TEMPORAL RELATIONSHIP OF PERIPHERAL VASODILATATION, PLASMA-VOLUME EXPANSION AND THE HYPERDYNAMIC CIRCULATORY STATE IN PORTAL-HYPERTENSIVE RATS

Peripheral vasodilatation and plasma volume expansion are required to generate the hyperdynamic circulatory state observed in portal hypertension. To determine which of these factors is the initial event and to assess their temporal relationship with the development of hyperdynamic circulation, we sequentially measured plasma volume (by I-125-albumin dilution), cardiac index (by thermodilution), mean arterial pressure (by catheterization), superior mesenteric and iliac arterial flows (by Doppler flowmetry) and calculated total and regional peripheral resistances in portal-hypertensive rats. Experimental groups were studied from day 1 through day 4 after partial portal-vein ligation (n = 110) or sham operation (n = 111). Decreased total peripheral resistance was detected within a day of portal-vein ligation (4.18 +/- 0.21 mm Hg . min . ml-1. 100 gm vs. 5.19 +/- 0.16 mm Hg . min . ml-1 . 100 gm; p < 0.01). Plasma volume increased significantly on day 2 (4.31 +/- 0.07 ml . 100 gm-1 vs. 3.86 +/- 0.04 ml . 100 gm-1; p < 0.05). Cardiac index and regional blood flows increased in parallel with plasma volume elevation. On day 4, maximum values of plasma volume (4.49 +/- 0.08 ml . 100 gm-1 vs. 3.73 +/- 0.03 ml . 100 gm-1) coincided with fully developed hyperdynamic circulation, as shown by a significant elevation in cardiac index (32.3 +/- 0.6 ml . min-1 . 100 gm-1 vs. 25.5 +/- 1.2 ml . min-1 . 100 gm-1), iliac and mesenteric blood flow. On day 1, vasodilatation was present in the iliac arterial circulation. In contrast, the superior mesenteric artery vascular bed showed vasoconstriction in response to the portal outflow block. Vasodilatation of the superior mesenteric artery bed was delayed until day 4, the time point at which plasma volume is maximally expanded. In portal hypertension, peripheral vasodilatation is the first hemodynamic event in the development of hyperdynamic circulation. Vasodilatation is detected first in the nonsplanchnic circulatory bed and precedes plasma volume expansion, which is then required for the development of the hyperdynamic circulatory state.