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Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets.

ABSTRACT: BACKGROUND:Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline) by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenation. METHODS:Twenty-four piglets had long and short infusions of the three vasopressor-inotropes titrated to raise mean arterial blood pressure (MAP) 10 mmHg in random order. Nonpharmacological increases in MAP were induced by inflation of a balloon in the descending aorta. We measured cerebral oxygenation (near-infrared spectroscopy), perfusion (laser-Doppler), oxygen consumption (co-oximetry of arterial and superior sagittal sinus blood), and microvascular heterogeneity (side stream dark field video microscopy). RESULTS:Vasopressor-inotropes increased cerebral oxygenation significantly less (p?0.01) compared to non-pharmacological MAP increases, whereas perfusion was similar. Furthermore, cerebral total hemoglobin concentration increased significantly less during vasopressor-inotrope infusions (p?=?0.001). These physiologic responses were identical between the three vasopressor-inotropes (p>0.05). Furthermore, they induced a mild, although insignificant increase in cerebral metabolism and microvascular heterogeneity (p>0.05). Removal of the scalp tissue did not influence the mismatch (p>0.05). CONCLUSION:We demonstrated a moderate vasopressor-inotrope induced mismatch between cerebral perfusion and oxygenation. Scalp removal did not affect this mismatch, why vasopressor-inotropes appear to have direct cerebral actions. The statistically nonsignificant increases in cerebral metabolism and/or microvascular heterogeneity may explain the mismatch. Alternatively, it may simply reflect a vasopressor-inotrope-induced decrease in the arterial-to-venous volume ratio as detected by near-infrared spectroscopy.

SUBMITTER: Hahn GH

PROVIDER: S-EPMC3659109 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets.

Hahn Gitte H GH Hyttel-Sorensen Simon S Petersen Sandra M SM Pryds Ole O Greisen Gorm G

PloS one 20130520 5

<h4>Background</h4>Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline) by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenati ...[more]

PMID: 23700412

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Project description:BackgroundHypotensive neonates who have been treated with dopamine have poorer neurodevelopmental outcome than those who have not been treated with dopamine. We speculate that dopamine stimulates adrenoceptors on cerebral arteries causing cerebral vasoconstriction. This vasoconstriction might lead to a rightward shift of the cerebral autoregulatory curve; consequently, infants treated with dopamine would have a higher risk of low cerebral blood flow at a blood pressure that is otherwise considered "safe".MethodsIn anaesthetized piglets, perfusion of the brain, monitored with laser-doppler flowmetry, and cerebral venous saturation was measured at different levels of hypotension. Each piglet was studied in two phases: a phase with stepwise decreases in MAP and a phase with stepwise increases in MAP. We randomized the order of the two phases, whether dopamine was given in the first or second phase, and the infusion rate of dopamine (10, 25, or 40 μg/kg/min). In/deflation of a balloon catheter, placed in vena cava, induced different levels of hypotension. At each level of hypotension, fluctuations in MAP were induced by in/deflations of a balloon catheter in descending aorta.ResultsDuring measurements, PaCO2 and arterial saturation were stable. MAP levels ranged between 14 and 82 mmHg. Cerebral autoregulation (CA) capacity was calculated as the ratio between %-change in cerebrovascular resistance and %-change in MAP induced by the in/deflation of the arterial balloon. A breakpoint in CA capacity was identified at a MAP of 38±18 mmHg without dopamine and at 44±18, 31±14, and 24±14 mmHg with dopamine infusion rates of 10, 25, and 40 μg/kg/min (p = 0.057). Neither the index of steady-state cerebral perfusion nor cerebral venous saturation were affected by dopamine infusion.ConclusionDopamine infusion tended to improve CA capacity at low blood pressures while an index of steady-state cerebral blood flow and cerebral venous saturation were unaffected by dopamine infusion. Thus, dopamine does not appear to impair CA in newborn piglets.

Project description:BackgroundMost research on galacto-oligosaccharides (GOS) has mainly focused on their prebiotic effects on the hindgut, but their beneficial effects on the small intestine (SI) have received little attention. Since jejunum is the important place to digest and absorb nutrients efficiently, optimal maturation of the jejunum is necessary for maintaining the high growth rate in the neonate. Therefore, this study investigates the effect of the early intervention with GOS on the intestinal development of the jejunum.MethodsA total of 6 litters of neonatal piglets (10 piglets per litter; Duroc × Landrace × Large White) with an average birth weight of 1.55 ± 0.05 kg received 1 of 2 treatments based on their assignment to either the control (CON) group or the GOS (GOS) group in each litter. Piglets in the GOS group were orally administrated 10 mL of a GOS solution (reaching 1 g GOS/kg body weight) per day from the age of 1 to 7 d; the piglets in the CON group were treated with the same dose of physiological saline. All piglets were weaned on d 21. On d 8 and 21 of the experimental trial, 1 pig per group from each of the 6 litters was euthanized.ResultsThe early intervention with GOS increased the average daily gains in the third week (P < 0.05). Decreased crypt depth was also observed in the jejunum of the piglets on d 21 (P < 0.05). The early intervention with GOS increased the jejunal lactase activity on d 8, maltase activity and sucrase activity on d 21 (P < 0.05). In addition, the early intervention with GOS also facilitated the mRNA expression of Sodium glucose co-transporter 1 (SGLT1) on d 8 and the mRNA expression of Glucose transporter type 2 (GLUT2) on d 21 (P < 0.05). It was further determined that GOS up-regulated the mRNA expression of preproglucagon (GCG), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF-1R) and epidermal growth factor (EGF). GOS also up-regulated the protein expression of glucagon-like peptide-2 (GLP-2) and EGF in the jejunum of the piglets. Furthermore, it was also found that GOS enhanced the protein expression of ZO-1 and occludin on d 8 (P < 0.05), as well as increased the mRNA expression of TGF-β and decrease the mRNA expression of IL-12 (P < 0.05).ConclusionsThese results indicate that GOS have a positive effect on piglet growth performance in addition to decreasing the crypt depth and enhancing functional development in jejunum of suckling piglets.

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Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets.

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Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets.

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