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PubMed2005

The novel cytosolic RING finger protein dactylidin is up-regulated in brains of patients with Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a progressive degeneration of neurons along with deposition of amyloid plaques and the formation of neurofibrillary tangles. Neurodegeneration in AD follows both a spatial pattern of selective vulnerability and temporal staging of affected neurons. In order to address transcriptional changes associated with this selective vulnerability, we used subtractive hybridization of transcripts derived from human frontal cortex, which degenerates in late stages of AD, against transcripts of the inferior temporal cortex, which is affected both heavily and early in the course of AD. Moreover, we compared these to brain sections obtained from age-matched control subjects. We isolated a differentially expressed novel gene encoding a polypeptide that contained an amino-terminal C3HC4 RING finger domain, called dactylidin. It is ubiquitously expressed in all tissues examined and in situ hybridization of mouse brain sections revealed specific expression in neurons. Further, heterologous expression studies revealed a cytoplasmic localization of dactylidin and as all known cytoplasmic RING finger proteins function as ubiquitin protein ligases, an E3-like ligase function of dactylidin is probable. However, the up-regulation of dactylidin in highly vulnerable brain tissues of AD patients was confirmed by a quantitative PCR approach, suggesting that dactylidin may function early in the progression of neurodegenerative diseases.

Aged↗

PubMed2005

Chromatin configuration within the germinal vesicle of horse oocytes: changes post mortem and relationship to meiotic and developmental competence.

We evaluated the relationship of initial chromatin configuration to time of oocyte recovery and to nuclear maturation after culture in horse oocytes having compact (Cp) and expanded (Ex) cumuli. In addition, we evaluated the effect of oocyte type, time of recovery, and duration of culture on blastocyst development after intracytoplasmic sperm injection. In oocytes collected within 1 h of slaughter, fibrillar and intermediate chromatin configurations were more prevalent in Cp than in Ex oocytes (68% and 12%, respectively). In Cp oocytes collected after a 5- to 9-h delay, the proportions in the fibrillar and intermediate configurations decreased significantly, and the proportions of degenerating and homogeneously fluorescent configurations increased. When cultured, 20% of oocytes classified as having fibrillar chromatin resumed meiosis, whereas 82% of intermediate and 81% to 86% of condensed chromatin oocytes did so. Meiotic resumption was higher in oocytes recovered immediately after slaughter, but these oocytes took longer to mature. Duration of maturation significantly affected blastocyst development rates in Cp oocytes recovered after a delay (13% and 38% for oocytes matured 24 and 36 h, respectively). Oocytes recovered after a delay had higher blastocyst development rates than did those collected immediately after slaughter. We conclude that the fibrillar and intermediate chromatin configurations may degenerate during ovary storage, resulting in decreased maturation rates, especially of Cp oocytes. Time of oocyte recovery and duration of maturation significantly affect the rate of blastocyst development. Oocytes with Cp and Ex cumuli have similar developmental competence to the blastocyst stage.

Animals↗

PubMed2001

Immunohistochemical alterations after intravital and post-mortem traumatic myocardial damage.

Two series of experiments have been carried out on heart tissue for the occurrence of post-mortem and intravital myocardial damage. The first series was carried out on 18 porcine hearts collected immediately after the pigs were killed in a slaughterhouse. The hearts were subjected to stab wounds post-mortem, varying between 5 min and 140 min after death. The second series investigated were human hearts with intravital damage, i.e. 4 stab wounds, 1 gunshot, 13 contusions and ruptures. The time the trauma occurred before death varied between 0 and 30 min. The investigation comprised the four myocyte structural proteins myoglobin, FABP, troponin C, desmin and the three plasma proteins fibrinogen, fibronectin and C5b-9. Both series exhibited a variety of direct traumatic changes with a much broader zone in vital damage compared to post-mortem damage. In vital damage the zone of direct damage is in continuity with a further zone of indirect damage which is a three dimensional network. The signs of damage are contraction bands, depletion of structure antigens, contraction-associated accumulation of structure proteins, accumulation of plasma proteins on the cell surfaces and in the interstitium. In vital damages there is in addition an intrasarcolemmal accumulation of plasma proteins. The pattern of all damage is much broader and much more variegated in vital damage, thus vital damage can be clearly differentiated from post-mortem damage. bin, heart-type fatty acid binding protein (FABP), troponin, desmin, fibrinogen and fibronectin (Amberg 1995; Brinkmann et al. 1993; Glatz et al. 1994; Kleine et al. 1993; Leadbetter et al. 1989; Ortmann et al. 2000a, 2000b; Osuna et al. 1998; Thomsen and Held 1994, 1995). The aim of the present study was to elaborate reaction patterns of these marker proteins in mechanical heart trauma induced ante- and post-mortem and to explore their value for wound age determination in forensic casework.

