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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 431-436 
    ISSN: 1432-1912
    Keywords: Key words 2 ; 3-butanedione-monoxime ; Negative ; inotropic effect ; Phosphorylation ; Phosphatase ; Phospholamban ; Inhibitory subunit of troponin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the mechanisms of action of a negative inotropic compound, 2,3-butanedione-monoxime (BDM), which has been suggested to be a cardioprotective agent. In guinea-pig papillary muscles the negative inotropic effect of BDM started at 100 μmol/l amounting to 18.32±2.09% of predrug value at 10 mmol/l without any effects on time parameters (n = 12, each). 30 mmol/l BDM totally abolished force of contraction; this effect was reversible after washout. In the presence of the phosphatase-inhibitor cantharidin (30 μmol/l) the concentration response curve on force of contraction was shifted to higher concentrations of BDM. 100 mmol/l BDM decreased the phosphorylation state of the inhibitory subunit of troponin (TnI) and phospholamban (PLB) in [32P]-labeled guinea-pig ventricular myocytes to 76.5±4.7% and 49.7±4.2%, respectively (n = 7). Furthermore, BDM enhanced the activity of phosphorylase phosphatases in guinea-pig ventricular homogenates amounting to a stimulation to 203.5±10.4% at 100 mmol/l whereas type 1 phosphorylase phosphatase activity increased only by 24.5% (n = 5). PLB phosphatase activity was enhanced to 155.9±11.7% by 100 mmol/l BDM (n = 5). It is concluded that the effects of BDM on contractile parameters are accompanied by decreased phosphorylation of the cardiac regulatory proteins TnI and PLB which could in part be due to activation of type 1 or 2A phosphatase activity. Hence, it is suggested that BDM affects the phosphorylation state of TnI and PLB not directly, but via activation of their phosphatases.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 431-436 
    ISSN: 1432-1912
    Keywords: 2,3-butanedione-monoxime ; Negative inotropic effect ; Phosphorylation ; Phosphatase ; Phospholamban ; Inhibitory subunit of troponin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the mechanisms of action of a negative inotropic compound, 2,3-butanedione-monoxime (BDM), which has been suggested to be a cardioprotective agent. In guinea-pig papillary muscles the negative inotropic effect of BDM started at 100 μmol/l amounting to 18.32±2.09% of predrug value at 10 mmol/l without any effects on time parameters (n = 12, each). 30 mmol/l BDM totally abolished force of contraction; this effect was reversible after washout. In the presence of the phosphatase-inhibitor cantharidin (30 μmol/l) the concentration response curve on force of contraction was shifted to higher concentrations of BDM. 100 mmol/l BDM decreased the phosphorylation state of the inhibitory subunit of troponin (TnI) and phospholamban (PLB) in [32P]-labeled guinea-pig ventricular myocytes to 76.5±4.7% and 49.7±4.2%, respectively (n = 7). Furthermore, BDM enhanced the activity of phosphorylase phosphatases in guinea-pig ventricular homogenates amounting to a stimulation to 203.5±10.4% at 100 mmol/l whereas type 1 phosphorylase phosphatase activity increased only by 24.5% (n = 5). PLB phosphatase activity was enhanced to 155.9±11.7% by 100 mmol/l BDM (n = 5). It is concluded that the effects of BDM on contractile parameters are accompanied by decreased phosphorylation of the cardiac regulatory proteins TnI and PLB which could in part be due to activation of type 1 or 2A phosphatase activity. Hence, it is suggested that BDM affects the phosphorylation state of TnI and PLB not directly, but via activation of their phosphatases.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Zeitschrift für Herz-, Thorax- und Gefässchirurgie 14 (2000), S. 267-271 
    ISSN: 0930-9225
    Keywords: Schlüsselwörter Resternotomie – Nachblutung – sternale Wundinfektion – Sepsis ; Key words Resternotomy – bleeding – sternal wound infection – sepsis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Former studies on sternal wound infections indicate predisposing factors like diabetes, obesity, use of bilateral internal mammary grafts, impaired renal function and reoperation. We evaluated whether the time of resternotomy for postoperative bleeding has any influence on the development of a sternal wound infection and other complications.¶   In our department, 12315 patients underwent median sternotomy for cardiac surgery between 1987 and 1998. We analyzed the clinical data of all patients who were reoperated for postoperative bleeding, especially of patients with subsequent operations caused by sternal wound infections. All data were compared by T-test or X2-test and p〈0.05 was regarded as significant.¶   Of the 12315 patients 406 were re-explored because of postoperative bleeding (3.3%). Of these patients 57 (14%) died in the postoperative period of noninfectious complications. The remaining patients were divided into two groups: Group A (286 patients) (70.4%) did not suffer from any sternal wound complications, whereas group Bpatients (n=63) (15.6%) needed subsequent surgery because of sternal infection. There were no significant differences in the groups concerning age, clinical data and first operation. All patients had an average blood loss of 223 ml/h. The time before re-operation for bleeding was 5.3±1.7hours in group A compared to 11.1±4.2hours in group B (p〈0.05). A significant delay of reoperation for bleeding could also be found for patients with postoperative septic complications (∅: 5.2±1.9hours, +: 12.9±5.2hours), renal failure, mechanical ventilation 〉48hours and a stay in hospital 〉20 days.¶   Early reoperation for postoperative bleeding decreases the number of subsequent complications, e.g., sternal wound infections, septic complications and prolonged mechanical ventilation.
