Search PubMed⌕ Search

Biomedical subjects

K A Hossmann

Publications and source records attributed to K A Hossmann.

At least 127 records · Page 7Linked to original sources
PubMed1994

NMR imaging of the apparent diffusion coefficient (ADC) for the evaluation of metabolic suppression and recovery after prolonged cerebral ischemia.

Adult normothermic cats were submitted to 1-h complete cerebrocirculatory arrest by intrathoracic occlusion of the internal mammary, the innominate, and the subclavian arteries in combination with pharmacologically induced hypotension. After ischemia, recirculation was initiated at different blood pressure levels to manipulate the postischemia resuscitation conditions. The resulting spectrum of postischemic recovery was studied by combining nuclear magnetic resonance imaging of the apparent diffusion coefficient (ADC) with pictorial assays of brain tissue pH, ATP, glucose, and lactate. Before ischemia, the mean ADC (average of seven coronal slices of five cats) was 713 +/- 40 x 10(-6) mm2/s. After 10-min ischemia, ADC declined to 68% of control and after 50 min slightly further to 63% of control. During recirculation after 1-h ischemia, recovery of ADC varied depending on the initial reperfusion pressure and other systemic variables. In two animals ADC only transiently increased followed by a secondary decline below the postischemic level. In three other animals ADC returned to near control within 1 h of recirculation. The comparison of ADC changes with previously reported changes in extracellular volume revealed a close relationship, supporting the notion that ADC is a function of the intra/extracellular water compartmentation. Recovery of ADC correlated closely with tissue pH and metabolic recovery, studied 3 h after the initiation of recirculation. Animals without recovery of ADC exhibited global depletion of ATP and glucose and severe lactacidosis, whereas animals with recovery of ADC showed replenishment of ATP and glucose to near control and a substantial reversal of lactacidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Glutamate-mediated injury in focal cerebral ischemia: the excitotoxin hypothesis revised.

Neuronal injury following focal cerebral ischemia is widely attributed to the excitotoxic effects of glutamate. However, critical analysis of published data on glutamate toxicity in vitro and the comparison of these data with in vivo release of glutamate and the therapeutic effect of glutamate antagonists raises doubts about a neurotoxic mechanism. An alternative explanation for glutamate-mediated injury is hypoxia due to peri-infarct spreading depression-like depolarizations. These depolarizations are triggered in the core of the ischemic infarct and spread at irregular intervals into the peri-infarct surrounding. In ischemically uncompromised tissue, the metabolic workload associated with spreading depression is coupled to an increase in blood flow and oxygen supply, assuring maintenance of oxidative respiration. In the penumbra region of focal ischemia, the hemodynamic constraints of collateral blood circulation prevail the adequate adjustment of oxygen delivery, leading to transient episodes of relative tissue hypoxia. The hypoxic episodes cause a suppression of protein synthesis, a gradual deterioration of energy metabolism and a progression of irreversibly damaged tissue into the penumbra zone. The generation of peri-infarct spreading depressions and the associated metabolic workload can be suppressed by NMDA and non-NMDA antagonists. As a result, the penumbral inhibition of protein synthesis and the progressing energy failure is also prevented, and the volume of ischemic infarct decreases. Interventions to improve ischemic resistance should therefore aim at improving the oxygen supply or reducing the metabolic workload in the penumbra region.

Animals↗
PubMed1994

Diffusion nuclear magnetic resonance imaging in experimental stroke. Correlation with cerebral metabolites.

