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W Isselhard

Publications and source records attributed to W Isselhard.

At least 55 records · Page 3Linked to original sources
PubMed1994

[Recovery of healthy and hypertrophied hearts after global ischemia and gradual reperfusion].

The influence of pressure controlled reperfusion on the postischemic outcome of normal and normotensive hypertrophied rat hearts should be investigated. To induce normotensive cardiac hypertrophy, male Wistar rats received injections of isoprenaline (5 mg/kg s.c. bid for three days). Hearts were excised and perfused in the Langendorff-technique at a perfusion pressure of 75 mmHg for 30 min. After cardioplegia and 40 min of global ischemia at 25 degrees C the hearts were reperfused for 45 min. Reperfusion pressure was built up either abruptly (75 mmHg immediately) or gradually (from 40 mmHg to 75 mmHg within 30 min). Postischemic recovery was significantly affected by the mode of reperfusion in normal hearts where pressure controlled (gradual) reperfusion is superior to the abrupt reperfusion mode. In hypertrophied hearts the postischemic outcome did not differ from normal hearts if abrupt reperfusion was used, but gradual reperfusion only led to a comparably small amelioration of postischemic status.

Adenosine Triphosphate↗
PubMed1993

The effects of allopurinol and SOD on lipid peroxidation and energy metabolism in the liver after ischemia in an aerobic/anaerobic persufflation.

This study was aimed at examining the vulnerability of the liver to oxygen-free radicals upon reoxygenation after prolonged ischemia. Livers from male Wistar rats were first flushed with Ringer's and Euro-Collins solutions. After ischemic storage in Krebs-Henseleit solution at 37 degrees C for 60 min and in Euro-Collins solution at 4 degrees C for another 60 min, they were then persufflated with either gaseous O2 or N2 for 30 min at 37 degrees C, and rinsed again with Ringer's solution. Enzyme concentrations and calcium ion activities were measured in the effluent rinsing solution after passage through the liver. Treatment with superoxide dismutase (SOD) or allopurinol resulted in a significant reduction of tissue injury, determined by the enzyme loss, calcium uptake, and lipid peroxidation upon persufflation with O2. Allopurinol also improved the tissue levels of ATP and the sum of adenine nucleotides after aerobic persufflation, whereas SOD did not. Notwithstanding, neither treatment had any effect on anoxic persufflation with N2. Thus, we conclude that the postischemic liver is susceptible to oxygen-induced free radical injury and that allopurinol and SOD promote specific antioxidative protection of the liver, with the exclusion of side effects related to substrates or perfusion modalities.

Adenine Nucleotides↗
PubMed1993

Parenchymal and vascular endothelial cell injury in the hypoxic and reperfused rat liver. Evidence for superoxide anion generation by perfusion with ferricytochrome c.

Isolated perfused livers from rats fasted overnight were subjected to 90 min of low-flow hypoxia followed by reoxygenation for 30 min. Intra-hepatic generation of superoxide anion was analysed by continuous perfusion with 40 mumol/l of oxidized cytochrome c, the reduction of which was measured spectrophotometrically in the effluate. Reduction of cytochrome c as an indicator for hepatic superoxide anion generation remained constant during pre-hypoxic perfusion and during hypoxia. Upon reperfusion, an initial peak was observed to 47.2 +/- 3.8 nmol/g/min followed by a stable plateau above pre-hypoxic values. Both peak and plateau were significantly attenuated in the presence of 80,000 U/l superoxide dismutase (SOD). Accordingly, tissue contents of lipid peroxides were significantly lower at the end of reperfusion (976 +/- 73 vs 1153 +/- 71 nmol/g*), enzyme leakage [U/g/min] from the endothelium (PNP: 8.4 +/- 4.2 vs 17.2 +/- 3.4**) and from the hepatic parenchyma (Alt: 108 +/- 35 vs 170 +/- 23*) was significantly reduced during reperfusion and oxygen consumption was elevated in the presence of SOD (3.27 +/- 0.34 vs 2.71 +/- 0.37*). It is concluded that reactive oxygen species arise in the vascular lumen or the space of Disse after prolonged hypoxia of the liver, altering the functional outcome of the organ upon reoxygenation. SOD is able to protect against these alterations. * P < 0.05; ** P < 0.01.

Animals↗
PubMed1993

Platelet-activating factor antagonism enhances the liver's recovery from warm ischemia in situ.

