Neurological outcome and modifiable events after out-of-hospital cardiac arrest in patients managed in a tertiary cardiac centre: A ten years register / Desenlaces neurológicos y acontecimientos modificables tras parada cardíaca extrahospitalaria en pacientes tratados en un centro de atención cardíaca terciaria: registro de 10 años

OBJECTIVE: A study was made of the events occurring in the early post-resuscitation phase that may help to improve the outcomes at hospital discharge. DESIGN: A retrospective cohort study (2007-2017) of a prospective Utstein type registry database was carried using multivariate logistic regression analysis. Pre- and post-hospital admission events were investigated. SETTING: A tertiary cardiac centre. PARTICIPANTS: Unconscious victims of out-of-hospital cardiac arrest (OHCA) with documented ventricular tachycardia or fibrillation. MAIN VARIABLES OF INTEREST: Events occurring before and within 72h after intensive care unit (ICU) admission were recorded. The variables were analyzed to determine their impact on hospital survival and poor neurological outcome. One-year follow-up survival was also considered. Results are presented as odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: Of 245 patients admitted to our ICU after OHCA, 152 (62%) were alive and 131 (86.2%) presented good neurological outcomes (cerebral performance categories≤2) at hospital discharge. The one-year follow-up survival rate was 95.9%. Age >70 years (OR 2.0; 95%CI 1.1-4.1), previous myocardial infarction (OR 2.7; 95%CI 1.2-6.1), shock upon hospital admission (OR 2.9; 95%CI 1.3-6.2), time from call to return of spontaneous circulation (ROSC) >25min (OR 3.1; 95%CI 1.6-6.0) and anticonvulsant therapy (OR 18.2; 95%CI 5.5-60) were independent predictors of poor neurological outcome. Immediate admission to the cardiac centre (OR 0.5; 95%CI 0.3-0.9) and lactate clearance reaching plasma levels <2.5mmol/l at 12h (OR 0.4; 95%CI 0.2-0.8) were associated with better outcomes. CONCLUSIONS: Unconscious OHCA patients with documented ventricular tachycardia or fibrillation may benefit from direct admission to a reference cardiac centre. Initial haemodynamic support, urgent coronary angiography and targeted management in the cardiac ICU seem to increase the likelihood of good neurological outcomes

OBJETIVO: Llevar a cabo un estudio de los acontecimientos ocurridos en la fase inmediatamente posterior a la reanimación que puedan ayudar a mejorar los desenlaces en el momento del alta hospitalaria. DISEÑO: Se realizó un estudio retrospectivo (2007-2017) de cohorte de una base de datos de registro de tipo Utstein prospectivo mediante un análisis de regresión logística multivariable. Se investigaron los acontecimientos previos y posteriores al ingreso hospitalario. Ámbito: Un centro de atención cardíaca terciaria. PARTICIPANTES: Víctimas inconscientes de parada cardíaca extrahospitalaria (OHCA) con fibrilación o taquicardia ventricular documentada. VARIABLES PRINCIPALES DE INTERÉS: Se registraron los acontecimientos ocurridos antes y durante las 72h posteriores al ingreso en la unidad de cuidados intensivos (UCI). Se analizaron las variables para determinar su impacto en la supervivencia hospitalaria y los malos desenlaces neurológicos. También se tuvo en consideración la supervivencia en el seguimiento a lo largo de un año. Los resultados se presentan con valores de oportunidad relativa (OR) e intervalo de confianza del 95% (IC del 95%). RESULTADOS: De los 245 pacientes ingresados en nuestra UCI tras una OHCA, 152 (62%) seguían vivos y 131 (86,2%) presentaban unos buenos desenlaces neurológicos (categorías de rendimiento cerebral≤2) en el momento del alta hospitalaria. La tasa de supervivencia en el seguimiento a lo largo de un año fue del 95,9%. La edad>70 años (OR: 2,0; IC del 95%: 1,1-4,1), los antecedentes de infarto de miocardio (OR: 2,7; IC del 95%: 1,2-6,1), el choque en el momento del ingreso hospitalario (OR: 2,9; IC del 95%: 1,3-6,2), el tiempo transcurrido entre la llamada y el regreso a la circulación espontánea (ROSC)>25min (OR: 3,1; IC del 95%: 1,6-6,0) y la administración de tratamiento anticonvulsivo (OR: 18,2; IC del 95%: 5,5-60) fueron factores predictivos independientes de un mal desenlace neurológico. El ingreso inmediato en un centro de cuidados cardíacos (OR: 0,5; IC del 95%: 0,3-0,9) y el hecho de que el aclaramiento de lactato alcanzase unos niveles plasmáticos<2,5mmol/l al cabo de 12h (OR: 0,4; IC del 95%: 0,2-0,8) se asociaron con unos mejores desenlaces. CONCLUSIONES: Los pacientes inconscientes tras OHCA y con fibrilación o taquicardia ventricular documentada podrían beneficiarse del ingreso directo en un centro cardíaco de referencia. El apoyo hemodinámico inicial, la angiografía coronaria urgente y el tratamiento dirigido en la UCI cardíaca parecen aumentar la probabilidad de obtener unos buenos desenlaces neurológicos

