Effects of Pancuronium Bromide on Cerebral Blood Flow Changes during Seizures in Newborn Pigs

Abstract

ABSTRACT. We investigated the effects of pancuronium bromide pretreatment on cerebral blood flow (CBF) during bicuculline-induced seizures in anesthetized piglets. Arterial blood pressure, gases, pH, cerebral electrocortical activity, and CBF (radioactive microsphere) were monitored at baseline, 10 min after administration of pancuronium (0.3 mg/kg i.v.; n = 9) or vehicle (normal saline; n = 8), and again at 5, 15, and 60 rnin after bicuculline (3 mg/ kg i.v.). No change in CBF from baseline was observed at 10 rnin after either saline or pancuronium treatment, before induction of seizures. In the saline group, CBF was 36 f 3 mL. min-' . 100 g-' before bicuculline and increased to 166 k 24 and 205 f 35 mL,min-'.lo0 g-' at 5 and 15 min, respectively, after bicuculline, returning toward baseline by 60 min. In the pancuronium group at 5 min after bicuculline, CBF increased from 45 f 7 to 169 k 26 mL. m i d . 100 g-I, but fell to 88 f 17 mL. min-' . 100 g-' at 15 rnin in contrast to saline-treated piglets. Also, at 15 rnin of seizures, differences between groups were observed in arterial blood pressure, gases, and pH. Although these variables were in the normal range with pancuronium treatment, the saline-treated animals had increased arterial blood pressure (81 k 6 mm Hg) and Pco2 (6 5 0.4 kPa) and decreased Poz (7 2 0.5 kPa) and pH (6.91 f 0.06).Electrocortical activity was abnormal during seizures in both groups. At 60 min, reversal to normal activity was observed in six of nine pancuronium-treated animals versus two of eight saline-treated animals. These data suggest that pancuronium limits cerebral hyperemia during prolonged seizures by attenuating increases in blood pressure as a result of elimination of skeletal muscle activity. This leads to minimal alteration of arterial Pcoz, Poz, and pH during seizures. Supported in part by grants-in-aid from the American Heart AssociationTennessee Afliliate, the National Institutes of Health, and Obstetncs and Gynecology Special Education Fund. 6 dramatic increases in CBF (1). Factors contributing to augmented CBF are increased cerebral metabolic rate (2), metabolic and/or respiratory acidosis (3), and arterial hypertension (4-7). This rise in CBF is also exaggerated by neurogenic mechanisms (8). Babies prone to seizures often have respiratory problems and are given muscle relaxants to ease mechanical ventilation and oxygenation. However, inasmuch as pancuronium therapy has been reported to impair cerebrovascular autoregulation in neonatal animals (9), it is unclear whether such therapy would be beneficial.The purpose of this study was to examine the effects of pancuronium on seizure-induced cerebral hyperemia in newborn pigs. We tested the hypothesis that pancuronium would limit perturbations of arterial blood gases, pH, and blood pressure produced by skeletal muscle activity during prolonged seizures and consequently would limit increases in CBF during seizures. MATERIALS AND METHODSThe animal protocol was reviewed and approved by the Animal Care and Use Committee of Th...

Epileptic seizures cause extended postictal cerebral vascular dysfunction that is prevented by HO-1 overexpression

“…Increased CO production correlated with the increase in pial arteriolar diameter during the ictal episode (12). Inhibition of HO-2 activity in the brain by tin protoporphyrin (SnPP) or chromium mesoporphyrin greatly reduced the amplitude and the duration of the cerebral vasodilator response to seizures (12,34). Although SnPP also reduced neuronal activation during the ictal episode (31), the functional consequences of HO inhibition in cerebral microcirculation were of much greater potency compared with the neuronal effects.…”

“…Inadequate blood supply to the brain may contribute to seizure-induced neuronal damage and to the overall postictal state. During seizures, blood flow to the brain increases in patients (7, 9) and in animal models (11,34). In newborn piglets, neuronal activation at the onset of bicuculline-induced seizures is accompanied by the immediate increase in diameter of pial arterioles, major resistance vessels of the brain that determine the cerebral blood flow (30).…”

“…In newborn piglets, spontaneous sustained seizures can be caused by systemic administration of bicuculline, a GABA receptor blocker (11,34). Bicuculline-induced seizures are documented by an immediate (within 30 s) burst of neuronal activation (increased electroencephalographic amplitude and spectral power within a 1-to 15-Hz frequency range), which is sustained for over 2 h (30).…”

Seizure-Induced Alterations in Cerebrovascular Function in the Neonate

“…Arterial hypoxia and hypercapnia directly dilate the cerebral blood vessels, and arterial hypertension further increases the CBF due to the diminished pressure autoregulation. In contrast, anaesthesia, pancuronium paralyzation, and artificial ventilation largely alleviate the systemic effects of seizures [48] rather reflecting the state of electrographic seizures. The combination of anaesthesia, ventilation and muscle relaxation thus allows a more specific examination of seizure-induced cerebrovascular changes.…”

“…The combination of anaesthesia, ventilation and muscle relaxation thus allows a more specific examination of seizure-induced cerebrovascular changes. Under these conditions, a number of studies have found that the CBF is significantly elevated during seizures [15,28,48,49] . These data suggest that altered blood gas levels and/or elevations in mean arterial blood pressure (MABP) are not essential for the development of ictal cerebral hyperaemia.…”