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O Haraldseth

Publications and source records attributed to O Haraldseth.

45 records · Page 3Linked to original sources

Quicker metabolic recovery after forebrain ischemia in rats treated with the antioxidant U74006F.

We used phosphorus-31 nuclear magnetic resonance spectroscopy in a rat model of 10 minutes' severe incomplete forebrain ischemia (two-vessel occlusion with hypotension) to study the effects of preischemic and postischemic treatment with 3 mg/kg i.v. U74006F on the recovery of high-energy phosphates and intracellular pH during early reperfusion. The mean +/- SD time to 85% recovery of phosphocreatine was 14.1 +/- 8.4 minutes in the control group (n = 10) compared with 6.6 +/- 3.5 minutes (p less than 0.05) in the preischemic (n = 8) and 4.2 +/- 1.0 minutes (p less than 0.001) in the postischemic (n = 11) treatment groups. The mean +/- SD time to 80% recovery of adenosine triphosphate was 15.4 +/- 8.5 minutes in the control group compared with 6.3 +/- 1.8 (p less than 0.005) and 5.4 +/- 2.8 (p less than 0.001) minutes in the preischemic and postischemic treatment groups, respectively. There were no differences in intracellular pH between the control and either of the treatment groups. We conclude that U74006F led to quicker recovery of high-energy phosphates during early reperfusion, and this beneficial effect was also seen with postischemic treatment.

Adenosine Triphosphate↗

31 phosphorous nuclear magnetic resonance spectroscopy of rat brain with temporary global cerebral ischemia--methodology.

31 P Magnetic Resonance Spectroscopy offers a technique for measuring intracellular pH and the high energy phosphates Phosphocreatine (PCr) and ATP in vivo. The 2-vessel occlusion model of temporary global cerebral ischaemia in the rat was adopted in this technique. This approach gave reliable results for intracellular pH and valuable information about PCr and ATP with an accurate time resolution for the changes during ischaemia and early reperfusion. The method may be a useful tool to evaluate possible benefits from different kinds of pre- and post ischaemic drug intervention.

Adenosine Triphosphate↗

The NMDA antagonist MK-801 improved metabolic recovery after 10 minutes global cerebral ischaemia in rats measured with 31 phosphorous magnetic resonance spectroscopy.

The blockade of postsynaptic receptors for excitatory amino acids is a promising new field for the possible treatment of cerebral ischaemia. The most important receptor seems to be the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptors and MK-801 is a potent non-competitive antagonist to the NMDA receptor. 31P NMR Spectroscopy was used to measure the recovery of intracellular pH and the high energy phosphates Phosphocreatine (PCr) and ATP after ten minutes of temporary global cerebral ischaemia in the rat. Cerebral ischaemia was obtained by combining bilateral carotid ligation and systemic hypotension (2 vessel occlusion model). Two intervention groups with intravenous injection of MK-801 in doses of 0.25 mg/kg and 0.5 mg/kg 15 minutes before onset of ischaemia were compared to a control group. Both intervention groups showed a more rapid recovery of PCr and ATP than the control group, but there were no significant differences for intracellular pH.

Adenosine Triphosphate↗

Effect of Gd-DTPA-BMA on magnetization transfer: application to rapid imaging of cardiac ischemia.

The addition of a paramagnetic contrast agent reduces the magnetization transfer effect between the free and restricted proton pools in both agar phantoms and cardiac muscle tissue. This reduction is due to the reduction in the intrinsic T1 of the free proton pool and increases the signal observed after a given magnetization transfer sequence. Images of ex vivo piglet hearts were obtained with a segmented snapshot FLASH (fast low-angle shot) sequence with a 128 x 128 matrix, four segments, and two signals averaged, resulting in an imaging time of 7 seconds. Magnetization transfer was induced by applying a DANTE (delays alternating with nutations for tailored excitations) pulse sequence in the intersegment interval. This was an efficient method of inducing magnetization transfer because it excites the restricted proton pool across the full frequency spectrum. Ischemia due to occlusion of the left anterior descending branch of the coronary artery could be visualized after infusion of gadolinium diethylenetriaminepentaacetic acid-bis(methylamide) (DTPA-BMA). Although the ischemia could be seen with the basic sequence, the contrast between ischemic and non-ischemic tissue improved when the magnetization transfer sequence was included. The most marked improvements in magnetization transfer were achieved with low doses of Gd-DTPA-BMA.