    Notes: Zusammenfassung In früheren Untersuchungen zur Sternuminfektion konnten als prädisponierende Faktoren Diabetes mellitus, Übergewicht, beidseitige Verwendung der A. mammaria interna und eine eingeschränkte Nierenfunktion identifiziert werden. Wir wollten herausfinden, ob der Zeitpunkt einer Rethorakotomie wegen postoperativer Nachblutung einen Einfluss auf die Entwicklung einer sternalen Wundheilungsstörung oder weiterer Komplikationen hat.¶   12315 Patienten unterzogen sich einem herzchirurgischen Eingriff mittels Sternotomie zwischen 1987 und 1998. Wir haben die klinischen Daten aller Patienten mit Rethorakotomie wegen Nachblutung ausgewertet, v.a. bei den Patienten mit nachfolgender Wundinfektion.¶   406 der 12315 Patienten mussten wegen einer Nachblutung rethorakotomiert werden (3,3%). 57 (14%) dieser Patienten verstarben postoperativ an nicht-infektiösen Komplikationen. Die übrigen wurden in 2 Gruppen aufgeteilt: Gruppe A (286 Pat.) (70,4%) entwickelte keine sternalen Wundkomplikationen, wogegen Gruppe B-Patienten (n=63) (15,6%) wegen einer Wundinfektion erneut chirurgisch behandelt werden mussten. Die Zeit vor der 1. Reoperation war 5,3±1,7 Std. in Gr. A verglichen mit 11,1±4,2 Std. in Gr. B (p〈0,05). Eine signifikant spätere Reoperation konnte auch bei Patienten mit postoperativen septischen Komplikationen, Nierenversagen und einer Beatmungsdauer 〉48 Std. gefunden werden.¶   Eine frühzeitige Rethorakotomie wegen Nachblutung senkt das Risiko nachfolgender Komplikationen, insbesondere sternaler Wundheilungsstörungen und septischer Verläufe.
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  • 4
    ISSN: 0930-9225
    Keywords: Schlüsselwörter Vorhofflimmern – extrakorporale Zirkulation –β-Blocker – Digitalis – aortokoronarer Bypass ; Key words Atrial fibrillation – extracorporeal circulation –β-blockers – digitalis – CABG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Atrial fibrillation (AF) is the most common sustained arrhythmia after extracorporeal circulation (ECC). There seems to be a higher incidence of AF in patients on β-blockers in the preoperative period without re-establishing this therapy after surgery. In our study we tried to determine additional factors. We analyzed 616 elective patients with preoperative sinus rhythm, who were operated using extracorporeal circulation. Coronary artery bypass grafting (CABG) was performed on 460 patients, 108 underwent valve surgery, 48 patients a combined procedure. A preoperative therapy with β-blockers was stopped perioperatively. Atrial fibrillation occurred postoperatively in 24% of the CABG patients (valve: 30%, combination: 35%). In the CABG group we found a preoperative therapy with β-blockers in 86% of patients with postoperative AF (group A), compared to 51% of the patients without AF (group B) (p〈0.05). There were also significant differences concerning the patients age, preoperative ejection fraction, duration of ECC, and duration of myocardial ischemia. Furthermore there was a significant difference in the need for respiratory support and in the ICU stay. In this study, we were able to show that the incidence of a postoperative AF is significantly higher in patients with preoperative use of β-blockers. Subsequently, it is recommended that β-blockers should be given postoperatively as early as possible.