Neurological outcome and modifiable events after out-of-hospital cardiac arrest in patients managed in a tertiary cardiac centre: A ten years register.

OBJECTIVE: A study was made of the events occurring in the early post-resuscitation phase that may help to improve the outcomes at hospital discharge. DESIGN: A retrospective cohort study (2007-2017) of a prospective Utstein type registry database was carried using multivariate logistic regression analysis. Pre- and post-hospital admission events were investigated. SETTING: A tertiary cardiac centre. PARTICIPANTS: Unconscious victims of out-of-hospital cardiac arrest (OHCA) with documented ventricular tachycardia or fibrillation. MAIN VARIABLES OF INTEREST: Events occurring before and within 72h after intensive care unit (ICU) admission were recorded. The variables were analyzed to determine their impact on hospital survival and poor neurological outcome. One-year follow-up survival was also considered. Results are presented as odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: Of 245 patients admitted to our ICU after OHCA, 152 (62%) were alive and 131 (86.2%) presented good neurological outcomes (cerebral performance categories≤2) at hospital discharge. The one-year follow-up survival rate was 95.9%. Age >70 years (OR 2.0; 95%CI 1.1-4.1), previous myocardial infarction (OR 2.7; 95%CI 1.2-6.1), shock upon hospital admission (OR 2.9; 95%CI 1.3-6.2), time from call to return of spontaneous circulation (ROSC) >25min (OR 3.1; 95%CI 1.6-6.0) and anticonvulsant therapy (OR 18.2; 95%CI 5.5-60) were independent predictors of poor neurological outcome. Immediate admission to the cardiac centre (OR 0.5; 95%CI 0.3-0.9) and lactate clearance reaching plasma levels <2.5mmol/l at 12h (OR 0.4; 95%CI 0.2-0.8) were associated with better outcomes. CONCLUSIONS: Unconscious OHCA patients with documented ventricular tachycardia or fibrillation may benefit from direct admission to a reference cardiac centre. Initial haemodynamic support, urgent coronary angiography and targeted management in the cardiac ICU seem to increase the likelihood of good neurological outcomes.

Multiregion whole-exome sequencing of matched primary and metastatic tumors revealed genomic heterogeneity and suggested polyclonal seeding in colorectal cancer metastasis.

