J. Seifert

Stromafree haemoglobin solution as a blood replacement fluid actual state and problems

SummaryThe present status of stromafree haemoglobin solution does not allow its application as a blood replacement fluid in patients. Although there is conclusive evidence of no renal toxicity there are two basic disadvantages:1.Insufficient intravascular persistence and significant transcapillary leakage;2.Increased oxygen affinity of haemoglobin solution as compared to red cell haemoglobin. It is concluded that the original haemoglobin molecule has to be modified chemically to fullfil both requirements. Studies with crosslinked haemoglobin products have shown that the ideal solution for the near future probably consists of a compromise: The haemoglobin molecule should be crosslinked to other colloids to improve its intravascular persistence; the connection, however, should be flexible enough to allow the physiologic mobility and interaction of the four polypeptide chains necessary for proper oxygen binding and release characteristics.

Differential effects of gastrointestinal hormones on the blood flow of the alimentary tract of the dog.

SummaryThe blood flow of the alimentary tract in anesthetized dogs was measured with radioactively labeled 15-µm microspheres before and after i.v. application of the gastrointestinal hormones glucagon, vasoactive intestinal polypeptide (VIP), secretin, and somatostatin. After 5 min glucagon in a dose of 75 µg/kg bolus + 5 µg/kg·min−1 infusion increased significantly the blood flow in liver, stomach, duodenum, jejunum, ileum, and colon as well as the cardiac output by 160%, 761%, 662%, 576%, 817.3%, 320%, and 108%, respectively. A dose of 3 ng/kg·min−1 resulted in reduction of the circulation in liver, gastric fundus, duodenum, and colon by 27.7%, 19.1%, 16.2%, and 10.7% after 5 min while the cardiac output was not affected.Vasoactive intestinal polypeptide (VIP) infused in a dose of 3.3 pmol/kg·min−1 for 5 min increased the blood flow in the pancreas by 30% and reduced it in the spleen and gastric corpus by 26.9% and 41.5%, respectively.Secretin, another member of the glucagon family, after a 5-min infusion of a dose of 0.5 CU/kg·min−1 increased the cardiac output by 49.96% and the renal circulation by 120.7%. In the gastrointestinal tract circulation of the gastric antrum was stimulated by 474%, of the duodenum by 93.5% and of the ileal mucosa by 178%.Infusion of the pancreatic hormone somatostatin (3.5 µg/kg bolus followed by infusion of 3.5 µg/kg ·h−1) increased the blood flow in the liver by 13%, in the pancreas by 23.15%, and in the spleen by 29.8%, while it reduced it in the fundic mucosa by 17.1% and corpus mucosa by 28.8%.In summary, the gastrointestinal hormones examined exert marked and distinct effects on the circulation of the gastrointestinal tract, each hormone in different parts of the digestive tract. Thus, the local microcirculation of the gastrointestinal tract seems to be subject to hormonal in addition to nerval control.

Elimination rate of human serum albumin in paraplegic patients.

Investigations in 30 paraplegic patients and ten voluntary controls showed that in paraplegics the albumin elimination rate is significantly increased with the highest values of 35.2 ± 6.5 per cent/hour in tetraplegics compared to normal values of 76 ± 0.5 per cent/hour. This finding could not be explained by immunological mechanisms. There were no antibodies against human albumin in the sera of the patients nor positive skin tests. The disappearance curve of homologous and autologous 125-J-Albumin according to the antigen elimination technique corresponded without difference to a normal metabolic situation. Clinical criteria (height of the lesion) indicate that permeability changes due to central nervous mechanisms may be regarded as an aetiologic factor. A chronic pressure sore can accentuate the symptoms by its additional protein loss.

[The antigen-elimination technique in dogs. Evaluation of the method].

