The patho- and thanatological aspects of overcooling

Pathomorphological changes in the lungs of patients dying from supercooling were studied. The material included patients who died immediately after the cessation of the etiological factors, those who underwent reanimation and those who died after long-term hospitalization.     

ECG spectral analysis in quick death, during clinical death, and in the early postresuscitation period

The article deals with the results of ECG amplitude-frequency analysis conducted in 17 experiments on dogs in the process of quick death, clinical death, and early postresuscitation period. In group 1 (8 animals) circulatory arrest occurred after ventricular fibrillation, in group 2 (9 animals) clinical death was induced by acute blood loss. The ECG was recorded in 3 orthogonal leads after Frank. The spectral analysis was conducted on a Cb-1-ts-02 spectrobiograph. The spectral form coefficient was calculated to study the relationship of the high- and low- frequency components of the spectrum. The total power of the spectrum was evaluated according to the sum value of maximum frequency peaks in 4 fixed ranges. Analysis of changes of the spectral components of the ECG signal showed them to occur in phases in the process of dying and in restoration of vital functions. The use of the method provides for a new quantitative and qualitative evaluation of the ECG.     

T lymphocytes in infectious mononucleosis. I. T cell death in vitro.

A large proportion of T lymphocytes isolated from the peripheral blood of acute infectious mononucleosis (IM) patients rapidly die when cultured in vitro, with greater than 50% dying within 12-15 h of seeding and up to 80% dying within 24 h. The cells die by apoptosis, a morphologically distinct mode of cell death that occurs in circumstances where death is a regulated event such as in embryonic development and hormone-dependent atrophy. In contrast, the level of cell death remained low in cultures of lymphocytes from controls and in the T cell depleted subpopulation from acute IM patients, with less than 2% and 10% of the lymphocytes dying by apoptosis after 36 h in culture, respectively. The rapid death of acute IM T cells in vitro does not involve soluble factors (including the serum fraction) or T cell to T cell contact. It is suggested that this observation may necessitate a re-evaluation of IM T cell function in vitro.     

Natural history of twin disruption sequence

Intrauterine death of one fetus in a monochorionic twin pregnancy is associated with high morbidity and mortality in the surviving co-twin. Thromoboplastic material from the dead twin may pass to the circulation of the living twin via placental anastomoses and cause tissue necrosis by direct embolization or by activating intravascular coagulation. Alternatively, acute blood loss into the dying twin through placental anastomoses may result in hypotension and hypoxic-ischemic damage to cerebral and visceral tissue in the surviving twin. The resulting clinical picture is referred to as twin disruption sequence. Affected twins have rarely been followed beyond the neonatal period and the long-term development of such children is unknown. Here, we present a natural history and neurological assessment of 18 patients with twin disruption sequence, whom we have followed over several months to years.     

The effect of FMRFa-like peptides on rats reanimated after clinical death

The effects of the endogenous, paraopioid FMRFa and FMRFa-like peptides are compared upon reanimation of rats after clinical death caused by acute hemorrhage. It is found that FMRFa restores cardiohemodynamics and respiratory function more effectively than RFa and RF×2HCl. The nonpeptide opioid antagonist naloxone does not alleviate the effects of acute hernorrhage. It is assumed that the reanimating effect of the studied peptides is realized via mechanisms that are not associated with opiates. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 4, pp. 417–419, April, 1996     

Structure of the respiratory cycle during extinction and restoration of vital functions

Summary Acute experiments on dogs were made to study by means of electromyography the structure of the respiratory cycle of the main and accessory respiratory muscles at various stages of extinction of the vital functions during death from blood loss and in the first 1.5–3 h of resuscitation after a 3–5 min clinical death. Dying of the animals is accompanied by disturbances in the reciprocal relations between the inspiratory and expiratory centers, as a result of which in the agonal state the expiratory and accessory respiratory muscles contract during inspiration. The mechanisms ensuring an active expiration are more sensitive to hypoxemia; during dying the expiratory muscles are excluded from the respiratory activity earlier and are restored to function later than the inspiratory muscles. Normalization of the activity of the expiratory muscles depends on the restoration of the parts of the brain stem on the border between the medulla oblongata and the pons Varoli. As evidenced by EMG data, the degree of pulmonary ventilation corresponds to the structure of the respiratory cycle much more than to its pneumographic characteristics.(Presented by Academician V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 59, No. 5, pp. 35–40, May, 1965.     

