EARLY excision of deep dermal burns changes the pathophysiological events and may shorten healing time provided the wounds can be covered with grafts (Haynes, 1969; Janžekovič, 1970; Mac Millan, 1971; Burke et al., 1976). Major blood loss is difficult to avoid and makes excision difficult or impossible. Vasopressin, a powerful peripheral vasoconstrictor, has been found to increase cardiac output and to improve the perfusion of vital organs under hypovolemic conditions (Ericsson, 1971; Wetterlin et al., 1977). Such effects may prove favourable during early excision of burns. In order to study the effects of lysine-vasopressin (LVP) on bleeding and haemodynamics, pigs were burned and submitted to acute excision with and without LVP-treatment.

A technique is described for determination of cardiac output in the mouse. The method is basically a tracer dilution technique using 86-rubidium as soluble indicator, where a microsampler is used for blood collection and in which the gamma function fitting is applied for area determination.

With the aid of radioactive microspheres (labeled with 169Yb, 85Sr and 141Ce, respectively), the effect of halothane anesthesia on circulation was studied for 30 min and (group A) for 120 min of halothane anesthesia in thiopental‐sedated dogs. Measurements were also carried out on recovery from halothane anesthesia. Besides such well‐known general circulatory changes as reduction in cardiac output, pulse rate, left ventricular work, arterial mean blood pressure and left atrial mean blood pressure, in both groups there was also a reduced coronary blood flow. The flow to the lungs, kidneys and the brain was well preserved, despite the reduction in both the cardiac output and arterial mean blood pressure. The flow to the liver, however, did not change during short halothane anesthesia; but during long anesthesia there was a marked reduction, due mainly to a decrease in the flow to the preportal area. On recovery from halothane anesthesia, the changes had mostly returned to the preanesthetic values.

Earlier published results have shown an increased 5-day survival in burned mice treated with Triglycylvasopressin. In order to analyze the cause of the increased survival, the distribution of cardiac output was studied in 51 mice divided into three groups. The investigation was performed on the 5th day after burn using a soluble indicator technique (86Rb). The first group consisted of unburned animals. In the second and third groups, a standardized burn of 15% of the body surface was undertaken. The animals in the second group were used as controls and received isotonic saline solution for 5 days. The third group were used as controls and received isotonic saline solution and in addition Triglycylvasopressin, a vasopressin with prolonged effect, 100 microgram/kg body weight subcutaneously twice a day in such a way that the total volume of fluid was identical in the different groups. Cardiac output distribution showed an increased fraction to kidney, liver and small bowel and a decreased fraction to carcass in the Triglycylvasopressin-treated animals compared to burned controls.

The haemostatic effect of triglycylvasopressin (TGLVP) on the gastric mucosa was evaluated in an experimental model in the rat. TGLVP was found to reduce the bleeding significantly compared with the untreated controls. The haemostatic effect was most pronounced and prolonged when 200 µg/kg b. w. was given intravenously. The clinical application of this finding is discussed.

Radioactive microspheres, labeled with ytterbium (169Yb), strontium (85Sr) and cerium (141Ce) were used in an investigation of the cardiovascular response to superficial thiopental anesthesia. The course was followed for 90 min and measurements were carried out at 30, 60 and 90 min, respectively. Between 30 and 60 min of anesthesia there was a slight decrease in cardiac output and left ventricular work. The blood flow was reduced to the lungs, kidneys and the liver. Between 60 and 90 min there were, except for the coeliac artery and total liver, no further changes, which indicated a circulatory steady state.

Different techniques for determining cardiac output distribution in the mouse have been studied. The soluble indicator technique using injection of rubidium on the right side of the heart was found to give a satisfactory reproducibility which made it possible to determine cardiac output fractions in the normal mouse. The use of radioactivity-labelled microspheres, which must be injected on the side of the heart, was found to give unreliable and non-reproducible results. This was due to difficulty in depositing the microspheres into the left ventricle both when a catheter was inserted via the right carotid artery, or by means of cardiac puncture.