Adolescent↗

PubMed2006

Expression of neurotrimin in the normal and injured adult human spinal cord.

STUDY DESIGN: Neurotrimin (Ntm) is a member of the family of neural cell adhesion molecules. Its expression pattern suggests that Ntm promotes axonal fasciculation, guides nerve fibers to specific targets and stabilizes synapses as it accumulates coincident with synaptogenesis. Strong labeling of Ntm was observed in motor and sensory areas of the postnatal rat cortex. It is not known whether Ntm is present in adult human spinal cord (SC). In the present study, a monoclonal antibody specific for Ntm (1B1), is applied to the first study of the expression of Ntm in normal and injured adult human SC. OBJECTIVE: (1) To investigate the expression pattern of Ntm in adult normal human SC, and (2) to observe the changes of Ntm expression after SC injury and compare the differences between normal and injured adult human SC. METHODS: Human SC tissue was obtained from necropsies of patients with (n=5) and without (n=4) SC injury. The 1B1 Ntm monoclonal antibody was used for immunohistochemical staining on paraffin embedded sections with an ABC kit. RESULTS: (1) In total, 12 slides were analyzed for each group from both cervical and thoracic levels. Motor neurons and Clarke's neurons and glial-like cells were mild to moderately positive in all uninjured SC specimens. (2) In injured SC, no staining was observed in the injury epicenter between two and three levels proximally and distally, but was detected five levels away. (3) In patients older than 67 years of age, Ntm-positive inclusions were present in the white matter of the SC with or without injury. (4) Some meningeal cells were strongly Ntm-positive, especially in the uninjured human SC. CONCLUSION: Ntm is expressed by motor and Clarke's neurons and glial cells in uninjured human SC. The downregulation of Ntm in the injured SC suggests that its expression is regulated by afferent input.

Age Factors↗

PubMed2005

The primate thalamus is a key target for brain dopamine.

The thalamus relays information to the cerebral cortex from subcortical centers or other cortices; in addition, it projects to the striatum and amygdala. The thalamic relay function is subject to modulation, so the flow of information to the target regions may change depending on behavioral demands. Modulation of thalamic relay by dopamine is not currently acknowledged, perhaps because dopamine innervation is reportedly scant in the rodent thalamus. We show that dopaminergic axons profusely target the human and macaque monkey thalamus using immunolabeling with three markers of the dopaminergic phenotype (tyrosine hydroxylase, dopamine, and the dopamine transporter). The dopamine innervation is especially prominent in specific association, limbic, and motor thalamic nuclei, where the densities of dopaminergic axons are as high as or higher than in the cortical area with the densest dopamine innervation. We also identified the dopaminergic neurons projecting to the macaque thalamus using retrograde tract-tracing combined with immunohistochemistry. The origin of thalamic dopamine is multiple, and thus more complex, than in any other dopaminergic system defined to date: dopaminergic neurons of the hypothalamus, periaqueductal gray matter, ventral mesencephalon, and the lateral parabrachial nucleus project bilaterally to the monkey thalamus. We propose a novel dopaminergic system that targets the primate thalamus and is independent from the previously defined nigrostriatal, mesocortical, and mesolimbic dopaminergic systems. Investigating this "thalamic dopaminergic system" should further our understanding of higher brain functions and conditions such as Parkinson's disease, schizophrenia, and drug addiction.

Aged↗

PubMed2000

Mitochondrial DNA sequences in prehistoric human remains from the Alps.