SummaryAfter repeated i. v. applications of 8 mg/kg b. w. ultracentrifuged horse-IgG a specific immunological tolerance was observed in 65% of the treated dogs by means of the antigen-elimination technique. Corresponding results were obtained with the simultaneously performed passive hemagglutination test. A comparison of the antigen-elimination with Ouchterlonys test and the immunelectrophoresis, however, shows that precipitating antibodies can be found only in 15% of an accelerated immune-elimination. Lines of precipitated antibodies (H-IgG) could not be detected during a non-immune elimination.Examining the immune-response in H-IgG-tolerant dogs after the i. v. infusion of allogenous antibodies against H-IgG with the antigen-elimination technique only one third of the animals showed on accelerated elimination of the testantigen, which changed to the original type of a non-immune elimination within 4 weeks.The determination of the radioactivity in various organs of the animals during the testperiod gives a hint to the fate of the radioactive testantigen. A significant increase of the radioactivity in the lymphnode, liver, spleen, lung and kidney from day 4 of the antigen-elimination is characteristic of an accelerated immune-elimination.The results give the evidence that the elimination of an antigen is just as a sensitive test as the passive hemagglutination. The specificity is comparable with that of Ouchterlonys test or the immunelectrophoresis. Since the technique combines high sensitivity with high specificity the result of thisin vivo test is more reliable than that of anin vitro testmethod. The antigen elimination should always be performed to investigate the immune-response of organisms.ZusammenfassungNach wiederholter i. v. Verabreichung von ultrazentrifugiertem P-IgG in einer Dosis von 8 mg/kg KG wurde bei erwachsenen Hunden in 65% eine Immuntoleranz mit Hilfe des Antigeneliminationstestes beobachtet. Die gleichzeitig durchgeführte passive Hämagglutination führt zu völlig gleichen Ergebnissen. Ein Vergleich der Antigenelimination mit dem Agargeldoppeldiffusionstest bzw. der Immunelektrophorese zeigt jedoch, daß nur in 15% einer beschleunigten Antigenelimination ein positiver Nachweis von präcipitierenden Antikörpern gelingt. Weiterhin wurden in keinem Fall einer Nichtimmunelimination Präcipitationslinien gegen P-IgG gefunden.Prüft man die Immunantwort mit der Antigeneliminationstechnik bei P-IgG-toleranten Hunden, denen passiv allogene gegen P-IgG gerichtete Antikörper zugeführt worden sind, so kann man nur in einem Drittel der Tiere eine beschleunigte Elimination des Testantigens feststellen, die sich nach 4 Wochen wieder in die ursprüngliche Form einer Nichtimmunelimination umwandelt.Einen Hinweis auf den Verbleib des radioaktiv markierten Testantigens während einer Immun- bzw. einer Nichtimmunantwort liefert die Bestimmung der Organaktivität während der Testperiode. Ein signifikanter Anstieg der Radioaktivität in Lymphknoten, Leber, Milz, Lunge und Niere ab dem 4. Tag ist charakteristisch für die Antigenelimination vom Immuntyp.Die Ergebnisse zeigen, daß die Antigenelimination mindestens ein ebenso empfindlicher Test ist wie die passive Hämagglutination und daß die Spezifität mit der des Ouchterlony bzw. der Immunelektrophorese vergleichbar ist. Da in diesem Test einmal hohe Spezifität mit hoher Empfindlichkeit vereint ist und darüber hinaus die Aussagekraft dieses in vivo-Testes immer der Aussage eines in vitro Testes überlegen ist, sollte man die Immunantwort eines Organismus mit der Antigenelimination prüfen.

Induktion einer Immuntoleranz gegen Pferdeserum-IgG beim erwachsenen Hund

SummarySpecific immunological tolerance can be induced in adult dogs after injecting intravenously ultracentrifuged horse-IgG in doses of 8 mg/kg body weight. The tolerance-inducing threshold dose ranged at least between a tenth power. Tolerance can be achieved by one single injection of ultracentrifuged horse-IgG, but multiple injections increase the incidence of tolerant states, in opposition to the combined injection of methotrexate. — The minimum induction time seems to be 24 h. The state of tolerance to normal horse-IgG is maintained after stronger immunization with either horse antilymphocyte serum or normal horse serum plus complete Freunds adjuvant in a great percentage. The induction of immunological tolerance to horse-IgG prior to the administration of horse antilymphocyte globulin is preferable in two ways: 1. Prevention of anaphylactic reactions during or after treatment with the foreign protein material. 2. Possible increase of the immunosuppressive potency of the antilymphocyte globulin due to the lack of the accelerated immune elimination of the applied protein material.ZusammenfassungDurch intravenöse Verabreichung von ultrazentrifugiertem Pferde-IgG (PIgG) in einer Dosis von 8 mg/kg Körpergewicht kann bei erwachsenen Hunden eine spezifische immunologische Toleranz induziert werden. — Die toleranzinduzierende PIgG-Dosis zeigt eine Schwankungsbreite von mindestens einer Zehnerpotenz. Eine einmalige Injektion von ultrazentrifugiertem PIgG reicht aus, um ein Toleranzstadium zu erzeugen, mehrmalige Injektionen erhöhen jedoch —im Gegensatz zur zusätzlichen Gabe von Methotrexat — die Trefferquote. Die minimale Induktionszeit zur Toleranzerzeugung scheint 24 Std zu betragen. Eine einmal induzierte Immuntoleranz gegen PIgG wird durch nachträgliche Verabreichung von Pferdeantihundelymphocytenserum oder Pferdeserum plus komplettem Freundschem Adjuvans im Großteil der Fälle nicht mehr durchbrochen. — Für eine geplante Therapie mit Antilymphocytenglobulin vom Pferd im Experiment oder in der Klinik böte die vorangehende Induktion einer Immuntoleranz gegen PIgG zwei Vorteile: 1. Ausschaltung sämtlicher anaphylaktischer Reaktionen während oder nach Verabreichung des Fremdeiweißes. 2. Mögliche Steigerung der immunsuppressiven Wirksamkeit der antilymphocytären Globuline infolge Ausbleibens des durch Antikörperbildung bedingten raschen Immunabbaus der Eiweißkörper.