Cardiac output distribution, blood pressure and flow in a carotid artery catheter during the first five days after a standardized 15% third degree burn were studied in groups of mice treated with triglycylvasopressin, and in groups used as controls. All animals received isotonic saline solution amounting to 20% of the body weight twice daily, and the treated groups received in addition triglycylvasopressin (TGLVP), a vasopressin analogue with prolonged effect, 100 microgram/kg body weight twice daily. Cardiac output distribution was determined by the 86Rubidium-technique, and showed in burned animals a decreasing fraction to kidneys and small bowel as well as an increased share to the carcass during the experimental period. These changes were partly counteracted by TGLVP-treatment. Flow in the carotid artery catheter in the treated group far exceeded that in the controls, which might be explained by a lower viscosity of the blood in the treated group.

Cardiac output and regional blood flow to different organs were determined at one hour and at 24 hours after burn in untreated mice and in mice treated with triglycylvasopressin (TGLVP). A decrease in cardiac output was found in all animals at one hour after burn. At 24 hours cardiac output was decreased in the burned untreated group, while cardiac output of TGLVP-treated animals did not differ from that of unburned animals. Organ blood flow was decreased in all animals at one hour after burn. Such a decrease was seen in the untreated group also at 24 hours after burn, while organ blood flow in the TGLVP-treated group had returned to preburn values.

Standardized skin burn injuries were induced in 253 NMRI mice. The burned surface corresponded to 15% of the total surface of a 25-gram mouse. All animals received intraperitoneal injection of an isotonic saline solution in a dose of 20% of body weight/day for 5 days. The material was divided into three groups, i.e. group A (controls) which received no further treatment, groups B and C which, in addition, received triglycylvasopressin (a vasopressin with prolonged effect) 100 and 200 mug/kg body weight, respectively, subcutaneously twice a day. The highest survival rate was registered in group B (61%), while the controls had a survival of 36%.

: Nalpha-glycyl-glycyl-glycyl-(8-lysine)-vasopressin, a hormone analogue with prolonged pharmacological action due to slow release of active nonapeptide by enzyme action in vivo, has been administered to 5 control subjects and to 14 patients actively bleeding from upper gastrointestinal sites. The control subjects showed a prolonged pressor response to 100mug/kg body weight associated with a rise in cardiac output, with no ECG signs of myocardial toxicity. 13 of the 14 bleeding patients showed not only pressor responses and haemodynamic and clinical improvement when administering doses of 20-100 mug/kg, but clear signs of standstill of upper gastrointestinal bleeding.

Nα-glycyl-glycyl-glycyl-(8-Lysin)-Vasopressin ist ein Hormonanalog mit prolongierter pharmakologischer Wirkung aufgrund der Tatsache, daß in vivo das aktive Nonapeptid nur langsam durch enzymatische Spaltung freigesetzt wird. Es wurde bei 5 Kontrollpersonen und 14 im oberen Gastrointestinaltrakt blutenden Patienten angewandt. Die Kontrollpersonen zeigten bei einer Dosierung von 100 µg/kg Körpergewicht für längere Zeit einen erhöhten Blutdruck, begleitet von einem vergrößerten Herzminutenvolumen, ohne EKG-Hinweis auf Myocardtoxizität. 13 der 14 blutenden Patienten zeigten nicht nur eine pressorische Wirkung sowie eine hämodynamische und klinische Besserung nach 20–100 µg/kg, sondern auch deutliche Zeichen von Blutstillung sowohl bei peptischen Ulcera als auch Oesophagusvaricen.

Nalpha-glycyl-glycyl-glycyl-(8-lysine)-vasopressin, a hormone analogue with prolonged pharmacological action due to slow release of active nonapeptide by enzyme action in vivo, has been administered to 5 control subjects and to 14 patients actively bleeding from upper gastrointestinal sites. The control subjects showed a prolonged pressor response to 100mug/kg body weight associated with a rise in cardiac output, with no ECG signs of myocardial toxicity. 13 of the 14 bleeding patients showed not only pressor responses and haemodynamic and clinical improvement when administering doses of 20-100 mug/kg, but clear signs of standstill of upper gastrointestinal bleeding.