approach to dis-/qualify the myth of valve prosthesis-patient mismatch?

OBJECTIVES: Left ventricular hypertrophy in patients with critical aortic stenosis (AS) is an adaptive process that compensates for high intracavitary pressure and reduces systolic wall stress followed by an increase in myocardial masses. In the present prospective clinical trial, we investigated long-term compensatory changes in left ventricular geometry and function after aortic valve replacement using mechanical bileaflet prostheses with the main emphasis on the small-sized aortic annulus and valve prosthesis-patient mismatch. METHODS: A total of 58 patients with critical AS were assigned to the following groups according to the predictive value of prosthetic valve area index (VAI): group EXMIS: 29 patients (VAI < or =0.99), expected mismatch; group NOMIS: 29 patients (VAI < or =0.99), no mismatch. At controls T(0) (before operation/operation (OP), T(1) and T(2) (4 and 20 months after OP) the left ventricular geometry was recorded by means of Imatron electron beam tomography and the transprosthetic velocities were measured by echocardiography. RESULTS: Statistical analysis showed a consistent reduction in the absolute (P=0.04) and indexed (P=0.04) left ventricular myocardial mass for both cohorts; furthermore, there was a significant difference between EXMIS and NOMIS patients concerning the factors, time and mass reduction (P=0.005), because of distinct baselines. A logistic regression report revealed preoperative cardiac output, absolute left ventricular myocardial mass, perfusion, body surface area and the native valve orifice area as predicting coefficients and factors for a minimum mass reduction of 25%. We explain a mathematical formula that turned out to be the most sensitive for correctly classified factors. CONCLUSIONS: The left ventricular geometry and transprosthetic velocities resulted in the same postoperative recovery for both EXMIS and NOMIS patients. The presented data showed that valve prosthesis-patient mismatch had no influence in several stepwise logistic regression models. We conclude that modern mechanical bileaflet prostheses allow both acceptable hemodynamics and recovery of left ventricular hypertrophy, even in small aortic annuli.

Aged↗

Differing beta-blocking effects of carvedilol and metoprolol.

BACKGROUND: Metoprolol is a beta(1)-selective beta-adrenergic antagonist while carvedilol is a non-selective beta-blocker with additional blockades of alpha(1)-adrenoceptors. Administration of metoprolol has been shown to cause up-regulation of beta-adrenoceptor density and to decrease nocturnal melatonin release, whereas carvedilol lacks these typical effects of beta-blocking drugs. AIMS: To compare beta-blocking effects of metoprolol and carvedilol when applied orally in healthy subjects. METHODS: We investigated the effects of single oral doses of clinically recommended amounts of metoprolol (50, 100 and 200 mg) and carvedilol (25, 50 and 100 mg) to those of a placebo in a randomised, double-blind, cross-over study in 12 healthy male volunteers. Two hours after oral administration of the drugs heart rate and blood pressure were measured at rest, after 10 min of exercise, and after 15 min of recovery. RESULTS: Metoprolol tended to decrease heart rate during exercise (-21%, -25% and -24%) to a greater extent than carvedilol (-16%, -16% and -18%). At rest, increasing doses of metoprolol caused decreasing heart rates (62, 60 and 58 beats/min) whereas increasing doses of carvedilol caused increasing heart rates (62, 66 and 69 beats/min), 50 and 100 mg carvedilol failed to differ significantly from the placebo (71 beats/min). CONCLUSIONS: We conclude that clinically recommended doses of carvedilol cause a clinically relevant beta-blockade in humans predominantly during exercise where it appears to be slightly (although not significantly) less effective than metoprolol. On the other hand, the effects of carvedilol on heart rate at rest appear rather weak, particularly in subjects with a low sympathetic tone. This might be caused by a reflex increase on sympathetic drive secondary to peripheral vasodilation resulting from the alpha-blocking effects of the drug. These results might be helpful in explaining why carvedilol, in contrast to metoprolol, may fail to cause up-regulation of beta-adrenoceptor density and does not decrease nocturnal melatonin release. This, in turn, may be a reason for the weak side-effects of carvedilol resulting from the beta-blockade. In addition, our data might be of interest in the interpretation of the forthcoming results of the COMET trial, although it has to be emphasised that they were derived from healthy subjects and, therefore, cannot be directly extrapolated to patients with heart failure.

Administration, Oral↗

Thromboelastography for monitoring prolonged hypercoagulability after major abdominal surgery.

