Vasoactive components of dialysis solution

Abstract

Background: Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components causing such vasoactivity are still controversial. This study was conducted to define the vasoactive components of conventional and new PD solutions.

Methods: Three visceral peritoneal microvascular levels were visualized by intravital video microscopy of the terminal ileum of anesthetized rats. Anesthesia-free decerebrate conscious rats served as control. Microvascular diameter and blood flow by Doppler measurements were conducted after topical peritoneal exposure to 4 clinical PD solutions and 6 prepared solutions designed to isolate potential vasoactive components of the PD solution.

Results: All clinically available PD solutions produced a rapid and generalized vasodilation at all intestinal microvascular levels, regardless of the osmotic solute. The pattern and magnitude of this dilation was not affected by anesthesia but was determined by arteriolar size, the osmotic solute, and the solution's buffer anion system. The greatest dilation occurred in the small precapillary arterioles and was elicited by conventional PD solution and heat re-sterilized solution containing low glucose degradation products (GDPs). Hypertonic mannitol solutions produced a dilation that was approximately 50% less than the dilation obtained with glucose solutions with identical osmolarity and buffer. Increasing a solution's osmolarity did not produce a parallel increase in the magnitude of dilation, suggesting a nonlinear relationship between the two variables. Lactate dissolved in an isotonic solution was completely non-vasoactive unless the solution's H(+) concentration was increased. At low pH, isotonic lactate produced a rapid but transient vasodilation. This vascular reactivity was similar in magnitude and pattern to that obtained with the isotonic 7.5% icodextrin solution (Extraneal; Baxter Healthcare, Deerfield, Illinois, USA).

Conclusions: (1) Hyperosmolarity is the major vasoactive component of PD solution. (2) Hyperosmolarity and active intracellular glucose uptake account together for approximately 75% of PD solution-induced dilation, whereas GDPs contribute to approximately 25%. (3) Lactate is vasoactive only at low pH (high [H(+)]). (4) The magnitude of PD solution-mediated vasodilation is partially dependent on the nature of the osmotic solute, the GDP contents, and the [H(+)], which determine the vasoactivity of the lactate-buffer anion system. Studies are required to define the molecular mechanisms of PD-induced vasodilation and to determine the vasoactive properties of these solutions after chronic infusion.

Figure 1

The intestinal visceral peritoneal microcirculation. A1 = inflow first-order arteriole; A2 = branching second-order arteriole; A3 = pre-mucosal third-order arteriole.

Figure 2

Time-line of experimental protocol. BL = baseline measurements; ACh = acetylcholine; SNP = sodium nitroprusside; bold arrow heads = time-point for microvascular image recording and hemodynamics data acquisition.

Figure 3

Mean arterial blood pressure (upper panel) and A1 arteriolar blood flow (lower panel). A1 = inflow first-order arteriole. *p < 0.01 for each test solution versus corresponding baseline by two-way ANOVA and Bonferroni post-test. [Delflex manufactured by Fresenius USA, Ogden, Utah, USA. Physioneal and Nutrineal manufactured by Baxter Healthcare, Deerfield, Illinois, USA.]

Figure 4

Peritoneal dialysis solutions’ effect on the visceral peritoneal microvasculature. A1 = inflow first-order arteriole; pA3 = proximal pre-mucosal third-order arteriole; dA3 = distal pre-mucosal third-order arteriole. *p < 0.01 for each test solution versus corresponding baseline by two-way ANOVA and Bonferroni post-test; †p < 0.01 for Delflex versus other solutions by two-way ANOVA and Bonferroni post-test; †p < 0.05 for 2.5% mannitol (lactate) versus all other solutions by two-way ANOVA and Bonferroni post-test. [Delflex manufactured by Fresenius USA, Ogden, Utah, USA. Physioneal and Nutrineal manufactured by Baxter Healthcare, Deerfield, Illinois, USA.]

Figure 5

Effects of peritoneal dialysis solution’s pH and lactate-buffer system on the visceral peritoneal microvascular diameter: isotonic lactate (left panel) and Extraneal (right panel). A1 = inflow first-order arteriole; pA3 = proximal pre-mucosal arteriole; dA3 = distal pre-mucosal third-order arteriole. *p < 0.01 versus corresponding baseline; †p < 0.01 versus lactate pH 8 group; §p < 0.01 for A1 versus A3 precapillary arterioles by two-way ANOVA and Bonferroni post-test. [Extraneal manufactured by Baxter Healthcare, Deerfield, Illinois, USA.]

Figure 6

Intestinal visceral peritoneal microvascular response (left panel) and hemodynamics (right panel) in anesthesia-free conscious decerebrate rats during exposure to Delflex. A1 = inflow first-order arteriole; pA3 = proximal pre-mucosal third-order arteriole; dA3 = distal pre-mucosal third-order arteriole; MAP = mean arterial pressure. *p < 0.01 versus corresponding baseline by one-way ANOVA and Dunnett’s post-test. [Delflex manufactured by Fresenius USA, Ogden, Utah, USA.]