The spread of agriculture that started in the Near East about 10 000 years ago caused a dramatic change in the European archaeological record. It is still unclear if that change was caused mostly by movement of people or by cultural transformations. In particular, there is disagreement on what proportion of the current European gene pool is derived either from the pre-agricultural, paleolithic and mesolithic people, or from neolithic farmers immigrating from the south-east. To begin to characterise the mtDNA gene pool of prehistoric Europe we examined five human remains from the Eastern Italian Alps, dated between 14 000 and 3000 years ago. Three of them yielded sufficient amount of mtDNA for analysis. DNA extracts were prepared in two independent laboratories, and PCR products from the first hypervariable segment of the mtDNA control region were cloned and sequenced. Together with the 5200 year old 'ice man', these DNA sequences show that European mtDNA diversity was already high at the beginning of the neolithic period. All the neolithic sequences have been observed in contemporary Europeans, suggesting genealogical continuity between the neolithic and present-day European mtDNA gene pool. The mtDNA sequence from a 14 000 year-old specimen was not observed in any contemporary Europeans, raising the possibility of a lack of continuity between the mesolithic and present-day European gene pools.

Agriculture↗

PubMed1984

Temporal changes after death in primate diaphragm muscle oxidative enzyme activity.

We have previously reported that muscle fibers in fresh samples of the diaphragm muscle of prenatal baboons have moderate to high oxidative capacity and are resistant to fatigue in vitro. These conclusions are in conflict with those of others on diaphragmatic muscle fibers studied in autopsy specimens from human infants. Reasons for these divergent interpretations could include species difference and the use of autopsy specimens rather than fresh tissue samples. We have, therefore, tested whether characteristics of human infant diaphragm muscle fibers differ from those of premature baboons, and whether the use of autopsy specimens alters interpretations of histochemical results. Samples obtained from premature, newborn, or adult baboons were quick-frozen immediately after death or after storage for as long as 24 h. Samples were obtained at autopsy from human infants at 4 to 24 h after death. Histochemical assay for NADH-TR activity was performed on cross sections. Samples from baboons at any age showed deterioration with storage, but the muscles from premature and newborn animals were considerably more susceptible to damage than those of adults. Fibers in human infant diaphragm obtained within 10 h of death looked remarkably similar to those of the infant baboons. However, samples obtained at later times after death showed deterioration and loss of oxidative enzyme activity. We conclude that diaphragmatic muscle fibers of humans and nonhuman primates are similar in enzymatic profile, but that elapsed time after death can reduce the intensity of mitochondrial enzyme assays. The decrement in tissue preservation with elapsed time after death is less pronounced in more mature muscles.

Animals↗

PubMed2006

Concentration of nucleosides and related compounds in cerebral and cerebellar cortical areas and white matter of the human brain.

1. Nucleosides potentially participate in the neuronal functions of the brain. However, their distribution and changes in their concentrations in the human brain is not known. For better understanding of nucleoside functions, changes of nucleoside concentrations by age and a complete map of nucleoside levels in the human brain are actual requirements. 2. We used post mortem human brain samples in the experiments and applied a recently modified HPLC method for the measurement of nucleosides. To estimate concentrations and patterns of nucleosides in alive human brain we used a recently developed reverse extrapolation method and multivariate statistical analyses. 3. We analyzed four nucleosides and three nucleobases in human cerebellar, cerebral cortices and in white matter in young and old adults. Average concentrations of the 308 samples investigated (mean+/-SEM) were the following (pmol/mg wet tissue weight): adenosine 10.3+/-0.6, inosine 69.5+/-1.7, guanosine 13.5+/-0.4, uridine 52.4+/-1.2, uracil 8.4+/-0.3, hypoxanthine 108.6+/-2.0 and xanthine 54.8+/-1.3. We also demonstrated that concentrations of inosine and adenosine in the cerebral cortex and guanosine in the cerebral white matter are age-dependent. 4. Using multivariate statistical analyses and degradation coefficients, we present an uneven regional distribution of nucleosides in the human brain. The methods presented here allow to creation of a nucleoside map of the human brain by measuring the concentration of nucleosides in microdissected tissue samples. Our data support a functional role for nucleosides in the brain.