Microcirculation and blood volume in rats before and after spinal cord injury

Blood flow, cardiac output, blood pressure, indicator mixing time and blood volume were measured in rats before and after spinal cord injury. After cutting off the spinal cord blood flow decreases markedly in the paraplegic area but also in the main organs of the animals. Only the blood supply of the lung increases by this manipulation. As blood volume and the blood pressure is decreased and the indicator mixing time delayed the situation of the spinal cord injury can be compared with the situation after acute blood loss. Therefore it is proposed to include circulatory disturbances into the conception of the acute spinal shock situation.

Are bloodflow changes after selective proximal vagotomy responsible for a necrosis in the gastric wall

SummaryAnimal experiments were performed to investigate bloodflow distribution before and after selective vagotomy to explain gastric mucosa necrosis found in some patients after vagotomy.Flow measurements were made using the microsphere technique. Changes in the microcirculation were determined under basal and stimulated conditions (250 mg 2-desoxy-D-glucose). After selective vagotomy a reduction in bloodflow of up to 50% could be observed in all layers of the stomach. There were no differences in the bloodflow along either the lesser or greater curvature under basal conditions.In the stimulated stomach, however, the increase in bloodflow along the lesser curvature was higher, although the vessels of this region were mostly altered by SPV operative procedure. From these results it can be concluded that a reduction of arterial input after selective proximal vagotomy is probably compensated for by intramucosal or submucosal anastomoses. Therefore, necrosis in the gastric wall is not due to SPV but probably to other accompanying diseases.

Versuch zur Induktion einer immunologischen Toleranz gegen Pferde-IgG am Menschen

ZusammenfassungAls Versuch zur Erzeugung einer spezifischen immunologischen Toleranz gegen Pferdeimmunglobulin G (PIgG) erhielten 6 Patienten vor der geplanten ALG-Therapie 2 intravenöse Injektionen des ultrazentrifugierten Serumproteinantigens in einer Dosierung von 10 mg/kg bzw. 30 mg/kg Körpergewicht.Während und nach Absetzen der ALG-Behandlung konnten mit der passiven Hämagglutinationsmethode keine zirkulierenden Antikörper gegen PIgG im Serum der behandelten Patienten nachgewiesen werden. Der nach Beendigung der ALG-Behandlung durchgeführte Antigen-Eliminationstest zeigte, daß intravenös injiziertes131J-markiertes PIgG in allen Fällen im Sinne eines Nichtimmunabbaus aus der Blutbahn eliminiert wurde. Diese Befunde deuten darauf hin, daß möglicherweise der Zustand einer immunologischen Toleranz gegen PIgG induziert wurde, der die Patienten vor anaphylaktischen Reaktionen oder Erscheinungen einer Serumkrankheit als Folge der Fremdserumbehandlung zu schützen vermag.SummaryAs a trial to induce immunological unresponsiveness to horse-IgG, 6 patients received two intravenous injections of the ultracentrifuged serum protein antigen in doses of 10 mg/kg and 30 mg/kg body weight respectively prior to the ALG-therapy.During and after ALG-treatment no antibodies against horse-IgG could be detected in the serum of the ALG-treated patients using the passive hemagglutination technique. The antigen-elimination tests, carried out after the offset of ALG, showed a typical non-immune elimination of the131J-labelled horse-IgG from the circulation.These findings suggest the possible induction of an immunological tolerance to horse-IgG, which may prevent foreign serum reactions in patients receiving anti-lymphocyte globulin.

Messung der Magenwanddurchblutung beim Hund mit radioaktiven Microspheres nach trunculärer Vagotomie

Die trunculare Vagotomie wird auser zur Behandlung des peptischen Ulcus auch zur Therapie diffuser erosiver Magenblutungen angewandt. Hier ist das Behandlungsergebnis auser von der Reduktion der Sekretion moglicherweise auch von der Beeinflussung der Magen wanddurchblutung abhangig. Es erschien daher sinnvoll, der Frage nachzugehen, wie sich die trunculare Vagotomie (TV) auf die Durch blutung der Regionen (Corpus, Antrum) und Wandanteile (Mucosa, Muscularis) des Magens auswirkt. Zur Messung der Durchblutung wurden radioaktiv markierte spharische Partikel nach RUDOLPH und HEYMANN (2) in die arterielle Zirkulation injiziert.

Concentration and Transport of Different Sugars in the Lymph of the Thoracic Duct and in Blood of the Portal Vein in Dogs after Enteral and Parenteral Administration

The uptake and distribution of glucose, galactose, fructose and inulin in dogs was investigated in the lymph of the thoracic duct and in different blood vessels after enteral and parenteral administration. Whereas inulin could be detected neither in the lymph nor in portal venous blood after enteral administration, all other sugars were found in different concentrations in blood and lymph. Although the concentration of different sugars in the lymph after enteral and parenteral application can be compared to that in serum, the amount of sugars transported via the lymphatics is so small that it can be neglected.