Hepatic outcome after ischemia is compromised by anoxic injury and by release of oxygen free radicals or other pathological mediators at reperfusion. The platelet-activating factor (PAF) is an endogenous lipid-mediator which plays a key role in catalysing various pro-inflammatory processes. In this study the possible influence of platelet-activating factor antagonism was investigated on the integrity of the vascular endothelium, on free radical-mediated peroxidation and on post-ischemic functional outcome of the liver in the rat. Animals under pentobarbital anesthesia were subjected to 60 min of ischemia of the left and median liver lobes followed by 30 min of reperfusion in vivo. Pre-ischemic injection of the platelet-activating factor antagonist BN 52021 resulted in a significant reduction of endothelial enzyme loss into the plasma (purine nucleoside phosphorylase 56.2 vs. 83.1 U/l), and lowered hepatic lipid peroxidation (malondialdehyde 830 vs 932 nmol/g), leading to a significant improvement of postischemic bile flow and higher tissue levels of ATP. This suggests that the platelet-activating factor may play an important role in hepatic ischemia-reperfusion injury and that PAF antagonists like BN 52021 may be useful for clinical treatment.

Adenosine Triphosphate↗
PubMed1993

Role of the hepatovasculature in free radical mediated reperfusion damage of the liver.

This study was undertaken in order to assess the role of purely circulation-related effects upon free-radical-mediated reperfusion injury in the liver by comparing the respective effects of the oxygen free-radical scavenger superoxide dismutase (SOD) and the vasodilative action of papaverine in an ischemia/reperfusion model of the liver. Livers from male Wistar rats were rinsed blood free via the portal vein and stored ischemically (60 min at 37 degrees C in Krebs-Henseleit solution and 60 min at 4 degrees C in Euro-Collins solution). Reperfusion was carried out at a constant flow of 30 ml/min for 45 min at 37 degrees C in a nonrecirculating manner. Warm ischemic damage was evident in untreated livers compared to control livers, submitted solely to cold ischemia for 2 h at 4 degrees C, by increased vascular resistance upon reperfusion, enhanced enzyme leakage from the parenchyma (glutamate pyruvate transaminase, glutamate dehydrogenase) and from the endothelium (purine-nucleoside phosphorylase), reduced tissue content of ATP and enhanced lipid peroxidation. Preischemic treatment with SOD or papaverine (the latter also given during reperfusion) significantly reduced hepatic vascular resistance and parenchymal enzyme loss in a comparable manner. Both drugs resulted in a significant increase of hepatic tissue content of ATP at the end of reperfusion. SOD, but not papaverine, prevented the leakage of purine-nucleoside phosphorylase and significantly reduced the tissue levels of lipid peroxides.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

[Recovery of healthy and hypertrophic hearts after global ischemia and graduated reperfusion].

The influence of pressure controlled reperfusion on the postischemic outcome of normal and normotensive hypertrophied rat hearts should be investigated. To induce normotensive cardiac hypertrophy, male Wistar rats received injections of isoprenaline (5 mg/kg s.c. bid for three days). Hearts were excised and perfused according to the Langendorff-technique at a perfusion pressure of 75 mm Hg for 30 min. After cardioplegia and 40 min of global ischemia at 25 degrees C the hearts were reperfuse for 45 min. Reperfusion pressure was increased either abruptly (75 mm Hg immediately) or gradually (from 40 mm Hg to 75 mm Hg within 30 min). Post-ischemic recovery was significantly affected by the mode of reperfusion in normal hearts, in which pressure controlled (gradual) reperfusion was superior to the abrupt reperfusion mode. In hypertrophied hearts, the post-ischemic outcome did not differ from normal hearts when abrupt reperfusion was used, but gradual reperfusion only led to a comparably small improvement of the post-ischemic status.

Adenine Nucleotides↗
PubMed1992

Absence of mitochondrial enhancement in the remnant liver after partial hepatectomy in cirrhotic rats.

