Prolonged Recovery Phase Research Articles

Canopy gaps to climate change - extreme events, ecology and evolution.

Canopy gaps to climate change - extreme events, ecology and evolution.

A simple algorithm improved physicians' diagnostic performance for patients presenting with syncope

(2000) Eur Heart J 21, 935. Ammirati F, Colivicchi F, Santini M, on behalf of the investigators of the OESIL study. . Diagnosing syncope in clinical practice. Implementation of a...

Effects of aminoguanidine and L-NAME on histamine-induced blood pressure drop in the rat.

Mean arterial blood pressure changes in response to i.v. administration of histamine were monitored in the anaesthetized rat in the absence or presence of the diamine oxidase (DAO) inhibitor aminoguanidine (AMG, 10 mg kg-1). AMG prolonged the duration of the transient drop in blood pressure induced by a bolus injection of histamine (0.05 mg kg-1) by 34%. In animals pretreated with AMG, no potentiation of the decrease in pressure in response to a 10 min infusion of histamine was observed. However, when infusion was stopped, the time needed for pressure recovery was twice as long in animals treated with AMG as in controls. Blood samples were taken prior to infusion and during the recovery phase and the quantities of histamine were determined by liquid chromatography. The prolonged recovery phase observed in animals pretreated with AMG was associated with five times higher levels of histamine. The duration of histamine-induced hypotension (0.01 mg kg-1) was 50% shorter in the presence of the nitric oxide synthase inhibitor L-NAME (10 mg kg-1). We suggest that DAO, through elimination of histamine from the bloodstream, is important for the recovery from histamine-induced hypotension, and that the duration of histamine-induced pressure drop is influenced by formation of nitric oxide.

Derangement in aerobic and anaerobic energy metabolism in skeletal muscle of critically ill and recovering rats

As part of our research into the mechanisms of protein wasting and muscle weakness during critical illness, we here investigate various aspects of energy metabolism. Intraperitoneal injection of zymosan in rats leads to an acute phase of critical illness followed by a prolonged recovery phase. Previously we observed low activities of mitochondrial enzymes, reduced protein synthesis rates and low concentrations of glutamine in skeletal muscle of zymosan-treated rats. In the present study we investigated (1) whether decreases in high energy phosphates are present in skeletal muscle of these rats and (2) whether an impairment in the glycolytic pathway or the tricarboxylic acid cycle leads to these decreases. Concentrations of creatine phosphate and ATP were decreased in zymosan-treated rats to approx. 85% of pair-fed control values respectively on day 2 and on days 4 and 6 after treatment. Concentrations of tricarboxylic acid (TCA) cycle intermediates were decreased to 80% on day 6 after zymosan treatment. Lactate/pyruvate ratio and concentrations of lactate and glycogen were normal at all sampling times. We conclude that no major changes in concentrations of high energy phosphates and in concentrations of intermediates of TCA cycle, glycolysis and glycogenolysis were present. This indicated that, although the maximal oxidative capacity (mitochondrial content) is decreased, no derangement in energy metabolism seems to be present in skeletal muscle of critically ill and recovering rats.

Prolonged Changes in Protein and Amino Acid Metabolism after Zymosan Treatment in Rats

1. Intraperitoneal injections of zymosan were given to rats, according to a modified procedure, in order to create a pattern of illness with an acute critical phase for 36 h followed by a prolonged recovery phase lasting for at least 10 days. Changes in amino acid and protein metabolism were studied in both phases. 2. Differences between this modified and the original zymosan model are a lower mortality (16%), which is limited to the first 36 critical hours, and the absence of signs of severe illness during the prolonged recovery phase. 3. Wasting of muscle protein and decreased protein synthesis rates in muscle were observed during the acute phase of illness. Liver size and liver protein synthesis rates were increased during the same period. The decrease in the total amount of muscle protein and the increase in liver weight were still present 12 days after zymosan treatment, despite a normalization of protein synthesis rates. Large decreases were observed in the concentrations of the conditionally essential amino acids glutamine and arginine in muscle over 6 days. Decreases in plasma glutamine and arginine on day 12 after zymosan indicated that the rats were still not fully recovered on this day. 4. We conclude that injection of a single dose of zymosan in rats leads to metabolic derangements both during the acute phase of critical illness and during the prolonged recovery phase. The model seems suited for investigating the biochemical mechanisms behind these metabolic derangements and for studying therapeutic and nutritional interventions during recovery from critical illness.

Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 mRNA levels during septicemic and localized Pseudomonas pseudomallei infection.

