Clinical response and failure to alter lymphatic function in a guinea pig model (Part 3)

In: Octreotide

5 Aug 2012

Under intraluminal perfusion (2.5 pL/min) with a physiological saline solution, mesenteric lymphatic vessels spontaneously and rhythmically constricted at a frequency between nine and 26 constrictions/min. In preparations from the six animals tested, octreotide (4 pM) applied into the superfusion solution during 4 min periods did not affect either the constriction frequency or lymphatic vessel pumping activity (Figure 1A). Figure 1B shows the absence of an effect of octreotide over a wide concentration range (20 nM to 10 pM). Despite the absence of response to octreotide, these vessels responded to treatment with 0.5 pM 5-HT with a decrease in constriction frequency (47±11% of control) and to the application of 1 pM histamine with an increase in pumping (288±101% of control) as previously described. In summary, although pumping of guinea pig mesenteric lymphatic vessels could be altered by known modulatory agents, it was not affected by octreotide over a wide range of concentrations.

This is the first published report, that we are aware of, in which octreotide therapy failed to improve clinical parameters in a patient with primary intestinal lymphangiectasia. Furthermore, our laboratory studies failed to show that octreotide altered lymphatic function as assessed by monitoring contractile frequency.

Effect of octreotide on the contractile activity of guinea pig

Figure 1) Effect of octreotide on the contractile activity of guinea pig mesenteric lymphatic vessels. (A) Time course histogram showing the mean response (± SEM) of five vessels to 4 p.M octreotide applied for 4 min (horizontal bar). (B) Concentration-response relationship of the effect of octreotide. (C) Histograms of the effects of 5-hydroxytryptamine (5-HT) and histamine on the contractile activity in the same vessels investigated in A and B. *P<0.05, paired Student’s t test 

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