The effects of inflammatory and acidosis insult on placental blood vessels reactivity

To examine the effects of two stress stimuli that correspond to pathophysiological processes that occur in placental mediated vascular disorders, leading to adverse pregnancy outcome. The effects of inflammatory stress and acidosis on placental blood vessels reactivity were studied by using the ex-vivo placental perfusion model were studied. Term placentas were obtained immediately after cesarean deliveries and selected cotyledons were cannulated and dually perfused ex-vivo within 30 minutes. Each cotyledon was initially perfused under standard conditions for 30 min (Figure 1). Then placentas were perfused with 3 different perfusion protocols: culture medium (M199-controls, n=5), culture medium with lipopolysaccharide (LPS,1μg/ml, n=5), acidotic culture medium (M-199, pH: 6.9-7, n=6). Each perfusion experiment was maintained for 3 hr. Fetal perfusion pressure was measured continuously. Placental blood vessels reactivity in response to angiotensin II (AT II) was compared between the (LPS) (the inflammatory stress stimuli) perfused placentas, and the acidotic perfused placentas, with controls. LPS stress stimuli significantly increased the vasoconstriction response to ATII in fetal placental blood vessels as compared with control perfused cotyledons as expressed by increased area under the curve (AUC) 822.6±387 vs.156.4±55, respectively, p=0.005 (Figure 2), and higher increased perfusion pressure, 40.4 ± 28 vs. 14± 2.5 mmHg, respectively, p=0.06. The vasoconstriction response to ATII in acidotic medium did not differ from control perfused cotyledons, (AUC) 276±173 vs.156.4±55, p=0.15. There were no differences between the groups in relaxation factor, indicating the rate of pressure return to its baseline level. Inflammatory stimuli has a stronger effect on feto-placental vasculature reactivity than acidosis, suggesting a major inflammatory role in the pathogenesis of placental vascular compromise.View Large Image Figure ViewerDownload Hi-res image Download (PPT)