PubMed Health⌕ Search

Biomedical subjects

S Schüler

Publications and source records attributed to S Schüler.

At least 19 recordsLinked to original sources
PubMed2002

[Space occupying lesion of unknown origin in the pulmonary trunk: targeted differential diagnosis and surgical therapy in a patient with B symptoms and thoracic pain].

Leiomyosarcomas are only rarely found in routine cardiac surgery. For the patient they hold, however, a very high-risk potential as only an early diagnosis, and immediate surgical therapy leads to long-term survival. Awareness, timely diagnosis, and immediate radical surgical therapy is imperative. This report describes the case of a 21-year old male with a strong suspicion of leiomyosarcoma of the pulmonary artery. Due to his clinical symptoms, the patient was transferred to operation immediately after completion of all diagnostic measurements. Postoperatively the diagnosis of a leiomyosarcoma proved to be false; instead a rare fibro-histologic tumor was found. Even in the case of a suspected leiomyosarcoma, rapid and radical surgical therapy is imperative due to the poor prognosis of leiomyosarcoma.

Adult↗
PubMed2002

Pharmacokinetics of pravastatin in heart-transplant patients taking cyclosporin A.

BACKGROUND: Heart transplantation is an established tool for the treatment of terminal heart failure. Hyperlipidemia is a common problem following heart transplantation and has been implicated as an additional risk factor in the development of transplant coronary artery disease (TxCAD). Therefore, heart recipients are commonly treated with inhibitors of cholesterol synthesis (HMG-CoA reductase inhibitors). However, these patients have an increased risk of developing rhabdomyolysis due to elevated concentrations of HMG-CoA reductase inhibitors under co-administration with the immunosuppressive cyclosporin A (CsA). AIM OF THE STUDY: Aim of our study was to obtain pharmacokinetic data on pravastatin whilst monitoring the safety and efficiency of the lipid lowering therapy in heart-transplant recipients under immunosuppression with CsA and to compare these data to those of a healthy control group. SUBJECTS, MATERIALS AND METHODS: Eleven patients (30.2 +/- 12.3 months after transplantation) receiving immunosuppressive therapy consisting of cyclosporin A, prednisone and azathioprine with LDL cholesterol (LDL-C) concentrations exceeding 3.9 mmol/l and 8 control subjects were included into the study. In addition to the immunosuppressive therapy, the patients received a daily dose of 40 mg/day pravastatin for the first 8 days which was then reduced to 10 mg/day administered until Day 29. Blood was sampled for pharmacokinetic profiling (maximum concentration of the drug (Cmax), time to reach Cmax (tmax), area under the concentration vs. time curve (AUC(0-24h)), elimination half-life time (tcl)) and measurement of the parameters of clinical chemistry on Days 1, 8 and 29. The control group received a single dose of 60 mg pravastatin and the values of Cmax and AUC(0-24h) were normalized for a dose of 10 mg. RESULTS: Pravastatin 40 mg/day for 1 week in the patient group caused a significant reduction in total cholesterol (C) and LDL-C from 8.11 +/- 1.20 mmol/l and 5.88 +/- 1.15 mmol/l to 6.91 +/- 1.01 mmol/l and 4.72 +/- 1.05 mmol/l, respectively (p = 0.005 and p = 0.003). Triglycerides and HDL cholesterol (HDL-C) concentrations did not change significantly. Mean values for Cmax of pravastatin were 384.2 ng/ml, 392.0 ng/ml and 115.1 ng/ml in patients on Days 1, 8 and 29, respectively. After normalization for a dose of 10 mg, the corresponding values of C(max-DN10mg) and Cmax were 96.0 ng/ml, 98.0 ng/ml and 115.1 ng/ml on study Days 1, 8 and 29. These values were 7-8 times higher than the normalized value of C(max-DN10mg) for the control group (13.7 ng/ml). The corresponding values of AUC(0-24h) were 1228.2 ng/ml x h, 1214.1 ng/ml x h and 345.9 ng/ml x h in the patient group on study Days 1, 8 and 29 as well as 157.5 ng/ml x h in the control group prior to normalization. After normalization for a dose of 10 mg, the values of AUC(0-24h-DN10mg) in the patient group were approximately 12 times higher than those of the control group. However, no significant differences between the 2 groups were observed in tmax and tcl. Within the patient group, no significant increase in Cmax or AUC was found on Day 1 to Day 8. The results of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) showed also no significant increase during the observation period. CONCLUSION: Heart-transplant recipients treated with the HMG-CoA reductase inhibitor pravastatin generally show higher plasma concentrations of this drug than control subjects. However, our data suggest that the HMG-CoA reductase inhibitor pravastatin can be used effectively in these patients receiving the immunosuppressive cyclosporin A. The pharmacokinetic data obtained indicate that there is no significant cumulation of the drug following multiple dosages in spite of increased drug concentrations after a single oral dosage.