BACKGROUND: Distant metastasis accounts for 90% of deaths from colorectal cancer (CRC). Genomic heterogeneity has been reported in various solid malignancies, but remains largely under-explored in metastatic CRC tumors, especially in primary to metastatic tumor evolution. PATIENTS AND METHODS: We conducted high-depth whole-exome sequencing in multiple regions of matched primary and metastatic CRC tumors. Using a total of 28 tumor, normal, and lymph node tissues, we analyzed inter- and intra-individual heterogeneity, inferred the tumor subclonal architectures, and depicted the subclonal evolutionary routes from primary to metastatic tumors. RESULTS: CRC has significant inter-individual but relatively limited intra-individual heterogeneity. Genomic landscapes were more similar within primary, metastatic, or lymph node tumors than across these types. Metastatic tumors exhibited less intratumor heterogeneity than primary tumors, indicating that single-region sequencing may be adequate to identify important metastasis mutations to guide treatment. Remarkably, all metastatic tumors inherited multiple genetically distinct subclones from primary tumors, supporting a possible polyclonal seeding mechanism for metastasis. Analysis of one patient with the trio samples of primary, metastatic, and lymph node tumors supported a mechanism of synchronous parallel dissemination from the primary to metastatic tumors that was not mediated through lymph nodes. CONCLUSIONS: In CRC, metastatic tumors have different but less heterogeneous genomic landscapes than primary tumors. It is possible that CRC metastasis is, at least partly, mediated through a polyclonal seeding mechanism. These findings demonstrated the rationale and feasibility for identifying and targeting primary tumor-derived metastasis-potent subclones for the prediction, prevention, and treatment of CRC metastasis.

Assessment of 126,913 inguinal hernia repairs in the Emilia-Romagna region of Italy: analysis of 10 years.

PURPOSE: Inguinal hernioplasty could be used as an indicator of the surgical quality offered in different health institutions and countries, thereby establishing a scientific basis from which the procedure can be critically assessed and ultimately improved. Quality assessment of hernioplasties could be conducted using two different methods: either analyzing dedicated regional/national databases (DD) or reviewing administrative databases (AD). METHODS: A retrospective study of inguinal hernioplasties was carried out in the Emilia-Romagna hospitals between 2000 and 2009. Data were obtained by analyzing Hospital Discharge records regional Databases (HDD). Descriptive and multivariate statistical analysis was performed. RESULTS: 126,913 inguinal hernioplasty procedures were performed. The annual rate was on average 34 per 10,000 inhabitants. An increase of the case mix complexity and relevant changes in procedure technique were recorded. From multivariate analysis, the following independent factors related to a hospitalization longer than 1 day emerged: procedures in urgent setting (OR 3.6, CI 3.4-3.7), Charlson's score ≥2 (OR 3.4, CI 3.1-3.7), laparoscopy (OR 2.1, CI 1.9-2.3), no mesh use (OR 2.1, CI 2-2.3), age >65 years (OR 1.9, CI 1.8-1.9), associated interventions (OR 1.9, CI 1.8-1.9), bilateral hernia (OR 1.7, CI 1.6-1.8), recurrent hernia (OR 1.2, CI 1.1-1.2) and female gender (OR 1.2, CI 1.2-1.3). Factors related to non-prosthetic hernioplasty were: bilateral hernia (OR 2.7, CI 2.5-2.9), female gender (OR 1.8, CI 1.8-2.0), emergency setting (OR 1.6, CI 1.5-1.8), recurrences (OR 1.5, CI 1.4-1.6) and associated interventions (OR 1.5, CI 1.4-1.6). CONCLUSION: Inguinal hernia should be treated as an outpatient procedure in the majority of patients. Precise guidelines are necessary. HDD demonstrated to be a good and trustworthy system to collect clinical data. When precise guidelines are lacking, legal/institutional indications play a pivotal role in shifting the hernia surgery toward a one-day surgery regimen.

Treatment of human cartilage defects by means of Nd:YAG Laser Therapy.

