Lysosomal enzyme activity influenced by various types of respiration during extracorporeal circulation.

The hypoxic damage of the lung as seen after extracorporeal circulation (ECC) is in correlation to lysosomal hydrolase and protease activation. In the recent study the effect of various types of respiration during ECC on lysosomal enzyme release were studied. 53 patients undergoing open heart surgery were divided into 4 groups: Apnoea, low frequency, continuous positive airway pressure, combination of low frequency and continuous positive airway pressure. Paired blood samples were withdrawn from the superior vena cava (SVC) and the left atrium (LA) throughout the cardiopulmonary bypass. A continuous increase of N-azetyl-beta-D-Glucosaminidase (NAG) in venous plasma and significant differences (SVC-LA) with higher activities in the LA in the apnoea group were detectable (p less than or equal to 0.05-p less than or equal to 0.01). In the other groups a time dependent course could also be evaluated, but the changes of the activities were not significant. The different types of respiration during ECC influenced the clinical course and outcome of the patients in correlation to the release of lysosomal enzymes from the lung. It is concluded that concentration gradients of lysosomal enzymes are an index for pulmonary damage due to the extracorporeal perfusion in open heart surgery. The activation of lysosomal enzymes in the lung circulation are positively influenced by "ventilation" during ECC.

Biochemical monitoring of the lung during and after extracorporeal circulation.

The activity of NAG, lysozyme and PMN-elastase has been investigated in the superior vena caval and left atrium blood collected from patients who underwent open heart surgery. The effect of various types of respiration on the enzyme release has been also documented. Concentration gradients between v. cava sup. and left atrium has been used as an index for pulmonary damage post operatively. We found a time dependent increase of all enzymes during extracorporeal circulation. However, only the release of NAG and lysozyme is characteristic for pulmonary damage. We observed significant higher enzyme release from the lung after Apnea ventilation compared with the PEEP and low frequency ventilation group. Also significant higher NAG and lysozyme activity was found in patients who needed longer respiration post-operatively. PMN-elastase seems to be not suitable for diagnosis of post perfusion lung because the main amount of elastase released by mechanical destroy of the granulocytes.

[Urinary enzyme excretion after prophylactic antibiotic therapy in patients following colorectal surgery (author's transl)]. / Harnenzymausscheidung nach präventiver antibiotikatherapie bei dickdarmresezierten patienten.

The urinary excretion of N-acetyl-beta-glucosaminade (NAG) and alanine aminopeptidase (AAP) was measured as an indicator for nephrotoxicity to neomycin and gentamycin in patients after colorectal surgery. We found that the continuous determination of urinary enzymes is a good indicator for the degree of kidney damage. The dose dependence of nephrotoxicity was influenced by the severity of colorectal surgery. The simple method of urinary enzyme determination seems to be a very valuable test to detect parenchymal damage of the kidney after prophylactic antibiotic therapy.

Effect of ATP-MgCl2 treatment on kidney preservation and on recovery of graft function.

The effect of ATP-MgCl2 treatment was investigated on the biochemical changes of preserved kidneys and on the functional recovery of hypoxically damaged and autotransplanted canine kidneys. We observed that ATP-MgCl2 administered before or during simple hypothermic storage did not protect the integrity of preserved kidney cells, as measured by enzyme wash-out (LDH and NAG) or by lactate release. If the compound was administered after 120 min or 180 min clamping of the renal artery, the solitary kidney showed a faster regeneration as measured by changes in serum creatinine level. The survival rates were significantly higher in the treated groups. Without warm ischemia of the kidney all of the autotransplanted dogs survived after surgery. After 60 min of warm ischemia the mortality rate was 100%, and the mean survival time in average 5 days. If ATP-MgCl2 was administered after the 60 min of warm ischemia, an improved recovery of the graft function was observed

Energy metabolism and lysosomal events in hemorrhagic shock after aprotinin treatment.

Changes in activity of lysosomal enzymes and levels of adenine nucleotides were investigated during hemorrhagic hypotension and following recovery in rat kidneys. The effect of aprotinin pretreatment on these parameters was also tested, and the results were compared to saline-treated controls. Hemorrhagic hypotension led to a release of lysosomal enzymes and to extreme depletion of ATP. The pretreatment with aprotinin inhibits the changes in enzyme activities, but it has no effect on ATP loss during the hypotension. After reinfusion of the shed blood, however, the pretreated animals showed a faster rate of ATP regeneration. The results suggest an interaction between lysosomal enzyme release and ability of mitochondria to resynthetize high-energy compounds during the recovery period.