Anticholesteremic Agents↗
PubMed2001

Molecular basis of downregulation of G-protein-coupled inward rectifying K(+) current (I(K,ACh) in chronic human atrial fibrillation: decrease in GIRK4 mRNA correlates with reduced I(K,ACh) and muscarinic receptor-mediated shortening of action potentials.

BACKGROUND: Clinical and experimental evidence suggest that the parasympathetic nervous system is involved in the pathogenesis of atrial fibrillation (AF). However, it is unclear whether changes in G-protein-coupled inward rectifying K(+) current (I(K,ACh)) contribute to chronic AF. METHODS AND RESULTS: In the present study, we used electrophysiological recordings and competitive reverse-transcription polymerase chain reaction to study changes in I(K,ACh) and the level of the I(K,ACh) GIRK4 subunit in isolated human atrial myocytes and the atrial tissue of 39 patients with sinus rhythm and 24 patients with chronic AF. The density of I(K,ACh) was approximately 50% smaller in myocytes from patients with AF compared with those in sinus rhythm, and this was accompanied by decreased levels of GIRK4 mRNA. The current density of the inward rectifying K(+) current (I(K1)) was 2-fold larger during AF than in sinus rhythm, in correspondence with an increase in Kir2.1 mRNA. The larger I(K1) in AF is consistent with more negative membrane potentials in right atrial trabeculae from AF patients. Moreover, action potential duration was reduced in AF, and the action potential shortening produced by muscarinic receptor stimulation was attenuated, indicating that the changes of I(K1) and I(K,ACh) were functionally relevant. CONCLUSIONS: Chronic human AF induces transcriptionally mediated upregulation of I(K1) but downregulation of I(K,ACh) and attenuates the muscarinic receptor-mediated shortening of atrial action potentials. This suggests that atrial myocytes adapt to a chronically high rate by downregulating I(K,ACh) to counteract the shortening of the atrial effective refractory period due to electrical remodeling.

Acetylcholine↗
PubMed2001

Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells.

OBJECTIVE: Secondary failure due to late restenosis continues to occur in 30-50% of individuals after PTCA. beta-Blockers play an important role in the treatment of CAD. The aim of this study was to investigate the effects of the new beta-blocker nebivolol on cell proliferation of human coronary smooth muscle cells (haCSMCs) and endothelial cells (haECs) in comparison to traditional beta-blockers. METHODS: The effect of nebivolol and other beta-blockers on proliferation of HaECs and HaCSMCs was analyzed by bromodeoxyuridine incorporation. Apoptosis was measured by determination of hypodiploid DNA in both cell types. Additionally, in HaECs NO formation, endothelin-1 transcription and secretion were determined. RESULTS: Incubation for 1, 2, 4, 7 or 14 days resulted in a concentration- and time-dependent reduction of proliferation up to 80% in HaECs and HaCSMCs. beta-Blockers such as propranolol, metoprolol or bisoprolol did not exert this effect. Nebivolol inhibited accelerated haCSMC proliferation even in the presence of growth factors such as TGFbeta(1) and PDGF-BB. Nebivolol concentration-dependently induced a moderate apoptosis (10(-5) mol/l: 23%) and a decrease of haCSMCs in the S-phase by 66%. HaECs showed comparable results. During nebivolol incubation NO formation of HaCEs increased, while endothelin-1 transcription and secretion were suppressed. CONCLUSION: Whereas classical beta-blockers do not affect cell growth, only nebivolol inhibits haCSMC or haEC proliferation and induces a moderate rate of apoptosis. Furthermore, in HaCEs NO formation increases and endothelin-1 secretion decreases suggesting that nebivolol may represent a beta-blocker with great promises in CAD therapy.