Articular cartilage lesions represent a challenging problem for orthopaedic surgeons. The purpose of this study was to evaluate the effect of a new pulsed Nd:YAG High Intensity Laser Therapy on the regeneration of cartilage tissue in patients with traumatic lesions. Clinical, histological and immunohistochemical evaluations were performed. Ten patients affected by chondral lesions scheduled for ACI procedure, were enrolled into the study. During the chondrocyte expansion for ACI procedure, cartilage from five patients was treated by Nd:YAG High Intensity Laser Therapy (HILT group). No laser treatment was performed in the remaining patients, who were used as controls. Cartilage repair was assessed by clinicians using two different scores: Cartilage Repair Assessment (CRA) and Overall Repair Assessment (ORA). Cartilage biopsy specimens were harvested to perform histological and immunohistochemical analyses at T0 (before laser treatment) and T1 (at the end of the treatment). A significant decrease in cartilage depth was noticed in the HILT group at T1. Histological and immunohistochemical evaluations showed some regenerative processes in cartilaginous tissue in terms of high amount of proteoglycans, integration with adjacent articular cartilage and good cellular arrangement in the HILT group. By contrast, a not well organized cartilaginous tissue with various fibrous features in the control group at T0 and T1 was observed. In conclusion, the use of this new pulsed Nd:YAG HILT resulted promising in the treatment of moderate cartilage lesions markedly in the young patients.

Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery.

BACKGROUND: : This study evaluated the incidence of postoperative delirium (POD) in elderly patients undergoing general surgery, the risk factors associated with POD, and its impact on hospital stay and mortality. METHODS: : Patients aged over 65 years who had emergency or elective operations were eligible for this case-control study. Risk factors significantly associated with POD using univariable analysis were entered into multivariable analysis, to establish those independently associated with POD. RESULTS: : A total of 351 patients (357 admissions) were enrolled in the study. The incidence of POD was 13.2 per cent (17.9 per cent for emergency operations). Independent variables associated with POD were: age above 75 years, co-morbidity, preoperative cognitive impairment, psychopathological symptoms and abnormal glycaemic control. Median length of hospital stay was 21 (range 1-75) days for patients with POD versus 8 (range 1-79) days for control patients (P < 0.001). The hospital mortality rate was 19 and 8.4 per cent respectively (P = 0.021). CONCLUSION: : The incidence of POD is high in elderly patients for both emergency and elective surgery, leading to an increase in hospital stay and perioperative mortality. To minimize POD, associated risk factors of co-morbidity, cognitive impairment, psychopathology and abnormal glycaemic control must be identified and treated.

Centrally administered PD 140.548 N-methyl-D-glucamine prevents the autonomic responses to duodenal pain in sheep.

Cholecystokinin (CCK) released in the CNS inhibits the analgesic action of exogenous opioids and may antagonize analgesia resulting from the activation of an endogenous pain inhibitory system. The aim of this study was to analyse the central action of PD 140.548 N-methyl-D-glucamine--a peptide antagonist of a specific peripheral type CCK receptor--on animal behaviour, catecholamines (CA) and cortisol concentration, as well as clinical symptoms of visceral pain induced by duodenal distension (DD). A 5 min distension of the duodenum wall, using a 10 cm long balloon filled with 40 and/or 80 ml of water (DD 40 and/or DD 80) at animal body temperature, produced a significant increase in plasma CA and cortisol levels, an increase in the heart rate, hyperventilation and other clinical symptoms (inhibition of rumen motility, bleating, teeth grinding, prostration, urination, defecation) that may be related to pain, proportionally to the degree of intestinal distension. Intracerebroventricular administration of PD 140.548 at the dose of 1 or/and 2 mg in toto 10 min before applying DD 40 completely blocked the increase in blood plasma cortisol, epinephrine (E), norepinephrine (NE) and dopamine (DA) concentration. It is suggested that the central inhibitory action of CCK antagonist on the cortisol and catecholamine release produced by visceral pain is due to the inhibition of peripheral CCK1 type receptors in the central centrifugal descending pain facilitatory system in sheep perhaps via the hypothalamic-pituitary-adrenal axis.

Enhanced non-esterified fatty acids and corticosterone in blood plasma of chickens treated with insulin are significantly depleted by reverse T: minor changes in hypoglycaemia.