BACKGROUND AND PURPOSE: Diffusion-weighted nuclear magnetic resonance imaging has been shown to detect early ischemia-related alterations in experimental stroke. This raises the question of whether the observed increase in signal intensity is correlated with changes in cerebral metabolism. After middle cerebral artery occlusion, nuclear magnetic resonance diffusion images were recorded and compared with the regional concentration of cerebral metabolites and with histology of identical planes. METHODS: Seven anesthetized Fischer rats were subjected to permanent occlusion of the middle cerebral artery. T1, T2, and diffusion images (b factors ranging from 0 to 1500 s/mm2) were measured in three to five planes after 7 hours. Thereafter, brains were frozen in situ for histology and quantitative bioluminescence imaging of ATP, glucose, lactate, and for fluorescence imaging of tissue pH. RESULTS: Seven hours after middle cerebral artery occlusion, the apparent diffusion coefficient was reduced from 615 +/- 97 x 10(-6).mm2.s-1 (contralateral brain) to 359 +/- 42 x 10(-6).mm2.s-1 (ischemic brain; mean +/- SD, P < .01). A precise topical coincidence was demonstrated between changes in nuclear magnetic resonance diffusion images, pattern of histological damage, ATP-depleted areas, and local tissue acidosis, the lesion area amounting to between 24.1% and 27.6% of the hemisphere at the level of the caudate-putamen. The area of elevated brain lactate clearly exceeded the acidic core of the infarct and included the slightly alkaline border zone. CONCLUSIONS: The data demonstrate that after 7-hour middle cerebral artery occlusion, the reduction of the apparent diffusion coefficient in nuclear magnetic resonance diffusion images reflects precisely the region of histological injury, breakdown of energy metabolism, and tissue acidosis.

Adenosine Triphosphate↗
PubMed1994

[Temperature effect on ischemic brain injury].

The effect of manipulating the brain temperature during cerebral ischemia was investigated in Wistar rats subjected to 30 min 4-vessel occlusion. Three brain temperature profiles were compared: 1. Spontaneous decrease in brain temperature during ischemia from 36 to 31 degrees C (spontaneous hypothermia; n = 5); 2. Constant brain temperature of 30 degrees C induced by selective head cooling (induced hypothermia; n = 5); and 3. Constant brain temperature of 36 degrees C induced by selective heating of the head (normothermia; n = 5). The core temperature was maintained constant at 37 degrees C in all groups. In the spontaneously hypothermic brains, 16% of the CA1 neurons survived after 30 min ischemia. Induced hypothermia significantly increased this percentage to 69%, but maintenance of the brain temperature at normothermia decreased neuronal survival to 1%. Normothermia of the brain also led to morphological injury outside the vulnerable regions, greater variability of the morphologic lesions, an increase in mortality, a marked loss of body weight, and prolongation of EEG suppression, as compared to in both hypothermic groups. These findings clearly demonstrate that maintaining the brain temperature at normothermia by selective heating of the head aggravates ischemic injury and, in consequence, should not be used to investigate the effectiveness of protective drugs for brain ischemia.

Animals↗
PubMed1993

MK-801, a glutamate antagonist, lowers flow threshold for inhibition of protein synthesis after middle cerebral artery occlusion of rat.

The effect of the glutamate antagonist MK-801 on the ischemic threshold of energy metabolism and protein synthesis (CPS) was studied in rats submitted to 3 h occlusion of the left middle cerebral artery (MCA). Local blood flow and CPS were measured by double tracer autoradiography, and local ATP content by bioluminescence imaging. In untreated animals breakdown of energy metabolism occurred at flow values below 15 +/- 1 and CPS inhibition below 51 +/- 15 ml/100 g/min (means +/- S.D.). MK-801 treatment (3 mg/kg immediately after MCA occlusion) did not change the ischemic flow threshold of energy failure (16 +/- 3 ml/100 g/min) but lead to a highly significant decline of the perfusion threshold for the inhibition of CPS to 19 +/- 4 ml/100 g/min (P < 0.01). Our data demonstrate that MK-801 dramatically reduces the threshold for the suppression of protein synthesis which could explain previously reported therapeutical effects on the reduction of brain infarct size.

Adenosine Triphosphate↗
PubMed1993

NMR-spectroscopic investigation of cerebral reanimation after prolonged ischemia.

