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HTK (histidine-tryptophane-ketoglutarate) organ preservation solution has been shown to be effective in human kidney transplantation, but the efficacy of HTK for extended liver preservation has not been determined. In this study, canine livers were preserved in HTK and compared with livers preserved in University of Wisconsin solution. First, the right and left liver lobes in dogs were flushed separately with cold HTK and UW, respectively, according to a double-flush method. After splitting the liver, the right and left lobes were stored at 4 degrees C in either solution for 24 hr and 48 hr and assessed microscopically for parenchymal cell swelling, and enzyme histochemically for 5'-nucleotidase (5'-NT) as a marker of ischemic liver injury. Unlike livers preserved in UW (n = 5), HTK-preserved livers (n = 5) showed progressive parenchymal cell swelling after 24-hr and 48-hr storage. The 5'-NT scores in HTK livers were lower than in UW livers, indicating increased storage injury (0-5% and 66-85% in HTK- and UW-preserved livers, respectively, after 48-hr storage). Second, graft function was tested in an orthotopic liver transplantation model in the dog. Whole livers were flushed in situ with cold HTK or UW and stored at 4 degrees C for 24 hr or 48 hr. Liver grafts stored in HTK were not washed out prior to reflow in the recipient, in contrast to grafts stored in UW. Livers preserved for 24 hr using HTK showed life-supporting function after transplantation (n = 5, survival 12 hr-8 days). All grafts preserved for 48 hr in HTK did not function (n = 5, survival < 10 hr). UW-preserved grafts all functioned after 24-hr storage (n = 5, survival > 6 days), as well as after 48-hr storage (n = 6, survival > 6 days). Peak serum glutamic oxaloacetic transaminase (SGOT) values after transplantation of 24-hr and 48-hr HTK-preserved livers did not differ from peak SGOT values of UW-preserved livers after similar preservation times. In conclusion, UW solution is more effective than HTK solution in extended preservation of canine liver grafts: 24-hr storage of livers preserved with HTK solution is feasible, whereas 48-hr storage results in a nonfunctioning graft.
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PMID:Preservation of canine liver grafts using HTK solution. 831 May 2

This study investigates how far mitochondrial swelling in the ischemic heart is influenced by factors pertaining to anaerobic energy turnover. Canine hearts were arrested by aortic cross clamping or cardioplegically with St. Thomas or HTK solution and incubated at 25 degrees C in the solution used for cardiac arrest. Samples of the left ventricle were taken at the end of cardiac arrest and during ischemia for structural evaluation and biochemical analysis. The extracellular pH in the interventricular septum was measured. Mitochondrial swelling was determined with the surface to volume ratio, a parameter independent of the reference space. Values obtained for different swelling were related to defined metabolite concentrations and pHe values to establish possible correlations between structural and biochemical parameters in the ischemic heart. At the onset of ischemia and during the breakdown of creatine phosphate (CP) to 3 mumol/g wet weight mitochondrial volume depends on the method of cardiac arrest and does not increase significantly in any of the three groups. The degree of mitochondrial swelling after depletion of CP correlates with the decline in ATP independent of the form of cardiac arrest. Characteristic values of the surface to volume ratio ascertained at different times of ischemia for all groups correspond to determined ATP concentrations. Acid pHe values seem to intensify mitochondrial swelling. With increased lactate concentrations mitochondria swell, but first initially the degree of swelling differs significantly in the forms of cardiac arrest investigated. Thus, the surface to volume ratio is a powerful and valid ultrastructural parameter, which makes correlations between mitochondrial structure and metabolism possible and furthermore indicates a strong correlation between mitochondrial swelling and ATP-concentration in the ischemic heart.
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PMID:Close correlations between mitochondrial swelling and ATP-content in the ischemic canine myocardium. A combined morphometric and biochemical study. 833 76