Patients suffering from serious bacterial infection present to the hospital after early inflammatory events, such as release of tumor necrosis factor (TNF), have been initiated. The role of other cytokines, such as interleukin-8 (IL-8), a neutrophil chemoattractant and activator, in the pathophysiology of human sepsis is not well characterized, and there are only limited data on IL-6. We studied serial concentrations of TNF, IL-6 (involved in the acute-phase response), and IL-8 in plasma and leukocyte levels of mRNA for these cytokines in patients with localized and septicemic Pseudomonas pseudomallei infection on admission to the hospital and during a prolonged recovery phase (up to 30 days). Of 18 patients, 8 had detectable plasma IL-8 and all had raised plasma IL-6 concentrations. In patients who died median initial concentration of IL-8 (167 pg/ml; range, 97 to 362 pg/ml) and IL-6 (4,800 pg/ml; range, 60 to 9,245 pg/ml) in plasma were higher than those in survivors (P less than 0.008 and P = 0.007, respectively). Septic patients who survived and patients with localized disease had similar cytokine levels. Plasma IL-8 and IL-6 concentrations were elevated throughout the inpatient period of recovery. Circulating leukocytes contained mRNA for IL-8 but not for IL-6 and TNF, and they may secrete IL-8. An elevated plasma IL-6 concentration (greater than 1,000 pg/ml) had 75% mortality) was the best predictor of mortality in P. pseudomallei sepsis. Fifty percent of patients with detectable plasma IL-8 concentrations died. In contrast, plasma TNF bioactivity did not relate to outcome; 75% of patients who did never had detectable plasma TNF activity.

Motility changes in opossum esophagus from experimental esophagitis.

We assessed how acute inflammation affects the contractile activity of the esophageal body. Two models of esophagitis were used: nine opossums had an esophageal perfusion of 100 meq hydrochloric acid for 2 hr and were studied at 24 hr. Ten had the perfusion for 4 h and their esophagitis were studied in vitro after 72 hr. Comparisons were made in all instances to animals who had esophageal saline perfusion for identical periods. All acid-perfused animals developed gross and histologic evidence of mucosal inflammation; in three animals, inflammatory changes extended into the submucosa and the muscularis propria. Manometric recordings in the acid-perfused animals revealed esophageal shortening, frequent failure of primary peristalsis and frequent occurrence of spontaneous contractions. Recordings of isometric tension of muscle in vitro revealed spontaneous contractions in strips from the mucosa and from the circular and from the longitudinal muscle. The amplitude of contractions in response to electrical stimulation was decreased, but the duration of contractions was increased largely because of a prolonged recovery phase. These changes in mechanical response occurred with stimulus parameters directed at both the muscle and the intrinsic nerves. We conclude that esophageal inflammation can lead to an increased irritability and decreased stimulus response of the smooth muscle of the esophagus even where it is not directly involved in an inflammatory response. These changes correspond to the functional abnormalities of the esophagus seen in patients with reflux esophagitis.

Changes in dopamine receptor sensitivity in humans after heavy alcohol intake.

Dopamine (DA) sensitivity, assessed through maximal growth hormone (GH) response to stimulation by apomorphine (APO) (0.18-0.24 mg iv) was studied in 16 chronic alcoholics newly admitted after a period of heavy alcohol intake. Repeated hormonal tests were thereafter performed during a 2-month period under strictly controlled conditions to avoid relapse into alcohol consumption. Eight healthy volunteers with alcohol consumption slightly less than that of the general population were used as controls. It was found that DA sensitivity in the early abstinence phase was higher than later in the 2-month recovery period but not significantly different from control values. The relatively higher DA sensitivity in the early abstinence phase might be responsible for a lower threshold for psychotic symptoms and neuroleptic-induced extrapyramidal side effects. The results of this study give further evidence of a prolonged recovery phase after heavy alcohol intake.

Asynchronous transmural perfusion during coronary reactive hyperaemia.

Dynamic variation in the transmural distribution of myocardial blood flow was studied in 36 anaesthetised open-chest dogs during the course of the reactive hyperaemia following a 90 s occlusion of the left anterior descending coronary artery. Myocardial blood flow was estimated from tissue uptake of radioactive microspheres, 9 to 10 micrometers in diameter. Endo/epi flow ratios indicated asynchronous reactive hyperaemic responses across the free wall of the left ventricle; flow was preferentially to subepicardium during the initial (pre-peak) phase, whereas flow was preferentially to subendocardium during the prolonged recovery phase. The mean of endo/epi flow ratios obtained during the peak plateau of coronary artery reactive hyperaemia indicated essentially uniform transmural distribution. However, further analysis indicated that this was result of ratios less than 1 early in the peak plateau and ratios greater than 1 late in the peak plateau. Reversal of the endo/epi flow ratios due to regionally asynchronous maximum flows is responsible for the prolonged plateau at peak flow observed in measurements of coronary artery reactive hyperaemia. Transmural asynchrony of peak reactive hyperaemic flow may also account for underestimates in vasodilator capability of ischaemia based on measurements of either coronary artery or myocardial blood flow.