The severity of brain injury following interruption of blood flow depends on a number of ischemic and post-ischemic variables. The most important ischemic variables are the duration of ischemia, the amount of residual blood flow, the type and depth of anesthesia, brain glucose content and temperature. Among the post-ischemic factors the no-reflow phenomenon, edema and a variety of biochemical disturbances are of particular importance. Due to the complex interaction of these factors irreversible brain injury usually occurs after less than 10 min cerebrocirculatory arrest in normothermia. However, the safe ischemia time of the brain can be substantially extended when appropriate therapeutic measures are used to alleviate post-ischemic injury. NMR-spectroscopy is particularly suited for the analysis of this process. Recording of 31P, 1H and 19F spectra allow the continuous non-invasive assessment of such basic parameters as brain energy state, tissue pH, the content of lactate and blood flow (using Freon-23 as an inert tracer). In addition, information is obtained about changes in the content of phosphomonoesters and -diesters, glutamate, glutamine, aspartate and N-acetyl aspartate. These measurements can be combined with in vivo electrophysiological and post-mortem biochemical investigations for the further refinement of functional/metabolic monitoring. We have used this approach to study the potentials of post-ischemic resuscitation after one hour complete ischemia of the normothermic cat brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1993

Expression of transforming growth factor-beta 1 and interleukin-1 beta mRNA in rat brain following transient forebrain ischemia.

Transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 beta mRNA expression were studied in rat brains after 30 min of global ischemia by in situ hybridization. Ischemia was produced by four-vessel occlusion followed by different recirculation times ranging between 15 min and 7 days. TGF-beta 1 mRNA could first be detected 3 days after ischemia in the hippocampus, in layers II/III of cortex, in the striatum and in parts of the ventral thalamus. At 7 days after recirculation a prominent increase in TGF-beta 1 mRNA was observed in the CA1 sector of the hippocampus. Induction of interleukin-1 beta mRNA, however, was less marked and limited to the rostral striatum 3 and 7 days after ischemia. TGF-beta 1 expression 7 days after ischemia correlated well with the histological localization of regions where neuronal degeneration and subsequent astrocytic and microglial activation had occurred. In adjacent brain sections, the distribution of TGF-beta 1 mRNA after 7 days closely resembled that of the immunostaining pattern of activated microglia, indicating that at this time point TGF-beta 1 mRNA was mainly produced by microglial cells. The late induction of TGF-beta 1 mRNA after ischemia points to an involvement in the persistent glial response rather than the initial glial activation. The differential pattern of interleukin-1 beta mRNA induction indicates regional variations of cytokine production after ischemic brain lesions.

Animals↗
PubMed1993

Heating of the brain to maintain normothermia during ischemia aggravates brain injury in the rat.

During brain ischemia temperature spontaneously declines. In animal experiments this decline is frequently prevented by stabilizing the temperature at the pre-ischemic level, using an external heat source. The present study examines whether this procedure influences the severity of ischemic injury. Wistar rats were submitted to 30-min four-vessel occlusion followed by 7 days recirculation. During ischemia and the 1st h of recirculation various systemic and electrophysiological variables were recorded. Seven days after the ischemia brains were perfusion-fixed for light microscopical examination. Three brain temperature profiles were compared: spontaneous decline of brain temperature during ischemia from 36 degrees to 31 degrees C (spontaneous hypothermia; n = 5); constant brain temperature of 30 degrees C induced by selective head cooling (induced hypothermia; n = 5); and constant brain temperature of 36 degrees C induced by selective head heating (normothermia; n = 5). Core temperature was maintained constant at 37 degrees C in all groups. In spontaneous hypothermia, 19% of CA1 neurons survived after 30-min ischemia. Induced hypothermia significantly increased this percentage to 69% (P < 0.05); maintenance of brain temperature at normothermia decreased neuronal survival to 1%. Normothermia also led to morphological injury outside the vulnerable regions, an increase in mortality, marked loss of body weight and a prolongation of the electroencephalographic suppression. These findings demonstrate that stabilizing brain temperature at a constant normothermic level by an external heart source introduces an aggravating pathological element that may interfere in an unpredictable way with the manifestation or treatment of ischemic injury.

