Biomedical subjects
Publications and source records attributed to G Kehrer.
Discrete subaortic stenosis is an uncommon congenital cardiac disorder in which the left ventricular outflow tract is narrowed. We report about the diagnostic procedures and the successful balloon dilatation of a 49-year old, highly symptomatic male patient suffering from discrete subvalvular aortic stenosis.
Two cases of uncommon side effects of non-steroidal anti-inflammatory drugs (NSAID) are presented which show that in special cases NSAID lesions can be located predominantly in the proximal colon, that NSAID-caused lesions may present themselves as diaphragm-like strictures and that alterations by NSAID in this part of the bowel may bring enormous problems for the differential diagnosis.
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Recently it has been shown that during liver ischemia at 25 degrees C the presence of glycogen, by supporting glycolytic supply, not only retards ATP decay but also leads to a corresponding delay of the rise of the electrical impedance of the ischemic organ. A sudden rise of impedance during ischemia is supposed to indicate the closure of gap junctions. Although similar effects on energy state do exist at low temperature, the impact of glycogen on the electrical impedance under storage conditions has still to be evaluated. Therefore, in a model with protected porcine livers, we examined the intraischemic effects of a preischemic glucose and potassium feeding on impedance changes, lactate production and ATP-content at a storing temperature of 5 degrees C. Impedance was measured both in the low frequency alpha- and the higher frequency beta-dispersion range. In addition, the same parameters were determined in a group of unprotected livers. In this group all animals had received glucose and potassium orally prior to ischemia. Whereas in case of preischemic glucose feeding the rise of impedance in the range of the beta-dispersion (e.g. 5kHz) roughly coincided with the exhaustion of ATP, the corresponding impedance changes in the protected group without a glucose premedication only occurred when glycolysis had already stopped and ATP had reached basal values for some hours. In contrast, in the alpha-dispersion range the impedance changes in the latter group just began at the time when ATP became exhausted and lactate production ceased.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to study perfusion effects of different liver preservation methods on liver structure, porcine livers were perfused with either Bretschneider's HTK (Histidine Tryptophane Ketoglutarat) solution, Euro-Collins (EC) solution or University of Wisconsin solution (UW) according to the respective recommended protocols. Subsequently, together with a group of unprotected livers, all organs were examined by light and electron microscopy including computer assisted morphometry. The width of the space of Disse, the continuity of endothelial cells and the ultrastructure of the hepatocytes were not impaired after cold perfusion with any of the 3 solutions. However, we found considerable differences between the groups with respect to removal of blood cells from liver sinusoids. Livers flushed according to the HTK-protocol had the lowest residual blood cell content followed by the livers of the EC- and the UW-group. Centrilobular regions of the liver lobules were generally better washed free of blood than periportal zones. Computer assisted morphometry did not reveal any significant difference between the size of hepatocytes of EC-, UW- and HTK livers. Only the hepatocytes of normothermic control livers (biopsy samples) were 10% larger than hepatocytes of cold flushed groups. None of the protective perfusion protocols showed structural signs of perfusion injury.
Liver resections are usually performed under occlusion of the hepatoduodenal ligament (Pringle manoeuvre) in order to limit operative blood loss. The maximal ischemic tolerance, although individually different, is generally accepted to be 60 min. Resections of centrally located tumors require precise preparation, sometimes combined with vascular reconstructions. In such cases a prolonged ischemic time is inevitable. A save prolongation of the ischemic tolerance could be useful for extensive liver resections. In an experimental study in pigs ischemic tolerance of the liver was studied under hypothermic protection with the HTK solution of Bretschneider during 2 and 3 h. Deterioration of liver function was compared with a warm ischemia during 2 h. Results showed significantly less serum transaminase activities and better hepatic blood flow (ICG test) after an ischemia under protection with the HTK solution compared to a warm ischemia during 2 h. A prolonged ischemia during 3 h under protection with the HTK solution was well tolerated. First clinical applications of hypothermic hepatic protection during resection were successful.
The influence of glycogen content, temperature, and Euro Collins (EC) solution on membrane potential (Vm) and intracellular sodium activity (aNai) were measured in cells of superfused porcine liver slices by means of double-barrelled ion-sensitive microelectrodes. Vm was -26.1mV in fasted pigs and -20.6mV after glucose feeding, when measured in HEPES-buffered solution (P less than 0.0001). aNai was not measurably affected by glucose feeding. During superfusion with Tyrode solution, lowering the temperature from 35.5 degrees C to 15.5 degrees C led to a fast Vm decrease of roughly 2mV followed by an increase of 1-3mV. At the same time, aNai increased from 12.8 to 18.2mM within 10 min. Superfusion with EC solution for 10 min caused comparable changes in fed and fasted pigs. Vm depolarized at either temperature by about 16mV. At 35.5 degrees C the initial aNai of 17.5mM was roughly halved, whereas at 15.5 degrees C it decreased from 21.0 to 14.3mM. The results suggest that the nutritional state markedly affects the electric properties of liver. However, the effect on membrane potential of high-potassium organ-protective solutions seems to be distinctly more pronounced. Moreover, cellular Na+ activity decreases in consequence of an extracellular Na+ reduction with protective solutions, which might be balanced to some extent by a simultaneous temperature decrease.