A significant proportion of early graft occlusions after aortocoronary revascularization using autologous saphenous vein grafts (SVG) are due to mechanical and/or metabolic or biochemical endothelial lesions. The morphological examination of the endothelium, usually carried out using light microscopy or by various types of scanning electron microscopy (SEM), does not give any indication of the functioning of the endothelium (E). Functionally intact E is capable of producing endothelium-derived relaxing factor (EDRF); a practicable in vitro test is the relaxation of pre-contracted vein segments (VS) in response to acetylcholine (ACh) application. To study the effect of the solution used to rinse and store the SVG between removal and implantation on the functional characteristics of the E, we performed in vitro tests on macroscopically intact VS removed from the saphenous vein of 30 male patients who underwent elective CABG surgery. Isolated VS rings were incubated for 60 min in heparinized whole blood (HWB), Bretschneider's cardioplegic solution (HTK), human albumin solution (HAS), or Ringer's solution (RS) and compared with the results obtained immediately after the removal of untreated control samples (C) taken from the same patients. After equilibration in carbogen aerated Krebs-Henseleit solution and precontraction by 3 x 10(-7) M noradrenaline (NE), relaxation induced by 10(-6) M ACh was measured. Only the samples stored in HWB (13.4 +/- 0.4 mN) showed similar maximal contractions with NE to those in the control group (14.4 +/- 0.5 mN), i.e. all those segments which showed both contractions with NE and relaxation with ACh.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelial damage of the venous graft in CABG. Influence of solutions used for storage and rinsing on endothelial function. 837 22

Bretschneider HTK solution is commonly used for myocardial preservation. In order to evaluate its protective effect for heart transplantation, a retrospective study was initiated in cooperation with Eurotransplant and five heart transplant centers. Seventy-six female and 524 male patients who underwent cardiac transplantations between 1981 and 1991 were included in this study. Using standardized questionnaires, donor and recipient laboratory data, immunosuppressive therapy and the preoperative, intraoperative and postoperative organ function were documented. The average ischemic time of the donor hearts was 160 min, ranging from 75 min-304 min. Immediate postoperative graft failure was observed in 25 transplantations (4.2%). Within the first 30 days 71 organs (11.8%) failed. Using the chi2-test, a statistically significant increase of acute graft failure and early mortality was evident when they were correlated with the length of ischemic time (P = 0.01). In addition, a higher incidence of early graft failure was observed when the perfusion volume was less than 1500 ml. The 1- and 5-year survival rates were 72% and 63%, respectively. Organ preservation with HTK shows good results as long as the ischemic time does not exceed 4 h. The possibility that an increased perfusion volume allows longer ischemic times cannot be excluded with this study.
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PMID:Myocardial preservation using HTK solution for heart transplantation. A multicenter study. 808 81

The present study compares the effect of organ preservation with Euro-Collins solution, cardioplegic histidine-tryptophan-ketoglutarate solution, and University of Wisconsin solution on immediate pancreatic function after cold storage at 4 degrees C for 24 hr. Postischemic organ quality of a porcine pancreas preparation was tested by quantification of physiological and biomedical parameters in a one-line reperfusion system. During reperfusion with a constant arterial pressure the arteriovenous flow rate was significantly higher for HTK (5.7 +/- 0.91 ml/min, n = 8; P < 0.05 vs. EC) and UW (7.4 +/- 0.81 ml/min, n = 8; P < 0.05 vs. EC) than for EC (3.0 +/- 0.26 ml/min, n = 6). The lowest lactate content in the reperfusate was found after HTK protection (HTK, 64.0 +/- 7.2 mumol/50 ml, n = 8; versus EC, 114.2 +/- 1.7 mumol/50 ml, n = 6, P < 0.001; versus UW, 148.0 +/- 28.6 mumol/50 ml, n = 8, P < 0.05). Amylase in the venous effluent was significantly lower (P < 0.05) for HTK or UW protection than for EC (HTK, 189 +/- 72.6 U/ml; UW, 188 +/- 39.4 U/ml; EC, 416 +/- 71.7 U/ml). Oxygen consumption during reperfusion was significantly higher for HTK (2.15 +/- 0.22 microliters/g/min, P < 0.001) and UW (1.80 +/- 0.52 microliters/g/min, P < 0.05) than for EC (0.47 +/- 0.13 microliters/g/min). We conclude that immediate postischemic organ quality and pancreatic function after protection with HTK is not inferior to preservation with UW.
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PMID:The effect of different solutions for organ preservation on immediate postischemic pancreatic function in vitro. 842 35