Adrenergic beta-Antagonists↗
PubMed2001

Prevention of human smooth muscle cell proliferation without induction of apoptosis by the topoisomerase I inhibitor topotecan.

Despite significant improvements in the treatment of atherosclerotic disease involving procedures such as angioplasty, bypass grafting, endartherectomy, or stent implantation, secondary failure due to late restenosis still occurs in 30-50% of individuals. Restenosis and later stages of atherosclerotic lesions arise from a complex series of fibroproliferative responses to vascular injury that are triggered by potent growth-regulatory molecules and finally result in vascular smooth muscle cell proliferation, migration, and neointima formation. The aim of this study was to investigate the antiproliferative effects of the topoisomerase I inhibitor topotecan on human arterial coronary smooth muscle cells. Following incubation of cells with different drug concentrations, mitotic indices were measured by bromodeoxyuridine incorporation, while cellular mitochondrial activity was evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Continuous incubation with topotecan for 7 days resulted in a complete and dose-dependent reduction of smooth muscle cell proliferation, and topotecan inhibited cell proliferation in the presence of growth factors as well. In contrast, mitochondrial activity was only partially decreased. Remarkably, although even short-term incubations for 20 min were sufficient to induce a long-lasting growth inhibition, topotecan did not induce apoptosis. Our results therefore suggest that, based on its drug profile, the topoisomerase I inhibitor topotecan may be a promising drug to inhibit restenosis occurring after coronary angioplasty with local devices.

Apoptosis↗
PubMed2001

Primary cutaneous microangiopathy in heart recipients.

In this study we investigated whether a disturbance in microcirculation is detectable in heart recipients with cardiac allograft vasculopathy (CAV) and severe hypercholesterolemia (n = 11) and in 7 heart recipients without CAV in comparison to patients with severe coronary artery disease (n = 49) and age-matched apparently healthy subjects (n = 100). For this purpose, the flow velocity of erythrocytes through cutaneous capillaries at the nail fold of the finger was measured under resting conditions. In addition, reactive hyperemia in the same capillaries after a 3-min ischemia was determined. Patients with CAV and severe lipid disorder showed a pathological reduction in mean capillary erythrocyte velocity under resting conditions with v(RBC) = 0.10 +/- 0.07 mm/s. The latter was significantly and relevantly lower than in patients with coronary three-vessel disease (v(RBC) = 0.46 +/- 0.35 mm/s). It was notable that under resting conditions temporary cessation of flow occurred in 8 of the 11 patients which did not occur in healthy subjects and rarely in patients with three-vessel disease (1 of 49 patients). In comparison to age-matched healthy subjects (v(max) = 1.46 +/- 0.52 mm/s), the patients with three-vessel disease showed a significant reduction in postischemic maximum erythrocyte velocity (v(max) = 0.85 +/- 0.55 mm/s), with a considerable shortening of the duration of reactive hyperemia. Patients with CAV demonstrated a total loss of postischemic reactive hyperemia (only 1 of the 11 patients presented a weak reactive hyperemia). Since no macroangiopathy was detectable in the upstream arm arteries, primary cutaneous microangiopathy can be assumed in patients with cardiac allograft vasculopathy and severe hypercholesterolemia.

Adult↗
PubMed2001

Early experience with a quadrileaflet stentless mitral valve.