Previously, it has been observed that dexamethasone or adrenaline-induced hyperlipaemia in blood of chicken was significantly reduced after administration of reverse triiodothyronine (rT3). The present experiment was performed on chicken to determine the altered circulating non-esterified fatty acids (NEFA) induced by physiologically enhanced endogenous corticosterone and catecholamines may also be influenced by rT3. Rise of both hormones were induced by insulin administration. Changes in circulating glucose, corticosterone and catecholamines were additionally measured. Following insulin injection blood glucose fell on the average by 32.7% below control at 2 h of the experiment. Additional treatment with rT3 (rT3 + insulin group) gradually attenuated this decrease and at 4 and 6 h of the experiment it was 17.1% and 12.9% below control, respectively, suggesting on slight inhibition by rT3 of insulin-stimulated glucose utilization. Exposure to insulin significantly increased NEFA levels to about 670% above control group. Additional treatment with rT3 reduced this increase to 309% of control, suggesting inhibition of lipolysis by rT3. Similar alterations were observed in plasma corticosterone levels. Insulin treatment peaked the corticosterone levels maximally by 507.6% above control. Additional treatment with rT3 abolished this rise in the averages to 194.2% above control, possibly by interaction of rT3 with hypothalamo-adrenal axis. Insulin injection increased plasma catecholamines on the average by 21.5% and 53.4% for adrenaline and noradrenaline respectively. Supplementary treatment with rT3 intensified this rise by 55.6% and 71.6% respectively. The obtained results suggest on inhibitory effect of rT3 on hypoglycaemia, hyperlipaemia and plasma corticosterone concentrations in chickens treated with insulin. Contrary to this, rT3 enhanced the rise of plasma catecholamines due to insulin treatment. The obtained data favour the assumption that hypometabolic properties of rT3 depends mainly upon reduced supply of NEFA as a result of restricted lipolysis and to a lesser extent upon the supply of glucose.

Impact of regionalisation of cardiac surgery in Emilia-Romagna, Italy.

STUDY OBJECTIVE: Assessment of the impact of the regionalisation of cardiac surgery through the organisational form of a hub&spoke model introduced in the year 2000. DESIGN: Case mix adjusted before (1998-1999)-after (2000-2002) comparison of: (a) in-hospital and 30 days mortality rates; (b) proportion of patients timely (within one day) referred for surgery from spoke to hub centres; (c) patients' waiting times to surgery. SETTING: Emilia-Romagna, an Italian region with four million residents. PATIENTS: 16,512 patients aged > or =18 years and referred to cardiac surgery over the period 1998-2002. MAIN RESULTS: Overall, taking into account differences in case mix across the whole study period, the implementation of the regionalisation policy was associated with a 22% reduction (OR: 0.79, 95%CI: 0.66 to 0.93) in in-hospital mortality rate. The corresponding figure for 30 day mortality was 18% (OR: 0.82: 95%CI: 0.69 to 0.98). The individual centres' volume of cases changed over the study period for all hospitals but two, and the biggest reduction in mortality was seen at the centre with the largest increase in caseload. CONCLUSIONS: This study provides additional evidence on the benefit of regionalisation of cardiac surgery interventions. The system allowed each centre to reach the minimum caseload required to assure good quality of care. These findings suggest that policies aimed at increasing cooperation rather than competition among health service providers have a positive impact on quality of care. Timely referrals for surgery increased by 21% (95%CI: 1.12 to 1.31), and mean waiting times were reduced by 7.5 average days (95%CI: -10.33 to -4.71).

Immunohistochemical study of lymphocyte populations infiltrating the gastric mucosa of beagle dogs experimentally infected with Helicobacter pylori.

Experimental infection of beagle dogs with Helicobacter pylori induces recruitment to the gastric mucosae of neutrophils at early stages and later of mononuclear cells that organize into lymphoid follicles. These structures become macroscopically evident and consist of peripheral CD4(+) T lymphocytes and central CD21(+) B lymphocytes. Furthermore, transient expression of interleukin-8 (IL-8) parallels the presence of neutrophils in the gastric mucosae, whereas expression of IL-6 tends to persist chronically.