Importance of Early Ileostomy Closure to Prevent Chronic Salt and Water Losses after Necrotizing Enterocolitis

Six infants with necrotizing enterocolitis were discharged after periods of prolonged hospitalization (two to nine months) with intact ileostomies. Their initial hospitalization was complicated by feeding difficulties, chronic diarrhea, sepsis, rickets, and developmental delay. All were rehospitalized within three months, with severe acidosis and dehydration after a presumed viral-type illness. Each had large-volume ileostomy output, which was rich in electrolytes and bicarbonate. A prolonged recovery phase (two to eight months) again was punctuated with episodes of diarrhea, problems in starting oral feeding, and sepsis. After reanastomosis of the remaining bowel, no infant has had a similar life-threatening episode. It is speculated that the infants' recurrent "salt-and-water-losing states" are secondary to either an anatomic or functional loss of the colon. This problem appears to be a poorly recognized sequela of bowel surgery and necrotizing enterocolitis, and early reanastomosis of discontinuous bowel should be of benefit.

Patient recovery from type A botulism: morbidity assessment following a large outbreak.

A large outbreak of foodborne botulism provided an opportunity to study the recovery from type A botulism in a group of 27 patients. Patients were interviewed either nine or 13 months after the outbreak, and a written questionnaire was mailed at 24 months, to obtain information on each patient's symptom complex and on subsequent symptom resolution. Recovery from symptoms of botulism was slow. Patients reported that resolution of 50 per cent of their original symptoms occurred by an average of 5 months. Thirteen of 14 patients contacted 13 months after onset of botulism reported some persistent symptoms. This study, although limited to interview data, strengthens the concept of a prolonged recovery phase in botulism, as previously suggested in individual case reports. Physicians and other health workers caring for patients with botulism should anticipate physical and psychological problems resulting from a lengthy and difficult convalescent period.

Lecithin appearance and apparent biologic half-life in term newborn rabbit lung.

Summary: The lung lecithin of term newborn rabbits was labeled by injecting the lecithin precursors palmitic acid and cholme into the pregnant doe shortly before delivery of the newborn rabbits by cesarean section. The newborn lungs were lavaged to yield an alveolar wash lecithin sample and the tissue was homogenized and fractionated into lamellar body and microsomal fractions by differential and density gradient centrifugation. Lecithin was isolated from the lung parenchyma, microsomes, lamellar bodies, and alveolar wash by two-dimensional thin layer chromatography, and the specific activity of the lecithin in each fraction was determined. Comes are presented showing the time of appearance of the radioactive lecithin in each lecithin fraction. The apparent biological half-life of lecithin in each fraction was measured. The specific activity of lecithin was high in microsomal fractions soon after palmitic acid or choline administration. The lamellar body fraction was free of radioactive lecithin for 3 hr, and maximal specific activity of lamellar body lecithin was reached only after 20 hr. The appearance of radioactive alveolar lecithin followed a curve very similar to that of the lecithin in the lamellar body fraction. The apparent half-life of lung parenchymal lecithin from newborn lung labeled with palmitic acid was 57 hr, whereas the apparent half-life of alveolar lecithin was 136 hr. The lecithin in lung and alveolar wash labeled with choline had a longer halflife than did lecithin labeled with palmitic acid. Measurements of lecithin appearance and apparent half-life are compared to similar measurements in adult rabbits. Speculation: The striking characteristics of newborn lung lecithin are the 3-hr lag before the appearance in the alveolus of de novo synthesized lecithin, the prolonged time (20 hr) before maximal specific activity of alveolar lecithin is achieved, and the very long apparent half-life of alveolar lecithin. If these measurements are applicable to other term and premature mammals, they must rely entirely on lecithin stored in anticipation of birth to maintain alveolar stability at birth. The long lag before significant lecithin synthesized de novo can reach the alveolar space precludes synthesis contributing to alveolar stability until many hours after birth. The recovery from the respiratory distress syndrome may not depend on maturation of the ability to synthesize lecithin; rather, the prolonged recovery phase may reflect the long times required for appreciable quantities of de novo synthesized lecithin to reach the alveolar space. However, once alveolar stability is achieved, short interruptions of lecithin synthesis, by reversible acidosis, for example, should not cause respiratory distress mediated by lecithin deficiency.