title: Cerebral metabolic response and mitochondrial activity following insulin-induced hypoglycemia in newborn lambs.
abstract: We evaluated the newborn lamb's cerebral cellular activity and metabolism following acute insulin-induced hypoglycemia. Eleven animals received an insulin bolus followed by a continuous infusion to maintain a plasma glucose of 1 mM/l for 2 h, while 8 other animals received an equivalent dose of saline. Following the induction of hypoglycemia, the animals became quiet and transient seizures were observed in 3 animals. A significant increase in heart rate (p less than 0.01), and a decrease in arterial PaCO2 at 30 min (p less than 0.01), and pH at 2 h (p = 0.02), following hypoglycemia, were observed in the experimental group. Hypoglycemia did not significantly alter the cerebral blood flow, mitochondrial respiratory control ratio or the state-3 activity. The cerebral arteriovenous difference (CAVD) for oxygen did not change, while the glucose CAVD was significantly reduced from 0.47 +/- 0.21 to 0.24 +/- 0.16 mM/l (p less than 0.05) at the end of the hypoglycemia period, suggesting consumption of alternate substrates of energy by the brain. Insulin-induced hypoglycemia was associated with a significant increase in arterial lactate (p less than 0.01), and a significant correlation (p less than 0.01) between arterial and CAVD for lactate and beta-hydroxybutyrate (BOB) was observed. Cerebral consumption of alternate substrates of energy was inconsistent, and only observed for lactate in 5 and for BOB in 3 experimental animals following hypoglycemia. These data indicate that the newborn lamb's cerebral cellular activity is not affected by the degree of hypoglycemia achieved in these studies.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: J
authors.initials: J
authors.lastname: Belik
authors.forename: L C
authors.initials: LC
authors.lastname: Wagerle
authors.forename: C A
authors.initials: CA
authors.lastname: Stanley
authors.forename: L M
authors.initials: LM
authors.lastname: Sacks
authors.forename: D W
authors.initials: DW
authors.lastname: Herbert
authors.forename: M
authors.initials: M
authors.lastname: Delivoria-Papadopoulos
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D012016:Reference Values; D012756:Sheep
chemical_list: D007328:Insulin; D005947:Glucose; D010100:Oxygen