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Biomedical subjects

W Isselhard

Publications and source records attributed to W Isselhard.

At least 73 records · Page 4Linked to original sources

Biochemistry: index of the functional state of the heart?

The description of metabolic patterns during well defined conditions has been, and will be, a very helpful tool in characterizing reactions of cells, tissues and organs to physiological and pathophysiological situations. As a rule, the measurements yield global values. Discrimination between the integrity of different cellular compartments and individual cell functions is difficult and possible only in particular circumstances. Metabolism is not a static, but a dynamic cellular activity. Status analyses are like stills from a movie. With the present state of the art, however, it seems neither possible nor justified to describe or predict functional performance of the heart using analyses of metabolism, which can be performed simply, rapidly, reliably and with general validity. The best way to assess functional performance is to measure function! Metabolism and metabolites are the fuel and constituent parts of structure and its functions. Because of this, there must be a link between function, structure and metabolic activities and metabolite patterns. The successful symptomatic therapy of myoadenylate deaminase deficiency in patients by administration of ribose [20, 21] is just one good example of the relation between metabolism and function, and of the value of subtle studies of metabolism and analyses of metabolic patterns in animals and in man.

Adenosine Triphosphate↗

Miniature equipment for the perfusion of rat limbs.

A simple, reliable and efficient miniaturized extracorporeal circulation system for the use in small animals, especially for the perfusion of rat hind limbs, has been described. The system consists of a newly devised bubble oxygenator and heat exchanger and of commercially available roller pumps, polyethylene cannulas and silicone tubes. The minimal and maximal priming volume of the entire system is 4.7 and 16.7 ml, respectively. The efficiency of the system is reflected in a high value of oxygen uptake in the range of 0.061 ml O2 X min-1 X ml-1 blood, a heat transfer coefficient ranging from 0.96 to 0.31 at flow rates between 1 and 20 ml X min-1, a low pulsation amplitude of the roller pump, a constant flow resistance at the arterial cannula, which implies optimal flow conditions, and in a low blood trauma with plasma hemoglobin concentrations of 47.5 +/- 5 mg dl-1 after 60 min of in vitro perfusion.

Animals↗

[A new model for the regional perfusion of the extremities in rats: metabolism and hemodynamics].

A pelvic extremity of the rat was recirculatorily perfused by means of a self-developed perfusion equipment in a perfusion pressure of 65 +/- 6 mmHg and a blood temperature of 35 degrees C during one hour. Tissue specimens were taken away in the end of the perfusion and 3 weeks later and the metabolite contents was determined in comparison with control groups. No change of the metabolite status was provable by the perfusion. The technical practicability of the perfusion of rat extremities could be shown, therefore, contrary to hitherto existing assumptions.

Animals↗

Evaluation of a short-time, oxygen carrier-free perfusion model in rat liver: mitochondrial energy metabolism and insulin effect.

Livers of rats fasted for 18 hr were perfused for 60 min at 37, 35, and 32 degrees C in a simple noncirculating system with a carbogen (95%, 5% CO2) equilibrated, oxygen carrier-free, glucose-containing (200 mg X dl-1) cristalloid perfusate (pH 7.4, 280 mosmol X kg-1) without or with the addition of insulin (10 U X hr-1), and analyzed for tissue ATP, ADP, AMP, acetoacetate, and beta-hydroxybutyrate as well as for parameters of the energy metabolism of isolated mitochondria. Perfusion without insulin at 37 degrees C caused significant alterations: ATP and total adenine nucleotides (TAN) dropped to 62 and 74% of the control values (3.33 and 4.57 mumol X g-1), respectively. The energy charge potential ECP decreased from 0.842 to 0.713. Also, the mitochondrial phosphorylation rate (PR), the respiratory control ratio (RC), and the state 3 respiration rate (ST 3) were significantly depressed to 62, 54, and 72% of the control values. Perfusion with insulin maintained a normal metabolic pattern: ATP 105%, TAN 97%, ECP 0.877, PR 94%, RC 69%, and ST 3 105%. The metabolic deterioration during insulin-free perfusion was decreased at 35/32 degrees C: ATP 67/82%, PR 72/95%, RC 74/87%. At 35 degrees C, insulin ameliorated the metabolic pattern, but normal ranges were no longer reached. At 32 degrees C, insulin had no effect.