BACKGROUND: Presently no ideal prosthesis for mitral valve replacement exists. The quadrileaflet mitral valve (SJM-Quattro-MV; St. Jude Medical, Inc, St. Paul, MN) is a chordally supported stentless bioprosthesis. Due to its specific geometry it seems to be particularly suited for mitral valve replacement. METHODS: From March 1999 to October 2000, 12 patients (ages 71+/-2 years) received the SJM-Quattro-MV. Six patients suffered from valvular stenosis and 6 patients from incompetence. Preoperatively, all patients were in New York Heart Association functional class III, with left ventricular ejection fraction amounts of 54%+/-17%. RESULTS: Eleven patients received a medium size SJM-Quattro-MV and one patient received a large size SJM-Quattro-MV. Cross-clamp time was 99.8+/-4.9 minutes. Additional procedures were coronary artery bypass grafting (n = 3) and left atrial microwave ablation (n = 2). Postoperative mortality (n = 1) was procedure related. At follow-up of 11.6+/-5.4 months, all patients were well, the transvalvular pressure gradient was 5.0+/-1.4 mm Hg, and the effective orifice area 2.7+/-0.2 cm2. CONCLUSIONS: Our preliminary experiences with the SJM-Quattro-MV presented good clinical results and promoted an optimistic way of thinking about the further development of these valve prostheses.

Aged↗
PubMed2001

p21/waf1/cip1 in gastric cancer: associations with histopathological subtypes, lymphonodal metastasis, prognosis and p53 status.

BACKGROUND: Cyclins and cyclin-dependent kinases are determining factors of the cell cycle. In the present study, we investigated the role of p21 and p53 in the biology of gastric cancer, focusing on its influence on progression and prognosis (n = 195). METHODS: P21 and p53 immunoreactivity was analysed immunohistochemically, applying monoclonal antibodies. The p53 status was comparatively evaluated by PCR-SSCP analysis of p53 mutations in selected tumours. RESULTS: Fifty-eight percent of the carcinomas were p21+ in more than 5% of the cancer cell nuclei, whereas 19% exhibited a p21 immunoreactivity in more than 20% of the nuclei. On the other hand, p53 was over-expressed (in more than 50% of the nuclei) in about 45% of the specimens. P21 immunoreactivity in more than 5% of the nuclei was inversely related to the pN as well as pTNM cancer stage, whereas only a strong p21 expression (in >20% of the nuclei) was correlated with a better survival probability in a univariate analysis. The p53 status was associated with lymphonodal metastasis, but not with prognostic data. In multivariate survival analyses, neither p21 nor p53 emerged as independent prognostic factors. Compared with the results of p53 mutation analysis by PCR-SSCP. p21 immunoreactivity was reduced in p53-mutated cases. CONCLUSIONS: These features show an association of p21 over-expression with certain clinico-pathological parameters of gastric cancer. In this context, our data suggest that p21 immunoreactivity in more than 5% of the tumour cells has a predictive value for the course of adenocarcinoma of the stomach.

Adenocarcinoma↗
PubMed2001

Pharmacokinetics and pharmacodynamics of fluvastatin in heart transplant recipients taking cyclosporine A.