Animals↗

Early detection of regional myocardial ischemia in ex vivo piglet hearts: MR imaging with magnetization transfer.

The effects of regional myocardial ischemia and reperfusion on magnetization transfer (MT) contrast were investigated in an ex vivo perfused piglet heart model. The extent of the ischemic area was defined with perfusion magnetic resonance (MR) studies performed with use of extracellular contrast agents. Relative MT contrast was calculated for a total of 106 regions of interest in nine hearts. In the areas defined as being severely ischemic in the perfusion studies, a small but significant increase in the MT contrast of 18% +/- 9 (standard deviation) (n = 35) was found as early as 10 minutes after the start of ischemia. This contrast difference was reduced to 11% +/- 10 after 2 hours of total occlusion. The contrast between normal and ischemic tissue can be explained in part by the effect of inflowing blood, which leads to changes in both equilibrium magnetization and the apparent T1 of the perfused tissue. However, theoretical estimation suggests that these flow-related changes would produce a maximal relative change in MT contrast of approximately 4%. The most likely explanation for the rest of the observed changes is alteration in the distribution of cellular water related to the so-called intracellular edema that is known to be associated with the acute phase of myocardial ischemia.

Algorithms↗

Comparison of dysprosium DTPA BMA and superparamagnetic iron oxide particles as susceptibility contrast agents for perfusion imaging of regional cerebral ischemia in the rat.

The aim of the study was to compare the first-passage profiles of dysprosium diethylenetriamine penta-acetic acid bis(methylamide) (DTPA BMA) and the superparamagnetic iron oxide particles NSR 0430 in regions with severe and moderate cerebral ischemia. In seven rats subjected to middle cerebral artery occlusion, two dynamic MR perfusion imaging series were acquired after intravenous bolus injections of .5 mmol/kg dysprosium DTPA BMA and .06 mmolFe/kg iron oxide particles, respectively. The doses were chosen to obtain similar maximum signal change in normally perfused brain. The first-passage profiles were compared in a region of interest (ROI) in the core area with severe ischemia and in a ROI in the penumbra area of moderate ischemia. The results were compared both as the calculated mean signal intensity versus time curves for all seven rats and statistically for an estimated mean transit time (MTT) after gamma variate fitting of the calculated concentration versus time curves. The first-passage profiles for the two contrast agents were similar, both in the core area of severe ischemia and in the penumbra area of moderate ischemia. In this rat stroke model, dysprosium DTPA BMA and the superparamagnetic iron oxide particles NSR 0430 were found to be equally efficacious for the diagnosis of the perfusion deficit, but if safe for human investigations, iron oxide particles would have an advantage as equal susceptibility effect may be achieved with smaller injection volumes.

Animals↗

MRI of cerebrum and cervical columna within two days after whiplash neck sprain injury.

The present study was undertaken to evaluate if MRI within 2 days of a motor vehicle accident could reveal pathology of importance for understanding long-term disability after whiplash neck-sprain injuries. As part of a prospective study cervical and cerebral MRI was performed on 40 neck sprain patients with whiplash injury after car accidents. The imaging was done within 2 days of the injury to make sure that any neck muscle bleeding, oedema or other soft tissue injuries could be detected. The MRI findings from the patients were both correlated to reported symptoms 6 months after the accident and compared to a control group of 20 volunteers. The MRI of both brain and neck revealed no significant differences between the patients and the control group. When the patients were grouped according to the main MRI findings at intake and compared according to the development of subjective symptoms reported by the patients, the only significant difference was more headaches at 6 months in the groups with disk pathology or spondylosis when compared to the group with no pathology. In conclusion, MRI within 2 days of the whiplash neck-sprain injury could not detect pathology connected to the injury nor predict symptom development and outcome.

