Search PubMed⌕ Search

Biomedical subjects

F Plum

Publications and source records attributed to F Plum.

At least 55 records · Page 3Linked to original sources
PubMed1985

Hydrogen ion buffering during complete brain ischemia.

As a first step to quantify [H+] changes in brain during ischemia we used H+-selective microelectrodes and enzyme fluorometric techniques to describe the relationship between interstitial [H+] ([H+]o) and peak tissue lactate after cardiac arrest. We found a step function relationship between [H+]o and tissue lactate rather than the linear titration expected in a homogeneous protein solution. Within a blood glucose range from 3-7 mM, brain lactate rose from 8-13 mmol/kg along with a rise in [H+]o of 99 +/- 6 nM(0.44 +/- 0.02 pH). At higher blood glucose levels (17-80 mM), brain lactate accumulated to levels of 16-31 mmol/kg; concurrently [H+]o rose by 608 +/- 16 nM (1.07 +/- 0.02 pH). The unchanging level of [H+]o between 8-13 and 16-31 mmol/kg lactate implies that [H+]o is at a steady-state, but not equilibrium with respect to [H+] in other brain compartments. We propose that ion-transport characteristics of astroglia account for the observed relationship of [H+]o to tissue lactate during complete ischemia and suggest that brain infarction develops after plasma membranes in brain cells can no longer transport ions to regulate [H+].

Animals↗
PubMed1985

Predicting outcome from hypoxic-ischemic coma.

Outcome from coma caused by cerebral hypoxia-ischemia (eg, cardiac arrest) was compared with serial neurological findings in 210 patients. Thirteen percent of patients regained independent function at some point during the first postarrest year. Computer application of new multivariate techniques to the prospectively observed findings generated easily utilized rules that classified patients by likely outcome. At the time of initial examination, 52 patients (one fourth of the total population) had absent pupillary light reflexes, and none of these patients ever regained independent daily function. By contrast, the initial presence of pupillary light reflexes, the development of spontaneous eye movements that were roving conjugate or better, and the findings of extensor, flexor, or withdrawal responses to pain identified a smaller group of 27 patients, 11 (41%) of whom regained independence in their daily lives. By 24 hours after onset, 93 poor-outcome patients were identified by motor responses that were absent, extensor, or flexor and by spontaneous eye movements that were neither orienting nor roving conjugate; only one regained independent function. This contrasts with recovery in 19 (63%) of 30 patients who at that time showed improvement in their eye-opening responses and obeyed commands or had motor responses that were withdrawal or localizing. Similarly simple rules distinguished between good- and poor-prognosis patients on postarrest days 3, 7, and 14.

Adult↗
PubMed1983

Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus.

Animal experiments employing controlled degrees of cerebral ischemia have demonstrated that elevated blood-brain glucose concentrations greatly enhance the extent and degree of subsequent brain damage. The question of whether or not a similar relationship applies in man was examined by retrospectively segregating patients admitted with the diagnosis of ischemic stroke into diabetic (n = 35) and nondiabetic (n = 72) groups. A separate nondiabetic population with ischemic stroke was prospectively analyzed by dividing patients into those with an admission blood glucose level above (n = 14) or below (n = 17) 120 mg/dl. The neurologic status at discharge was used to stratify outcome as good, fair, or poor in the retrospective study. The ability or inability to return to work was used to separate good and poor outcomes in the prospective study. Neurologic outcome in diabetic patients with stroke was significantly worse (p less than 0.05) than in nondiabetic patients, and the diabetic patients had a greater (p less than 0.05) number of stroke-related deaths. In the prospective study, neurologic outcome also was worse with high blood sugar levels, only 43 percent of the patients with blood glucose values above 120 mg/dl returned to work, whereas 76 percent of those with lower blood sugar values regained employment (p = 0.061).

Aged↗
PubMed1983

Acute hyperammonemia in the young primate: physiologic and neuropathologic correlates.