    Notes: Zusammenfassung Vorhofflimmern (VHF) ist die am häufigsten auftretende Rhythmusstörung nach Operationen mit extrakorporaler Zirkulation (EKZ). In der vorliegenden Studie wurde versucht, Einflußgrößen für die Inzidenz eines postoperativen Vorhofflimmerns herauszuarbeiten. Wir untersuchten 616 elektive Patienten, die präoperativ einen Sinusrhythmus aufwiesen und mittels EKZ operiert wurden. Bei 460 Patienten wurde eine aortokoronare Bypass-Operation (ACB) durchgeführt, 108 unterzogen sich einem Klappeneingriff, und 48 Patienten einer Kombination von beidem. Eine bestehende Therapie mit β-Blockern wurde bei uns perioperativ ausgesetzt. Vorhofflimmern trat nach ACB bei 24% der Patienten auf. In dieser Gruppe fand sich bei den Patienten mit postoperativen VHF (Gruppe A) in 86% der Fälle eine präoperative β-Blocker-Therapie, verglichen mit 51% in der Gruppe ohne VHF (Gruppe B) (p〈0,05). Signifikante Unterschiede ergaben sich in den Gruppen A und B auch für das Patientenalter, die präoperative Ejektionsfraktion, die EKZ-Dauer und die Länge der Myokardischämie. Auch die Intubationsdauer und der Intensiv-Aufenthalt waren in der Gruppe A signifikant länger. Diese Ergebnisse zeigen, daß– neben weiteren Risikofaktoren – die Unterbrechung einer präoperativen β-Blockade ein Auslöser für postoperatives VHF ist. Wir empfehlen daher, eine präoperative β-Blocker Therapie möglichst früh postoperativ fortzuführen.
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  • 5
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary New lanthanide methods for the histochemical detection of non-specific alkaline phosphatase in the light microscope are described and compared with already existing techniques for the light microscopical demonstration of this enzyme. To avoid formation of insoluble lanthanide hydroxide at alkaline pH citrate complexes with the capture ions cerium, lanthanum and didymium were used. A molar ratio of 11 mM citrate/14 mM capture reagent is proposed. For preincubated sections, pretreatment in chloroform-acetone and fixation in glutaraldehyde, for non-preincubated sections fixation in glutaraldehyde yielded the best results. 4-Methylumbelliferyl and 5-Br-4-Cl-3-indoxyl phosphate were found to be the most suitable substrates. For routine purposes 4-nitrophenyl, 1-naphthyl, 2-naphthyl and 2-glycerophosphate were also sufficient; naphthol AS phosphates were inferior but still suitable. After incubation for 5–60 min at 37° C lanthanide phosphate was converted into lead phosphate which was visualized as lead sulfide. At pH 9.2–9.5 enzyme activity was demonstrated at many sites such as intestinal, uterine, placental, renal and epididymal microvillous zones, plasma membranes of arterial, sinus and capillary endothelial cells, vaginal and urethral epithelium, smooth muscle cells, myoepithelial cells as well as excretory duct cells of salivary and lacrimal glands and in secretory granules of laryngeal glands. In comparison with Gomori's calcium, Mayahara's lead, Burstone's and Pearse's azo-coupling, McGadey's tetrazolium salt and Gossrau's azoindoxyl coupling technique the lanthanide methods detected alkaline phosphatase activities at identical or additional sites depending on the respective procedure. However, in contrast to the other methods especially the cerium citrate procedure yielded a more precisely localized and more stable reaction product, can be used with all available alkaline phosphatase substrates including those up till now less suitable or unsuitable for light microscopic alkaline phosphatase histochemistry.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 88 (1988), S. 375-381 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary New, improved techniques for the ultrastructural localization of acid and alkaline phosphatase activity using lanthanide cations as the trapping agent were developed. Delayed penetration of the capture ions and the incubation constituents into cellular compartments was prevented by pretreating specimens with borohydride/saponin. Both the concentration of the capture agent in the incubation medium and the incubation time of the tissue specimens were optimized to achieve a satisfactory cytochemical reaction and to avoid precipitation artefacts caused by local matrix effects. The conversion of cerium phosphate into the almost insoluble cerium fluoride minimized losses of the reaction product during postincubation processing. Moreover, lanthanum itself as well as lanthanides other than cerium, e.g., gadolinium and didymium (praseodymium, neodymium), were successfully applied and can be recommended as capture agents for phosphatase cytochemistry.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Histochemistry and cell biology 90 (1988), S. 289-297 