During the last decades, transplantation has become an established tool for the treatment of terminal organ failure. Beside immunological factors, hyperlipidemia is the main problem after heart transplantation, causing rapid transplant coronary artery disease (TxCAD) and poor long-term prognosis at the beginning of the transplantation. Heart transplant recipients are now effectively treated with lipid lowering substances, of which HMG-CoA-reductase inhibitors are the most potent. However, treatment with these substances correlates with an increased risk for the development of rhabdomyolysis due to therapy with the immunosuppressive cyclosporine A. Our study monitored the safety and efficacy of treatment with the HMG-CoA reductase inhibitor fluvastatin in heart transplant recipients compared to healthy controls. We investigated 10 patients receiving immunosuppressive therapy consisting of cyclosporine A, prednisone, and azathioprine who had increased concentrations of LDL-cholesterol (LDL-C), and 10 age-matched healthy controls. The patients were treated with 40 mg/day fluvastatin for 4 weeks and 20 mg/day for 4 additional weeks. Control individuals received 40 mg/day fluvastatin for 4 weeks only. Parameters of fluvastatin pharmacokinetics (maximum concentration of the drug (C(max.)), time (t(max.)) to reach C(max.), area under the concentration vs. time curve (AUC(0h-24h)), elimination half-life time (t(1/2))), apparent total body clearance (CL), blood cyclosporine A concentration, plasma lipids, and safety parameters were determined in both study groups at the beginning of the study and after 4 weeks. The latter were determined in the patient group also after 8 and 12 weeks. Treatment with 40 mg/day fluvastatin caused a significant decrease in total cholesterol (patients: 5.47 +/- 1.32 mmol/L vs. 7.30 +/- 1.83 mmol/L; controls: 4.69 +/- 0.64 mmol/L vs. 5.81 +/- 0.72 mmol/L), LDL-C (patients: 3.28 +/- 1.25 mmol/L vs. 5.00 +/- 1.85 mmol/L; controls: 2.58 +/- 0.63 mmol/L vs. 3.50 +/- 0.70 mmol/L), and triglycerides (patients: 1.99 +/- 0.77 mmol/L vs. 2.50 +/- 1.00 mmol/L; controls: 1.24 +/- 0.46 mmol/L vs. 1.72 +/- 0.67 mmol/L) in both study groups, whereas HDL-C was not significantly changed (patients: 1.29 +/- 0.35 mmol/L vs. 1.17 +/- 0.32 mmol/L; controls: 1.55 +/- 0.30 mmol/L vs. 1.53 +/- 0.26 mmol/L). Values of C(max.) and AUC(0h-24h) were higher in the patient group than in the control group (day 1, patients vs. controls, C(max.): 869.4 +/- 604.0 ng/mL vs. 211.9 +/- 113.9 ng/mL; AUC(0h-24h): 1948.8 +/- 1347.9 ng/mL*h vs. 549.4 +/- 247.4 ng/mL*h), whereas the corresponding value of CL was lower in the patient group (33.3 +/- 24.5 L/h vs. 107.9 +/- 95.8 L/h), and the values of t(max.) and t(1/2) showed no differences. In addition, values of C(max.) and AUC(0h-24h) after administration of 40 mg/day fluvastatin for 4 weeks in both groups were slightly higher than at the beginning, whereas the value of CL was slightly lower (day 28, patients vs. controls, C(max.): 1530.4 +/- 960.4 ng/mL vs. 254.7 +/- 199.8 ng/mL; AUC(0h-24h): 2615.3 +/- 1379.4 ng/mL*h vs. 841.8 +/- 421.4 ng/mL*h; CL: day 28, 21.4 +/- 15.3 L/h vs. 61.5 +/- 36.6 L/h). Except for an intermittent increase of creatine kinase, safety parameters showed no increases within the observation period. Our data suggest that fluvastatin effectively lowers plasma concentrations of cholesterol and LDL-C in patients after heart transplantation, however, the metabolism of fluvastatin is affected by concomitant therapy with cyclosporine A. Serum concentrations of fluvastatin should be monitored in cases of concomitant therapy with other substances interfering in the metabolism by competing cytochrome enzymes.

Adult↗
PubMed2001

Acute hemodynamic effects during immunoadsorption in patients with dilated cardiomyopathy positive for beta 1-adrenoceptor autoantibodies.

In two recent studies immunoadsorption improved left ventricular function in patients with dilated cardiomyopathy (DCM) who were positive for cardiostimulatory autoantibodies against the human beta 1-adrenoceptor (beta 1-AAB). In this study we invasively measured acute hemodynamics during immunoadsorption. Three patients with DCM, who were positive for beta 1-AAB (NYHA-class III, left ventricular ejection fraction < 0.3), were treated with 1 immunoadsorption session daily on 5 consecutive days. Immunoadsorption induced a strong decrease of cardiac index, whereas systemic vascular resistance increased. Baseline levels were reached again several hours after therapy ended. We conclude that during immunoadsorption substantial hemodynamic changes occur in patients positive for beta 1-AAB.

Adult↗
PubMed2000

G-Protein beta(3)-subunit 825T allele is associated with enhanced human atrial inward rectifier potassium currents.

