Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
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31P NMR spectroscopy was used to study the time course of changes in the concentration of high-energy metabolites and intracellular pH in the dog myocardium during hypothermic ischaemia at 9 degrees C in Bretschneider (HTK-B) and St. Thomas' Hospital (StTH) cardioplegic solutions. It was found that ATP and phosphocreatine degrade slowlier in HTK-B than in StTH, with phosphocreatine depletion occurring within 7.9 +/- 1.4 h in HTK-B and within 6.2 +/- 1.4 h in StTH. The values are virtually identical with the time intervals at which ATP concentration falls below the critical level (60% of initial ATP concentration). In agreement with biochemical analysis, a higher concentration of phosphomonoesters was noted until the 180th minute of ischaemia in HTK-B, a finding suggesting more rapid glycogen degradation in HTK-B. Even though HTK-B contains a high concentration of histidine buffer, higher values of intracellular pH were found during ischaemia in StTH. The effect of extracellular concentration of sodium ions on intracellular pH is discussed.
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PMID:The phosphate pool of isolated dog heart during global ischaemia: comparison of two cardioplegic solutions with 31P NMR spectroscopy. 181 21

ANF is totally filtrated by the kidney and is degradated in the brush border of the tubuli. In an experimental transplant model in dogs excretion of ANF is investigated after a cold ischemia period of 48 h and HTK-protection. The ANF-renin-antagonism was of interest respectively. The experiments demonstrated that the filtration in the glomeruli and the function of the endopeptidases in the brush border is normal after a cold ischemia period of 48 and HTK-protection. There is a linear correlation between the concentration of ANF in the renal vein and the aorta. An antagonism of ANF and renin could not be found. ANF is discussed as an additional ischemia parameter in renal transplantation.
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PMID:[Clearance behavior of the kidney in relation to ANF in the autologous dog transplantation model]. 183 13

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.
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PMID:[Measuring electric impedance of organs--methodologic principles]. 185 5

During open heart surgery, reperfusion-induced arrhythmias arising after short periods of ischaemia may originate from subendocardial Purkinje fibres. We investigated the ultrastructure of these fibres during 30 min of global ischaemia at 25 degrees C. The effects both with myocardial protection (HTK cardioplegia) and without it (pure ischaemia) were compared qualitatively and morphometrically. After 30 min pure ischaemia overcontraction of sarcomeres, hypercontraction and contraction bands, together with considerable changes in organelles, predominate over cellular oedema. In Purkinje fibres, both cellular and mitochondrial swelling were significantly increased within this 30-min time period from the onset of pure ischaemia. In contrast, following HTK cardioplegia and 30 min ischaemia, cellular and mitochondrial swelling remain moderate and over-contractions are almost entirely lacking. This means that despite remarkable differences between pure ischaemia and HTK cardioplegia in the degree of protection attained it is clear that, compared with the working myocardium, subendocardial Purkinje fibres do not display a higher resistance to early global ischaemia. Further investigations of this sensitivity of Purkinje fibres to global ischaemia and certain drugs may bring about new insights into myocardial protection and pharmacotherapy of arrhythmias.
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PMID:The ultrastructural effects of global ischaemia on Purkinje fibres compared with working myocardium: a qualitative and morphometric investigation on the canine heart. 189 64

Preservation of the lung is still one of the most challenging problems, because due to limited procurement time not all organs available can be used. The most common procurement technique is flush perfusion of the pulmonary artery system. Alternative methods in clinical use are either the autologous working heart-lung preparation or donor core-cooling (DCC). The own concept presented here, modified to the special demands of multi-organ-procurement, combines DCC and interstitial equilibration adapted to intracellular ion concentration. DCC is induced by extracorporeal circulation (ECC) using a transportable heart lung machine including a highly effective cooling system: cooling circuit based on two parallel heat exchangers with ice-water cooling produced by a high-pressure overflow of a low-temperature ice block (-40 degrees C). While cooling by ECC stepwise hemodilution is achieved by priming volume and incorporation of the cardioplegic solution (Bretschneider-HTK). The aim of equilibration is to lower the extracellular levels of sodium and calcium, and to increase the level of potassium. Additionally, the buffer capacity of donor blood is increased by the incorporated histidine-buffer system (alpha-stat). To avoid donor organ edema the time of ECC should be as short as possible. Using our system donor organ temperatures below 10 degrees C are reached within less than 30 min. In addition to ECC, lung surface cooling is achieved by external overflow with cold arterial blood (internal mammary artery). Besides lung preservation the main advantage of this concept is the profound precooling of all visceral organs before their individual flush perfusion.
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PMID:[The concept of lung and heart-lung preservation within the scope of multiple organ procurement]. 190 76