Changes in energy metabolism after 70% partial hepatectomy were investigated in normal and carbon-tetrachloride-(CCl4)-induced-cirrhotic rats by evaluating hepatic mitochondrial ATP synthesizing activity as well as liver tissue levels of adenine nucleotides and lipid peroxide. Preoperative concentrations of ATP and total adenine nucleotides (TAN: ATP + ADP + AMP) in mumol/g dry weight (dw) and the energy charge potential (ECP) in the cirrhotic livers were 8.53 SEM 0.25, 14.73 SEM 0.54, and 0.74 SEM 0.01, respectively, and were significantly lower than those of normal livers (12.04 SEM 0.34, 15.75 SEM 0.12, and 0.86 SEM 0.01, P less than 0.01 in TAN). There was no difference in the preoperative mitochondrial phosphorylation rate (PR = x 10(-10) mol ATP/sec per mg mitochondrial protein) between normal and cirrhotic livers (21.01 SEM 0.95 and 21.55 SEM 1.03, respectively). After hepatectomy, in the normal livers these values decreased slightly after 12 h, remained low until 48 h, and returned to the preoperative value at 72 h. PR was remarkably enhanced and reached the maximum level of 32.54 SEM 2.07 at 24 h (P less than 0.001, compared to the sham-operated rats) and gradually returned to the preoperative value at 72 h. In the cirrhotic livers, ATP and ECP levels were drastically decreased at 12 h and recovered to the preoperative levels within 24 h, while TAN level remained unchanged. Enhancement of PR was not observed in any of the cirrhotic livers during the experiment. Lipid peroxidation was transiently increased postoperatively with no difference between normal and cirrhotic livers both in the sham-operated and the hepatectomized rats. These findings suggest that the energy status was more depressed in the cirrhotic livers than in normal livers both before and after hepatectomy. This depressed energy status might be attributed to the low preoperative tissue levels of adenine nucleotides and ECP level in the cirrhotic livers as well as to the absence of the enhancement of PR in the remnant livers.

Adenine Nucleotides↗
PubMed1992

Conversion of mitochondrial redox state toward oxidation by prostacyclin in 70%-hepatectomized rats.

Arterial blood ketone body ratio (KBR) and hepatic mitochondrial phosphorylation rate (PR) were investigated in partially (70%) hepatectomized rats treated with 100 micrograms/kg body weight prostacyclin (PGI2) analogue i.p. after operation and every 12 h thereafter up to 72 h. Sampling was performed at 12, 24, 48, and 72 h after operation. In sham-operated rats, KBR significantly increased from the preoperative values of 0.34 +/- 0.03 and 0.38 +/- 0.03, to 0.55 +/- 0.03 and 0.58 +/- 0.02 at 12 h in the groups with and without PGI2 treatment, respectively (P less than 0.001). KBR returned to the preoperative levels after 24 h in the PGI2-treated group, while it tended to be in the lower normal range in the untreated group. In the hepatectomized rats, KBR significantly decreased in the untreated group compared with the preoperative values and the values in the sham-operated group. It returned to the preoperative range within 72 h. In the PGI2-treated group, KBR increased significantly, to values above 0.54, after a 24-h delay and was maintained at those levels for 72 h. Concentrations of total ketone bodies (TKB) in the untreated groups remained in the upper range of preoperative values (above 200 nmol/ml) in the sham-operated rats and decreased significantly in the hepatectomized group (234 to 126 nmol/ml). TKB in the treated groups tended to decrease only in the sham-operated group (205 to 166 nmol/ml), and was massively reduced in the hepatectomized group (167 to 81 nmol/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1992

Evaluation of antioxidant treatment with superoxide dismutase in rat liver transplantation after warm ischemia.

In order to investigate the effects of the exogenously administered radical scavenger superoxide dismutase (SOD) on the orthotopic liver graft, livers from male Wistar rats were transplanted after subjection to 40 min of warm ischemia and 30 min of storage at 4 degrees C. SOD was given at the onset of ischemia and before reperfusion as a supplement (6,000 IU) to the washout solutions. 30,000 IU were infused into the recipient. SOD reduced tissue levels of thiobarbituric acid-reacting substances at the end of ischemia (737 vs. 956 nmol/g; p < 0.01) and 60 min after the onset of reperfusion (629 vs. 947 nmol/g; p < 0.001) and preserved total adenine nucleotides after reperfusion (11.69 vs. 10.40 mumol/g; p < 0.01). Survival 2 weeks after transplantation was 18% (2/11) in the SOD group versus 10% (1/10; nonsignificant) in untreated animals. It is concluded that SOD protects the ischemically altered liver from radical mediated peroxidation and preserves hepatic energy stores upon reperfusion. However, in our model no major improvement in organ viability could by achieved.

Adenine Nucleotides↗
PubMed1991

Hepatocellular metabolic change after orthotopic liver transplantation in rats.