A conventional beagle dog model for acute and chronic infection with Helicobacter pylori.

Helicobacter pylori has been widely recognized as an important human pathogen responsible for chronic gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Little is known about the natural history of this infection since patients are usually recognized as having the infection only after years or decades of chronic disease. Several animal models of H. pylori infection, including those with different species of rodents, nonhuman primates, and germ-free animals, have been developed. Here we describe a new animal model in which the clinical, pathological, microbiological, and immunological aspects of human acute and chronic infection are mimicked and which allows us to monitor these aspects of infection within the same individuals. Conventional Beagle dogs were infected orally with a mouse-adapted strain of H. pylori and monitored for up to 24 weeks. Acute infection caused vomiting and diarrhea. The acute phase was followed by polymorphonuclear cell infiltration, interleukin 8 induction, mononuclear cell recruitment, and the appearance of a specific antibody response against H. pylori. The chronic phase was characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of the typical macroscopic follicles that in humans are considered possible precursors of MALT lymphoma. In conclusion, infection in this model mimics closely human infection and allows us to study those phases that cannot be studied in humans. This new model can be a unique tool for learning more about the disease and for developing strategies for treatment and prevention.

Acute reserpine treatment alters the catecholamine, glucocorticoid and opioid response to walking exercise in sheep.

The aim of the study was to examine the effects of reserpine on the plasma levels of adrenaline, noradrenaline, cortisol and alpha-neoendorphin in sheep under control conditions and during walking exercise. One hour of walking (5 km/h) caused a significant increase in both catecholamines and cortisol between 10 and 30 min of stress, and transiently decreased the level of alpha-neoendorphin at the same time. Reserpine at the dose of 0.3 mg/kg i.v. given before stress significantly lowered the basal levels of all tested parameters. A combination of the reserpine and walking exercise significantly attenuated the stress-induced changes in the plasma level of measured hormones.

Responses of heat stressed chickens to exogenous reverse triiodothyronine (rT3).

Heat stress is accompanied by a decrease in basal metabolic rate and plasma thyroid hormones. Unlike 3,5,3'-triiodothyronine (T3) and thyroxine (T4), 3,3',5'-triiodothyronine (rT3) displays hypometabolic properties and antagonizes the hypermetabolic effect of T3. This study analyses the role of rT3 in heat (38-39 degrees C) stressed immature chickens. Two experiments which differed in frequency of rT3 injections (one or two times a day), duration of heat stress (72 or 48 h) and blood sampling were performed. The dose was 14 micrograms rT3/100 gb.wt./injection (s.c.). It has been shown that rT3 treatment aggravates heat stress symptoms (enhances circulating corticosterone, catecholamines and free fatty acids) and increases mortality. The critical survival time of the rT3 treated and heated birds was at first 24 h of stress. No more chickens died during the next days of the experiment despite the continuation of rT3 injection, suggesting that rT3 might disturb the adaptation to heat. Reverse T3 in heat stressed chickens led to the highest reduction in food consumption (69.9%) and body weight gain (14.0% compared to initial weight). The opposite effect in water consumption (216.9%) was observed. In a neutral environment, rT3 significantly suppressed body temperature 6 h after injection (40.4; control; 41.1 degrees C), confirming its hypometabolic properties. However, at the same time rT3 significantly enhanced body temperature in heat stress (43.03 versus heated control 42.56 degrees C). In addition, in rT3 treated birds decreased plasma triglycerides (TG; 24.3%) and increased plasma free fatty acids (FFA; neutral temperature; 26.4% heat stress: 57%) were demonstrated. A correlation between corticosterone and FFA (r = 0.52) shows that some of the FFA may originate from lipolysis since hormones of the pituitary-adrenocortical axis accelerate lipolysis. The remaining part of the increased FFA appears to be due to suppressed utilization of FFA as a consequence of hypometabolic properties of rT3. Low and negative relation between TG and FFA (r = -0.26; P < 0.05) may support such an assumption. The two times higher peak of corticosterone in the rT3 and the overheated group, as compared to the heated control, occurred at 6 h of heat stress and indicates that rT3 increases the unfavourable effect of high temperature. This was also confirmed by elevated plasma adrenaline and noradrenaline in rT3-injected and heated chickens (55.5 and 120%, respectively). However, a single and two times higher peak of adrenaline at 24 h of heat stress was observed in saline treated birds, but not in rT3 supplemented animals, suggesting that this difference might explain one of the factors responsible for high mortality. In conclusion, the results obtained demonstrate that physiological doses of rT3, a hypometabolic hormone, enhance the unfavourable effect of heat stress in chickens.