This study compares the ultrastructure of beating canine hearts with that of hearts subjected to different clinically common forms of cardiac arrest. The contraction state per test field was ascertained according to a specially developed classification. The volume density of myofibrils and the surface to volume ratio of mitochondria were used as parameters for cellular and mitochondrial swelling. Contraction bands were not found in any of the differently pretreated hearts. Following immersion fixation, contractions as well as over- and hypercontractions in beating, fibrillating, and St. Thomas-arrested hearts are significantly more pronounced than in HTK-arrested hearts. Cellular and mitochondrial volumes were similar in beating and fibrillating hearts. St. Thomas-perfusion significantly decreased cellular and mitochondrial volume compared to beating hearts, but these values were in the same range as in fibrillating hearts. Only HTK-solution actually led to a strong reduction of these compartments. Compared to immersion, perfusion fixation after coronary perfusion with cardioplegic solutions led to comparable cellular volumes, but significantly elevated the percentage of relaxed sarcomeres and significantly reduced mitochondrial swelling. The best structural preservation of myocytes was found after HTK-perfusion and perfusion fixation. Such ultrastructural quantitative and morphometrical parameters are powerful tools since results confirm that the degree of myocardial preservation depends on the method of cardiac arrest. This forms the basis for the choice of preconditions for subsequent ischemia. Furthermore, significant alterations of myocardial ultrastructure depend on a combination of the functional state of the heart, the method of cardioplegia, and the technique of fixation.
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PMID:Preservation of cardiac myocytes subjected to different preconditions: a comparative morphometric study of beating, fibrillating, and cardioplegically arrested canine hearts. 843 Sep 12

The regeneration of peripheral nerve grafts was evaluated in a rat model, after pretreating the grafts with Schwann cell culture medium, HTK organ preservation solution, and normal saline, under cold ischemic conditions for different time periods. Following orthotopic replantation of the grafts into donor animals, the quality of regeneration was assessed after 6 weeks, compared to positive controls (autologous transplantation) and negative controls (acellular grafts). The regenerative quality in the Schwann cell culture groups with ischemic periods of 32 and 72 hr was comparable to normal controls. Significantly minor regeneration was detected in specimens undergoing 14 and 120 hr of ischemia in the Schwann cell culture medium and in the HTK and normal saline groups, regardless of ischemic time. Among the conclusions was that controlled proliferation of Schwann cells seems to be a basic principle for preservation of peripheral nerve grafts.
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PMID:Preservation of peripheral nerve grafts: a comparison of normal saline, HTK organ preservation solution, and DMEM Schwann cell culture medium. 858 58

The aim of this study was to investigate the efficacy of HTK solution for cardioplegia in the continuous 120-minute cross-clamping method in comparison with the conventional GIK method. In an experimental model, the efficacy of ketoglutarate and tryptophan in recovering cardiac function after 6 hours' preservation was evaluated. In Group A, in which ketoglutarate was excluded from the HTK solution, percent developed pressure was significantly decreased (p<0.01) and the released enzyme (CK-MB) was significantly increased, but coronary flow was not significantly changed. In Group B, in which tryptophan was excluded from the HTK solution, a significant decrease in percent developed pressure and coronary flow was seen (p<0.01). This indicated that ketoglutarate and tryptophan were effective in protecting the myocardium during the ischemia. In the clinical study, 54 open heart operations were performed with cardioplegic solution, using either HTK solution or GIK solution. In the HTK Group, the heart was exposed to 120 minutes' of ischemia after the infusion of HTK solution (3L). In the GIK group, intermittent GIK perfusion was performed every 30 minutes in association with continuous cold blood perfusion. Percent fraction shortening and cardiac index were not significantly different. However, CK-MB and HBDH were increased in the GIK group, postoperatively. Histological findings showed deterioration of the mitochondria and myocytes during ischemia in the GIK group. These data suggest that the effect of the cardioplegias in heart preservation was satisfactory in both groups, although the interval of intermittent perfusion was prolonged to 120 minutes in the HTK solution.
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PMID:Effect of HTK solution for myocardial preservation. 869 63