3-Hydroxybutyric Acid↗

Derangement of hepatic energy metabolism in lead-sensitized endotoxicosis.

Lead-sensitized endotoxicosis was investigated in rats in terms of hepatic energy metabolism. Lead acetate (Ld, 20 mg/kg BW) or endotoxin (Etx, 4 mg/kg BW) caused no deaths within 48 h. Ld plus Etx resulted in a lethality of 50 and 100% within 6 and 12 h respectively. Etx or Ld alone caused a slight but significant decrease in the hepatic tissue levels of total adenine nucleotides and/or ATP at 3 and 6 h after the application. The energy charge potential (ECP) remained normal. The ketone bodies acetoacetate and beta-hydroxybutyrate and the ratio AcAc/beta-OHB as well as the mitochondrial oxidative phosphorylation tended to increase; the hepatic tissue levels of pyruvate and lactate were increased after 3 h, indicative of an accelerated glycolysis. These alterations were no longer detectable after 6 h. In lead-sensitized endotoxemia (Ld + Etx), the total adenine nucleotides and ATP of the liver tissue decreased significantly to 84% (86%) and 71% (52%) of the controls within 3 and 6 h respectively, and the ECP had decreased from 0.865 to 0.684 at 6 h. The ketone bodies were increased, while the ratio AcAc/beta-OHB was significantly decreased at 6 h. The hepatic tissue lactate remained elevated. The mitochondrial activity was significantly reduced. A hyperglycemia (175 mg . dl-1) at 3 h changed into a hypoglycemia (50 mg . dl-1) at 6 h. It is suggested that Ld plus Etx causes a rapid impairment of hepatic mitochondria which leads to a drastic disturbance of the hepatic energy metabolism including hypoglycemia and contributes to an enhanced lethality in Ld-sensitized endotoxicosis.

Adenine Nucleotides↗

Energy metabolism and histomorphological findings in replanted rat hind limbs using various conservation methods.

Using various storage and conservation methods, we examined amputated and subsequently replanted limbs for their ischaemia tolerance level by investigating the changes in the adenylphosphocreatine system and glycolysis cycle. After replantation, amputated limbs that had been stored at room temperature (21.0 +/- 1.5 degrees C) for 2 hours were examined 14 days after operation. The adenosine triphosphate level of the skeletal muscle was reduced to 51% and the creatine phosphate to 77% of that of the control group. The glycogen was 13% of the normal value. The biochemical findings correlate with the histomorphological findings. After 2 hours ischaemia, the cross striations of the skeletal muscle and nuclear staining remained intact. There is a breakdown of the biochemical systems after 4 hours of ischaemia. They are no longer intact and the ischaemic limb does not recover. Histologically, muscle necrosis can be observed.

Adenosine Triphosphate↗

The limit of hyperthermic strain on skeletal muscle tissue during regional perfusion.

In experiments with dogs (n = 43), we studied the influence of different temperatures on the hind leg subjected to an isolated perfusion over a period of 1 and 2 h. The main supplying vessels of a hind leg were clamped, cannulated, and connected to an extracorporeal circulation unit which consisted of a roller pump, an oxygenator, and a heat exchanger. Whole blood was used for the regional perfusion at a flow rate of 10 ml . min-1 . 100 g-1 of tissue. Intramuscular (i.m.) temperatures were set at 38 degrees 40 degrees, 42 degrees, and 43.5 degrees C, respectively. The perfusion pressure, the osmotic resistance of the erythrocytes and the metabolic status in specimens of skeletal muscle obtained at the end of the perfusion period or after an 8-day follow-up observation served as parameters. A perfusion of 1 and 2 h at temperatures of up to 42 degrees C did not result in alterations of the energy metabolism. When the i.m. temperature was raised to 43.5 degrees C, a significant decrease in muscular high-energy compounds and an accumulation of lactate occurred. Only under this condition was there a rise in the perfusion pressure and a drastic reduction in the blood pH value in the venous line of the extracorporeal circulation. Acidosis and hyperthermia of 43.5 degrees C produced a marked reduction in the osmotic resistance of the erythrocytes.