Infusion-induced acute (less than or equal to 24 h) hyperammonemia to concentrations up to five times normal (0.19 +/- 0.03 versus 0.90 +/- 0.08 mM) was studied in eleven 6-9-month-old Macaca mulatta. The young primates developed a progressive reduction of consciousness that correlated in severity directly with the elevation of blood ammonia concentration. Hyperventilation, electroencephalographic slowing, occasional seizure activity, and, eventually, apneustic breathing also occurred. Intracranial pressure rose from 76 +/- 7 to 167 +/- 12 mmH2O. Arterial oxygen and blood pressure remained within normal limits. Neuropathologic examination showed early astrocytic changes, consisting primarily of swollen perikaryal cytoplasm and processes, and membranous whorls. The absence of neuronal pathology suggests that the acute, limited insult, as occurs in many of the childhood hyperammonemic syndromes, is fully reversible.

Acetates↗
PubMed1983

What causes infarction in ischemic brain?: The Robert Wartenberg Lecture.

Improved treatment of associated cardiovascular and hematogenous abnormalities has favorably influenced the incidence and outcome of cerebral vascular disease during the past 25 years. Strong evidence now indicates that attention to the carbohydrate content of the brain also may influence outcome from brain ischemia. With brain lactate levels above approximately 16 mmol per kilogram, ischemia produces tissue infarction; ie, the lesion includes astrocytic and endothelial necrosis as well as neuronal death. We find that equal degrees of ischemia accompanied by lower tissue lactate values produce only selective neuronal damage in predictably vulnerable areas; astrocytes and endothelia are spared and extracellular or progressive postischemic cerebral edema fails to develop. The findings suggest that astrocytes can function to defend brain tissue against the damaging effects of acute anoxia but that during such conditions, they are potentially vulnerable to high tissue lactate levels. Initial clinical evidence suggests that scrupulous attention to blood sugar may reduce the risk of human cerebral infarction after ischemia.

Animals↗
PubMed1982

Temporal profile of neuronal damage in a model of transient forebrain ischemia.

This study examined the temporal profile of ischemic neuronal damage following transient bilateral forebrain ischemia in the rat model of four-vessel occlusion. Wistar rats were subjected to transient but severe forebrain ischemia by permanently occluding the vertebral arteries and 24 hours later temporarily occluding the common carotid arteries for 10, 20, or 30 minutes. Carotid artery blood flow was restored and the rats were killed by perfusion-fixation after 3, 6, 24, and 72 hours. Rats with postischemic convulsions were discarded. Ischemic neuronal damage was graded in accordance with conventional neuropathological criteria. Ten minutes of four-vessel occlusion produced scattered ischemic cell change in the cerebral hemispheres of most rats. The time to onset of visible neuronal damage varied among brain regions and in some regions progressively worsened with time. After 30 minutes of ischemia, small to medium-sized striatal neurons were damaged early while the initiation of visible damage to hippocampal neurons in the h1 zone was delayed for 3 to 6 hours. The number of damaged neurons in neocortex (layer 3, layers 5 and 6, or both) and hippocampus (h1, h3-5, paramedian zone) increased significantly (p less than 0.01) between 24 and 72 hours. The unique delay in onset of ischemic cell change and the protracted increase in its incidence between 24 and 72 hours could reflect either delayed appearance of ischemic change in previously killed neurons or a delayed insult that continued to jeopardize compromised but otherwise viable neurons during the postischemic period.

Animals↗
PubMed1982

Edema and vascular permeability in cerebral ischemia: comparison between ischemic neuronal damage and infarction.

The respective influences of ischemic neuronal damage and infarction on the development of abnormal blood-brain barrier (BBB) permeability and cerebral edema were evaluated in a rat model of temporary four-vessel occlusion in which ischemic neuronal damage with only infrequent infarction is produced. Survival times ranged from 40 minutes to 5 days after ischemia. Evans blue and horseradish peroxidase (HRP) were given before sacrifice. The majority of brain showed moderate ischemic neuronal damage inthe striatum. In these areas there was neither leakage of Evans blue nor extravasation of HRP. Astrocytic processes were moderately swollen. Large, grossly-visible unilateral infarcts were present in only 5 animals, and all showed abnormal BBB permeability of HRP which occurred via enchanced pinocytosis, and occasionally via diffuse leakage through necrotic vessels. Astrocytic processes were markedly swollen and their plasma membranes were disrupted. Whole brain and regional water content in a parallel series of animals were measured from 15 minutes (min) to 48 hours (h) postischemia. They showed a transient, 1% increase in whole brain water content from 15 to 60 min postischemia, but no increase in regional water content at any postischemic interval. These studies suggest that ischemia produces BBB permeability to large molecules, and sustained cerebral edema only when the process damages blood vessels and astrocytes; neuronal necrosis alone is insufficient.

