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Decreased oxygen consumption as a toxic manifestation of protamine sulfate reversal of heparin anticoagulation.

Protamine sulfate has been observed to interfere with the control of isolated mitochondrial respiration in vitro. This study was designed to determine if oxygen consumption changes in intact animals occur in vivo during protamine administration. Oxygen consumption was assessed in seven dogs anticoagulated with heparin (150 IU/kg) and reversed 30 minutes later with protamine sulfate (1.5 mg/kg). Oxygen saturations measured included arterial (SaO2 arterial), mixed venous (SvO2 systemic), jugular (SvO2 jugular), portal (SvO2 portal), and coronary (SvO2 coronary). Cardiac output (CO) and carotid artery flow determinations allowed calculation of systemic oxygen consumption (VO2 systemic) and cerebral oxygen consumption VO2 cerebral. Hemodynamic measurements included arterial blood pressure (BP), pulmonary artery systolic and diastolic pressures (PAS, PAD), and heart rate (HR). Protamine sulfate administration resulted in hypotension (delta BP -64 mm Hg), pulmonary hypertension (delta PAS + 13 mm Hg, delta PAD + 11 mm Hg), and bradycardia (delta HR -30). Shortly after protamine administration, CO fell 54% and carotid artery flow fell more than 50%, yet declines in SvO2 systemic and SvO2 jugular were not observed. In fact these parameters increased 3% and 2%, respectively. VO2 systemic fell 55% and VO2 cerebral fell 57%. Similarly, SvO2 portal and SvO2 coronary increased 6% and 9%, respectively. Significant correlations existed between changes in VO2 systemic and BP (r = 0.05, p less than 0.001), HR (r = 0.3, p less than 0.01, PAD (r = -0.3, p less than 0.05, and CO (r = 0.8, p less than 0.001). Impaired oxygen utilization was most evident during the first 5 minutes after protamine administration. This investigation, for the first time, establishes that protamine sulfate decreases in vivo oxygen consumption, a finding that may account for certain of the drug's adverse side effects.

Animals↗

Influences on children's attitudes toward alcohol consumption.

PURPOSE OF THE STUDY: To determine whether children's attitudes toward alcohol consumption changed as they grew older and to what extent peers might influence the decision to drink alcoholic beverages. METHOD: A cross-sectional descriptive study of 500 children ages 8-15 years was performed using a questionnaire. Data analysis included descriptive statistics and contingency analysis. RESULTS: Age was the only variable significantly related to decision making. Attitudes toward alcohol were more favorable in older children. Peer influence did not appear to affect drinking behavior. CONCLUSION: Older children (ages 14-15) are more favorably disposed to drinking than younger children. Children may be more influenced by parents than is realized. Parental guidance just prior to age 14 may be an effective intervention.

Adolescent↗

[The lacto-tampon concept. Determination and prevention of an increased risk for caries].

The lactobacillus count and buffer capacity (final pH) of whole stimulated saliva was assessed and related to the caries increment over the next 12 months in 327 teenagers. The caries increment was 3-4.5 times higher in children having a high lactobacillus count combined with a low buffer capacity, compared with other lacto-buffer combinations (P less than, 01-,001). The protective influence of a high buffer capacity seems to be stronger than the caries-promoting influence of high sugar consumption, indicated by a high lactobacillus count. On the one hand a low sugar consumption seems to have a decisive determining preventive effect even in children having impaired buffer systems. On the other hand a high sugar consumption strongly promotes caries when the buffer capacity is low. It is also demonstrated that consumption changes during a longitudinal study may impair the relationships between the salivary parameters, assessed at baseline, and the caries increment during the study.

Adolescent↗

[Neurogenic control of oxidative metabolism in the liver].