Sensory neuroprotection, mitochondrial preservation, and therapeutic potential of N-acetyl-cysteine after nerve injury

Neuronal death is a major factor in many neuropathologies, particularly traumatic, and yet no neuroprotective therapies are currently available clinically, although antioxidants and mitochondrial protection appear to be fruitful avenues of research. The simplest system involving neuronal death is that of the dorsal root ganglion after peripheral nerve trauma, where the loss of approximately 40% of primary sensory neurons is a major factor in the overwhelmingly poor clinical outcome of the several million nerve injuries that occur each year worldwide. N-acetyl-cysteine (NAC) is a glutathione substrate which is neuroprotective in a variety of in vitro models of neuronal death, and which may enhance mitochondrial protection. Using TdT uptake nick-end labelling (TUNEL), optical disection, and morphological studies, the effect of systemic NAC treatment upon L4 and 5 primary sensory neuronal death after sciatic nerve transection was investigated. NAC (150 mg/kg/day) almost totally eliminated the extensive neuronal loss found in controls both 2 weeks (no treatment 21% loss, NAC 3%, P=0.03) and 2 months after axotomy (no treatment 35% loss, NAC 3%, P=0.002). Glial cell death was reduced (mean number TUNEL positive cells 2 months after axotomy: no treatment 51/ganglion pair, NAC 16/ganglion pair), and mitochondrial architecture was preserved. The effects were less profound when a lower dose was examined (30 mg/kg/day), although significant neuroprotection still occurred. This provides evidence of the importance of mitochondrial dysregulation in axotomy-induced neuronal death in the peripheral nervous system, and suggests that NAC merits investigation in CNS trauma. NAC is already in widespread clinical use for applications outside the nervous system; it therefore has immediate clinical potential in the prevention of primary sensory neuronal death, and has therapeutic potential in other neuropathological systems.     

Renin-angiotensin system in sudden cardiac death: biochemical and morphological aspects

The renin activity of the blood plasma (RAP), renal cortex (RARC), juxtaglomerular apparatus (JGA) and renal microcirculation were studied in 330 male patients after sudden death. The activity of the renin-angiotensin system (RAS) is shown to be increased in sudden cardiac death (SCD) particularly in patients dying in the presence of alcoholic intoxication. The values of RAP and RARC and their correlation depend on the ethanol concentration in the blood. In cases of SCD with chronic alcoholic intoxication the signs of JGA hyperfunction are found (diffuse hypertrophy of the JGA structural elements). The investigation of the kidney microcirculation revealed two main phenomena of the circulation disturbance--juxtamedullary shunting and congestion. The interconnection between the degree of RAS activity and the type of the microcirculatory damage is established. The congestion was more frequently observed at the low and medium RAP values while the juxtamedullary shunting--at the high levels of the renin activity.     

Structural basis of functional heart failure during the postresuscitation period

Light and electron microscopic study of the myocardium of dogs two weeks after clinical death caused by the loss of blood was carried out and showed that the structural bases of the myocardium contractile function insufficiency during the postresuscitation period included the damage of the contractile apparatus of cardiomyocytes (microlysis and fragmentation of myofibrils, deformation of Z-bands, relaxation of sacromeres) and marked lysis of the sacrotubular system leading to the violation of the excitation-contraction coupling. Cardiomyocyte damages are associated with changes in the microcirculatory channel causing the worsening of transcapillary exchange that provides the tissue homeostasis.     

