EFFECT OF NARCOTIC AGENTS AND OF BLEEDING ON SYSTEMIC AND RENAL HEMODYNAMICS IN HEALTHY AND CCL4-TREATED CIRRHOTIC RATS

1, The haemodynamic effects of different narcotic agents have been tes ted in healthy rats and in rats with cirrhosis, 2, Pentobarbital suppr esses the sympathetic nervous system, Susceptibility to ketamine is un predictable, leading to both insufficient pain relief and narcosis rel ated mortality, The combination diazepam-fluanisone induces profound h ypotension, After insertion of catheters, awake, freely moving rats ar e stable and not distressed, This allows repeated measurements after m anipulation, Moreover, procedure-related mortality is low and rats hav e a better stress response, 3, In the awake animal, arterial pressure is 126 +/- 10 for healthy animals, and 111 +/- 16 and 102 +/- 10 mmHg for cirrhotic animals without and with ascites, respectively (P = 0.01 8), The respective values for portal pressure are 6.9 +/- 1.4, 11.6 +/ - 2.5 and 16.2 +/- 2.9 mmHg (P = 0.0001), After a bleeding, arterial p ressure is better preserved than portal pressure in the three groups ( P<0.0001), Plasma volume in cirrhotic rats exceeds that of healthy rat s, Plasma renin activity, aldosterone and catecholamines do not differ between the groups studied, In cirrhotic rats with and without ascite s, glomerular filtration rate tends to be higher (P = 0.12), renal pla sma flow is elevated (P = 0.001) and filtration fraction is lower (P = 0.002) than in healthy rats, 4, In conclusion, haemodynamic experimen ts in the cirrhotic rat should be performed in the awake rat, Arterial hypotension, impaired filtration fraction, enlarged plasma volume and portal hypertension are present in cirrhosis before the development o f ascites, This can as well be explained by splanchnic pooling of bloo d, as by peripheral vasodilatation. The decrease in portal pressure wi th preserved arterial pressure after a bleeding protects cirrhotic rat s from ongoing variceal bleeding.