In acute experiments on dogs, stimulation of the hypothalamic ventromedial nucleus induced changes of hepatic circulation and increased the rate of O2 consumption by the liver. In stimulation of supraoptic and lateral hypothalamic nuclei the hepatic O2 consumption changed insignificantly. The hypothalamic effects on the liver tissue respiration was blocked by obsidan (propranolol) but not by atropine. A correlation exists between shifts of the O2 consumption rate and those of temperature in the liver. The data suggest that hypothalamus can modify the liver oxidative metabolism through the sympathetic nervous system and beta-adrenergic receptors of the hepatocytes and redistribute the energy of this metabolism between processes of thermogenesis and endothermic reactions in the liver.

Animals↗

Comparison of the effects of lateral and ventro-posterior hypothalamic damage on the predatory behavior of cats.

Two groups of seven cats estimated preoperatively as good mice-killers were subjected to the damage of either the lateral hypothalamus (LH) or the ventro-posterior hypothalamus (VPH). The LH damage produced global impairment of the predatory behavior, such as interest in, catching, killing, or consuming the mouse, whereas VPH damage left intact most components of the predatory act, except for mouse consumption. Changes in food preference, i.e. the choice between mice and meat, were found in both groups of cats. Instead of the preoperative preference of mouse over meat, postoperative preference of meat was found in both groups. Postoperative restoration of the predatory behavior, observed in both groups, proceeded faster in the VPH cats than in the LH cats, for which the impairment lasted for several months.

Animals↗

Objective and useful mobility assessment of patients with arthropathy of the hip and knee.

Walking ability was objectively assessed by measurements of endurance, oxygen consumption, and pulse rate response. Twenty-four control subjects and 38 patients with arthropathy of the hip or knee were asked to walk on a treadmill, initially at 1 km/hour, for four minutes. The speed was increased by 1 km/hour every four minutes, until the subjects has walked for four minutes at 7 km/hour, or until they could not continue. Oxygen consumption, heart rate, cadence, and step length were measured. The controls could all walk for 1400 m, reaching a walking speed of 6 km/hour, and showed a consistent relation between heart rate, oxygen consumption, and speed of walking. The majority of arthritic patients failed to reach either this distance or speed. They had a significantly increased metabolic cost, and there was a good correlation (r = 0.65 to 0.99) between the changes in pulse rate and oxygen consumption in each individual patient. The endurance, heart rate response, and oxygen consumption changes shown by patients proved to be reproducible characteristics in patients whose disease was static.

Adult↗

Effect of decreased O2 affinity of hemoglobin on work performance during exercise in healthy humans.

A reduction in O2 affinity of hemoglobin should increase tissue oxygenation or maintain tissue oxygenation and at the same time spare cardiac work. Large, sustained reductions in O2 affinity of hemoglobin are induced best by primary (non-Bohr effect) stimulation of red blood cell 2,3-diphosphoglycerate (DPG) caused by a dual, cumulative effect on O2 affinity for hemoglobin, direct, from DPG itself, and indirect, from DPG-induced red blood cell acidosis. In an attempt to induce significant, sustained reductions in O2 affinity of hemoglobin by primary DPG stimulation, six normal humans were given a diphosphonate (etidronate disodium [Didronel] 20 mg/kg/day p.o.) followed by infusion of 10% fructose (0.5 L/hr for 3 hours) with added phosphate (0.28 mmol/kg/hr) and, subsequently, fructose-phosphate by itself. Participants underwent exercise testing (bicycle ergometer) and cardiopulmonary parameters were measured before and after administration of Didronel plus fructose-phosphate infusion, as well as before and after fructose-phosphate infusion alone. The sum of DPG and adenosine triphosphate as well as the P50 increased significantly after infusion of fructose-phosphate with and without prior administration of Didronel. DPG-ATP correlated closely with P50. When P50 was elevated, the cardiac index at high work load was lower than when P50 was normal (with comparable O2 consumption); changes in P50 correlated inversely with changes in cardiac index. Thus, with reduced O2 affinity of hemoglobin, participants could perform at comparable work loads and utilize the same amount of O2 with less cardiac work. Future studies should include adapting these findings to states of O2 deficit.

2,3-Diphosphoglycerate↗

[Toxic effects of endotoxin perfusion on isolated rat bowel].