[The effect of proteinase inhibitor aprotinin on RNA-synthesis rate after partial hepatectomy in rats (author's transl)]. / Der Einfluss des Proteinase-Inhibitors Aprotinin auf die RNS-Synthese nach partieller Hepatektomie bei Ratten.

The effect of Aprotinin has been investigated on RNA-synthesis rate--measured by the incorporation of 3H-uridine--after partial hepatectomy in rats. In the control group two maxima of the incorporation of 3H-uridine into the regenerating liver were obtained after hepatectomy. On the other hand no increase of the 3H-uridine incorporation was detectable after Aprotinin pretreatment. The results indicate that Aprotinin inhibits the early events of liver regeneration by inhibition of proteinase enzymes.

Clinical experiences in the Gambro-preservation unit: analysis of 101 human cadaver kidneys.

101 human cadaver kidneys were preserved by means of hypothermic pulsatile perfusion in the Gambro perfusion unit with human albumin as perfusate. Perfusate flow and some biochemical parameters were assessed during perfusion and correlated with renal function after transplantation. There is a good correlation between perfusate flow and recovery of physiological renal function. LDH released to the perfusate as viability test is of limited value: a direct correlation was only found between LDH activity and perfusion time, and LDH activity and ischemia time. Determination of pH and lactic acid level 1 h after beginning of perfusion is without practical value according to our experience. The quality of albumin in perfusion solution influences the immediate graft function.

Late prognosis in acute posttransplant renal failure in 102 patients.

An ivestigation was made of the effect of the duration of posttransplant renal failure on the late prognosis of graft as well as patient survival and on the frequency of complications in 102 patients who had a functioning graft at three months after transplantation. A direct correlation was found between duration of acute tubular necrosis (ATN) and the late prognosis of the graft. The creatinine clearance was significantly higher and the frequency of complications was lower in the group with immediate resumption of renal function. The mortality rate increased with the duration of ATN.

Effect of high-dose prednisone on renal hemodynamics of normal and transplanted dog kidneys.

The effect of prednisone therapy on renal hemodynamics was studied in normal, autotransplanted as well as homotransplanted dog kidneys. After intravenous administration of prednisone (8 and 16 mg/kg/min) the total blood flow decreased and vascular resistance increased significantly. This effect was more pronounced if the drug was directly injected into the arteria renalis. The same changes were observed in autotransplanted and homotransplanted kidneys and in kidneys in rejection. Our results suggest that high dosage of prednisone decreases the renal blood flow and this adverse effect has to be considered in the therapy. The administration of the drug directly into the arteria renalis may have to be avoided.

Continuous determination of various enzymes and sodium concentration in urine. a usable method for diagnosis of kidney graft rejection.

We investigated changes in urinary enzyme activity and sodium concentration of kidney transplant patients. We found that the increase of the activity of brush border enzymes is one of the earliest signs of tubular damage following rejection. The decrease in the urinary sodium concentration points also to rejection episodes. Despite the unspecificity of both variables, their continuous determination and combined analysis of the results could improve the differential diagnosis of rejection after transplantation and might give important information about the pathogenesis of the graft damage.

Frequency of leukopenia incidents following azathioprine therapy after kidney transplantation.

The frequency of leukopenia incidents and its dependence on the dose of azathioprine and kidney function were analyzed in 149 patients during the first 3 months after kidney transplantation. The results were compared with the data of 42 transplantation centers of the world. We found that the frequency of leukopenia increases significantly following azathioprine dosage exceeding 1.99 mg/kg body weight/day. The toxicity of the drug depends on the kidney function. Most of the leukopenia incidents were detected during the first 5 weeks after kidney transplantation. In 70% of the cases a first leukopenia incident is followed by a second. Low azathioprine dosage after the first episode diminishes the number of second incidents.

[Biochemical parameters for determination of graft viability during the early postoperative period (author's transl)]. / Biochemische Parameter zur Feststellung der Lebensfähigkeit allogener Nierentransplantate.

In 54 patients with graft failure the changes of urine sodium concentration and of urinary enzyme activities (alanine aminopeptidase, AAP) were investigated. It was found that: (1) the kidneys with irreversible acute tubular necrosis are characterised by high urine sodium level, and low AAP activities. These changes correspond to the end stage of renal insufficiency. (2) Low concentration of sodium and extremely high AAP excretion are characteristic in grafts with severe rejection episodes. (3) If kidneys lost their function due to irreversible rejection, the biochemical variables showed the same changes as in the first group. We concluded that by continuous determination of sodium levels and enzyme activities in urine and by their correlation it is possible to detect the non-functioning grafts in the early posttransplantation period.