UNLABELLED: Despite clinical and laboratory evidence of perioperative hypercoagulability, there are no consistent data evaluating the extent, duration, and specific contribution of platelets and procoagulatory proteins by in vitro testing. We tested the hypothesis that the parallel use of standard and abciximab-cytochalasin D-modified thromboelastography (TEG) can assess 7 days' postoperative hypercoagulability and can estimate the independent contribution of procoagulatory proteins and platelets. Thromboelastograms were performed before surgery, at the end of surgery, 6 h after surgery, and on postoperative days 1, 2, 3, and 7; they were analyzed for the reaction time and the maximal amplitude (MA). We calculated the elastic shear modulus of standard MA (G(t)) and modified MA (G(c)), which reflect total clot strength and procoagulatory protein component, respectively. The difference was an estimate of the platelet component (G(p)). There was a 10% perioperative increase of standard MA, corresponding to a 50% increase of G(t) (P < 0.0001) and an 86%-90% contribution of the calculated G(p) to G(t). We conclude that serial standard and modified thromboelastography may reveal prolonged postoperative hypercoagulability and the independent contribution of platelets and procoagulatory proteins to clot strength. IMPLICATIONS: Postoperative hypercoagulability, occurring for at least 1 wk after major abdominal surgery, may be demonstrated by standard and modified thromboelastography. This hypercoagulability is not reflected by standard coagulation monitoring and seems to be predominantly caused by increased platelet reactivity.

Abdomen↗

Coronary artery plaque burden and perioperative cardiac risk.

BACKGROUND: Electron-beam computed tomography-derived coronary calcium score correlates with the morphologic severity of coronary artery disease, reflecting both global atherosclerotic plaque formation and coronary artery luminal narrowing. The current study examines the impact of coronary atherosclerotic plaque burden, measured by coronary calcium score, on the potential for perioperative myocardial cell injury, as assessed by cardiac troponin T elevations in patients undergoing elective vascular surgery. The authors further investigated whether perioperative myocardial cell injury in those patients adversely affects noninvasive measures of left ventricular systolic function, such as ejection fraction and wall motion score. METHODS: Fifty-one consecutive patients scheduled for vascular surgery were enrolled in this prospective study. In addition to standard preoperative evaluation, including patient history and physical examination, electron-beam computed tomography scan, 12-lead electrocardiography, and transthoracic echocardiography were performed on the day before surgery. Subsequent evaluations on postoperative days 2 and 7 included transthoracic echocardiography and 12-lead electrocardiography. Cardiac troponin T determinations were performed on the day before surgery, immediately preoperatively, and on postoperative days 1, 2, 3, and 7. RESULTS: The median coronary calcium score of the 51 patients was 997.0 (25th percentile, 202.5; 75th percentile, 1,949.5). Cardiac troponin T elevations exclusively occurred in patients with a coronary calcium score greater than 1,000. The six patients (12%) with perioperative cardiac troponin T elevations had a 2.5-fold higher coronary calcium score than those without cardiac troponin T elevation (P = 0.021). In these patients, the ejection fraction decreased from 61 +/- 10% to 52 +/- 13% (mean +/- SD) on postoperative day 2 and was 54 +/- 16% on postoperative day 7 (P = 0.022). CONCLUSION: A high electron-beam computed tomography coronary calcium score, reflecting substantial coronary plaque burden, carries an increased risk for myocardial cell injury after vascular surgery. In these patients, myocardial damage may result in deterioration of global systolic left ventricular function.

Aged↗

Evaluation of right ventricular performance with a right ventricular ejection fraction thermodilution catheter and MRI in patients with pulmonary hypertension.

STUDY OBJECTIVES: We sought to compare catheter studies using a right ventricular ejection fraction (REF) catheter together with echocardiography and MRI in patients with pulmonary hypertension. PATIENTS AND METHODS: We compared hemodynamic findings, echocardiography, and MRI studies in 16 patients with pulmonary hypertension. Six healthy volunteers served as control subjects for the MRI studies. RESULTS: MRI imaging provided accurate assessment of cardiac output in all but two patients. As compared with MRI, the REF catheter constantly underestimated the REF and overestimated right ventricular volumes in patients with pulmonary hypertension. REF, end-systolic and end-diastolic right ventricular volumes, and right ventricular muscle mass, as determined by MRI, were almost identical in patients with preserved cardiac function and those with low-output failure. The only factor that was different in both groups was the severity of tricuspid regurgitation. CONCLUSION: Right ventricular dimensions and muscle mass do not differ in patients with pulmonary hypertension who have low cardiac output and those who do not. According to our results, the major determinant of cardiac output in these patients appears to be the severity of tricuspid regurgitation. The REF catheter provides invalid data on right ventricular dimensions in patients with pulmonary hypertension.

