vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Burns

Two selective V1 and V2 receptor antagonists of arginine vasopressin, d(CH2)5Tyr(Me)AVP and d(CH2)5[D-Ile2, Ile4, Ala9-NH2]AVP, were given intravenously in burn shocked rats to investigate the respective effects of V1 and V2 receptor blockade on the haemodynamic variables in burn shock.. Computer assisted on line real time measurements of mean arterial blood pressure, diastolic blood pressure, left ventricular systolic pressure, dP/dtmax, and heart rate were used to study the effects of the receptor antagonists during burn shock. In addition, the radioactive microsphere method was used to measure the changes of cardiac output and regional blood flows to heart, kidney, and liver in response to the antagonists during burn shock. Third degree burns extending over 30% of body surface area were made by dipping the rat's shaved back into water at 100 degrees C for 20 s.. Male Sprague-Dawley rats (250-300 g) were used in groups of 6-9 per experiment.. Mean and diastolic arterial blood pressures, left ventricular systolic pressure, dP/dtmax and heart rate were measured for 8 h after burns. Cardiac output and regional blood flow were measured at 3 h and 8 h postburn. Results showed that blockade of V1 receptor lowered mean and diastolic arterial blood pressures throughout the 8 h period, and raised left ventricular systolic pressure and dP/dtmax only during the early phase of shock. Cardiac output and blood flows to heart, kidney, and liver were increased by the V1 antagonist at 3 h but not at 8 h postburn. The V2 receptor antagonist increased mean and diastolic arterial blood pressures, left ventricular systolic pressure, and dP/dtmax both during the early and during the late phases of burn shock. It also improved cardiac output and blood flows to the heart, kidney, and liver during the early and late phases of burn shock. However, heart rate was not affected by V1 and V2 receptor antagonists.. The V2 like receptor may be the dominating receptor mediating vasopressin's inhibitory effect on the heart. V1 receptor mediated coronary vasoconstriction contributes to the myocardial depression possibly only at the compensatory phase of shock. In addition V1 receptor mediated vasoconstriction is important in maintaining blood pressure during burn shock.

Topics: Angiotensin Receptor Antagonists; Animals; Arginine Vasopressin; Blood Pressure; Burns; Cardiac Output; Coronary Vessels; Heart Rate; Kidney; Liver; Male; Rats; Rats, Inbred Strains; Receptors, Vasopressin; Regional Blood Flow; Shock, Traumatic; Vasoconstriction

It has been suggested that post-burn myocardial depression may be due to coronary constriction which results in myocardial ischaemia. It has been demonstrated that the levels of vasopressin, a potent natural constrictor of blood vessels, increase four- to six-fold immediately after thermal trauma. Therefore, this substance could be responsible for post-burn coronary constriction and myocardial depression. This was tested using the dog anaesthetized with sodium pentobarbital receiving a 15 per cent total body surface area full thickness flame burn as the experimental model. Cardiac output was measured by the thermal dilution technique. Arterial blood pressure was sensed by a Stathem P-23 transducer. Cardiac force of contraction was measured by a Walton-Brody strain gauge arch sewn on the left ventricle. The results of this study showed a significant decrease in cardiac output, increase in peripheral resistance and decrease in myocardial force of contraction immediately after thermal trauma in untreated animals. The decrease in cardiac output and increase in peripheral resistance remained for the duration of the experimental observations (3 h). The decrease in force of contraction returned to pre-burn levels 1 h post-burn. Pretreatment of the experimental animals with d(CH2)5 Tyr(Me)AVP (SK&F 100273), a vasopressin V-1 receptor blocking agent, prevented the initial decrease in cardiac output, increase in peripheral resistance and decrease in the force of contraction. A correlation plot of peripheral resistance vs. cardiac force of contraction showed a positive correlation between these two variables in the pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Burns; Cardiac Output; Dogs; Myocardial Contraction; Premedication; Receptors, Angiotensin; Receptors, Vasopressin; Vascular Resistance; Vasopressins

Using the dog anaesthetized with sodium pentobarbital receiving a 15 per cent total body surface full skin thickness flame burn as an experimental model, it was observed that administration of the vasopressin, V-1 receptor, blocking agent d(CH2)5Tyr(Me)AVP (SK&F100273) prior to burn could significantly reduce the increase in peripheral resistance which occurs in untreated burned animals. At 30 min post-burn peripheral resistance was 60.2 +/- 7.8 units in treated animals and 117.1 +/- 16.8 units in untreated animals. At 60 min post-burn these values were 71.3 +/- 7.2 units and 117.0 +/- 13.5 units, respectively. Changes in cardiac output were significantly less in treated than untreated experimental animals. The mean arterial blood pressures were not significantly different. Plasma levels of vasopressin were measured by radio-immunoassay prior to burn and at 30-min intervals for 6 h following burn. At the time of taking blood samples for vasopressin levels, mean arterial blood pressure and cardiac output were measured and peripheral resistance was calculated. The results of this study showed that immediately post-burn vasopressin plasma levels increased from 6.2 +/- 2.2 pg/ml to 27.3 +/- 9.5 pg/ml and peripheral resistance increased from 62.3 +/- 6.3 units to 128.0 +/- 20.3 units. During the remaining 6 h of the experimental study both vasopressin plasma levels and peripheral resistance remained elevated. These results show that following thermal injury there is a significant release of vasopressin and suggest that the increase in peripheral resistance observed could be due in part to the vasoconstrictor action of the released vasopressin.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Burns; Cardiac Output; Dogs; Vascular Resistance; Vasopressins