Myocardial infarction in consequence of a coronary artery occlusion presents a serious problem. It is the aim of any emergency revascularization to minimize the ischemia-induced damage or to salvage reversibly injured myocardium. In experiments on 8 anesthetized pigs, myocardial protection by orthograde perfusion with a high-volume cardioplegic solution was studied under controlled conditions. The left anterior descending artery (LAD) was occluded for 60 min. Then cardiopulmonary bypass was instituted and cardioplegia induced by 8 min perfusion of Bretschneider HTK solution into the aortic root. After 15 min global ischemia, the LAD was "revascularized' and 150 min reperfusion followed. Except for the early relaxation (dP/dtmin) and mean thickening velocity in the ischemic myocardium, all variables remained essentially unchanged during LAD occlusion. During the entire reperfusion, heart rate was significantly increased compared to control: 93 +/- 23 vs. 126 +/- 20/min. Left-ventricular (LV) peak pressure was significantly decreased at the end of the reperfusion, 104 +/- 33 and 77 +/- 22 mmHg, as was dP/dtmax:2155 +/- 655 vs. 1720 +/- 895 mmHg/s. Cardiac output was insignificantly decreased at the end of reperfusion, 2.6 +/- 0.6 vs. 2.4 +/- 0.5 L/min, whereas stroke-work index exhibited a significant deterioration: 1.2 +/- 0.6 vs. 0.5 +/- 0.3 mmHg.ml/kg. LV dP/dtmin was significantly impaired after ischemia and at the end of reperfusion, -1575 +/- 385 vs. -855 +/- 310 mmHg/s, while LV end-diastolic pressure exhibited only a moderate increase: 8 +/- 5 vs. 9 +/- 3 mmHg. MVO2, in turn, remained almost constant throughout the protocol for each of two methods by which it was predicted. The results show that global work, MVO2, and external efficiency were unchanged during early and late occlusion compared to control. During the entire reperfusion the myocardium was stunned, i.e. cardiac work was decreased at maintained MVO2. Thus, external efficiency was decreased. From these results we conclude that in reperfused myocardium after cardioplegic arrest, the oxygen is only inefficiently converted to develop force.
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PMID:Cardiac efficiency during coronary occlusion and during reperfusion after emergency revascularization under cardioprotection. 872 96

One of the main factor inducing rejection of the allogenic graft are the donor MHC-class II antigens. The cytotoxic damage or the elimination of these cells from the organ may influence his function after grafting. In this study, the influence of the continuous perfusion of the rat kidney with monoclonal antibody against rat MHC-class II antigens (MoAb 25D5) on graft survivals was investigated. For the perfusion, the HTK solution containing MoAb 25D5, rat complement (C) and Pentoxifilline (Ptx) was used. After one-hour perfusion at 21 degrees C kidney were transplanted to the syngenic (LEW-LEW) or allogenic (Da-LEW) recipients, kidney perfused with the solution containing MoAb 25D5 and C survived statistically longer (14.0 +/- 2.4 days) than in the control group without perfusion (7.7 +/- 0.5 days) or after perfusion with the solution containing only Ptx (7.8 +/- 0.8 days). It seems likely that the continuous perfusion of the rat kidney with HTK protective solution containing MoAb against MHC-class II antigens and C can reduce the immunogenicity of the graft.
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PMID:[Prolongation of allogenic rat renal graft survival after perfusion the organ with anti-MHC class II antibody]. 875 5


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