Adult↗

Paradoxical vestibular disease with trigeminal nerve-sheath tumor in a dog.

A thirteen-year old spayed female poodle was referred because of atrophy of temporal and masseter muscles on the left and head tilt and episodical circling to the right side. Additionally, decreased facial sensation, absent menace reaction, palpebral and corneal reflexes on the left side, as well as ipsilateral hemiparesis and tongue palsy were noticed. Generalised vestibular ataxia and hypermetria in the front limbs were present. Based on the clinical signs, the presumptive anatomical localization of the lesion was the cerebellopontine angle including parts of the caudal brainstem with involvement of the trigeminal, facial and hypoglossal nerves. Involvement of either flocculonodular lobe or the caudal cerebellar peduncle on the left side causing paradoxical vestibular disease was suspected. On magnetic resonance imaging a large enhancing lesion in the area of the left cerebellopontine angle involving the trigeminal nerve and compressing cerebellum and brainstem was seen. Because of the poor prognosis the dog was euthanized on the owner's request. This space occupying lesion could be identified as a trigeminal neurofibrosarcoma/schwannoma on post mortem histopathological examination.

Animals↗

Kinetics of CXCR4 and CCR5 up-regulation and human immunodeficiency virus expansion after antigenic stimulation of primary CD4(+) T lymphocytes.

The chemokine receptors CCR5 and CXCR4 are coreceptors for the human immunodeficiency virus (HIV) and determine the cell tropism of different HIV strains. Previous studies on their regulation were performed under conditions of unspecific T-lymphocyte stimulation and provided conflicting results. To mimic physiologic conditions, highly purified primary Staphylococcus enterotoxin B (SEB)-reactive CD4 T lymphocytes were stimulated in the presence of autologous antigen-presenting cells and the kinetics of CCR5 and CXCR4 surface expression and HIV replication were studied. Both chemokine receptors were transiently up-regulated with maximal expression at day 3 after stimulation. The stimulated T cells were equally susceptible to productive infection with R5-and X4-tropic virus strains. Thus, antigenic stimulation of T cells promotes efficient replication of both, T cell-tropic and macrophage-tropic HIV. (Blood. 2000;96:1853-1856)

CD4-Positive T-Lymphocytes↗

Excitation functions of the analyzing power in pp--> scattering from 0.45 to 2.5 GeV

Excitation functions A(N)(p(p),Theta(c.m.)) of the analyzing power in pp--> elastic scattering have been measured with a polarized atomic hydrogen target for projectile momenta p(p) between 1000 and 3300 MeV/ c. The experiment was performed for scattering angles 30 degrees </=Theta(c.m.)</=90 degrees using the recirculating beam of the proton storage ring COSY during acceleration. The resulting excitation functions and angular distributions of high internal consistency have significant impact on the recent phase shift solution SAID SP99, in particular, on the spin triplet phase shifts between 1000 and 1800 MeV, and demonstrate the limited predictive power of single-energy phase shift solutions at these energies.

Journal Article↗

Cytotoxic T lymphocyte epitopes of HIV-1 Nef: Generation of multiple definitive major histocompatibility complex class I ligands by proteasomes.

Although a pivotal role of proteasomes in the proteolytic generation of epitopes for major histocompatibility complex (MHC) class I presentation is undisputed, their precise function is currently the subject of an active debate: do proteasomes generate many epitopes in definitive form, or do they merely generate the COOH termini, whereas the definitive NH(2) termini are cleaved by aminopeptidases? We determined five naturally processed MHC class I ligands derived from HIV-1 Nef. Unexpectedly, the five ligands correspond to only three cytotoxic T lymphocyte (CTL) epitopes, two of which occur in two COOH-terminal length variants. Parallel analyses of proteasomal digests of a Nef fragment encompassing the epitopes revealed that all five ligands are direct products of proteasomes. Moreover, in four of the five ligands, the NH(2) termini correspond to major proteasome cleavage sites, and putative NH(2)-terminally extended precursor fragments were detected for only one of the five ligands. All ligands are transported by the transporter associated with antigen processing (TAP). The combined results from these five ligands provide strong evidence that many definitive MHC class I ligands are precisely cleaved at both ends by proteasomes. Additional evidence supporting this conclusion is discussed, along with contrasting results of others who propose a strong role for NH(2)-terminal trimming with direct proteasomal epitope generation being a rare event.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Active recombinant human tyrosine kinase c-Yes: expression in baculovirus system, purification, comparison to c-Src, and inhibition by a c-Src inhibitor.