Animals↗
PubMed1982

Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat.

We compared the effects of glucose injection with those of saline or mannitol on ischemic brain damage and brain water content in a four-vessel occlusion (4-VO) rat model, which simultaneously causes severe forebrain ischemia and moderate hindbrain ischemia. Glucose given before onset of ischemia was followed by severe brain injury, with necrosis of the majority of neocortical neurons and glia, substantial neuronal damage throughout the remainder of forebrain, and severe brain edema. By comparison, saline injection before forebrain ischemia resulted in only scattered ischemic damage confined to neurons and no change in the brain water content. Mannitol injection before 4-VO or D-glucose injection during or after 4-VO produced no greater forebrain damage than did the saline injection. Morphologic damage in the cerebellum, however, was increased by D-glucose injection given either before or during 4-VO. The results demonstrate that hyperglycemia before severe brain ischemia or during moderate ischemia markedly augments morphologic brain damage.

Animals↗
PubMed1982

Experimental cerebral ischemia produced by extracranial vascular injury: protection with indomethacin and prostacyclin.

To determine whether the production of brain ischemia is modified by antiplatelet agents administered at the time of extracranial endothelial injury, we modified a four-vessel occlusion rat model so that an electrogenic platelet thrombus in one carotid artery produced cerebral ischemia. DC current was passed through an anode around the left carotid artery of 11 rats with preoccluded vertebral and contralateral carotid arteries. Five of six untreated rats became unresponsive because of carotid occlusion and resultant cerebral ischemia; none of five animals pretreated with indomethacin and infused with prostacyclin (PGI2) were clinically affected. Light- and electronmicroscopic studies showed arterial platelet-fibrin thrombi and ischemic brain damage in untreated rats. All rats had received radiolabeled platelets; radioactivity was increased in the electrogenically injured left carotid arteries from treated and untreated rats, but counts were reduced by more than 80% in indomethacin/PGI2-treated rats (p less than 0.01).

Animals↗
PubMed1981

Hypoxic-ischemic brain injury and the vegetative state: clinical and neuropathologic correlation.

We studied 10 patients who survived for 2 to 8 weeks in a vegetative state, including 8 with cardiopulmonary failure and 2 with subarachnoid hemorrhage. Within days of onset, they regained brainstem function and awoke, but none had evidence of cognitive awareness. All patients opened their eyes within 2 weeks, and eight had roving conjugate eye movements. Pupillary and corneal responses were intact within 1 week, and seven patients had tonic oculovestibular responses (OVR) within 24 hours. By the end of 1 day, only three patients failed to move limbs in response to noxious stimuli. At postmortem, all patients had widespread ischemic neuronal damage in the cerebral hemispheres. The brainstems lacked morphologic abnormality, except that one patient had a single microinfarct in the superior colliculus.

Adult↗
PubMed1981

Prognosis in nontraumatic coma.

We conducted serial neurologic examinations on 500 patients in nontraumatic coma to identify factors predicting recovery. Overall, 81 patients (16%) led an independent life at some point within the first year; the remainder either died without recovery from coma (61%), never improved beyond the vegetative state (12%), or regained consciousness but remained dependent on others for daily activities (11%). Functional recovery did not depend on age but was to some degree related to the cause of coma (subarachnoid hemorrhage and other cerebrovascular disease having the worst recovery; hypoxia-ischemia, intermediate; and hepatic and miscellaneous causes, best) and especially to early clinical signs of brain dysfunction. Even within hours of the onset of coma, only one of 120 patients lacking two of corneal, pupillary, and oculovestibular responses ever regained independent function. The study identifies clinical features of comatose patients that appear within the first week and that are important for predicting recovery and designing future therapeutic trials.

Adult↗