Adult↗

PubMed2000

Glial swelling with eosinophilia in human post-mortem brains: a change indicative of plasma extravasation.

Swollen, intensely eosinophilic glial cells are often observed in the vicinity of hemorrhagic lesions in post-mortem human brains. We sought to determine the nature of this change. Thirty adult human brains removed at autopsy and three surgical specimens were obtained 6h to 60 days following a hemorrhagic event. They were subjected to a battery of histochemical and immunohistochemical stains. The swollen cells, which were observed in the majority of autopsy specimens in which hemorrhage had occurred within the previous 9 days, stained intensely red with Masson stain and were immunoreactive for IgG, IgM, IgA, and fibrinogen. Some were also immunoreactive for glial fibrillary acidic protein, particularly in subpial and subependymal areas, if the lesions were more than 3 days old. In white matter some of the cells were immunoreactive for CNPase. There was no labeling with markers for macrophage/microglial cells. The absence of DNA fragment detection by TUNEL suggests that the cells were not dying. Mild glial cytoplasmic eosinophilia without swelling was observed in surgical specimens. No eosinophilic swollen glia were seen in perfusion-fixed rat brains with experimental intracerebral hemorrhage, although they were seen in rat brains that were not promptly fixed. We conclude that human macroglia, including astrocytes and oligodendrocytes, ingest plasma proteins that have been released into brain parenchyma. This likely represents a homeostatic mechanism that maintains the composition of the extracellular environment. If the tissue is not promptly fixed the cells become more swollen and eosinophilic.

Adolescent↗

PubMed2004

Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain.

Abnormal phosphorylation of tau is a feature of Alzheimer's disease (AD), which develops prematurely in Down syndrome (DS) patients. Cognitive impairment is also recognized as a clinical characteristic of schizophrenia, which does not appear to be associated with tau-aggregate formation. Several kinases can phosphorylate tau in cell-free assays. Here we show increased activity of mitogen-activated protein kinases (MAPKs) (including ERK1/2, SAPKs and p38) in post mortem AD and DS brains, which could not be accounted for by expression changes. In contrast, glycogen synthase kinase-3 activity (GSK-3 alpha beta) was reduced significantly. Examination of tau in AD and DS using antibodies selective for MAPK phosphorylation sites showed increased immunoreactivity. In addition, phosphorylation of S(199), reportedly a selective substrate for cyclin-dependent kinase-5 (cdk5) or GSK-3 alpha beta was only observed in AD samples, which showed a concomitant increase in the expression of p25, the enhancing cofactor for cdk5 activity. However, in schizophrenia brain, MAPK-phosphorylated tau was unchanged compared to matched controls, despite similar expression levels to those in AD. The activities of the MAPKs and GSK-3 alpha beta were also unchanged. These data demonstrate that in AD and DS, enhanced MAPK activity, which has an established role in regulating neuronal plasticity and survival, can account for irregular tau phosphorylation, and that the molecular processes involved in these neurodegenerative disorders are distinct from those in schizophrenia. These data also question the significance of GSK-3 alpha beta, as much previous work carried out in vitro has placed this kinase as a favoured candidate for involvement in the pathological phosphorylation of tau.

Aged↗

PubMed2006

Ezrin immunoreactivity reveals specific astrocyte activation in cerebral HIV.

The actin-binding protein ezrin is associated with cellular shape changes, motility, tumor invasion, and lymphocyte activation. We have earlier shown that ezrin immunoreactivity (IR) is faintly present in normal astrocytes but increased in malignant human astrogliomas. We studied the role of ezrin in astrocyte activation, applying immunostaining on serial paraffin sections from human autopsied brain tissues (51 cases). Cerebral HIV infection was chosen as a model displaying consistent exemplary astrocyte activation. Semiquantitative ezrin-IR was compared with the common glial markers GFAP, ferritin, and HLA-DR in relation to clinical and morphologic criteria of HIV encephalopathy. In all cases with HIV infection, GFAP-, HLA-DR-, and ferritin-IR were elevated in comparison to normal brain tissues. In contrast, high ezrin-IR in HIV infection strictly correlated with additional HIV encephalopathy. HIV encephalopathy with particularly high ezrin-IR was correlated with neuronal apoptosis (TUNEL). Combined ezrin-IR and GFAP-IR thus reveals 2 distinct states of astrocytic activation. Normal ezrin-IR, when paralleled by upregulated GFAP, reflects astroglial activation not associated with neuronal apoptosis. High ezrin-IR indicates specific astrocyte stressors related to cellular damage within the central nervous system. Ezrin-IR might also provide a diagnostic tool for the classification of HIV encephalopathy.