The isolated small bowel from duodenojejunal junction to ileocecal junction with intact SMA and SMV was perfused with Krebs-Ringer solution intraluminally in rat. After all the branches from aorta and portal vein other than SMA and SMV were ligated, aorta and portal vein were cannulated and perfused with Krebs-Dextran solution. The isolated perfused bowel was transferred immediately to the chamber equipped with constant temperature and humidity. For the purpose of studying the direct toxicity to the bowel tissue, B4 endotoxin (Difco) was added to intravascular perfusate. Significant physiological and chemical changes listed below were observed as compared with those of the control group which was perfused with endotoxin free perfusate. Active transport of D-glucose was decreased. Net entry of water into the gut lumen was decreased. pH in intravascular fluid was significantly decreased. Lactic acid level in intravascular fluid was significantly high, which was well correlated with pH change. O2 consumption change was not marked, but CO2 accumulation in intravascular perfusate was significant. These were the results of the toxic effects of endotoxin on the rat bowel.

Animals↗

[Oxygen consumption as an indicator of the adaptation of animals to altitude hypoxia].

Altitude chamber experiments have shown that the quantity of oxygen consumption in the posthypoxic period as an index of adaptation to hypoxia is of a low informative value: during the normal course of adaptation, oxygen consumption changes insignificantly or decreases slightly; it increases somewhat if the hypoxic atmosphere contains CO2 (pCO2 = 19 - 27 mm Hg) and declines significantly (by 22.6%) only if adaptation is disordered. At the same time oxygen consumption can be a highly informative index, characterizing the efficiency of adaptation to hypoxia only if it is measured immediately after exposure to acute hypoxia. In this experimental design the magnitude of oxygen consumption increases with increasing oxygen debt which, as follows from our experiments, shows the degree of conditioning to altitude hypoxia.

Adaptation, Physiological↗

[Blood flow and oxygen tension and consumption in skeletal muscles after hypothalamic stimulation].

In acute experiments on dogs under nembutal anesthesia, stimulation of different parts of the hypothalamus increased the muscle blood flow and O2 consumption and decreased vascular resistance. PO2 in m. gastrocnemius altered in both directions as a function of blood flow and O2 consumption changes. There was a good correlation between the initial level of PO2 and its shifts caused by hypothalamic stimulation. In most cases flow reactions were blocked with atropine. The stimulation of the hypothalamus seems to evoke cholinergic vasodilatation in skeletal muscles. The data suggest that initial level of muscle PO2 determines the redistribution of the increased blood flow between nutritional and non-nutritional vessels within the skeletal muscles and thus affects transcapillary exchange and O2 consumption during cholinergic vasodilatation.

Animals↗

Oxygen transport and tissue oxygenation under moderate and extreme hemodilution during coronary bypass surgery.

Oxygen transport and tissue oxygenation were investigated in twelve patients undergoing coronary bypass surgery under normovolemic moderate and extreme hemodilution. Moderate hemodilution, that was carried out after induction of anesthesia, decreased the mean hematocrit from 0.43 to 0.33. Concurrently, the cardiac index and the left ventricular filling pressure increased slightly whereas the systemic oxygen transport declined by 20%. This was associated with elevated oxygen extraction. The subcutaneous tissue oxygen tension underwent a transient increase during moderate hemodilution. During cardiopulmonary bypass and extreme hemodilution the mean hematocrit declined to 0.16. Simultaneously, the tissue PO2 decreased clearly reaching its minimum at the deepest hypothermia. After coming off bypass and reinfusion of the autologous blood the tissue PO2 approached the preoperative levels. In general, total body oxygen consumption changed parallelly with the tissue oxygen tension. Lactate concentration in the mixed venous blood increased in the beginning of the extracorporeal circulation and remained rather stationary thereafter. All patients recovered normally without any perioperative myocardial infarctions.

Adult↗

[Blood supply and oxygen consumption in cat musculus gastrocnemius during isometric tetanus and intra-arterial infusion of norepinephrine].

