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ORIGINAL ARTICLES |
1 Department of Physiology and Biophysics2 and Department of Surgery, University of Louisville; 3 Veterans Affairs Medical Center, Louisville, Kentucky, USA
Correspondence to: E.R. Zakaria, Department of Physiology and Biophysics,
Health Sciences Center A-1115, University of Louisville, Louisville, Kentucky
40292
USA.
erzaka01{at}louisville.edu
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.
KEY WORDS: Peritoneal dialysis solutions; hyperosmolarity; vasodilation; intestinal microcirculation; lactate; glucose; pH; glucose degradation products.
Received 27 March 2007; accepted 17 November 2007.
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