PubMed Health⌕ Search

Biomedical subjects

P G Spieckermann

Publications and source records attributed to P G Spieckermann.

At least 19 recordsLinked to original sources
PubMed1999

Protection of reoxygenated cardiomyocytes against sarcolemmal fragility: the role of glutathione.

This study addressed the question of whether the sarcolemmal fragility of cardiomyocytes after anoxia and subsequent reoxygenation can be altered by modulation of the cellular glutathione state. Isolated ventricular cardiomyocytes (from adult rats) were exposed to 120 min anoxia and subsequently to 30 min reoxygenation. Osmotic stress was generated by reduction of medium osmolarity from 270 to 80 mosmol/l and sarcolemmal fragility assessed by the leakage of lactate dehydrogenase (LDH). Under normoxic conditions 6.7+/-1.0 % of total LDH activity was found extracellularly. Hyposmolar reoxygenation, but not hypoosmolar anoxia, increased LDH release (17.9+/-2.7% of total, P<0.05). Increasing cellular glutathione content by pretreatment with N-acetylcysteine (1 mM) reduced LDH release following hyposmolar reoxygenation (12.3+/-1.9% vs. 18.2+/-2.9% of LDH in medium, P<0.05). Depletion of glutathione content by pretreatment with buthionine sulphoximine (BSO, 200 microM), increased LDH release following osmotic stress already in normoxia (10.5+/-1.8% of LDH in medium; P<0.05 vs. no BSO), and even further after reoxygenation (21.8+/-3. 2%, P<0.05 vs. normoxia). We conclude that the increased sarcolemmal fragility in reoxygenated cardiomyocytes is due to reoxygenation in the presence of reduced antioxidant defence.

Acetylcysteine↗
PubMed1999

Urea induces macrophage proliferation by inhibition of inducible nitric oxide synthesis.

BACKGROUND: Atherosclerosis is a major cause of morbidity and mortality in chronic renal failure and is associated with the proliferation of macrophages within atherosclerotic lesions. METHODS: Because the progression of atherosclerosis as a consequence of decreased nitric oxide synthesis has been described, we investigated the correlation between the inhibition of inducible nitric oxide synthase (iNOS) by urea, macrophage proliferation as assayed by cell counting, tritiated thymidine incorporation and measurement of cell protein, and macrophage apoptosis. RESULTS: Urea induces a dose-dependent inhibition of inducible nitric oxide synthesis in lipopolysaccharide-stimulated mouse macrophages (RAW 264.7) with concomitant macrophage proliferation. Macrophage proliferation, as determined by cell counting, became statistically significant at 60 mM urea, corresponding to a blood urea nitrogen level of 180 mg/100 ml, concentrations seen in uremic patients. iNOS protein expression showed a dose-dependent reduction, as revealed by immunoblotting when cells were incubated with increasing amounts of urea. The decrease of cytosolic DNA fragments in stimulated macrophages incubated with urea shows that the proliferative actions of urea are associated with a decrease of NO-induced apoptosis. CONCLUSIONS: Our data demonstrate that the inhibition of iNOS-dependent NO production caused by urea enhances macrophage proliferation as a consequence of diminished NO-mediated apoptosis.

Animals↗
PubMed1998

Comparison of the solutions of Bretschneider, St. Thomas' Hospital and the National Institutes of Health for cardioplegic protection during moderate hypothermic arrest.

We evaluated three cardioplegic solutions, Bretschneider's cardioplegic solution (HTK), St. Thomas' Hospital solution (STH) and the solution of the National Institutes of Health (NIH), a solution with added nitroglycerin and lidocaine, for their ability to minimize ischemia-reperfusion injury in a working rat heart model. After cardioplegic arrest at 4 degrees C and subsequent 45 min of ischemic storage at 25 degrees C the function recovery of hearts was examined during 1 h of normothermic crystalloid reperfusion using Krebs-Henseleit buffer as perfusion medium. We noted a significantly better preservation of the maximum (+dp/dt(max)) and minimum (-dp/dt(max)) velocity of pressure development and a significantly higher coronary flow with the use of HTK (2,657 mm Hg/s, 2,122 mm Hg/s, 17 ml/min) compared to STH (1,600 mm Hg/s, p < 0.05; 1,591 mm Hg/s, p<0.05; 11 ml/ min, p<0.05), and an intermediate level of preservation of hemodynamic parameters with NIH (2,149 mm Hg/s, 1,766 mm Hg/s, 12 ml/min). Concerning the cardiac output, however, no major difference was found between the HTK (41 ml/min), the STH (34 ml/min) and the NIH group (36 ml/min). The decay of the myocardial energy charge was significantly lower in both the HTK and the NIH group as compared with conservation in STH solution. Lactate was lowest in the HTK group, CK and LDH releases in the effusate remained lowest after HTK and NIH preservation. The data of this study suggest that HTK and NIH most perfectly reduce the impairment of myocardial function and provide better myocardial protection during ischemic arrest at 25 degrees C and superior recovery compared to STH solution.

