Concentrations of Energy Metabolites and Cyclic Nucleotides During and After Bilateral Ischemia in the Gerbil Cerebral Cortex

132

Summary: CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anaesthesia. This has been correlated with changes in local pH, tissue lactate, and phosphorus energy metabolites measured in the same an imals with lH and 31p nuclear magnetic resonance spec troscopy. We demonstrate a threshold flow value for the The metabolic changes that are associated with reduced CBF have been extensively studied by many workers (Siesj6, 1978). When the flow falls sufficiently, there is a decline in high-energy phos phates, an increase in inorganic phosphate (P), an increase in lactate, and a decline in pH, and the time courses of these changes in acute ischaemia have been well documented in a number of animal models. However, much remains to be learned about the precise relationship between flow, energy consumption, and metabolic state. For example, can we define a critical threshold value of flow at which the energy status of the brain tissue becomes impaired, and how does this relate to thresholds for brain function? The results of Eklof and Siesj6Received December 11,1986; accepted February 20,1987 394 metabolic changes associated with energy failure at a level similar to the values previously reported for elec trical failure and tissue water accumulation, but higher than that associated with breakdown of extracellular po tassium homeostasis.

Section: Unilateral and Bilateral Occlusionsupporting

confidence: 90%

Acute Cerebral Ischaemia: Concurrent Changes in Cerebral Blood Flow, Energy Metabolites, pH, and Lactate Measured with Hydrogen Clearance and³¹P and¹H Nuclear Magnetic Resonance Spectroscopy. II. Changes during Ischaemia

Crockard¹,

Gadian²,

Frackowiak

et al. 1987

132

“…�20% lower than those reported by Kobayashi et al (1977) and Mrsulja et al (1984). In light of the consistency of our results, this probably reflects a systematic difference in tissue sampling that would not alter the interpretation of our data.…”

Section: Resultscontrasting

confidence: 54%

Effect of Nimodipine on Cerebral Metabolism during Ischemia and Recirculation in the Mongolian Gerbil

Heffez

Passonneau

1985

Self Cite

Summary:The effect of nimodipine on cerebral metab olism during ischemia and reflow was studied in female mongolian gerbils. Animals were divided into three ex perimental groups. Group 1 received 1 mg/kg nimodipine i.p. 1 h prior to ischemia. Group 2 received an injection of the vehicle, 5% polyethylene glycol 400. Group 3 re ceived an equal volume of normal saline. Cerebral ische mia was induced by bilateral common carotid artery oc clusion for 1, 2, or 5 min. Recirculation was established for 0, 1, or 5 min. Sham-operated animals served as non ischemic controls. Gerbils were killed by microwave ir radiation. Regional levels of ATP, phosphocreatine, glu cose, glycogen, cyclic AMP, and cyclic GMP were mea sured in brain extracts using standard assay techniques.Attention has recently focused on the role of cal cium in mediating various forms of cellular injury (Schanne et aI.,

“…After 15 min of comparable ischemia in fed rats, extensive restoration of the phosphoryla tion state of the adenine nucleotide pool was noted at 5 min of recovery, with almost complete nor malization after 60 min (Blomqvist et aI., 1984). For comparable results in the gerbil and in the rabbit, see Kobayashi et al (1977) and Schutz et al (1973), respectively.…”

Section: Cortical Energy Statementioning

confidence: 86%

Lactic Acidosis and Recovery of Mitochondrial Function following Forebrain Ischemia in the Rat

Hillered

Smith

Siesjö

1985

139

Summary:The effect of different degrees of lactic aci dosis on the recovery of brain mitochondrial function, measured as respiratory activity in isolated mitochondria or cortical concentrations of labile phosphates and car bohydrate substrates, was studied during 30 min of recir culation following 15 min of near-complete forebrain isch emia in rats. During ischemia, there was a marked de crease in mitochondrial State 3 respiration in vitro and a depletion of energy stores (i,e" phosphocreatine, ATP, glucose, and glycogen) in vivo that was similar in the high-and low-lactate ischemia groups, However, lactate concentrations differed markedly (20 and 10 /-Lmol g-I, respectively). During recirculation, there was a near complete recovery of both respiratory activity in vitroIt is now well established that hyperglycemia ad versely affects revival of cell function following transient brain ischemia, probably by enhancing lactic acidosis at the tissue level (see Myers, 1979; Kalimo et aI. , 198]; Rehncrona et aI., ]98]; Siesjo, 1981; Pulsinelli et aI., 1982;Plum, 1983;Longstreth and Inui, ]984). Some results hint that there is a critical concentration of lactic acid in the IS-to 2S /-Lmol g-1 range (Siesjo, 1981; Plum, ]983; Siesjo and Wieloch, 1984). However, the existence of such a threshold value has not been proven, nor is it known by what mechanisms the lactic acidosis ex erts its harmful effects.Circumstantial evidence exists that failure of mi tochondrial function following long periods of isch emia may be due to excessive lactic acidosis. Thus, such recovery was noted following 30 min of com- 259and adenylate energy charge (EC) in vivo regardless of the differences in lactic acidosis during ischemia. Respi ratory activity and EC were well correlated, The changes in Ca2 + homeostasis during ischemia, an increase in tissue and a decrease in mitochondrial Ca2+ content, were reversed rapidly after ischemia in both high-and low lactate ischemia animals and did not hinder an early re covery of mitochondrial function. It is concluded that lactic acidosis. with lactate levels reaching 20 /-Lmol g-I during IS-min ischemia, does not adversely affect early postischemic recovery of mitochondrial function.