Promazine이 出血性 shock에 미치는 影響

Abstract

[한글]

[영문]

Since investigators first became interested in hemorrhagic shock, a major problem has been the elucidation of the nature of irreversible shock state. Although numerous factors such as fluid loss, toxic humoral agents, acidosis and neurogenic factor etc. have been reported to play an important role in development of

hemorrhagic shock, the initiating mechanism of irreversible shock state is still unknown.

Most authorities agree that protective mechanism is mediated through the sympathetic nervous system to maintain a blood supply to vital organs. Subsequent studies have shown that adrenergic blocking agents, especially phenoxybenzamine (POB) and chlorpromazine (CPMZ), could protect from the lethal effects of

hemorrhagic hypotension (Hershey, Fitts, Lotz, Lillehei).

Although promazine has been shown to be an effective agent in hemorrhagic shock, the mechanism by which protects the animals from irreversible hemorrhage status is obscure. The present studies, therefore, were undertaken to elucidate the protective mechanism of promazine from hemorrhagic shock.

Having first established the effect of promazine on the survival rate from the hemorrhagic hypotention, the role of this drug in the recovery of renal function after reinfusion of blood withdrawn into the hemorrhagic hypotensive dogs.

Healthy mongrel doss, weighing 12-17 kg, were anesthetized with Nembutal (30 mg/kg), given intravenously. A femoral artery and vein were exposed and cannulae were inserted into the both vessels: the arterial cannula was used for bleeding or withdrawal of blood sample and the vein cannula for the administration of drugs.

The other femoral artery was also exposed and connected to a mercury manometer for continuous recording of changes in artery blood pressure on a smoked drum.

Polyethylene catheters were inserted into bath ureters and urine was collected throughout the experiment.

After adequate measurement of rates of heart beat and respiration, a hypotensive state was produced by rapid bleeding through femoral artery until arterial blood pressure reached a level of 40 mmHg, and this hypotension was maintained for 4 hours and then the withdrawn blood was reinfused. Promazine in a dose of 0.5 mg/kg was administered by adding into the withdrawn blood.

The clearance of inulin and PAH, concentrations of Na, Cl, and K in plasma and urine and urinary osmotic pressure were determined at an interval of 12 hours after the reinfusion of withdrawn blood and compared with those observed before hemorrhage.

At the end of experiment, heart, liver, adrenal gland and kidney were dissected and catecholamine contents in these tissues were determined spectrophotofluorometrically according to the procedure described by Shore and Olin. The analysis of renal tissue was made by the method of Boylan and Asshauer.

The results obtained may be brifly summarized as follows:

1. Normal dogs were maintained at the hemorrhagic hypotensive state (40 mmHg of arteial blood pressure) for 4 hours and then the withdrawn blood was reinfused into the femoral vein. Six out of these 12 dogs died within 12 hours, indicating 50 per cent mortality rate. The administration of promazine along with the reinfusion of blood markedly reduced the mortality of animals under the above hemorrhagic hypotensive condition. That is, only one out of 15 dogs treated with promazine succumbed, showing 7 2% mortality rate.

2. The changes of blood pressure, respiration and heart rate after the reinfusion of withdrawn blood could not be used for the prediction of survival of animals and were not influenced by promazine.

3. Glomerular filtration rate (GFR) as judged by inulin clearance was 16.9 ml/min within 12 hours after the reinfusion of withdrawn blood. When promazine was administered, it was 21.8 ml/min, indicating that this drug hasten the restoration of the impaired GFR due to hemorrhagic hypotension.

4. Renal plasma Hew (RPF) as judged by PAH clearance was 104 ml/min within 12 hours after the reinfusion of blood, when promazine was administered, it was 112 ml/min, indicating that promazine increases RPF after the hemorrhagic hypotension.

5. The urine flow was 0.16 ml/min within 12 hours after the reinfusion of withdrawn blood. In the dogs treated with promazine, it was 0.31 ml/min, which is significantly greater than the former.

6. The urinary concentrations of Na and Cl were markedly decreased, while of K increased after there infusion of blood, as compared to those observed before hemorrhage. These changes of uninary electrolytes were not significantly influenced by promazine. However, the urinary osmotic pressure was markedly increased by the administration of promazine.

7. Immediately after reinfusion of withdrawn blood, complete abolition of Na and Cl gradient in medullary renal slices was observed in hemorrhagic hypotensive dogs of bath untreated control and promazine treated. The gradient was appearently restored following 12 hours elapse in both animals and was gradually increased in a time course of more than 12 hours after reinfusion in hemorrhagichypotensive animals, particulary in the case of promazine·treated.

From the above results, it may be concluded that promazine markedly reduced the mortality of dogs subjected to hemorrhagic shock- The reduction of mortality appears to be related with the beneficial effects of this drug on the restoration of renal function of hemorrhagic animals as evidenced by the increase of GFR, RPF and urine flow.