BACKGROUND: A C825T polymorphism was recently identified in the human gene encoding for the beta(3)-subunit of heterotrimeric G proteins. The 825T allele is associated with a splice variant of Gbeta(3) and enhanced signal transduction. We hypothesized that patients carrying the 825T allele exhibit the modified Gbeta(3) phenotype. The resulting enhancement of signal transduction should be detectable in the Gbetagamma-dimer-mediated acetylcholine-stimulated K(+) current (I(K,ACh)). METHODS AND RESULTS: Seventy patients undergoing cardiac surgery were genotyped for the C825T polymorphism. In right atrial myocytes from these patients, the inward rectifier K(+) currents (I(K1), I(K,ACh)) were studied with the whole-cell patch-clamp technique. Background current I(K1) was measured with depolarizing ramp pulses and quantified as inward current at -100 mV; mean amplitudes were (pA/pF) 4.98+/-0.49 (n=30/93 patients/cells) in patients with CC genotype, 4.25+/-0.36 (n=31/121 patients/cells) with TC, and 7. 46+/-1.14 (n=9/32 patients/cells; P<0.05) with TT. Conversely, mean I(K,ACh), which is maximally activated by carbachol (2 micromol/L), was reduced in patients with TT genotype (pA/pF, 4.30+/-1.33, n=9/27 patients/cells; P<0.05) compared with the other 2 groups (6.56+/-0. 54, n=30/80 and 6.16+/-0.45, n=31/117 patients/cells, for CC and TC genotype, respectively). Essentially similar results were obtained with adenosine (1 mmol/L). CONCLUSIONS: We found an association between the Gbeta(3) 825T allele and amplitude of human atrial I(K1) and I(K,ACh). Increased background current density in TT carriers could shorten action potential duration and may be due to I(K,ACh) being constitutively active in this genotype.

Aged↗
PubMed2000

[Symptomatic coronary patient with pathological coronary angiogram requiring surgery].

Bypass surgery has become a routine procedure for the treatment of coronary artery disease. Due to increase numbers of high-risk patients minimally invasive techniques were introduced in cardiac surgery with excellent clinical results. In addition molecular methods have been applied for primary and secondary treatment of coronary artery disease.

Coronary Angiography↗
PubMed2000

Wrist-enhanced instrumentation: moving toward totally endoscopic coronary artery bypass grafting.

BACKGROUND: With the introduction of the da Vinci robotic surgical system (Intuitive Surgical, Mountain View, CA) into minimally invasive cardiac operations the outlook for performing coronary artery bypass operations "closed chest" became a reality. METHODS: Between May 1999 and December 1999 this new wrist-enhanced instrumentation was used in 61 patients. Six patients suffering from single-vessel coronary artery disease and one female patient with double-vessel disease underwent totally endoscopic coronary artery bypass. Thirty-seven patients with single-vessel disease underwent a minimally invasive direct coronary artery bypass procedure. Seventeen patients with double-vessel disease were treated using the robotic-enhanced Dresden technique. RESULTS: Perioperative survival was 100%. In all patients the internal mammary arteries were safely harvested endoscopically and had excellent quality. In both totally endoscopic coronary artery bypass groups all patients were operated on through three stab incisions. CONCLUSIONS: Our preliminary experience with this new surgical technique using robotic-enhanced minimally invasive methods for coronary artery disease promotes optimism regarding further development of these procedures and application in patients with coronary artery disease.

Coronary Artery Bypass↗
PubMed2000

Robotic-enhanced arterial revascularization for multivessel coronary artery disease.