Animals↗

Relationship of deranged energy metabolism in liver and kidney to arterial ketone body ratio following liver ischemia in rats.

Changes in energy metabolism in the liver and kidney in liver ischemia induced in rats were simultaneously studied, in terms of energy charge (EC) and mitochondrial oxidoreduction state. Mean arterial blood pressure, glucose and lactate, total ketone bodies (acetoacetate + beta-hydroxybutyrate) and the ketone body ratio in arterial blood (KBR) were also investigated. During and after liver ischemia, both organs showed similar patterns of reversibility, and KBR, which reflects the mitochondrial oxidoreduction state, correlated well with EC, in both organs. Referring to the mortality and changes in substrates above mentioned, KBR is a pertinent parameter for detection of viability following induced liver ischemia. It was also suggested that KBR may indicate a regulating role by the liver, in kidney energy metabolism.

Adenine Nucleotides↗

[Behavior of some functional parameters of acute incomplete drainage-impeded kidney in animal experiments].

The 131-hippuran clearance was determined preoperatively in 24 female Alsatian dogs. At three times (days 1, 7 and 28) after antireflux grafting operation, PAH, inulin, and 131I-hippuran clearances of the two kidneys were determined separately on both sides with a radioisotope nephrogram. There was a postoperative functional restriction of the operated or contralateral kidney at no time and for none of the clearance substances. However, there was a significant increase of the tubulosecretory partial function of both kidneys on the 1st postoperative day. The single findings of the radioisotope nephrograms of interest are discussed.

Acute Disease↗

[Transanal endoscopic surgery of the rectum - testing a new method in animal experiments].

Surgery of the lower third of the rectum can be done without difficulty through the anus using an endoscopical approach. Polyps or tumors located in the upper two thirds of the rectum can be removed using the Mason or Kraske procedure, or by the transabdominal approach. A new endoscopic technique has been developed with the aim, to allow surgery in the whole rectum through the anus. The rectum is being dilated by mechanical means and air insufflation. An oblique angle stereoscopic endoscope as well as modified surgical instruments are used. In animals 47 excisions of mucosa were done, and the incisions were closed by continuous suture. Application of this technique in a clinical setting is planned.

Anal Canal↗

The upper urinary tract following a ureteroneocystostomy (UNC) in animal experiments: I. Functional findings.

A ureteroneocystostomy (UNC) was carried out on 32 dogs. A standardised measurement of flow across the ureterovesical anastomosis revealed a significant obstruction on the day of the operation itself and on the first 5 days after the operation. On the 1st, 7th and 28th day after the operation there was no significant reduction in either tubulo-secretory or glomerular function on the operated and non-operated kidneys.

Animals↗

The upper urinary tract following a ureteroneocystostomy (UNC) in an animal experiment: II. Morphological findings.

This report deals with the macroscopic and microscopic histopathological findings of the upper urinary tract following a unilateral ureteroneocystostomy (UNC) in dogs. Both sides, operated and unoperated, were examined. The area of antireflux surgery was of particular significance. The decrease of flow which was always present on the operated side was caused by submucosal oedema of the bladder and not by the fatty tissue deposited intramurally or by the bladder muscle itself. The morphological findings were less pronounced than was to be expected following the significant obstruction on the operated side caused by anti-reflux surgery (ARS) and shown by the flow measurement and the sequential findings on scintigraphy.