The hepatocellular metabolic change after liver transplantation following 2 hr cold ischemia was investigated. Of 55 orthotopic liver transplantation in male Wistar rats, 47 animals were sacrificed at 3 hr, and 1, 2, 7 and 30 days to determine hepatic metabolite levels, in the form of adenine nucleotides, lactate and glycogen. Using the other 8 recipients, biochemical examinations were done at 1, 3, 5, 7, 30 and 60 days and metabolic levels estimated at 60 days. The SGOT and SGPT levels decreased gradually after a remarkable increase on the first postoperative day, while the alkaline phosphatase level revealed a peak value at 30 days. All levels recovered to within the normal range in 60 days. The total adenine nucleotide level reached the normal range within 3 hr following the blood reflow and remained at a normal level thereafter. However, all the metabolic levels apart from total adenine nucleotides deteriorated to reach their worst level at 7 days. The results of this investigation indicate that the posttransplanted deterioration of metabolic levels were possibly caused by the imperfect oxygenation due to cellular edema after blood reflow. However, the levels of these metabolites recovered within 60 days after transplantation.

Adenine Nucleotides↗
PubMed1991

Involvement of oxygen in harvesting injury of the liver. An experimental study including substrate free organ persufflation to evaluate a specific therapeutic approach.

The present study was undertaken to assess the role of oxygen free radicals relating to cell damage upon reoxygenation of the ischemically altered isolated rat liver. Livers were excised and flushed via the portal vein with Ringer's solution and Euro-Collins solution, to which superoxide dismutase (SOD) was added in the experimental group. After warm ischemia at 37 degrees C and cold storage at 4 degrees C, the livers were reperfused via the portal vein with carbogen-saturated Krebs-Henseleit solution. Other livers were subjected to a retrograde persufflation via the infrahepatic caval vein with either oxygen or nitrogen and then rinsed with Ringer's solution. During reperfusion, SOD-treated livers showed markedly reduced vascular resistance, lower enzyme release and enhanced VO2 accordingly, energy charge at the end of reperfusion was significantly higher in the treated group. With reference to the tissue content of malondialdehyde, SOD-treated livers showed significantly less damage than the corroboration for these data. Enzyme activities in the eluate were significantly reduced under anoxic conditions as well as in the presence of SOD. We conclude from these data that oxygen free radicals do exert a detrimental impact on the reoxygenated liver, which could be specifically suppressed by application of exogenous SOD.

Adenosine Triphosphate↗
PubMed1991

Impairment of grafts by short-term warm ischemia in rat liver transplantation.

The mechanism of warm ischemic damage was investigated by assessing hepatic energy metabolism, mitochondrial functions, and lipid peroxidation (LP) of transplanted liver grafts in rats. Donor livers were stored ischemically either for 90 min at 4 degrees C (control) or for 20 min at 37 degrees C and 70 min at 4 degrees C (warm ischemia). In the control group, adenosine 5'-triphosphate (ATP) recovered within 8 min to 86% of the normal preischemic value (10.30, SEM 0.26 mumol/g dw). Total adenine nucleotides (TAN) recovered to 14.83 (SEM 0.22) mumol/g dw within 30 min, as compared with a normal level of 15.44 (SEM 0.36) mumol/g dw. The energy charge potential (ECP) immediately recovered to 0.79 (SEM 0.01) within 8 min (normal, 0.81, SEM 0.01). Mitochondrial phosphorylation rate (PR) was not significantly altered. LP averaged 451 (SEM 10) nmol/g dw in normal livers and did not change even during reperfusion (504, SEM 79, nmol/g dw, at 15 min). In contrast, in the warm ischemic group, ATP recovered only to 65% of the normal value even at 30 min (P less than 0.01), and TAN remained significantly lower than the control value (12.39, SEM 0.47, mumol/g dw, P less than 0.001). PR was normal at the end of warm ischemia, was significantly reduced at the end of the total ischemic period (P less than 0.001 and P less than 0.01, as compared with control and normal values, respectively), and gradually recovered over 30 min. LP increased and reached the maximum of 795 (SEM 84) nmol/g dw at 15-min reperfusion (P less than 0.05). In grafts treated with 50 mg/kg bw allopurinol (i.v.) 10 min prior to the onset of warm ischemia, ATP and ECP recovered to normal values at 30 min, and TAN was significantly higher than in the warm ischemic group (13.28, SEM 0.28, mumol/g dw, P less than 0.05). PR was maintained at normal values, and LP was increased but to a lesser degree than in the ischemic group. It is concluded that the delayed recovery of ATP metabolism in the warm ischemic group might be due to the loss of adenine nucleotides and the decreased PR, and that allopurinol has a protective effect against warm ischemic damage.

Allopurinol↗
PubMed1991

Miniaturized heart-lung machine.