AIDS Dementia Complex↗

PubMed2006

Calprotectin in microglia from frontal cortex is up-regulated in schizophrenia: evidence for an inflammatory process?

Schizophrenia is associated with a number of pathological changes, including alterations in levels of specific proteins. Calprotectin is a novel 36 kDa calcium-binding protein of the S100 family and appears to be a nonspecific marker of inflammation. Calprotectin has not previously been investigated in brain tissue. Samples of post-mortem brain tissue from Brodmann area 9 were obtained from prefrontal cortex from subjects with schizophrenia, bipolar affective disorder, major depression, and from controls. Calprotectin levels were determined by ELISA. To determine cellular localization, immunocytochemical and fluorescent double-labelling analyses were performed. Exogenous calprotectin was added to retinoic acid-differentiated human SH-SY5Y neuroblastoma cell cultures in order to investigate mechanisms of action of calprotectin. Calprotectin was detectable in all samples, and mean levels were noted to be highest in schizophrenic brains (P < 0.05) and lowest in controls. Levels were intermediate in bipolar affective disorder and major depression. Exogenous calprotectin appeared to induce dendritic extension in SH-SY5Y cell culture in a dose-dependent manner. Calprotectin was found to be localized to microglia. These findings suggest that increased levels of calprotecitn in the brain may reflect inflammatory processes, which play a role in the pathogenesis of major psychiatric disorders. Furthermore, calprotectin may influence dendritic plasticity.

Analysis of Variance↗

PubMedDate not supplied

Changes in renal vascular sensitivity and arterial pressure associated with sodium intake during long-term intrarenal norepinephrine infusion in dogs.

Experiments were performed on conscious uninephrectomized dogs to determine the comparative effects of chronic intrarenal and intravenous norephrine (NE) infusion (0.27 microgram/kg/min) on the steady-state values for arterial pressure, plasma renin activity (PRA), and renal function at four levels of sodium intake (5, 40, 120 and 240 mEq/day). Arterial pressure was monitored continuously 24 hr/day with on-line computer techniques. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and plasma renin activity (PRA) were determined after sodium and water balance was achieved. During intrarenal NE infusion, ERPF and GFR decreased progressively from 15% to 30% and from 24% to 46% respectively, while renal vascular resistance increased progressively from 40% to 140% as sodium intake was increased from 10 to 240 mEq/day. Both ERPF and renal resistance, but not GFR, returned to control levels during intravenous NE infusion at each level of sodium intake and after terminating NE infusion. During intrarenal NE infusion the steady-state value for mean arterial pressure increased from a control of 105 to 118 mm Hg when the sodium intake was 10 mEq/day. Pressure then increased progressively from 118 to 135 mm Hg as the sodium intake was elevated from 10 to 240 mEq/day. Increases in arterial pressure associated with intravenous NE infusion were significantly smaller at each sodium level than those achieved with intrarenal NE infusion. At each level of sodium intake, PRA was elevated during intrarenal NE infusion and returned to control after NE infusion. Intravenous NE infusion did not increase PRA above control levels. The data are compatible with the concept that enhanced renal adrenergic activity could initiate and sustain hypertension chronically by basic alterations in renal function.

Animals↗

PubMed2004

Decrease in GTP-sensitive high affinity agonist binding of muscarinic acetylcholine receptors in autopsied brains of dementia with Lewy bodies and Alzheimer's disease.