BETA-CELL APOPTOSIS IS RESPONSIBLE FOR THE DEVELOPMENT OF IDDM IN THE MULTIPLE LOW-DOSE STREPTOZOTOCIN MODEL

Although insulin-dependent diabetes mellitus (IDDM) results from irreversible loss of beta cells, the mode of cell death responsible for this loss has not previously been categorized. In this study, the multiple low-dose streptozotocin (stz) model (intraperitoneal injection of stz at a concentration of 40 mg/kg body weight per day for five consecutive days) was used to investigate beta-cell death during the development of IDDM in male C57B1/6 mice. Apoptotic cells were evident by light microscopy within the islets of Langerhans of treated animals from day 2 (the day of the second stz injection) until day 17. Immunohistochemical localization of insulin to the dying cells confirmed the beta-cell origin of the apoptosis. Two peaks in the incidence of beta-cell apoptosis occurred: the first at day 5, which corresponded to an increase in blood glucose concentration, and the second at day 11, when lymphocytic infiltration of the islets (insulitis) was maximal. Insulitis did not begin until day 9, by which time treated animals had developed overt diabetes as revealed by blood glucose and pancreatic immunoreactive insulin (IRI) measurements. Beta-cell apoptosis preceded the appearance of T-cells in the islets and continued throughout the period of insulitis. Thus, whether induced by stz or a subsequent immune response, apoptosis is the mode of cell death responsible for beta-cell loss in the multiple low-dose stz model of IDDM.     

Genetics professionals' experiences with grief and loss: implications for support and training

Geller G, Rushton CH, Francomano C, Kolodner K, Bernhardt BA. Genetics professionals' experiences with grief and loss: implications for support and training. This study was designed to determine the degree to which clinical genetics professionals are comfortable with grief and loss, whether discomfort with grief and loss is associated with clinician distress, and what factors predict comfort with grief and loss for the purpose of developing recommendations for support and training. We surveyed 300 clinical geneticists (MDs), genetic counselors (GCs) and genetic nurses randomly selected from their professional associations. Out of 225 eligible clinicians, 172 completed surveys (76% response rate). The vast majority of respondents have clinical interactions with patients and families who are experiencing grief, loss and/or death. However, nearly 20% of respondents reported that they did not feel ‘comfortable in the presence of grief and loss'. Twenty‐nine percent of respondents disagree or strongly disagree that they ‘have been adequately trained to address issues of death, dying, grief/bereavement, and end of life care’. Reported discomfort with grief and loss was strongly correlated with clinician distress. Predictors of comfort with grief and loss included perceived adequacy of training, tolerance for uncertainty, significant personal experiences of loss and deriving meaning from patient care. In conclusion, as follows. A significant minority of clinical genetics professionals experience discomfort in the presence of grief and loss, and feel inadequately prepared for such experiences. Greater attention should be paid to training clinicians in how to deal with grief and loss, and supporting them through such difficult experiences in an effort to reduce their distress.     

Postmortem blood ferritin concentrations in sudden infant death syndrome.

AIMS--To confirm the observation of extremely high concentrations of ferritin in postmortem serum samples in sudden infant death syndrome (SIDS); to examine the factors influencing blood ferritin concentrations postmortem; to determine whether or not these high blood ferritin concentrations are characteristic of SIDS. METHODS--Postmortem samples of cardiac blood were obtained from 58 full term infants who died of SIDS and 14 full-term infants who died of a variety of other causes. Whole blood and serum ferritin concentrations were determined and compared with age at death, liver iron concentration, serum iron concentration, and serum lactate dehydrogenase activity. RESULTS--The median postmortem blood ferritin concentration for all infants was 18,600 micrograms/l, which is about 200 times the concentration found in the serum of normal, live infants. Serum iron concentrations were high and there was a highly significant correlation between serum ferritin and iron concentrations suggesting that much of the serum iron was contributed by ferritin. There was no significant difference between serum and whole blood ferritin concentrations. H to L type ferritin ratios were higher in blood from the left than the right ventricle of the heart but the ferritin was always predominantly L type. Blood ferritin concentrations rose rapidly after death but in samples collected at postmortem examination there was a significant correlation with liver iron concentration and an inverse correlation with age. Median values for blood ferritin were higher in SIDS (22,500; n = 58) than in control cases (6900; n = 7) dying under one year of age; however, in both groups ferritin concentrations decreased with age. CONCLUSIONS--Release of ferritin into the blood postmortem seems to be characteristic of infants dying before the age of one year rather than characteristic of SIDS. Two factors may cause such ferritin release postmortem: tissue breakdown and the high level of storage iron in cells of the reticuloendothelial system (including endothelial cells lining vessel walls). SIDS occurs when tissue iron concentrations are higher than at any other time of life. It is possible that the ready availability of iron enhances free radical damage which might be implicated in SIDS.     