Response of sympatho-adrenal axis and adrenal cortex to short-term restraint stress in sheep.

The sympatho-adrenal and pituitary-adrenal cortex axes are the most sensitive, and specific indicators of stress in animals. Increased plasma levels of catecholamines and glucocorticoids are generally considered as the classical response to stress. Most experiments on immobilization have been performed on rats and only a few of them concerned domestic animals. In this experiment we want to learn whether short-term restraint-a stressor most commonly used in animal husbandry-is a stressor for sheep (ewes) like in rats. For this reason we measured adrenaline (A), noradrenaline (NA) (radioenzymatic method), cortisol (RIA method), glucose and free fatty acids (FFA). Unlike in rats, in stressed sheep the peak of A appeared earlier than the NA peak, i.e. at 2 and 5 min. of stress, respectively. In contrast to rats, the basal and stress levels of NA exceeded the corresponding level of A. Cortisol concentration rose 7 fold above baseline and maximal concentration appeared at a time (15-30 min.) observed in other animal species. A similar time-related increase was observed in the plasma FFA concentration. It increased maximally 3.2 fold at 15 min. of stress. A significant correlation coefficient was found between plasma cortisol and FFA (r = 0.91) what may suggest the lipolytic effect of ACTH and/or a positive feedback of FFA on the hypophysis-adrenal axis. The plasma glucose of stressed animals rose only 1.47 fold above the basal level. A significant correlation was found between cortisol and glucose (r = 0.53) whereas no correlations have been obtained between A, NA and glucose or FFA.(ABSTRACT TRUNCATED AT 250 WORDS)

Modified responses of circulating cortisol, thyroid hormones, and glucose to exogenous corticotropin and thyrotropin-releasing hormone in food-deprived sheep.

In a previous experiment, food deprivation was found to suppress the increase of plasma cortisol and thyroid hormones in stressed animals. Because both the hypothalamo-adrenocortical and the thyroid axes are stimulated during stress, we investigated in this study whether a similar pattern of changes occurs in food-deprived sheep following corticotropin (ACTH) or thyrotropin-releasing hormone (TRH) administration. Each hormone was given as a bolus injection on the fifth day of food deprivation. Blood was sampled by venipuncture five times: 0.5 h before and 1, 3, 5, and 9 h after injection of the hormone. The peak of plasma cortisol in food-deprived sheep following ACTH administration exceeded fourfold the corresponding peak in fed animals. This suggests that food deprivation may enhance the sensitivity of the adrenocortical gland to ACTH and/or reduce binding sites for cortisol in target tissues. In fed animals, TRH was without effect on plasma cortisol level, whereas in food-deprived sheep cortisol transiently increased 2.5-fold, suggesting greater permeability of the blood-brain barrier for TRH. In food-deprived animals, plasma T3 was decreased to 22.6% of basal level, and elevated plasma cortisol after ACTH injection was not able to decrease it further. On the other hand, in fed sheep increased plasma cortisol did decrease plasma T3 as much as 4.2-fold. Circulating T4 was not affected by ACTH treatment. The delta increase of plasma T3 and T4 following TRH administration was comparable in fed and fasted animals.(ABSTRACT TRUNCATED AT 250 WORDS)