To determine changes in signal transduction from the muscarinic acetylcholine receptor (mAChR) to G protein in brain tissue of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we investigated GTP-sensitive agonist high affinity binding, which is considered an index of the formation of the mAChR-G protein complex. Brain tissue was obtained at necropsy from eight patients with DLB, nine patients with Alzheimer's disease and seven patients as controls. Membrane fractions were prepared from frontal and temporal cerebral tissues. Displacement curves of [(3)H]l-quinuclidinyl benzilate (QNB) binding by carbamylcholine were analyzed by the nonlinear least-squares methods. The proportion of and affinity for the agonist in GTP-sensitive agonist high affinity binding were estimated. The percentages GTP-sensitive agonist high affinity bindings were significantly decreased in DLB (P<0.01) and Alzheimer's disease (P<0.05) only in the frontal lobe. There were no significant differences in the temporal lobe. The ratio of agonist affinity (Kd value of low affinity component/Kd value of high affinity component) did not significantly differ among groups in either the frontal lobe or temporal lobe. The concentration of mAChR-G protein complex is considered reduced in the frontal lobe of brains with DLB and Alzheimer's disease. Therefore, signal transduction from mAChR to G protein was disturbed in the frontal lobe in these diseases.

Aged↗

PubMed2001

Post-mortem urinary myoglobin levels with reference to the causes of death.

To evaluate pathophysiological significance of post-mortem urinary myoglobin levels in determining the cause of death, we investigated 210 forensic autopsy cases, partially in comparison with serum levels. Post-mortem serum myoglobin levels were extraordinary high in most cases possibly due to post-mortem change. Urinary myoglobin levels did not correlate with the serum levels, showing possible post-mortem elevation in cases of a prolonged post-mortem period over 48h. A high (>1000 ng/ml), moderate (100-1000 ng/ml), slight (50-100 ng/ml) and not significant (<50 ng/ml) elevation of urinary myoglobin were observed in 26, 43, 31 and 110 cases, respectively. Half the highly elevated cases were those with a survival time over 24h. In cases of minor muscle injury such as head trauma, elevation of urinary myoglobin level was closely related to longer survival. In acute/subacute deaths with a post-mortem interval within 48h, a significant difference was observed in relation to the blood carboxyhemoglobin (COHb) levels of fire victims: myoglobinuria over 100 ng/ml was more frequently and markedly observed in cases with COHb below 60% than over 60%, suggesting muscle damage in fatal burns. Similar elevation was observed in heat stroke victims, and also in some cases of acute and subacute death from polytrauma, asphyxiation, drowning, electricity and spontaneous cerebral bleeding, but not in myocardial infarction. Thus, it was suggested that high post-mortem urinary myoglobin levels in acute and subacute death cases may be a possible indicator of antemortem massive skeletal muscle damage as well as exertional muscle hyperactivity or convulsive disorders associated with hypoxia.

Adolescent↗

PubMed2004

Vitreous humour as a complementary sample to blood for the detection/confirmation of diazepam: ante-mortem and post-mortem studies in an animal model.

The quantification of medical or toxic substances in vitreous humour (VH) could be very useful in forensic toxicology when blood sample determinations are impossible due to absence or deterioration. However, few studies have been made in this area and even fewer have tried to find a relationship between drug levels in both samples. To determine a correlation ratio between blood and VH diazepam (DZ) levels, we performed an experimental study using rabbits administered with a sub-toxic dose of DZ under known and controlled conditions. Blood and VH samples were collected 0.5, 1, 2, 3 and 6 hours after the drug administration in order to determine DZ and its main active metabolite, desmethyldiazepam (DMD). In addition, we have studied an animal group sacrificed 2 hours after intramuscular (i.m.) drug administration with blood and VH collection 24 hours later, to evaluate the existence of possible post-mortem changes. After DZ administration, a fast absorption phase was observed with a plasma Cmax value 1 hour after, followed by a rapid concentration decrease, with a half-life of 1 hour, indicating that, besides elimination, a fast distribution to other organs and tissues and/or hepatic metabolism occurred. Diazepam Cmax value in VH was achieved between 1 and 2 hours, when plasma concentrations had already decreased to half the value. The plasma/VH DZ ratio calculated at this time was 10. In the post-mortem study, while plasma DZ concentration at 24 hours was smaller, DMD levels were higher than those at the time of death. In the VH, both DZ and DMD concentrations at 24 hours were higher than those obtained at the time of death. That is, in both fluids DZ and DMD concentrations were different from those at the time of death and post-mortem distribution and redistribution phenomena occurred. The combination of ante-mortem and post-mortem studies has allowed the determination of a correlation ratio for DZ in the rabbit of 6 x, comparing the concentrations in VH collected 24 hours after death with the concentrations detected in plasma at the time of death. This study opens new perspectives for the use of VH as a complementary sample to blood for DZ detection and confirmation. The putative relevance of the correlation ratio obtained, for forensic toxicology practice with medical substances, namely benzodiazepines, recommends further studies in humans.