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary New light microscopic visualization methods were developed for the histochemical detection of non-specific alkaline and acid phosphatase, Mg-, Ca-and Na, K-dependent adenosine triphosphatase, myosin adenosine triphosphatase, glucose-6-phosphatase, 5′-nucleotidase and thiamine pyrophosphatase with cerium ions as trapping agents in cryostat and plastic sections. The techniques are based on the conversion of cerium phosphate into cerium perhydroxide by H2O2 which decomposes at 55°–60° C into cerium hydroxide and oxygen radicals. These radicals are able to oxidize diaminobenzidine (DAB) to DAB brown. Addition of nickel ions to the DAB-H2O2 mixture generates bluish-black stained nickel-DAB complexes. Compared with the classical metal precipitation, azo, azoindoxyl and tetrazolium procedures the H2O2-DAB and especially the H2O2-DAB-nickel methods provided identical or superior results in catalytic phosphatase histochemistry and immunohistochemistry when using non-specific alkaline phosphatase as the enzyme label.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 424-430 
    ISSN: 1432-1912
    Keywords: Key words PACAP ; Acetylcholine release ; Guinea-pig heart ; ω-conotoxin ; Patch-clamp technique ; cAMP ; Phosphorylation ; Chronotropy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Based on previous studies which indicated that pituitary adenylate cyclase activating peptide (PACAP) acts as a positive inotropic and chronotropic substance in different species via the cAMP signal transduction pathway, the objective of the present work was to investigate cAMP-regulated myocardial key proteins in response to PACAP in isolated ventricular cells of the guinea pig. Surprisingly, the two molecular forms of PACAP, PACAP(1–27) and PACAP(1–38), showed no effect on intracellular cAMP-levels, L-type Ca2+channel current or phosphorylation of troponin inhibitor (TnI) and phospholamban (PLB). Additionally, inotropy of isolated guinea-pig ventricular strips was not affected by the neuropeptide. However, in isolated spontaneously beating guinea-pig atria, PACAP(1–27) and PACAP(1–38), but not VIP induced severe bradycardia in a dose-dependent manner. This effect could be prevented by preincubation with the PACAP receptor antagonist PACAP(6–38), by atropine and by ω-conotoxin, a blocker of neuronal N-type Ca2+channels. PACAP stimulates release of [3H]-labelled acetylcholine. Only preparations showing an increase in [3H]acetylcholine release developed bradycardia, indicating a causal relationship between both phenomena. It was concluded that PACAP exerts no influence on guinea-pig ventricular tissue, but induces negative chronotropic effects in isolated guinea-pig atria by stimulation of acetylcholine release from parasympathetic neurons via PACAP type 1 receptors.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 424-430 
    ISSN: 1432-1912
    Keywords: PACAP ; Acetylcholine release ; Guinea-pig heart ; ω-conotoxin ; Patch-clamp technique ; cAMP ; Phosphorylation ; Chronotropy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Based on previous studies which indicated that pituitary adenylate cyclase activating peptide (PACAP) acts as a positive inotropic and chronotropic substance in different species via the cAMP signal transduction pathway, the objective of the present work was to investigate cAMP-regulated myocardial key proteins in response to PACAP in isolated ventricular cells of the guinea pig. Surprisingly, the two molecular forms of PACAP, PACAP(1–27) and PACAP(1–38), showed no effect on intracellular cAMP-levels, L-type Ca2+ channel current or phosphorylation of troponin inhibitor (TnI) and phospholamban (PLB). Additionally, inotropy of isolated guinea-pig ventricular strips was not affected by the neuropeptide. However, in isolated spontaneously beating guinea-pig atria, PACAP(1–27) and PACAP(1–38), but not VIP induced severe bradycardia in a dose-dependent manner. This effect could be prevented by preincubation with the PACAP receptor antagonist PACAP(6–38), by atropine and by ω-conotoxin, a blocker of neuronal N-type Ca2+channels. PACAP stimulates release of [3H]-labelled acetylcholine. Only preparations showing an increase in [3H]acetylcholine release developed bradycardia, indicating a causal relationship between both phenomena. It was concluded that PACAP exerts no influence on guinea-pig ventricular tissue, but induces negative chronotropic effects in isolated guinea-pig atria by stimulation of acetylcholine release from parasympathetic neurons via PACAP type 1 receptors.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1995), S. 385-390 
    ISSN: 1432-1912
    Keywords: Key words Flosequinoxan ; Positive inotropic effect ; Phosphorylation ; Phosphatase ; Phospholamban ; Inhibitory subunit of troponin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In guinea-pig papillary muscles the positive inotropic effect of flosequinoxan (BTS) starting at 100 μmol/l amounted to 287.6±34.2% at 300 μmol/l without any effects on time to peak tension (103.9±2%) and relaxation time (107.1±6.7% of predrug value, respectively). 10 μmol/l carbachol attenuated the positive inotropic effect of 300 μmol/l to 166.5±11.6% (n=10). The phosphorylation state of the inhibitory subunit of troponin (TnI) and phospholamban (PLB) in [32P]-labeled guinea-pig ventricular myocytes was increased starting at 100 μmol/l amounting to 142.5±12.6% and 130.9±2.2% at 300 μmol/l, respectively (n=5). Furthermore, BTS (300 μmol/l) decreased phosphorylase phosphatase activity by 23.1%. It is concluded that the contractile effects of BTS are accompanied by enhanced phosphorylation of regulatory proteins which could in part be due to inhibition of phosphorylase phosphatase activity.
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