Animals↗

[A new method for isolated regional perfusion of the liver in vivo. Experimental studies (author's transl)].

The canine liver was isolated from its blood supply and perfused for one hour normothermically be means of a new catheter and a perfusion system consisting of oxygenator, pump and heat-exchanger. Hemodynamic parameters, blood gas analyses, and tissue metabolites were evaluated during experiments. The venous return from the lower body and portal vein (1.113/1min) could be maintained with the catheter system so that the mean systemic arterial pressure was within normal limits. With a perfusion rate through the liver 0,55 ml/min/g and perfusion pressure of 10 cm H2O there was an adequate tissue perfusion; this was also shown by blood gas analyses and tissue metabolite concentrations. Using dye dilution methods the isolation of the liver was tested. This showed a leakage of 6-7% of the total perfusion volume. This new method makes it possible to carry out an isolated, normothermic, liver perfusion for one hour without irreversible tissue damage.

Animals↗

[A modified dye dilution method to estimate leakage during regional isolated perfusion of the extremity (author's transl)].

In experiments on dogs (n=13) we tested a procedure for estimating leakage during regional perfusion of the extremity by means of a dye dilution method. After systematic application of 0.5% Evans blue solution (0.1 ml/kg b.w.) we measured the dye concentration in plasma by means of a spectral photometer. The plasma volume (5.5 ml/100 gb.w.) and the disappearance rate of the dye (10%/h) were calculated. In a second procedure the supplying artery and vein of the extremity were proximally clamped and distally connected to an extracorporeal circulation unit consisting of oxygenator, pump, and heat exchanger, and the isolation of the extremity was tested. By simulated of leakage it was possible to detect a little amount of shunt of about 1% escaping from isolated region into the systemic circulation. There were no hints to toxicity when the same dye concentration. There were no hints to toxicity when the same dye concentration was applied. The standardized method was using during 132 cytostatic hyperthermic perfusion in man. In 20 patients we determined shunts of less than 5%, in 104 patients shunts between 5 and 10%, and in eight patients shunts of 10-20% of the extracorporeal circulation. The benefits of the described method are simplicity to carry out and missing of toxicity or radiation.

Animals↗

Effect of hypovolemic hypotension on plasma proteins and hepatic energy status in jaundiced rabbits.

Changes in plasma proteins and hematocrit (Ht) were studied in jaundiced rabbits subjected to hemorrhagic hypotension induced by the modified method of Wiggers and compared with changes in the hepatic energy status. At 48 h after common bile duct ligation, jaundiced rabbits showed hypoalbuminemia and a lower hepatic energy charge (EC), (ATP+1/2ADP)/(ATP+ADP+AMP). 30 min after induction of hypovolemic hypotension, in order to maintain a mean arterial pressure of 40 mm Hg, 86% of the blood collected in the reservoir (about 19% of the normal whole blood volume) had to be successively reinfused over a 2-hour period. Despite increases in Ht and plasma total protein (p-TP) occurring in parallel with the reinfusion, plasma albumin (p-Alb) and the ratio of p-Alb to plasma globulin (A/G) did not increase. On the other hand, in sham-operated rabbits small amounts of blood had to be frequently removed during the first hour (about 34% of the normal whole blood volume), and only 34% of it had to be reinfused over a 2-hour period. Despite removal of more blood and a concomitant decrease in Ht, p-Alb and A/G ratio were higher than in jaundiced rabbits. After marked decreases in EC and total adenine nucleotides (TAN) due to the initial blood loss, EC recovered somewhat and remained higher in sham-operated rabbits than in jaundiced rabbits, whereas TAN did not recover in either group. This seems to indicate that hemodilution functions effectively to maintain microcirculation following hemorrhagic hypotension in sham-operated rabbits, while in jaundiced rabbits a rapid breakdown of protective homeostatic mechanisms results in the earlier deterioration of the hepatic energy status.

Animals↗