C-Yes is a non-receptor-type tyrosine kinase of the Src family that is most closely related to c-Src. C-Yes has been implicated in development of some human cancers. Here we report on the expression, purification, and characterization of the active human recombinant c-Yes. A full-length human c-Yes clone has been generated and the protein was expressed in insect Sf9 cells. Active c-Yes was purified by liquid chromatography to yield a preparation with a high specific activity (160 nmol/min/mg using an optimal Src substrate peptide). In a comparison between human c-Yes and c-Src enzymes, relative phosphorylation efficiencies on nine protein and four peptide substrates were different. However, the recently described Src inhibitor CGP77675 inhibited human c-Yes with a potency similar to that of c-Src (IC(50) value of 6.5 nM). The purified preparation of active c-Yes provides a good basis for further enzymatic characterization and for the development of c-Yes-specific inhibitors.

Animals↗

Depression of nuclear transcription and extension of mRNA half-life under anoxia in Artemia franciscana embryos.

Transcriptional activity, as assessed by nuclear run-on assays, was constant during 10 h of normoxic development for embryos of the brine shrimp Artemia franciscana. Exposure of embryos to only 4 h of anoxia resulted in a 79.3+/-1 % decrease in levels of in-vivo-initiated transcripts, and transcription was depressed by 88. 2+/-0.7 % compared with normoxic controls after 24 h of anoxia (means +/- s.e.m., N=3). Initiation of transcription was fully restored after 1 h of normoxic recovery. Artificially lowering the intracellular pH of aerobic embryos to the value reflective of anoxia (pH 6.7) showed that acidification alone explained over half the transcriptional arrest. Initiation of transcription was not rescued by application of 80 % carbon monoxide under anoxia, which suggests that heme-based oxygen sensing is not involved in this global arrest. When these transcriptional data are combined with the finding that mRNA levels are unchanged for at least 6 h of anoxia, it is clear that the half-life of mRNA is extended at least 8.5-fold compared with that in aerobic embryos. In contrast to the activation of compensatory mechanisms to cope with anoxia that occurs in mammalian cells, A. franciscana embryos enter a metabolically depressed state in which gene expression and mRNA turnover are cellular costs apparently not compatible with survival and in which extended tolerance supercedes the requirement for continued metabolic function.

Animals↗

Signaling in human osteoblasts by extracellular nucleotides. Their weak induction of the c-fos proto-oncogene via Ca2+ mobilization is strongly potentiated by a parathyroid hormone/cAMP-dependent protein kinase pathway independently of mitogen-activated protein kinase.

Extracellular nucleotides acting through specific P2 receptors activate intracellular signaling cascades. Consistent with the expression of G protein-coupled P2Y receptors in skeletal tissue, the human osteosarcoma cell line SaOS-2 and primary osteoblasts express P2Y1 and P2Y2 receptors, respectively. Their activation by nucleotide agonists (ADP and ATP for P2Y1; ATP and UTP for P2Y2) elevates [Ca2+]i and moderately induces expression of the c-fos proto-oncogene. A synergistic effect on c-fos induction is observed by combining ATP and parathyroid hormone, a key bone cell regulator. Parathyroid hormone elevates intracellular cAMP levels and correspondingly activates a stably integrated reporter gene driven by the Ca2+/cAMP-responsive element of the human c-fos promoter. Nucleotides have little effect on either cAMP levels or this reporter, instead activating luciferase controlled by the full c-fos promoter. This induction is reproduced by a stably integrated serum response element reporter independently of mitogen-activated protein kinase activation and ternary complex factor phosphorylation. This novel example of synergy between the cAMP-dependent protein kinase/CaCRE signaling module and a non-mitogen-activated protein kinase/ternary complex factor pathway that targets the serum response element shows that extracellular ATP, via P2Y receptors, can potentiate strong responses to ubiquitous growth and differentiative factors.

Adenosine Triphosphate↗

Influence of beta-blockers on melatonin release.