Animals↗
PubMed1997

HTK versus UW solution for myocardial protection during moderate hypothermia.

The objective of this study was to assess the protective capacity of UW solution in comparison to Bretschneider's (HTK) cardioplegic solution under moderate hypothermic conditions (25 degrees C), as those usually present during intraoperative myocardial protection. Ischemia-induced alterations of cardiac function parameters were analyzed and compared for each solution after 45 min of ischemic storage and 60 min of reperfusion with oxygenated Krebs-Henseleit buffer (KHB), using a rat working-heart model. Compared to nonischemic values, left-ventricular systolic and diastolic pressure, +dp/dtmax and -dp/dtmax were significantly better maintained in the HTK (95 mm Hg, 7 mm Hg, 2,657 mm Hg/s and 2,122 mm Hg/s) than in the UW group (76 mm Hg, p < 0.05, 11 mm Hg, p < 0.05, 1,745 mm Hg/s, p < 0.05 and 1,600 mm Hg/s, p < 0.05). Concerning the myocardial contents of ATP, creatine phosphate and the energy charge, a minor decrease was observed after preservation in HTK compared to UW solution. The results of this study indicate superior myocardial protection with the use of HTK solution for protection of the heart at 25 degrees C compared to UW solution.

Adenosine↗
PubMed1996

Physiology with cool obsession: Carl Ludwig--his time in Vienna and his contribution to isolated organ methodology.

This short report presents new information on Carl Ludwig's move from Zurich to the chair of physiology in Vienna and the 10 years he spent here and characterizes some of his contributions to experimentation methodology in working with isolated organs. Two up to now unknown documents concerning his call to the chair of physiology and zoology at the Josephs Academy, a military academy; have been found in the Public Record Offices in Vienna: a secret service report and the letter of Ludwig with his conditions for accepting the appointment. Some characteristic sections are cited. The time in Vienna between 1855 and 1865 is depicted against the background of political processes in Europe after the 1848 revolution. Ludwig's and his pupils' work with isolated organs is analysed briefly with some examples, especially relating to heart and kidney and a kymographion shown with a 20-channel registration module. The first "heart-lung machine" is discussed.

Austria↗
PubMed1995

Small bowel tissue high-energy phosphate regeneration after 7 hr of cold ischemic storage: comparison of University of Wisconsin and Eurocollins solutions.

As adenine nucleotide content has been shown to correlate with post-transplant function of livers and hearts, it was the aim of our study to investigate the regeneration of rat small bowel tissue high-energy phosphates after 7 hr of cold storage followed by incubation of everted small bowel sacs in normothermic oxygenated KHB for 1 hr. We compared the University of Wisconsin (UW) and the Eurocollins (EC) solutions. Krebs-Henseleit-bicarbonate buffer (KHB) was used to point out the effect of simple cold ischemic storage. After 7 hr of cold storage only small bowel stored in UW and EC solutions retained the capacity for almost total regeneration of ATP necessary for optimal posttransplant function, whereas in the KHB group we found only minimal regeneration. A similar pattern was found for the energy charge. These data support the superiority of UW and EC solutions over simple cold storage in KHB for preservation of small bowel.

Adenosine↗
PubMed1995

Echocardiography for teaching cardiac physiology in practical student courses.

We have introduced echocardiography into the physiology courses for medical students to improve their understanding of cardiac physiology. Echocardiography allows a visualization of the events of the cardiac cycle and facilitates the correlation of anatomic structures with their physiological functions. The students record views on the human heart in the long and short axis, they follow wall and value motions, and they interpret the obtained data in correlation with electrocardiography and phonocardiography. Echocardiography offers the opportunity to measure the interval of isovolumetric contraction and isovolumetric relaxation and permits the calculation of parameters assigned to left ventricular contractility. An evaluation showed that medical students consider echocardiography to be the most significant and interesting part of the physiology courses. In conclusion, echocardiography has been shown to be a valuable tool for teaching cardiac physiology.

Echocardiography↗
PubMed1995

Spectrophotometric determination of ascorbic acid and dehydroascorbic acid.

