Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie最新文献

Ten adult patients with chronic nonhemolytic unconjugated (indirect) hyperbilirubinemia were analyzed by determining bilirubin uridine diphosphate-glucuronosyltransferase activity according to a more physiological and sensitive method (9 control cases, 0.457 +/- 0.163 nmole/mg protein/min). There was no overlap of the enzyme activities of 2 cases with Crigler-Najjar syndrome (type II) (0.006 nmole/mg protein/min on average) and 6 cases with Gilbert's syndrome (0.051 +/- 0.016 nmole/mg protein/min). The enzyme activities in 2 patients with post-hepatitic hyperbilirubinemia were within the normal range. A new classification of nonhemolytic unconjugated hyperbilirubinemia in adults is proposed according to the results of this enzyme activity and the recent data on the gene mutation of this enzyme.

Intact cardiac compensatory mechanisms are necessary to maintain adequate tissue oxygenation during acute normovolemic hemodilution (ANH). Left ventricular (LV) perfusion, oxygenation and function were analyzed in an experimental whole-body model of profound ANH (Hct 9%) and effectiveness of a perfluorocarbon-based oxygen carrier in maintaining myocardial oxygenation and function was evaluated. A total of 22 anesthetized dogs were hemodiluted to Hct 20% followed by a simulated, controlled blood-loss phase in which dogs were randomized to either: (1) 1:1 exchange of lost blood with autologous red blood cells (RBC-group), (2) 1:1 exchange with a colloid (control-group) and (3) 1:1 exchange with a colloid after a single dose of 1.8 g/kg BW perflubron i.v. (PFC-group). Myocardial oxygen delivery and consumption as well as endocardial perfusion were determined using radioactive microspheres. LV myocardial contractility (LV MC) was assessed from: (1) the relationship between maximum rate of LV pressure increase (LVdp/dtmax) and LV enddiastolic volume (LVEDV) and (2) analysis of the LV endsystolic pressure volume relationship (ESPVR). LV diastolic properties were reflected by (1) minimum rate of LV pressure increase (LVdp/dtmin), (2) slope and intercept of the enddiastolic pressure-volume relationship (EDPVR) and (3) the time-constant of isovolumic LV pressure decline "tau 1/2". Full sets of LV MC data were obtained from 18 dogs (n = 6 per group). LV MC (LVdp/dtmax-LVEDV relation) increased after perflubron administration. At the lowest Hct level, all parameters reflecting LV MC as well as LVdp/dtmin were significantly higher in the PFC-group than in the control-group. After profound normovolemic hemodilution (Hct 9%) superiority of LV MC and LV diastolic properties was found, when myocardial oxygenation was supported by i.v. perflubron emulsion, a temporary O2 carrier.

We prospectively studied the effect of a foam composite containing glycerin, propylene glycol, polyol, stearine, stearate and silicone oil, which is known to form a temporary barrier layer when applied to epithelial surface, on adhesion prevention in rats. The small intestine abrasion model was used for creation of adhesions. Sixty male Sabra rats of a mean weight of 295 +/- 23 g were randomly assigned into four groups: group 1 (n = 20) underwent laparotomy and abrasion; group 2 (n = 20) underwent laparotomy, abrasion and intraperitoneal instillation of the foam composite; group 3 (n = 10) underwent laparotomy with abrasion and a second laparotomy with adhesiolysis 2 weeks later; and group 4 (n = 10), was treated in the same way as group 3 but during the second laparotomy the foam composite was instilled intraperitoneally. All animals were relaparotomized 2 weeks (groups 1 and 2) and 4 weeks (groups 3 and 4) after the initial laparotomy for adhesion scoring performed by a blinded independent investigator using the standard 0-3 adhesion grading score. Representative specimens of small intestine and liver from animals in groups 2 and 4 were analyzed. A significantly lower mean adhesion score was noted in group 2 (1.15 +/- 0.3) compared with that of group 1 (2.65 +/- 0.1) or group 3 (2.60 +/- 0.1) (P < 0.01). Group 4 had a significantly lower score (1.4 +/- 0.3) than group 3 or group 1 (P < 0.05). There was no significant difference in the mean adhesion score between groups 1 and 3. Histological examination revealed no evidence of residual foam composite or adverse reaction to its use in the intestine and liver. The foam composite tested may reduce the severity of intestinal adhesions after laparotomy and may also reduce the severity of recurrent adhesions after adhesiolysis. Intraperitoneal use of this composite is safe in rats. The exact mechanism of action is unclear but may be related to the formation of a temporary microlayer that coats the injured surface of the intestine and facilitates healing without adhesion formation. Further investigation is needed to evaluate its full potential.