Accidentally created tension pneumothorax in patient with primary spontaneous pneumothorax--confirmation of the experimental studies, putting into question the classical explanation

BACKGROUND: The widespread explanation of patophysiology of tension pneumothorax is that compression to the mediastinum by the progressively accumulating intrapleural air causes torsion at the atrio-caval junction, impaired filling of the right heart and circulatory arrest as potentially life-threatening complication. Some experimental studies on animals put into question such an explanation, suggesting that respiratory arrest due to hypoxia of the respiratory center, not a circulatory arrest, represents dominant life threatening feature. CASE REPORT: we present a patient with spontaneous pneumothorax in whom tension pneumothorax occurred accidentally, i.e., in whom air was insufflated under great pressure from the aspirating system into the pleural cavity, immediately after insertion of a chest tube. As the situation was recognized immediately, urgent reanimation was undertaken--endotracheal intubation, ventilation through the balloon, reconnection of the chest tube to another aspirating system. Lung reexpansion was achieved and the patient was discharged after an uneventful course. In this patient, it was possible to register the sequence of events before, during and after the incident. Dominant clinical finding during resuscitation of this apnoic, cyanotic and unconscious patient was respiratory arrest in presence of evident maintenance of peripheral circulation, that supports results of experimental studies. Dominant findings in experiments with creation of tension pneumothorax was that, although pressures rose throughout the right side of the circulation, no developing pressure gradient was found on this side of the circulation; furthermore, respiratory arrest preceded cardiac arrest in these animals. Hypoxia of the respiratory center, caused by the increasing portion of pulmonary blood flow being shunted through nonventilated or hypoventilated lung, was suggested as primary cause of death of experimental animals. The same factor seems to be a cause of respiratory arrest in our patient. CONCLUSION: respiratory arrest, preceding circulatory arrest, seems to be the principal life threatening condition in patients with progressive tension pneumothorax.     

Pathogenesis of renal lesions in haemoglobinaemic and non-haemoglobinaemic leptospirosis

Hamsters were infected with Leptospira interrogans serovar ballum or Leptospira interrogans serovar pomona and the kidney lesions were compared by light and electron microscopy. Ballum and pomona both caused severe clinical signs and death within 6 days in some animals, although only ballum was associated with red blood cell destruction and haemoglobinaemic nephrosis. With ballum infections it is difficult to distinguish degenerate changes resulting from leptospiral "toxins" from those resulting from hypoxia and haemoglobinaemic nephrosis because large numbers of organisms and haemoglobinaemia coincide shortly before death. Although large numbers of leptospires were seen within the renal interstitium and blood vessels in animals dying shortly after infection, organisms were seen only in the proximal convoluted tubules of those surviving until 14 days. It is thought that leptospires are carried by the bloodstream and migrate at random throughout all body tissues. When antibody develops, only those in the renal tubules remain. The random migration results in some leptospires entering tubules at all levels of the nephron but there are good grounds for believing that the normal changes in composition of the glomerular filtrate as it passes through the nephron are increasingly deleterious to leptospiral survival. This probably explains why leptospires are found predominantly in the proximal convoluted tubules of animals after the development of specific immunity.     

An experimental study of the portal circulation in the agony period and during resuscitation from clinical death

Summary An inquiry was made into the regularities of the portal system of animals after fatal blood loss and resuscitation following clinical death. The mechanisms capable of providing blood accumulation in the portal circulation at the initial period of revivial were revealed. The following factors which could prevent normalization of the vital activity were noted: a) aggregation of erythrocytes obstructing some small blood vessels, b) possibility of fat drops penetrating into the circulation during agony, c) blood thickening in the portal circulation, inhibiting its movement along the capillary bed and oxygen exchange.(Presented by Active Member AMN SSSR A. V. Lebedinskii) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 55, No. 5, pp. 33–36, May, 1963     