Accidents, Traffic↗

(13)C MR spectroscopy study of lactate as substrate for rat brain.

In order to address the question whether lactate in blood can serve as a precursor for cerebral metabolites, fully awake rats were injected intravenously with [U-(13)C]lactate or [U-(13)C]glucose followed 15 min later by decapitation. Incorporation of label from [U-(13)C]glucose was seen mainly in glutamate, GABA, glutamine, aspartate, alanine and lactate. More label was found in glutamate than glutamine, underscoring the predominantly neuronal metabolism of pyruvate from [U-(13)C]glucose. It was estimated that the neuronal metabolism of acetyl CoA from glucose accounts for at least 66% and the glial for no more than 34% of the total glucose consumption. When [U-(13)C]lactate was the precursor, label incorporation was similar to that observed from [U-(13)C]glucose, but much reduced. Plasma analysis revealed the presence of approximately equal amounts of [1,2,3-(13)C]- and [1,2-(13)C]glucose, showing gluconeogenesis from [U-(13)C]lactate. It was thus possible that the labeling seen in the cerebral amino acids originated from labeled glucose, not [U-(13)C]lactate. However, the presence of significantly more label in [U-(13)C]- than in [2,3-(13)C]alanine demonstrated that [U-(13)C]lactate did indeed cross the blood-brain barrier, and was metabolized further in the brain. Furthermore, contributions from pyruvate carboxylase (glial enzyme) were detectable in glutamine, glutamate and GABA, and were comparatively more pronounced in the glucose group. This indicated that relatively more pyruvate from lactate than glucose was metabolized in neurons. Surprisingly, the same amount of lactate was synthesized via the tricarboxylic acid cycle in both groups, indicating transfer of neurotransmitters from the neuronal to the astrocytic compartment, as previous studies have shown that this lactate is synthesized primarily in astrocytes. Taking into consideration that astrocytes take up glutamate more avidly than GABA, it is conceivable that neuronal lactate metabolism was more prominent in glutamatergic neurons.

Acetyl Coenzyme A↗

Characterization of the microcirculation during ischemia and reperfusion in the penumbra of a rat model of temporary middle cerebral artery occlusion: a laser Doppler flowmetry study.

The dynamic changes in microcirculation were investigated with laser Doppler flowmetry in two selected regions of interest (ROI) of a stroke lesion during ischemia and early reperfusion using a rat model of temporary middle cerebral artery (MCA) occlusion. In each ROI measurements were made either during 30 min or 2 h of MCA occlusion followed by 1 h of reperfusion. On the periphery of the MCA territory, an area of mild ischemia with a mean reduction of flow to 38% (39.9% in the group with 30 min MCA occlusion and 35.9% in the group with 2 h MCA occlusion) of preischemic values was demonstrated. Closer to the center of the MCA territory, more severe ischemia with a mean reduction of flow to 21% (19.9% in the 30-min group and 22.9% in the 2-hour group) was seen. In the two groups with laser Doppler flowmetry in the ROI of mild ischemia, a compensatory increase in flow during the first 3-6 min after MCA occlusion could be seen. All rats displayed a peak hyperperfusion immediately after re-establishing of flow which then stabilized above, below, or equal to the preischemic level. This peak hyperemia was most abundant in the group in which flow was measured in the ROI of more severe ischemia after the 30-min MCA occlusion. In the same area a short hyperemic peak was followed by a significant hypoperfusion of 60% of preischemic flow after 2 h of MCA occlusion. In the groups with flow measurements in the ROI of mild ischemia, there was a return to preischemic flow after the 30-min ischemia and a tendency of preserved hyperemia after 2 h of MCA occlusion.

Animals↗