Animals↗
PubMed1993

Temperature effect on immunostaining of microtubule-associated protein 2 and synaptophysin after 30 minutes of forebrain ischemia in rat.

The regional distribution of the postsynaptic microtubule-associated protein 2 (MAP2) and the presynaptic marker protein synaptophysin was investigated by immunohistochemistry in brains of rats submitted to 30-min forebrain ischemia by four-vessel occlusion. The following brain temperature profiles during ischemia were compared: (1) constant brain temperature of 36 degrees C (normothermia; n = 5); (2) spontaneous temperature decline from 36 degrees to 31 degrees C (spontaneous hypothermia; n = 5) and (3) constant temperature of 30 degrees C (induced hypothermia; n = 5). Normothermia was produced by exposing the ischemic head to an external heat source, and induced hypothermia by cooling the head with liquid nitrogen vapours. Sham-operated animals were either kept at ambient temperature or exposed to the same heat source, as required for maintaining normothermia during ischemia. Seven days after sham operation or ischemia, brains were fixed by perfusion and processed for immunohistochemistry using monoclonal antibodies against MAP2 and synaptic vesicle-specific protein (synaptophysin). Normothermic ischemia resulted in complete loss of MAP2 immunostaining in the whole hippocampus, spontaneous hypothermic ischemia in complete loss of MAP2 in CA1 sector, and induced hypothermic ischemia only in variable loss of MAP2 in CA1 sector. Post-ischemic immunostaining of synaptophysin revealed a temperature-dependent increase in stratum lacunosum-moleculare of CA1 sector, the density of which correlated inversely with MAP2 staining. Comparison with morphological alterations showed a close relationship between loss of MAP2 staining and histological injury. The post-ischemic activation of synaptophysin may reflect regenerative processes associated with synaptic remodelling and, therefore, is an indirect marker of the severity of ischemic injury.

Animals↗
PubMed1993

The effect of global ischemia and recirculation of rat brain on protein synthesis in vitro.

Transient cerebral ischemia causes long-lasting inhibition of protein synthesis despite recovery of energy metabolism. We investigated the question if this inhibition is due to the formation of a suppression factor which interferes with the function of the protein synthesizing machinery. For this purpose rats were submitted to 20 minutes four vessel-occlusion followed by recirculation times from 30 minutes to 7 days. Post-mitochondrial supernatant (PMS) from various brain regions was added to a self-contained, cell-free rabbit reticulocyte translational system, and the effect on in vitro protein synthesis was assessed by measuring 14C-leucine incorporation over a duration of 45 minutes. PMS prepared at the end of ischemia from hippocampus, striatum and cerebellum inhibited in vitro protein synthesis by 40%-60% but there was only a minor inhibition by PMS from cerebral cortex. During post-ischemic recirculation cortical PMS transiently induced inhibition of in vitro protein synthesis by 30% but this effect gradually disappeared within one week. The inhibition caused by PMS from hippocampus, striatum and cerebellum was not reversed during recirculation and still amounted to about 40% after 7 days. Inhibition of in vitro protein synthesis could be blocked by heating PMS to 100 degrees C, indicating that the suppressor factor is a protein. The comparison of the in vitro effect of postischemic PMS with previously described in vivo inhibition of protein synthesis demonstrates that the here observed suppressor factor is not able to explain the overall disturbance of protein synthesis in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Brain resuscitation by extracorporeal circulation after prolonged cardiac arrest in cats.