We present a method for measuring ascorbic acid in methanol/trichloroacetic acid extracts prepared from human plasma after enzymatic oxidation of ascorbic acid to dehydroascorbic acid by ascorbate oxidase. Samples were assayed by spectrophotometrically monitoring the kinetics of the concentration-dependent absorbance changes of dehydroascorbic acid with phosphate-citrate-methanol buffers. Ascorbic acid was determined as the difference between dehydroascorbic acid and total ascorbic acid content. The detection limit was < 0.5 mumol/L. The calibration curve was linear (r > 0.995) over the range 0-1000 mumol/L. Analytical recovery of ascorbic acid added to plasma was 93-105%. The between-day variance was < 7%. Comparison of the spectrophotometric determination (y) with a chromatographic procedure (x) gave y = 1.02x - 0.653 (Sylx = 3.61) over the range of physiologically relevant concentrations. Total analysis time is < 10 min per sample and allows the simultaneous analysis of multiple samples.

Ascorbate Oxidase↗
PubMed1994

Spectrophotometric determination of dehydroascorbic acid in biological samples.

We describe a method for accurately and precisely measuring dehydroascorbic acid in perchloric acid extracts prepared from human plasma, lymphocytes, and mammalian cells. Samples were assayed by spectrophotometrically monitoring the kinetics of the concentration-dependent absorbance changes of dehydroascorbic acid with phosphate-methanol-containing buffers. The lowest detectable dehydroascorbate concentration using this assay is estimated to be below 0.1 mumol/liter. Total analysis time is less than 10 min and allows the simultaneous measurement of numerous samples. The calibration curve is linear (r > 0.995) over the range 0-200 mumol/liter. The dehydroascorbic acid concentrations measured in supplemented samples agree with known concentrations. Interference of ascorbic acid and 2,3-diketogulonic acid with this assay was excluded. The correlation with a highly specific chromatographic procedure gave comparable results over the range of physiologically relevant concentrations. The procedure avoids the most commonly applied method of measuring the native ascorbic acid, then reducing the dehydroascorbic acid, and finally measuring the total ascorbic acid and determining dehydroascorbic acid by the difference. Stabilization of ascorbic acid during assay was achieved by addition of desferrioxamine.

3T3 Cells↗
PubMed1994

Administration of atracurium during reperfusion of rat livers after 21 h of cold ischaemic storage in different solutions.

The pharmacokinetics of atracurium are not altered by impaired hepatic function. The drug is therefore used widely in liver transplant patients. In previous work on the hepatotoxic effects of atracurium in an isolated, perfused rat liver model, we could not detect biochemical (release of lactate dehydrogenase or aspartate aminotransferase) or histological evidence of liver cell damage, except a reduction in hepatic tissue ATP content. In the present study, rat livers were reperfused with Krebs-Henseleit bicarbonate buffer with or without atracurium after 21 h of cold ischaemic storage in University of Wisconsin (UW), Bretschneider's HTK or Euro-Collins solution. UW-protected livers showed a complete restoration of ATP, total adenine nucleotides and energy charge during reperfusion, but the addition of atracurium diminished the regeneration capacity to about 50%. The energy charge (an index for determination of liver viability) was also reduced markedly.

Adenine Nucleotides↗
PubMed1994

Influence of incubated atracurium on rat liver function.

Degradation of atracurium by Hofmann elimination and ester hydrolysis depends mainly on pH and temperature and is said to be independent of liver and kidney function. Consequently atracurium is used widely in patients with liver failure. However, there is evidence that incubation of atracurium at 37 degrees C and pH 8 leads to leakage of LDH from hepatocyte cell cultures. We have tested the hepatotoxic effects of incubated atracurium in an isolated perfused rat liver model. After equilibration, atracurium 2010 mumol ml-1 (preincubated at pH 8 and 37 degrees C for 120 min) was administered over a period of 10 min followed by perfusion of Krebs-Henseleit bicarbonate buffer for 60 min. We found that incubation resulted in considerable degradation of atracurium and formation of laudanosine. Administration of incubated atracurium did not produce either biochemical or morphological damage to liver cells, but caused considerable increase in bile flow. We conclude that administration of preincubated atracurium did not produce impairment of liver cell function. The increase in bile flow could be beneficial if it occurs clinically.

Animals↗
PubMed1992

Hepatotoxicity testing of atracurium and laudanosine in the isolated, perfused rat liver.

The pharmacokinetics of atracurium, which is degraded by Hofmann decomposition and ester hydrolysis, is not altered by impaired liver function. Atracurium should, therefore, be ideal for patients with heptic failure, and is now widely used in clinical practice. However, some studies reported considerable hepatotoxicity after atracurium, especially from its breakdown products--for example, leakage of lactate dehydrogenase (LDH) from isolated rat hepatocytes. Therefore, we have studied, in an isolated perfused rat liver model, biochemical and morphological changes after administration of either atracurium or its main metabolite, laudanosine. Despite using extremely high concentrations of these substances, we could not detect, biochemically (release of LDH or aspartate amino-transferase (AST)) or histologically, any signs of liver cell damage.

Animals↗