BACKGROUND: A tendency to reduce operative trauma is determining the evolution of cardiac surgical techniques lately. The introduction of robotic-enhanced endoscopic systems enables surgeons to perform arterial revascularization for multivessel disease without sternotomy. METHODS: From May 1999,17 (4 women, 13 men; median age 63+/-7.4 years) patients with multivessel coronary artery disease were treated surgically using arterial revascularization by means of bilateral internal mammary arteries. Both arteries were harvested endoscopically using the da Vinci system (Intuitive Surgical, Mountain View, CA). These vessels were anastomosed using the "Dresden technique." RESULTS: Survival was 100%. Mean duration of the operation was 255+/-40.4 minutes. Bilateral internal mammary artery harvesting took 88.5+/-15.9 minutes; cross-clamp time was 36+/-8.7 minutes. An average of 2.06 anastomoses were performed per operation. Postoperatively, patients remained in the intensive care unit for 21+/-13 hours. One patient (5.8%) needed reexploration due to bleeding. CONCLUSIONS: The robotic surgical system introduces a new treatment of coronary artery disease to surgical practice, and enables arterial revascularization with distinctly reduced surgical trauma.

Anastomosis, Surgical↗
PubMed2000

Closed chest bilateral mammary artery grafting in double-vessel coronary artery disease.

A clinical case of a closed chest double-vessel total endoscopic coronary artery bypass procedure was performed using a wrist-enhanced, three-dimensional-based robotic system. A patient suffering from lesions of the left coronary artery system was effectively treated surgically without median sternotomy or minithoracotomy. This encourages optimism for introducing closed chest endoscopic bypass operations into the surgical routine for patients suffering from double-vessel coronary artery disease.

Coronary Artery Bypass↗
PubMed2000

Evidence for Edg-3 receptor-mediated activation of I(K.ACh) by sphingosine-1-phosphate in human atrial cardiomyocytes.

Sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPPC) have been reported to activate muscarinic receptor-activated inward rectifier K(+) current (I(K.ACh)) in cultured guinea pig atrial myocytes with similar nanomolar potency. Members of the endothelial differentiation gene (Edg) receptor family were recently identified as receptors for SPP; however, these receptors respond only to micromolar concentrations of SPPC. Here we investigated the sphingolipid-induced activation of I(K.ACh) in freshly isolated guinea pig, mouse, and human atrial myocytes. SPP activated I(K.ACh) in atrial myocytes from all three species with a similar nanomolar potency (EC(50) values: 4-8 nM). At these low concentrations, SPPC also activated I(K.ACh) in guinea pig myocytes. In contrast, SPPC was almost ineffective in mouse and human myocytes, thus resembling the pharmacology of the Edg receptors. Transcripts of Edg-1, Edg-3, and Edg-5 were detected in human atrial cells. Moreover, activation of I(K.ACh) by SPP was blocked by the Edg-3-selective antagonist suramin, which did not affect basal or carbachol-stimulated K(+) currents. In conclusion, these data indicate that I(K.ACh) activation by SPP and SPPC exhibits large species differences. Furthermore, they suggest that SPP-induced I(K.ACh) activation in human atrial myocytes is mediated by the Edg-3 subtype of SPP receptors.

Analysis of Variance↗
PubMed1999

Evaluation of transmyocardial laser revascularization (TMLR) by gated myocardial perfusion scintigraphy.

TMLR is a novel treatment for patients with coronary artery disease. It comprises the creation of transmyocardial channels thought to improve myocardial perfusion. Gated Tc-99m sestamibi scintigraphy was used to evaluate changes in myocardial perfusion after TMLR. Twelve patients underwent TMLR using a carbon dioxide laser. Sestamibi scans were carried out following a standard protocol prior to and 1, 3, 6, and 12 months after TMLR. Both visual and semi-quantitative assessment showed improvement in 4 patients, deterioration in 2 patients, and no change in the remaining 6 patients each. However, visual and semi-quantitative assessment were concordant in 6 patients and discordant in 6 patients. In 3 of these, semi-quantitative assessment suggested a better outcome, and in 3 patients visual assessment gave better results. Our findings in a small group of patients suggest that about a third benefited from TMLR. Gated myocardial perfusion scintigraphy using technetium-99m sestamibi is suitable for visual evaluation of changes in the lased area over time, but does not allow semi-quantitative evaluation in the patient population typically treated with TMLR. Further investigations using optimized imaging protocols, including positron emission tomography and three dimensional image presentation, are warranted.

Aged↗