In anesthetized cats with maximal isometric tetanus induced by the n. ischiadicus stimulation, the initial oxygen consumption depended on the 2--fold reduction of initial blood flow, the anaerobic metabolism index remaining the same, at that. Stimulation of the nerve induces practically the same mechanical activity of the muscle in control and after i. a. administration of noradrenaline, but the working hyperemia with concomitant changes of the metabolism indices becomes weaker than in control. A correlation of muscle blood supply changes with oxygen consumption changes was revealed whereas there was no correlation between changes of these indices and changes of oxygen extraction from the blood. A possibility of effects of the primary increase in blood flow occurring in hyperemia following the mechanical factor action, on the oxygen consumption is discussed as well as effect of willed decrease in blood flow within non-hypoxic range upon the oxidated metabolism.

Animals↗

Effect of cardiac filling pressures on the release of atrial natriuretic peptide during exercise in heart transplant recipients.

OBJECTIVE: To determine the influence of body posture and central hemodynamics on the plasma levels of immunoreactive atrial natriuretic peptide (irANP) during exercise in cardiac transplant patients. METHODS: Central hemodynamics, mixed expired gas and ventilatory measurements, and venous blood sampling (for irANP determination) were obtained in cardiac transplant patients at rest and during supine (n = 12) or upright (n = 12) graded cycle exercise. Cardiopulmonary and irANP responses to exercise were compared between the upright and supine postures. RESULTS: At rest (supine), irANP concentrations were similar in both groups (172 +/- 87 pg/mL supine and 182 +/- 72 pg/mL upright) and did not correlate with resting supine central hemodynamics. During exercise, central filling pressures increased in both groups but patients exercising in the supine position had a greater increase. Peak exercise right atrial pressure was 12 +/- 4 mmHg supine versus 7 +/- 5 mmHg upright (P < 0.005). Peak exercise pulmonary capillary wedge pressure was 22 +/- 6 mmHg supine versus 14 +/- 5 mmHg upright (P < 0.005). At peak exercise, irANP levels were greater in the supine than upright position (419 +/- 166 pg/mL supine versus 277 +/- 40 pg/mL upright, P < 0.05). The change in irANP from rest to peak exercise correlated (P < 0.05) with changes in pulmonary capillary wedge pressure (r = 0.67), systolic pulmonary artery pressure (r = 0.78) and right atrial pressure (r = 0.53). There was, however, no correlation between change in irANP and peak oxygen consumption, change in heart rate or change in mean arterial blood pressure. CONCLUSIONS: In cardiac transplant recipients, exercise is a stimulus for ANP secretion, and augmentation in plasma irANP levels during exercise is modulated by changes in central hemodynamics.

Adult↗

[Alcohol consumption in a Danish cohort study over a period of 11 years].

A cohort living in Copenhagen County, originally consisting of 1198 persons, 577 men and 621 women, who were 40 years old in 1976, was reexamined in 1981 and again in 1987, 1052 (88%) participated in 1976, 922 (84%) in 1981, and 965 (85%) in 1987. The purpose of this study was to describe alcohol consumption changes in the cohort, with a view to identifying subgroups who significantly change their alcohol consumption behaviour. The same questionnaire was employed all three times to measure the alcohol consumption level and frequency. Alcohol consumption peaked in 1981 (45-years old) with 10.4 drinks on average a week. Men increased 8% and women 37%. There is an overall downward tendency in the consumption frequency among men whereas the opposite is the case among women. The two groups are converging toward a weekly consumption level. It seems now that the women are leading the change in the content of consumption with relatively more wine consumption. Therefore it is concluded that female consumption should be considered a target in future preventive programs.

Adult↗

The effect of ethanol on the pancreatic duct sphincter of Oddi.