Ischemia causes changes in organ tissue (e.g. during operation or transplantation) which may finally lead to irreversible injury, so that the organ can no longer be resuscitated. To the extent that these changes affect the electrical properties of the tissue they are manifested in the impedance spectrum. As an example, the course of impedance of a HTK-protected porcine liver is presented in the frequency range of 0.1 Hz to 10 MHz, which includes two dispersion--alpha- and beta-dispersion. Using a suitable electrical equivalent circuit analogue to the structure of the liver, the behavior of the alpha- and beta-dispersion is explained on the basis of gap junction closure and narrowing of the extracellular space due to cell swelling.
In order to further corroborate the recent findings on liver ischemia after perfusion with solutions containing an additive of heptanol, that the intraischemic loss of cell-to-cell communication in protected livers can be detected by electrical impedance measurement (1), we tried to induce uncoupling in porcine liver by tissue acidification applying acidified protective solutions. Moreover, the effects of preischemic inhaling of high concentrations of the decoupling anesthetic halothane were examined in unprotected ischemic livers (2-5). Electrical impedance, biochemical analyses, and pH measurements were applied in parallel. In addition, typical time courses of impedance parameters of unprotected liver and skeletal muscle were compared, because the latter is devoid of gap junctions. In spite of overlapping side-effects of the respective uncoupling measure, the results suggest that the loss of cell-to-cell communication in the liver is associated with measureable effects on the electrical impedance.
Several functional parameters were applied in an experimental model of ischemia to test the ability to localize the distribution of tubular lesions. Canine kidneys were perfused with protective solutions and rendered ischemic for definite periods. Renal function was determined during a subsequent 3-h reperfusion. The pattern and the extent of renal injury were influenced by varying the duration of ischemia and by modifying the protective solution used. The results suggest that by employing an appropriate selection of parameters it is possible to allocate renal injury to definite sections of the tubules. According to such an evaluation, under protection with HTK-solution, the proximal tubule limits the tolerance of renal ischemia. The thick ascending limb shows some vulnerability that is aggravated by disadvantageous modifications of the protective solution and that may become more pronounced in the course of reperfusion. In contrast, more distal parts of the nephron retain a remarkable reserve transport capacity after a tolerable level of ischemia.
So far two methods for prolonging the tolerance of renal ischemia are available: 1) surface cooling with crushed ice and 2) perfusion cooling with an extracellular-like solution. Both methods use only the principle of reducing metabolism through cooling. While rewarming during surgery the ischemic protection is lost, or the kidney must be cooled once again. Therefore, a new preservation solution should reduce energy consumption due to its composition in addition to cooling. For open heart surgery, the HTK solution by Bretschneider is already used clinically. In 71 dog kidney experiments, the ischemic time kidneys could tolerate was prolonged by this solution from 15 to 120 min at 35 degrees C and from 45 to 360 min at 25 degrees C. After 2 h of ischemia at 30 degrees C glomerular filtration rate was about 20 ml/min.100gww within 3 h of reperfusion. After six postoperative days the filtration rate was 40 ml/min.100 gww. No ischemic damage could be recognized by histological investigations. The clinical effectiveness of this method was shown in 7 clinical applications. Ischemic duration lasted up to 113 min, and blood creatinine was between 0.8 and 2.4 mg% at the 6th postoperative day. Use of this preservation technique thus leads to improved kidney function immediately following operation. Longer ischemia can be tolerated by a kidney thus protected, and using this technique excellent visibility can be achieved during intrarenal surgery, simplifying, for example, tumor extirpation.