The miniaturized heart-lung machine consists of commercially available roller pumps, a flexible heat exchanger, a newly devised bubble oxygenator, and polyethylene cannulas and silicone tubes. The minimum and maximal priming volume of the entire system is 4.7 and 16.7 mL, respectively. The efficiency of the system is reflected in an heat transfer coefficient ranging from 0.96 to 0.31 at flow rates between 1 and 20 mL/min, a high value of oxygen uptake in the range of 0.061 mL O2/min mL blood-1, and low blood trauma with plasma hemoglobin concentrations of 47.5 +/- 5.0 mg/dL after 60 min of in vitro perfusion. The system is a simple, reliable, and efficient miniaturized heart-lung machine for use in small animals.

Animals↗
PubMed1990

31P NMR spectroscopy for in vitro viability testing of porcine pancreatic islets.

The quality of pancreatic islets prepared by an intraductal pancreas collagenase perfusion technique was tested using three independent methods: 31P NMR spectroscopy, an insulin secretion test, and a staining method. The viability of pancreatic islet tissue was evaluated using the ratio of phosphate diester to phosphate monoester (PDE/PME) as a new criterion obtained by 31P NMR spectroscopy. According to this criterion, three types of tissue fragments could be characterized: vital (PDE/PME 0.5-0.9), damaged (PDE/PME less than 0.2), and necrotic (no PDE, no PME). The findings in the three different groups could be correlated to three trends of insulin secretion of the preparations following glucose challenge: good response to the glucose challenge, continuous decrease of insulin production, and no insulin secretion. We feel that 31P NMR spectroscopy offers a rapid and suitable method for classifying the viability of isolated pancreatic islets.

Animals↗
PubMed1990

Influence of colloidal carbon phagocytosis as a metabolic load on the hepatic energy metabolism in rats.

The influence of phagocytosis on hepatic energy metabolism was investigated in rats injected with colloidal carbon. Following injection of 6 mg colloidal carbon per 100 g body wt (BW) the hepatic energy charge potential (ECP) remained unchanged. However, oxidative phosphorylation of the isolated mitochondria (PR) increased significantly to 120 and 124% of the control at 1 and 3 hr, respectively, and returned to the normal range at 6 hr. The pyruvate level rose to 195 and 150% at 3 and 6 hr. The lactate level was elevated to 195 and 143% at 3 and 6 hr. Following injection of 20 mg colloidal carbon per 100 g BW, the ECP decreased from 0.865 to 0.783 at 1 hr, but recovered to the normal range thereafter. The PR increased more markedly to 135% at 1 hr, concomitant with an elevation of the ketone body ratio. At 3 hr it remained elevated at 118%, but returned to the normal level at 6 hr. The pyruvate and lactate levels increased to more than 250% at 1 and 3 hr. At 6 hr, the lactate level returned to the control level, but the pyruvate level showed still higher level than the control. These results indicate that phagocytosis exerts an acute metabolic load on the total liver. It was tentatively proposed that parenchymal and nonparenchymal cells in the liver have interrelation in the energy metabolism, and that an enhancement of hepatocellular mitochondrial phosphorylative activity occurs to assist the accelerated metabolism due to phagocytosis.

Adenine Nucleotides↗
PubMed1989

Pressure-controlled reperfusion improves postischemic recovery of LV-hypertrophied rat hearts.

The influence of pressure-controlled postischemic reperfusion (Rp) on functional and metabolic parameters in hearts of sham-operated rats and hypertrophied hearts of rats with aortic constriction were studied. Hypertrophied hearts are considered to be more susceptible to ischemia. The hearts were perfused in the Langendorff-technique for thirty minutes at 35 degrees C with Krebs-Henseleit bicarbonate buffer at a perfusion pressure (PP) of 75 mmHg and for five minutes at 15 degrees C with St. Thomas' Hospital cardioplegic solution at a PP of 60 mmHg. After a period of global ischemia of forty minutes' duration at 15 degrees C, reperfusion was started either abruptly (aRp: PP 75 mmHg immediately) or gently (gRp: PP 75 mmHg within thirty minutes); it lasted for forty-five minutes. Intraventricular peak systolic pressure (ISP) was monitored and energy-rich compounds (ATP, ADP, AMP, CrP, free Cr) were analyzed. In normal hearts, metabolic recovery was not affected by the mode of reperfusion, but functional recovery (ISP) averaged 88% of the preischemic control value after gRp as compared with 73% after aRp. In hypertrophied hearts, gentle reperfusion ameliorated both metabolic and functional recovery. At forty-five minute recovery, CrP averaged 5.1 mumol/g ww after aRp and 6.6 mumol/g ww after gRp (p less than 0.01), and ISP amounted to 73% of the preischemic control after aRp and to 85% after gRp.

Adenine Nucleotides↗