Fatty acids are promptly taken up, metabolised and eliminated by healthy cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are known to be associated with an impaired fatty acid metabolism. It was the aim of this study to investigate fatty acid metabolism in a rat heart transplant model and to correlate scintigraphic findings with histological changes. After right-side nephrectomy of Lewis recipients Brown Norway cardiac allografts were anastomosed to the renal vessels. Animals were given no immunosuppression. The metabolism of carrier-free 17-123 jodo-heptadecanoic acid (123J-HDA) with a specific activity of > 2 x 10(17) Bq/ml was scintigraphically measured between days 1 and 11. An increase in the grade of rejection was observed over time. Fifty-six frames of 30 s duration each were recorded. For the region of interest (native heart, transplanted heart, left kidney) frames 10-56 were superimposed, time-activity curves generated and monoexponentially fitted. Furthermore, elimination half-life and intercepts were calculated. Following scintigraphic evaluation the animals were killed and graft as well as native hearts excised for histological examination. The uptake of the tracer identified severe grades of rejection. Elimination half-life of the tracer was twice as long from hearts with mild rejection and more than 14 times as long in severe rejection compared with no rejection. Elimination half-life and amplitude did not permit discrimination between grades 1, 2 and 3 a, but significantly decreased in groups 3 b and 4. This method therefore seems to be a valuable tool for the noninvasive detection of severe acute cardiac allograft rejection. Since fatty acid metabolism is clearly stress-dependent it remains to be seen whether this method allows detection of earlier rejection in loaded hearts.

Unlabelled: The purposes of this study were to determine the tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels after the induction of acute necrotizing pancreatitis, and to establish the effects of pentoxifylline on cytokine production.

Methods: acute pancreatitis was induced by the retrograde injection of 200 microliters taurocholic acid into the pancreatic duct in male Wistar rats. The serum amylase activity, the wet pancreatic weight/body weight ratio, and the TNF and IL-6 levels were measured. Seven mg/kg pentoxifylline were administered intraperitoneally at the time of operation 6, 12 or 24 h later. Rats were killed 6, 24, 48 or 72 h after the operation.

Results: the TNF bioassay revealed high levels of TNF (30.2 +/- 5.4 U/ml, 35.0 +/- 5.0 U/ml and 36.6 +/- 6.0 U/ml) in the control group at 6, 24 and 48 h and (54.1 +/- 20 U/ml and 10.9 +/- 4.2 U/ml) in the pentoxifylline-treated group at 6 and 24 h, respectively, whereas the level had decreased to zero in the pentoxifylline-treated group at 48 h. The IL-6 bioassay likewise demonstrated high levels of IL-6 in the control group at 48 h and in the pentoxifylline-treated group at 6 and 24 h, and markedly decreased levels in the pentoxifylline-treated group at 48 h (7083 +/- 2844 pg/ml, 6463 +/- 1307 pg/ml, 10,329 +/- 5571 pg/ml vs 137.5 +/- 85.5 pg/ml, respectively, P < 0.05). The high mortality observed in the pancreatitis group (43%) was decreased by pentoxifylline administration to 11%.

Conclusion: these results demonstrate that pentoxifylline very effectively inhibits cytokine production in acute pancreatitis.

The aim of the present study was to investigate if hypothermia and rewarming, without accompanying cardiac ischaemia or cardioplegia, causes myocardial damage. Anaesthetized rats were subjected to a cooling procedure (4 h at 15-13 degrees C) where spontaneous cardiac electromechanical activity was maintained, followed by rewarming. Control rats, hypothermic rats and posthypothermic rats were perfusion-fixed, the hearts removed and the ventricles examined using an electron microscope. Based on morphometric methodology volume fractions as well as absolute volumes of cellular and subcellular components of the ventricles were assessed. In hypothermic hearts capillary volume fraction was significantly decreased, which was probably due to a decrease in perfusion pressure. The cytosolic volume increased in both absolute values and as a fraction of the myocyte: from 25 +/- 11 in controls to 43 +/- 8 microliters and from 0.067 +/- 0.023 to 0.102 +/- 0.013, respectively. There was a corresponding relative decrease in the volume fraction of myofilaments from 0.598 +/- 0.030 to 0.548 +/- 0.024. In posthypothermic hearts significant tissue swelling was apparent, dominated by a significant increase in myocyte volume from 372 +/- 66 in controls to 522 +/- 166 microliters. Similar changes were measured in mitochondrial and cytosolic volumes. In conclusion, the myocardial ultrastructure was altered during hypothermia as well as after rewarming. Posthypothermic myocardium showed generalized cellular swelling and areas of cellular necrosis.

