Changes in cerebrospinal fluid and cerebrovascular endothelin concentrations during hypotension and hypertension in newborn piglets with induced sterile meningitis

Abstract

The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets. Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery. The study group consisted of 14 newborn piglets injected with 0.5 mL heat-killed group B streptococcus (GBS) (10(9) colony forming unit (cfu) equivalents), into the right cerebral lateral ventricle; the control group consisted of 10 newborn piglets injected with sterile normal saline, in a similar fashion. Hypotension (mean arterial blood pressure (MABP) 20-59 mmHg; 1 mmHg = 133.3 Pa) and hypertension (MABP 110-140 mmHg) were induced 1.5-2 h apart in random sequence in each animal, by inflating balloon-tipped catheters placed at the aortic root and descending aorta, respectively. Cerebral blood flow (CBF) was measured using radiolabeled microspheres, 15 min before and after injection of GBS or saline (normotension), during the hypotension and hypertension episodes, and during recovery normotension, immediately prior to cerebrospinal fluid and blood sampling. ET-1 and big ET-1 concentrations (pg/mL) were measured using radioimmunoassay kits. The combined effect of induced sterile meningitis and induced hypotension resulted in a significant rise in the concentration of cerebrospinal fluid ET-1 (control, 5.1 +/- 0.1; GBS, 9.3 +/- 0.2 pg/mL; p < 0.01), cerebrospinal fluid big ET-1 (control, 0; GBS, 18.1 +/- 2.7 pg/mL; p < 0.01), and sagittal sinus (cerebrovascular) big ET-1 (control, 15.5 +/- 4.2; GBS, 47.5 +/- 9.6 pg/mL; p < 0.01). In contrast, the combined effect of induced sterile meningitis and induced hypertension resulted in a marked elevation in cerebrovascular ET-1 concentrations (control, 9.5 +/- 0.9; GBS, 28.5 +/- 6.1 pg/mL; p < 0.01), with no significant change in cerebrospinal fluid concentrations. In addition, cerebrovascular production of ET-1 increased dramatically during hypertension in the GBS group (control, 0; GBS, 161.7 +/- 13.2 pg.min-1.100 g-1; p < 0.001), and was maintained during the recovery period (133.7 +/- 10.8 pg.min-1.100 g-1). Cerebrovascular ET-1 concentrations correlated significantly with total CBF and MABP in both groups of animals (control, r = 0.49, p < 0.002; GBS, r = 0.64, p < 0.0001), but the response was of a much greater magnitude in the GBS group. There was an inverse relationship between cerebrovascular big ET-1 concentrations and total CBF (r = -0.53, p < 0.0001) and MABP (r = -0.71, p < 0.0001) in the GBS group. In the MABP range of 60-110 mmHg a positive relationship was observed between cerebrovascular ET-1 concentrations and cerebral vascular resistance, in the control group only (r = 0.59, p < 0.002). The combined insult of induced sterile meningitis and induced hypotension or hypertension may be associated with increased cerebrovascular ET-1 and (or) big ET-1 concentrations. Changes in these vasoactive agents may contribute to pressure passivity of CBF in the newborn with meningitis.