Alcohol ingestion causes pancreatitis to develop in some people, but the mechanism(s) by which alcohol causes pancreatitis are unclear. The effect of alcohol on the pancreatic duct sphincter of Oddi (PD-SO) may play a significant role. To better understand the effects of alcohol on the PD-SO, we studied 24 alcoholic subject's PD-SO before and after 80 g of alcohol was instilled into their stomachs. Seventeen of the subjects had a prior history of pancreatitis. The mean maximal alcohol level achieved by 30 min after the instillation was 98.1 +/- 47.9 mg/dl. The only prealcohol differences between the pancreatitis group and the nonpancreatitis group were higher mean basal PD-SO pressures and higher mean phasic contraction amplitudes (8.7 and 20.2 mm Hg higher, respectively) in the pancreatitis group. The acute change in the subjects' blood alcohol levels produced similar changes in both groups. A non-statistically significant fall in the mean basal PD-SO pressure of 2.7 mm Hg was observed. The phasic contraction mean amplitude decreased by 24.1 mm Hg (p < 0.001) and the mean duration decreased by 0.6 s (p = 0.0064). The frequency of phasic contractions did not change after ingestion of alcohol. There was a significant fall in the percentage of antegrade phasic contractions (-15.8%, p = 0.016), which was compensated for by nearly equal increases in the percentage of retrograde and simultaneous contractions. We conclude that acute alcohol ingestion in subjects with a history of chronic alcohol consumption changes the PD-SO motor activity in a way that could predipose to duodenopancreatic reflux. Thus, reflux of bile, activated enzymes, or other substances into the pancreatic duct might occur more readily and predispose one to pancreatitis after alcohol ingestion.

Adult↗

Taxes and the tobacco wars.

In this issue (see pages 187 to 191) Dr. Vivian H. Hamilton and associates demonstrate that tax reductions introduced in 5 Canadian provinces in 1994 slowed the rate of decline in cigarette consumption in those jurisdictions. Although both reductions and increases in taxation have been shown to influence tobacco consumption, changes in smoking habits must also be understood in the context of battles being waged on other fronts in the tobacco wars. In addition, more finely detailed analyses are needed to determine the impact of taxation and other factors on the smoking habits of specific subgroups of the population, particularly teenagers.

Adolescent↗

Etiology of Barrett's metaplasia and esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma in the United States is rising at an epidemic rate. Although the cause for this rapid rise is unclear, it is well established that nearly all cases of esophageal adenocarcinoma arise from a premalignant lesion of the esophagus, known as Barrett's esophagus. Although Barrett's esophagus is recognized as a precursor lesion, the etiology, prevalence, and malignant risk of this lesion remain unclear. The relatively short, two-decade time frame for the rise in esophageal adenocarcinoma incidence and the increase across populations is a strong argument for environmental factors as etiological agents, perhaps interacting with genetically determined characteristics that define personal susceptibility. Because of the strong link between Barrett's esophagus and esophageal adenocarcinoma and the link between Barrett's esophagus and gastroesophageal reflux disease, risk factors for gastroesophageal reflux disease have been the prime suspects offered as possible explanations for the rise in esophageal adenocarcinoma. A plethora of hypotheses have been advanced, implicating tobacco and alcohol consumption, changes in obesity and diet, and the changing pattern in use of medications that affect the upper gastrointestinal tract. The following text will review what is currently known about the epidemiology of Barrett's metaplasia, its risk for malignant transformation, and the proposed theories of etiogenesis.

Adenocarcinoma↗

Alcohol and the future health of Europe.

The impact of alcohol consumption on trends in the European health situation is analysed. Particular attention is given to the impact of alcohol on the widening of the East-West health gap in Europe. It is concluded that between 1950-75 the negative health impact of a rapid increase in per capita alcohol consumption in most European countries was hidden behind a strong positive development in many other socio-economic determinants of health. Between 1980 and 1995, health trends have been more closely parallel to trends in alcohol consumption. Changes in alcohol consumption explain a significant proportion of changes in life expectancy, particularly in the newly independent states of the former Soviet Union. Public health policy on alcohol, as part of a general development of public health policies outside the health sector, is important in reducing the East-West health gap and sustaining the positive health trend in western Europe.

Alcohol Drinking↗