OBJECTIVE: Melatonin is a mediator in the establishment of the circadian rhythm of biological processes. It is produced in the pineal gland mainly during the night by stimulation of adrenergic beta1- and alpha1-receptors. Sleep disturbances are common side-effects of beta-blockers. The influence of specific beta-blockade as well as that of combined alpha-and beta-blockade on melatonin production has not been investigated in humans before. METHODS: We performed a randomized, double-blind, placebo-controlled, cross-over study in 15 healthy volunteers. Subjects received single oral doses of 40 mg (R)-propranolol, 40 mg (S)-propranolol, 50 mg (R)-atenolol, 50 mg (S)-atenolol, 25 mg (R,S)-carvedilol, 120 mg (R,S)-verapamil or placebo at 1800 hours. Urine was collected between 2200 hours and 0600 hours, and 6-sulfatoxy-melatonin (aMT6s), the main metabolite of melatonin which is almost completely eliminated in urine, was determined by radioimmunoassay (RIA). RESULTS: Mean nocturnal excretion of aMT6s in urine after intake of the drugs was as follows (in microg): placebo 26; (R)-propranolol 24 (-7%, NS); (S)-propranolol 5 (-80%, P < 0.001); (R)-atenolol 27 (+7%, NS); (S)-atenolol 4 (-86%, P < 0.01); (R,S)-carvedilol 23 (-10%, NS); (R,S)-verapamil 29 (+14%, NS). These data show that only the specifically beta-blocking (S)-enantiomers of propranolol and atenolol decrease the nocturnal production of melatonin whereas the non-beta-blocking (R)-enantiomers have no effect. Unexpectedly, (R,S)-carvedilol which inhibits both alpha- and beta-adrenoceptors does not decrease melatonin production. CONCLUSION: These findings indicate that beta-blockers decrease melatonin release via specific inhibition of adrenergic beta1-receptors. Since lower nocturnal melatonin levels might be the reason for sleep disturbances, further clinical studies should investigate whether or not oral administration of melatonin might avoid this well-known side-effect of beta-blockers. The reason why (R,S)-carvedilol does not influence melatonin production remains to be determined.

Adrenergic beta-Antagonists↗

Results of spinal cord decompression and thoracolumbar pedicle stabilisation in relation to the time of operation.

Short-segment pedicle stabilisation, transpedicular disc resection and autologous cancellous bone grafting is performed in trauma patients being transferred to our trauma centre with thoracolumbar fracture/dislocations. A follow-up examination of 88 patients, who were operated during the years of 1985-1992, took place after an average time of 5.6 years. Our results suggest that the earlier operative decompression and spine stabilisation takes place, the better is the recovery rate in patients with neurologic deficits. The highest neurologic recovery rates were found in patients operated within 8 h after the initial trauma. High remission rates were still found, if the patients had been operated within 48 h. After this time there was no significant difference in the neurologic outcome compared to the time of operation.

Adult↗

Natriuretic peptides in patients with diastolic dysfunction due to idiopathic dilated cardiomyopathy.

AIMS: The degree of systolic dysfunction does not always correlate with functional impairment in patients with congestive heart failure. In contrast, diastolic dysfunction correlates well with functional impairment. In heart failure, both elevation of N-terminal proatrial natriuretic peptide and B-type natriuretic peptide are markers of a poor prognosis. METHODS: We investigated 32 patients (26 male, 6 female; mean age 55+/-2 years) with dilated cardiomyopathy and sinus rhythm. M-mode echocardiography and 2D-echocardiography were carried out in each patient. Pulsed-wave Doppler inflow signals were obtained and the following parameters were measured: maximal E wave and maximal A wave velocity, E/A ratio, E wave deceleration time, A wave deceleration time. Immediately after echocardiography blood samples were collected from patients in the supine position. N-terminal proANP and brain natriuretic peptide were measured using a radioimmuno assay. RESULTS: The left ventricular ejection fraction was 34+/-1%, the left ventricular end-diastolic diameter on M-mode echocardiography was 68+/-1 mm, while left atrial diameter was 45+/-1 mm. Univariate analysis revealed a significant correlation between both left atrial diameter and ejection fraction and N-terminal proANP and brain natriuretic peptide. All transmitral Doppler parameters showed a significant correlation with N-terminal proANP and brain natriuretic peptide. On forward stepwise regression analysis, left atrial diameter and ejection fraction were able to predict both N-terminal proANP and brain natriuretic peptide. However, of the diastolic parameters only the E/A ratio remained significant. Mildly symptomatic patients differed significantly from severely symptomatic patients in all Doppler parameters. Mildly symptomatic patients had significantly lower levels of N-terminal proANP (0.571+/-0.079 vs 2.282+/-0.340 nmol. l(-1);P<0.001) and brain natriuretic peptide (51+/-14.8 vs 474.2+/- 86.8 pg. ml(-1);P<0. 001). CONCLUSION: There is a close relationship between natriuretic peptides and diastolic Doppler parameters of left ventricular filling in patients with dilated cardiomyopathy. There is also a significant difference between patients with mild and severe functional impairment regarding both natriuretic peptides and transmitral Doppler parameters.