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.
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PMID:[In situ protection of the liver with Bretschneider HTK solution]. 190 77

The development of a successful method to preserve the heart for relatively long periods (24-48 hr) requires demonstrating successful orthotopic transplantation and long-term survival after preservation. There are, however, multiple variables that may affect the quality of heart preservation, and it is nearly impossible to systematically study all the variables in this complicated model. One model that may be useful to study how preservation parameters affect heart cell preservation is the isolated myocyte preparation. In this study myocytes were isolated from the rabbit heart and the effects of up to 24 hr cold storage on viability measured to determine if this would be a suitable preservation model. Myocytes were stored in various preservation solutions including; EuroCollins (EC), two cardioplegic solutions (Stanford [ST] and Bretschneider solution [HTK]) and the University of Wisconsin solution (UW) with or without the addition of polyethylene glycol. The viability of myocytes was judged by measuring the effects of preservation and rewarming after preservation on cellular morphology (percent rod-shaped cells), ATP concentration, and LDH release. Myocytes preserved in the cardioplegic solutions were least well preserved after 12 and 24 hr storage, as judged by the loss of rod-shaped morphology and lower ATP concentration. Preservation in EC resulted in a decrease in the percent rod-shaped cells after 12 hr and 24 hr storage that was greater than obtained in the UW solutions. The best preservation of myocyte morphology and highest content of ATP was obtained in myocytes stored in the UW solutions, especially those containing PEG. The myocyte model of heart preservation shows a loss of cell integrity that is related to the preservation solution (HTK greater than ST greater than EC greater than UW-PEG) and these results are similar to what has been shown in the past with other models of heart preservation. Thus the myocyte model appears to be a useful method to test how many preservation solutions and preservation variables affect heart cell metabolism. In the future, results from these types of studies may find use in developing improved heart preservation solutions for testing in the orthotopic transplant model.
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PMID:The use of myocytes as a model for developing successful heart preservation solutions. 190 42

This study reports on the first clinical use of HTK preservation solution devised by Bretschneider in renal transplantation. Using this HTK solution, nine living related donor kidneys subjected to cold ischemia for up to 4 h were consecutively transplanted between 1987 and 1989. The postoperative function of the donor and recipient kidneys is analyzed. The endogenous creatinine clearance and the plasma creatinine level are used as function parameters. Within 24-48 h after transplantation a postischemic normal graft function occurred. With triple drug therapy the transplanted kidneys showed an increase in renal function identical with that in the donor's single remaining kidney. Within 7 postoperative days no perfusion damage and no HTK or CyA nephrotoxicity was observed.
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PMID:[Post-ischemia normal function of living related kidney transplants after preservation with HTK solution]. 192 73

Cellular and mitochondrial swelling are regarded as typical intra-ischemic alterations ("IIA"), contraction band lesions (CBL), in contrast, as products of post-ischemic reperfusion. The occurrence of both types of structural deterioration was investigated in Purkinje fibres and subendocardial and intramural working myocardium: initially after St. Thomas- or HTK cardioplegia, then during ensuing global ischemia up to the "practical limit of resuscitability", and following post-ischemic reperfusion. Generally, Purkinje fibres are not better preserved than neighbouring working myocardium. Comparing St. Thomas- and HTK cardioplegia, considerable quantitative, but not qualitative differences in the reaction patterns of different cell types or layers arise. Immediately after cardioplegia, CBL are completely lacking in both cell types. During ischemia, CBL occur occasionally in Purkinje fibres and seldom in subendocardial working myocardium, "IIA" predominate. During post-ischemic reperfusion "IIA" tend to reverse in all layers, whereas CBL are found to remain in the subendocardial cell types. In intramural layers, CBL occur only during reperfusion. Thus, we deduce that cardioplegia only modulates the severity of "IIA" and the frequency of CBL, but cannot abolish the particular sensitivity of subendocardial Purkinje fibres to global ischemia. Prerequisites for the development of irreversible CBL are on the one hand ischemic metabolic alterations and corresponding energy deficits, and, on the other hand, a supply of oxygen. The oxygen may be inadequately supplied via diffusion during ischemia or may be subsequently provided by reperfusion.
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PMID:Patterns of structural deterioration due to ischemia in Purkinje fibres and different layers of the working myocardium. 194 65

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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PMID:Heptanol effects on protected livers. 208 22


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