Animals↗

PubMed2002

Evolution of the stone heart after prolonged cardiac arrest.

OBJECTIVES: We hypothesized that progressive impairment in diastolic function during cardiopulmonary resuscitation (CPR) precedes evolution of the "stone heart" after failure of CPR. We therefore measured sequential changes in left ventricular (LV) volumes and free-wall thickness of the heart during CPR in an experimental model. DESIGN: Prospective, observational animal study. SETTING: Medical research laboratory in an university-affiliated research and educational institute. SUBJECTS: Domestic pigs. METHODS: Ventricular fibrillation (VF) was induced in 40 anesthetized male domestic pigs weighing between 38 kg and 43 kg. After 4 min, 7 min, or 10 min of untreated VF, electrical defibrillation was attempted. Failing to reverse VF in each instance, precordial compression at a rate of 80/min was begun coincident with mechanical ventilation. Coronary perfusion pressures (CPPs) were computed from the differences in time-coincident diastolic aortic and right atrial pressures. Left ventricular (LV) systolic and diastolic ventricular volumes and thickness of the LV free wall were estimated with transesophageal echocardiography. The stroke volumes (SVs) were computed from the differences in decompression diastolic and compression systolic volumes. Free-wall thickness was measured on the hearts at autopsy. RESULTS: Significantly greater CPPs were generated with the 4 min of untreated cardiac arrest. Progressive reductions in LV diastolic and SV and increases in LV free-wall thickness were documented with increasing duration of untreated VF. A stone heart was confirmed at autopsy in each animal that failed resuscitative efforts. Correlations with indicator dilution method and physical measurements at autopsy corresponded closely with the echocardiographic measurements. CONCLUSION: Progressive impairment in diastolic function terminates in a stone heart after prolonged intervals of cardiac arrest.

Animals↗

PubMed1977

[The estimation of the time of death of corpses recovered from water (author's transl)].

Putrefaction, autolysis and maceration of water corpses follow a regular sequence depending on the water temperature and the interval in the water, the socalled water period. We have determined the beginning of characteristic exterior and interior changes in 395 water corpses of adult persons with known immersion intervals and water temperatures at the place of discovery at the time of recovery. The corpses had been kept in a cooling-rrom at 4 degrees C for 2 to 3 days until they were studied. Altogether 10 parameters have been considered and plotted (Fig. 1-3): intensive dyscoloration of the skin, gasformation, loosening of hair, loss of hair, putridity transsudate of more than 500 ml into the pleural cavitiesn, bloodlessness of heart, softening and liquefaction of the brain, loosening of fingernails, loss of washer-woman's skin from the hands and loss of fingernails. Several parameters are synchronous (Fig. 1,2). The studied intervals of exposure to water were from 2 to 47 days at water temperatures between 22 and 3 degrees C. - By means of the three diagrams it can be found out how many days at the minimum a corpse had been submerged, if the water temperature at the place of discovery is known and storage in a cooling-room has taken place for 2 to 3 days. Also statements are possible about the maximal period of time. - Corpses found in the Rhine will develop washer-woman's skin on hands and feet after no less than 5 hours, even at summer temperatures, and adipocere after no less than 2.5 to 3 months. There is no difference between running and stagnant water in the chronological developments of the parameters investigated. Also the degree of water pollution does not affect the estimation of the time of death.

Cadaver↗