OBJECTIVE: Brain reanimation after prolonged ischemia is limited by post-ischemic reperfusion deficits (no-reflow phenomenon). The present study was undertaken to establish whether after 30 min cardiac arrest extracorporeal circulation is able to restore brain reperfusion and to promote functional and metabolic recovery. DESIGN: Adult normothermic cats were submitted to 30 min cardiac arrest by KCl-induced cardioplegia. Resuscitation was carried out by extracorporeal circulation (ECC) until spontaneous heart function returned. The quality of brain recovery was assessed 3 h later by electrophysiological recording and by imaging of the regional distribution of brain energy metabolites. RESULTS: In 6 of 10 cats cardiac sinus rhythm returned after 32 +/- 15 min. In the other 4 cats cardiac function did not return or only intermittently returned during the 3 h observation period. Cerebral blood flow measured by laser Doppler flowmetry returned to 102% +/- 40% of control immediately after the beginning of resuscitation but then gradually declined to 43% +/- 32% after 3 h despite normotensive perfusion. In all cats pupils started to constrict within less than 5 min of recirculation but in 2 animals they secondarily dilated 1.5 and 2 h later, respectively. Spontaneous EEG activity reappeared in 4 of the 6 successfully resuscitated cats after 111 +/- 40 min but failed to recover in the others. Bioluminescent imaging of ATP after 3 h recirculation revealed near-complete depletion throughout the brain in all 4 cats without cardiac recovery. Of the 6 successfully resuscitated cats 5 exhibited patchy areas of low ATP, glucose and pH in 22%-92% of the cross sectional area of brain; in one cat recovery of energy metabolism and acid-base homoeostasis was homogeneous without any focal deficits. The cross sectional area of ATP recovery correlated directly with CBF and hematocrit and inversely with the plasma lactate level. CONCLUSIONS: This study demonstrates for the first time that ECC is able to restore electrophysiological and metabolic brain function after cardiac arrest of as long as 30 min, but recovery is heavily restricted by delayed post-ischemic disturbances of recirculation. Progress in cardiac resuscitation by ECC requires substantial improvement in the efficiency of cerebrovascular reperfusion.

Acid-Base Equilibrium↗
PubMed1993

Relationship between blood flow and blood-brain barrier permeability of sodium and albumin in focal ischaemia of rats: a triple tracer autoradiographic study.

Local cerebral blood flow, the permeability of the blood-brain barrier to sodium and serum albumin, and the content of electrolytes were investigated in rats before and at 4 h and 24 h following permanent occlusion of the middle cerebral artery (MCA). Measurements were carried out by triple tracer autoradiography, using 131I-iodoantipyrin, 22NaCl and 125I-iodinated bovine serum albumin, respectively. Regional sodium and albumin transfer coefficients were calculated by multiple time point analysis, and correlated with the corresponding flow and tissue electrolyte values. In sham operated controls regional sodium and albumin transfer coefficients ranged between 2.16-2.30 x 10(-3) and 0.22-0.48 x 10(-3) ml/min per g, respectively. Four hours after MCA occlusion sodium and albumin transfer coefficients were unchanged although tissue sodium content was already increased. After 24 h the sodium-but not albumin-transfer coefficient increased 2-3 fold but the rise in tissue sodium content was slower than after 4 h. At both ischaemia times the unidirectional sodium influx was substantially higher than the actual changes of tissue sodium content. The development of stroke oedema is, therefore, not limited by the alterations of barrier permeability.

Animals↗
PubMed1993

Sulfated glycoprotein-2 mRNA in the rat brain following transient forebrain ischemia.

Expression of sulfated glycoprotein-2 (SGP-2) mRNA was studied by in situ hybridization in rat brains submitted to transient forebrain ischemia of 30 min. Induction of this multifunctional protein has been previously observed following diverse types of brain lesions, and an involvement in programmed cell death and synaptic remodelling has been proposed. Ischemia was produced by four-vessel occlusion and followed by various recirculation times ranging from 15 min to 7 days. Up to 6 h after ischemia SGP-2 mRNA did not change in any brain region. After 12 h recirculation, SGP-2 mRNA induction was observed in the stratum lacunosum moleculare of CA1 sector of hippocampus. This induction peaked at 3 days recirculation and then declined. From 24 h recirculation onward, induction also occurred in patchy areas of the cortex, and after 7 days recirculation in the ventral thalamus and in a corona around lesioned parts of the striatum. No induction occurred at any recirculation time in pyramidal neurons of hippocampus or other neuronal populations that are damaged by ischemia. The combination of in situ hybridization with GFAP immunohistochemistry revealed that SGP-2 mRNA was mainly induced in reactive actrocytes. This excludes a direct involvement in ischemic neuronal death and supports the possible participation in the post-lesional reorganization of the tissue.