The lactate level as an indicator of the severity of the condition after massive blood loss

Comparison of the clinical and experimental material suggests that the maximal increase in the blood lactate level (70–80 mg%) in the early recovery period after clinical death from blood loss does not itself indicate a possible lethal outcome. However, if a state of clinical death does not develop, the critical blood lactate level can serve as a prognostic sign. A long-lasting raised lactate level can also serve as the basis for an unfavorable prognosis.Laboratory of Experimental Physiology of Resuscitation, Academy of Medical Sciences of the USSR. Department of Resuscitation, S. P. Botkin Hospital, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Fedorov.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 80, No. 9, pp. 29–31, September, 1975.     

Structural basis of impairment of the external respiratory function in the post-resuscitation period

External enhancement of free-radical processes followed by considerable tissue accumulation of toxic lipid peroxidation products in an early postresuscitation period is the main pathochemical mechanism which causes lung air-blood barrier disturbance. The basis of animal respiratory insufficiency morphogenesis after clinical death is ventilation failure (dis- and atelectasis), circulation disorder (edema, hemorrhage) being secondary. However, morphological examination of lungs of animals after four-minutes clinical death from an acute blood loss and resuscitation showed that it is the severity of circulation disorders that determines the animals condition in the postresuscitation period.     

Effects of actovegin on the central nervous system during postischemic period

In a rat model of 5-min clinical death caused by massive blood loss actovegin prevented the development of metabolic disorders induced by hypoxia and reoxygenation as well as the damage to the central nervous system in the early postresuscitation period. Intracarotid administration of actovegin increased the activity of reduction-oxidation enzymes, intensified aerobic metabolism of glucose, prevented lactate accumulation in the brain, reduced structural disorders in the central nervous system, and provided faster restoration of the major reflexes after a 5-min total ischemia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 395–398, October, 1998     

Intracerebral injection of autologous whole blood in rats: time course of inflammation and cell death

Intracerebral hemorrhage is associated with stroke and head trauma. The purpose of this study was to study brain inflammation and cell death in adult rats 1 h to 4 weeks after injection of blood into the striatum. Terminal dUTP nick-end-labeling positive dying cells were evident 4 h to 4 weeks post-hemorrhage. Neutrophil infiltration was brief and peaked at 48 h. CD8a immunoreactive lymphocytes, possibly natural killer cells, became apparent at 48 h and persisted for 1 week. Microglial reaction was evident at 4 h and persisted for 4 weeks. We conclude that extravascular blood causes a mixed inflammatory cell reaction in brains that is maximal from 48-72 h following hemorrhage. This is associated with death of brain cells over a prolonged period of at least 4 weeks.     

"It was haunting...": physicians' descriptions of emotionally powerful patient deaths.

PURPOSE: To understand the emotional experiences of physicians who care for dying patients and to identify educational opportunities for improving patient care and physician well-being. METHOD: Between 1999-2001, physicians at two quaternary care medical centers in Boston, Massachusetts, and Pittsburgh, Pennsylvania, participated in 90-minute, semistructured personal interviews on their most emotionally powerful patient death. Quantitative data was obtained through face-to-face surveys rated on ten-point scales that asked physicians about emotional characteristics of and emotional responses to the death. In the qualitative portion of the survey, physicians were asked to describe the details of the most emotionally powerful patient death, the types and sequence of their emotional reactions, their methods of coping, and subsequent changes in behavior. RESULTS: Physicians had powerful experiences with death during all stages of their careers. Experiences with patient death generally fit into one of three types: "good," "overtreated," or "shocking/unexpected." Housestaff often described coping in isolation with the disturbing emotions generated in the care of dying patients. Physicians learned how to care for and cope with dying patients from their experiences with patients whose deaths were most emotionally powerful and reported changes in their clinical behavior and career paths as a result. CONCLUSIONS: Physicians' emotional reactions to patient death can affect patient care and the personal lives of physicians. Supervising physicians have an opportunity to improve both the care of dying patients and house-staff coping with these deaths by using the "teachable moments" that are present for trainees as they care for the dying.