Reconstruction of choledochal wall defects in an experimental dog model by T-tube plus fascioperitoneal graft and an evaluation of the short-term results were the aims of this study. Twelve randomly selected mongrel dogs of both sexes, having an average weight of 22.15 +/- 1.85 kg, were anaesthetized with ketamine HCI and xylazine and underwent laparatomy. The front wall of choledoch canal were excised with its all layers 0.5 cm in diameter at the distal part of the cystic duct junctions. These defects were repaired by using grafts prepared of the same diameter from the dorsal fascias of rectus muscles and peritoneum. T-tubes were introduced into the common ducts on the proximal part of the grafts. One of the animals died in the postoperative period due to evantration. T-tube cholangiograms on the twelfth day did not indicate any extravasation or stricture. Histopathological examination of the graft regions on the sixtieth day revealed that the epithelialization had commenced on the border between the bile epithelium and grafts. Based on these early findings, it was suggested that if supported by further studies it may be thought of as a clinical method.

The study tested the hypothesis that the reduced [Na+]e and hypo-osmolality of normal pregnancy are causally linked to the attenuation of vascular smooth muscle reactivity in vitro. Aortic rings from nonpregnant female rats were incubated in physiological medium containing 114 mM NaCl/l and the contractile responses to phenylephrine, KCl and CaCl2 as well as the relaxations to acetylcholine and KCl were compared with those of rings incubated in normal medium containing 119 mM NaCl/l. There was no solute substituted for the lowered [Na+]. Experiments with phenylephrine were repeated using de-endothelialized rings and intact rings pretreated with indomethacin. Contractile responses of intact rings (n = 11) in hypo-osmolar solution to phenylephrine were significantly (P < 0.001) lower than of those in normal medium (n = 11). Responses were partially restored by endothelial denudation but not in the presence of indomethacin. Relaxations to acetylcholine (n = 7 for hypo-osmolar; n = 6 for normal solution) and KCl (n = 7 for each of hypo- and normal osmolar) were significantly enhanced (P < 0.05) in rings incubated in hypo-osmolar solution. There was no significant difference between the responses of the rings to KCl, and CaCl2 in either solution. These effects are similar to some of those previously described for vascular smooth muscle in normal pregnancy suggesting that the reduced [Na+]e and hypo-osmolarity of normal pregnancy may be contributing to the diminished vascular reactivity.

We studied the effects of experimental hemiparkinsonism upon sympathetic function in rat. The rats were divided into three groups: a group given intact control, one given lesioning with 6-hydroxydopamine (6-OHDA), and one given sham operation. One day after apomorphine testing following lesioning of the substantia nigra (SN) with 6-OHDA, heart rate (HR), mean arterial blood pressure (MAP), and electrocardiogram (ECG) were monitored. Plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) levels were measured. Thereafter, immunohistochemical examination was performed to detect the extent of 6-OHDA lesions, using the avidinbiotinylated peroxidase complex (ABC) method. There was no difference in the total number of tyrosine hydroxylase (TH)-positive cells and rotation responses between the right- and left-sided 6-OHDA-treated groups. On the other hand, injury of rats with unilateral 6-OHDA resulted in haemodynamic, electrocardiographic, and biochemical changes. A significant difference was found between the right-sided 6-OHDA-treated rats and the left-sided treated ones. The MAP increased in the group given left 6-OHDA treatment and to lesser extent in the sham-operated group. In contrast, MAP did not increase in the group given right 6-OHDA treatment and was significantly lower than values in both the intact control rats and the sham-treated rats. Also, only the group given right 6-OHDA injury showed a fall in the value of HR. The plasma NE level was significantly decreased in the group given right 6-OHDA treatment compared with all other groups (P < 0.005). Our results indicate that right-sided lesioning of the nigrostriatal DA pathway in the central nervous system (CNS) has greater sympathetic consequences than left-sided ones. These results also suggest that there is a differential effect of right-sided SN lesions on sympathetic cardiac innervation. The mechanism behind the confronting impairment of autonomic nervous system (ANS) could in this experiment be attributable to an asymmetric representation of sympathetic function in the brain. However, further studies will be needed before final conclusions can be made.

The objective of this study was to determine whether myenteric denervation of the abdominal esophagus using benzalkonium chloride (BAC) leads to esophageal achalasia with changes of the muscle propria and epithelial cell proliferation. The treatment led to megaesophagus 3 months after BAC application. Denervation of the esophagus induced muscle hypertrophy and increased epithelial cell proliferation. The imbalance of the neurotransmitters may play a role in these morphokinetic changes.