Animals↗
PubMed1993

Ischemia-mediated neuronal injury.

Resuscitation of the brain after a period of global ischemia is limited by two classes of post-ischemic pathologies: hemodynamic disturbances which prevent the adequate re-oxygenation of the ischemic brain, and metabolic disturbances which may lead to delayed neuronal death in so-called selectively vulnerable brain regions. The hemodynamic disturbances can be classified into the no-reflow phenomenon and the post-ischemic hypoperfusion syndrome. The no-reflow phenomenon results from a combination of increased blood viscosity and perivascular edema; the severity increases with the duration of ischemia, and the treatment is by combining arterial hypertension with dehydration and anticoagulation. The post-ischemic hypoperfusion syndrome is independent of the duration of ischemia, it develops after a delay and is due to an impairment of the metabolic/hemodynamic coupling mechanisms; there is no specific treatment at the present. The most important metabolic disturbance leading to delayed neuronal death is prolonged inhibition of protein synthesis. The injury is manifested already after 5 min ischemia but it progresses little if ischemia is prolonged to 1 h. Inhibition occurs at the translation level due to selective inhibition of polypeptide chain initiation. After brief periods of ischemia, the disturbance can be reversed by various anesthetics and hypothermia but there is no treatment if ischemia is prolonged. Exitotoxity, free radical-mediated reactions, disturbances of polyamine metabolism, acidosis and selective disturbances of gene expression may also be involved but are probably of lesser importance.

Animals↗
PubMed1993

NMR-contrast enhancement of experimental brain tumors with MnTPPS: qualitative evaluation by in vivo relaxometry.

The applicability of the synthetic manganese porphyrin MnTPPS as tumor-selective MRI-contrast agent for brain tumors was investigated quantitatively by in vivo relaxometry. To exclude toxic effects of side products, the purification method for MnTPPS was improved. As a result, MnTPPS+Cl- (free acid) with a purity of more than 99.8% was obtained. For the in vivo quantification of the contrast effect the magnetization M(0) and the transversal relaxation time T2 were evaluated in different regions of rat brains with or without implanted gliomas and in temporal muscle. Measurements were performed before and after the application of MnTPPS. The ratio of the magnetization M(0) (TR = 3.5 sec) of the tissue under investigation and the contralateral striatum was defined as contrast ratio Rc(0). Without MnTPPS Rc(0) of edema (0.93 +/- 0.08) and tumor (0.91 +/- 0.07) did not differ from normal brain tissue (corpus callosum: 0.96 +/- 0.07; cortex: 0.98 +/- 0.05). T2 of edema (110 +/- 12 msec) and intracranial tumor (93 +/- 7 msec) were significantly longer than in normal tissue (corpus callosum: 73 +/- 8 msec; parietal cortex: 75 +/- 6 msec; striate nucleus: 78 +/- 7 msec, p < .01). Two hours after the injection of MnTPPS, magnetization of neoplastic tissue was selectively enhanced (TR = 3.5 sec), and T2 was reduced. The smallest dose of 0.06 mmol/kg body weight (bw) increased Rc(0) to 1.12 +/- 0.04, and 0.38 mmol/kg to 1.30 +/- 0.13 (p < .01). T2 of tumor decreased to 85 +/- 6 msec after 0.06 mmol/kg and to 65 +/- 6 msec after 0.38 mmol/kg bw.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