Atrial Natriuretic Factor↗

N-terminal proatrial natriuretic peptide correlates with systolic dysfunction and left ventricular filling pattern in patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: To investigate the diastolic Doppler filling pattern in patients with idiopathic dilated cardiomyopathy and its relation to N-terminal pro-atrial natriuretic peptide (NT-pro-ANP). METHODS: 32 patients (26 male, six female) with idiopathic dilated cardiomyopathy were investigated. All were in sinus rhythm. Conventional M mode echocardiography and Doppler echocardiography was done in each patient. Pulsed wave Doppler inflow signals were obtained and the following variables were measured: maximum E wave, maximum A wave, E/A ratio, E wave deceleration time, A wave deceleration time. NT-pro-ANP was measured using radioimmunoassay. RESULTS: Mean (SD) left ventricular ejection fraction was 34 (7)% and mean left ventricular end diastolic diameter on M mode echocardiography was 69 (7) mm. Left ventricular filling indices were as follows: maximum E wave velocity, 0.86 (0.22) m/s; maximum A wave velocity, 0.71 (0.24) m/s; E/A ratio, 1.41 (0.65). Mean E wave deceleration time was 140 (50) ms; mean A wave deceleration time was 100 (20) ms. In a stepwise forward regression model, NT-pro-ANP correlated significantly with left atrial diameter (r = 0.603; p < 0. 001), left ventricular ejection fraction (r = -0.758; p < 0.001), and Doppler derived E/A ratio (r = 0.740; p < 0.001). CONCLUSIONS: In patients with idiopathic dilated cardiomyopathy there is a relation between NT-pro-ANP and both systolic and diastolic variables. In a multivariate model NT-pro-ANP correlated with left atrial diameter, left ventricular ejection fraction, and Doppler derived E/A ratio on transmitral inflow.

Aged↗

Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension.

Assessment of cardiac output is an important part of the management of patients with pulmonary hypertension. The accuracy of the thermodilution technique in patients with low cardiac output or severe tricuspid regurgitation has been questioned. To address this issue, we simultaneously compared 105 cardiac output measurements by the Fick method and thermodilution in 35 patients with pulmonary hypertension. Moreover, we evaluated the acetylene rebreathing technique, a noninvasive method of determining cardiac output. The mean difference +/- 95% limit of agreement between thermodilution and the Fick method was +0.01 +/- 1.1 L/min. The mean difference +/- 95% limit of agreement between acetylene rebreathing and the Fick method was -0.23 +/- 1.14 L/min. Neither the mean agreement nor the 95% limits of agreement of both thermodilution and acetylene rebreathing with the Fick method were affected by the presence of low cardiac output or severe tricuspid regurgitation. We conclude that thermodilution and acetylene rebreathing are useful tools for assessing cardiac output in patients with pulmonary hypertension, even in the presence of low cardiac output or severe tricuspid regurgitation.

Acetylene↗

P2Y receptor subtypes differentially couple to inwardly-rectifying potassium channels.

Subtypes of P2Y receptors are well characterized with respect to their agonist profile but little is known about differences in their intracellular signalling properties. When expressed in Xenopus oocytes, both P2Y2 and P2Y6 receptors effectively couple to endogenous Ca2+-dependent Cl--channels. However, only P2Y2 receptors increased currents mediated by inward-rectifier K+ channels of the Kir3.0 subfamily. This increase in Kir-current was sensitive to pertussis toxin, while activation of Ca2+-dependent Cl--channels was not. In contrast, suramin, a P2 receptor antagonist, inhibited activation of both channels. These observations suggest that, in contrast to P2Y6, P2Y2 receptors couple to two different classes of G proteins.

Adenosine Triphosphate↗