In ischemic canine kidneys protected by Bretschneider's HTK solution the glycolytic lactate production is limited by a low renal substrate content. However, for anaerobic energy supply ischemic organs depend on glycolysis. To evaluate the role of glycolysis in renal protection, the relationship between lactate production and anaerobic energy supply was examined in protected kidneys of dogs, sheep, and swine. Additionally, in canine kidneys an attempt was made to improve anaerobic energy provision by adding glucose to the protective solution. The results were as follows: (1) According to increasing lactate production from swine to dog to sheep, intraischemic ATP decay was delayed least in swine and most in sheep. (2) Glucose addition (10 mM) to the HTK solution roughly doubled the time for ATP to fall to 1 mumol/g dry wt (tATP) in dogs. (3) The greater the lactate production in all three species, the lower the decrease in SAN (ATP + ADP + AMP) from 5 to 120 min of ischemia. (4) A glucose additive in the protective solution led to a significant (p less than .005) increase of SAN in dogs at 120 min of ischemia. A sufficient substrate supply seems to be an essential component of a reliable renal protection.
Heptanol, an agent known for inducing closure of gap junctions in a variety of organs, was used to evaluate the influence of uncoupling on the electrical impedance of livers during ischemia. Heptanol was added to a modified HTK solution or to Belzer's UW-CSS solution. Livers of swine were then perfused for 8 min with either one of the solutions containing heptanol or a solution devoid of this additive. During the following ischemia the phase angle of impedance at 5 kHz, pH and different biochemical parameters were determined. Heptanol fundamentally changed the time course of impedance and made the otherwise characteristic fast increase of the phase angle of impedance disappear. Already early during ischemia the phase angle was raised in a dose-dependent manner up to even highest values at the beginning of the whole observation period in case of a fully developed effect. Heptanol also stimulated anaerobic energy turnover. The results suggest that, besides unspecific effects, heptanol induces uncoupling which is detectable by electrical impedance measurement.
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In order to evaluate the importance of glycogen for the hepatic tolerance to ischemia, livers of swine fed a glucose-potassium solution for premedication were perfused with either Bretschneider's HTK-solution (histidine-tryptophan-ketoglutarate) or with Euro-Collins-solution (EC) prior to subsequent ischemia at 25 and 5 degrees C. During ischemia, in regular intervals or continuously, energy rich phosphates, lactate, intrahepatic pH and the electrical impedance of liver tissue were determined. The results were compared with corresponding data from swine which had starved for 48 h. Corresponding to the higher glycogen content, energy supply during ischemia was markedly improved by the premedication. Despite high amounts of glucose in the EC-solution, energy supply after glucose-potassium premedication was no better with EC-solution than with HTK-solution. Moreover, glucose uptake led to concomitant cellular water uptake. Electrical impedance measurements during ischemia mirrored improved energetical protection by the glucose-potassium premedication.
Imperative indications for organ-sparing surgery of renal tumors are given mainly in existing or imminent restriction of renal function. Organ-sparing excision of renal tumors under in-situ protection with HTK-solution compared with operations without protection have the following advantages: 1. reduced blood loss, 2. longer ischemia, 3. better tissue differentiation with benefit for radicality, 4. shorter hospital stay.
Following renal ischemia under protection, the perfusion of the tubular system increases concomitant to the rise of GFR. The transport into urine of enzymes entering the tubular lumen due to ischemic injury is dependent on tubular flow. Thus, we examined if in the early postischemic phase urinary enzyme determinations can contribute to the evaluation of the ischemic injury despite the interference of a changing tubular washout. Canine kidneys were perfused with different protective solutions and subsequently rendered ischemic. From the beginning of reperfusion the endogenous creatinine clearance, the urine minute volume and the urinary LDH-concentration were determined. The urinary LDH-concentration allowed only a rough assessment of renal ischemic damage. The adjustment of the urinary LDH amounts to the GFR resulted in a better graduation according to the ischemic stress. With such a standardized LDH parameter the urinary LDH release was somewhat lower on the average when L-aspartate was added to the HTK solution in place of chloride. In conclusion, during the early postischemic recovery after renal protection the examination of the urinary enzyme release may be a useful diagnostic means for the assessment of the extent of the ischemic injury if an appropriate frame of reference is applied.
The addition of the disaccharides maltose (10, 20, 30 mM) and sucrose (30, 60 mM) to Bretschneider's organ protective HTK solution was evaluated to improve renal protection by an enhanced glycolytic energy supply. Canine kidneys were perfused for 8 min with either HTK solution or HTK solution containing additional disaccharides. After nephrectomy the kidneys were incubated at 25 degrees C and metabolic parameters were determined at regular intervals. Maltose and sucrose are slowly cleaved during renal ischemia but maltose distinctly faster than sucrose. Maltose increases intraischemic ATP supply. However, 30 mM maltose was no better than 10 mM. 60 mM sucrose was about as effective for glycolysis as 10 mM maltose. However, possibly due to fructose release there was an accelerated decrease of adenine nucleotides with sucrose. Although fructose enters glycolysis it seems to have negative side-effects. Hence, probably neither sucrose nor fructose are appropriate for renal substrate supply during ischemia.