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Effects of selective and non-selective beta-adrenergic blockade on coronary dynamics in man assessed by rapid atrial pacing.

The effects on coronary dynamics of propranolol and atenolol were studied in 12 patients undergoing cardiac catheterisation for suspected coronary artery disease. Myocardial blood flow was measured using the coronary sinus continuous thermodilution technique. Data were obtained immediately after drug administration and during rapid atrial pacing. The immediate effects were similar for both drugs. A significant reduction in heart rate was accompanied by a small reduction in myocardial oxygen consumption. Changes in coronary sinus flow induced by rapid pacing were closely related to changes in tension-time index. This relation was not modified by propranolol or atenolol. Neither propranolol nor atenolol therefore has significant coronary vasoconstrictor properties. Cardioselectivity appears to be unimportant with respect to beta-adrenergic blockade and the coronary circulation.

Adult↗

Interaction between cold and altitude exposure on pulmonary circulation of cattle.

Hereford calves were exposed in a temperature-controlled hypobaric chamber to environmental temperatures of -2 to 1 degree C (cold) at altitudes of 1,524 m (resident altitude) and 3,048 m 1) to characterize the effects of cold exposure on the pulmonary circulation; 2) to examine the role of cold-induced hypoventilation on the pulmonary circulation; and 3) to examine the interaction between cold and hypoxia on the pulmonary circulation. Cold exposure produced a significant increase in pulmonary arterial pressure (Ppa), pulmonary arterial wedge pressure (Ppaw), and pulmonary vascular resistance (PVR) at both 1,524 and 3,048 m without affecting cardiac output. Concomitantly, cold exposure caused reductions in minute ventilation, respiratory rate, end-tidal O2 tension (PETO2), and arterial O2 tension (PaO2). Tidal volume, end-tidal CO2 tension, and arterial CO2 tension increased. Neither arterial pH nor O2 consumption changed during cold exposure. These results indicated that both pulmonary arterial and venous vasoconstriction were responsible for the pulmonary hypertension associated with cold exposure. Acute exposure to 3,048 m during cold exposure produced increases in Ppa and PVR that were similar to those elicited by cold exposure at 1,524. It was concluded that altitude exposure neither attenuated nor potentiated the effect of cold exposure on the pulmonary circulation; rather, altitude and cold exposure interacted additively. O2 administered during cold exposure to restore PETO2 and PaO2 to control values partially restored Ppa and PVR to control values. This suggested that a portion of the pulmonary hypertension associated with cold exposure was due to hypoxic pulmonary vasoconstriction elicited by the cold-induced alveolar hypoventilation.

Altitude↗

Immediate effects of hydralazine-isosorbide dinitrate combination on exercise capacity and exercise hemodynamics in patients with left ventricular failure.

Resting hemodynamics improve during vasodilator administration in patients, with congestive heart failure (CHF), but the effects of these agents on exercise is unknown. Twenty-two patients with class II or III CHF performed bicycle exercise to symptomatic maximum before and 90 minutes after random double-blind administration of oral hydralazine (100 mg) and isosorbide dinitrate (40 mg) (11 patients, group 1) or placebo (11 patients, group 2). Exercise duration was unchanged after treatment in either group. Maximal oxygen consumption changed insignificantly in both groups, from 12.6 +/- 1.2 (SEM) to 13.6 +/- 1.6 ml/kg/min in group 1, and from 11.7 +/- 1.4 to 13.4 +/- 1.7 ml/kg/min in group 2. Maximal cardiac index was unchanged in both group 1 (4.00 +/- 0.33 to 4.41 +/- 0.29 l/min/m2) and group 2 (4.11 +/- 0.43 to 4.14 +/- 0.42 l/min/m2). Systemic vascular resistance at peak exercise was also unchanged in both group 1 (14.1 +/- 1.6 to 11.8 +/- 1.0 units) and group 2 (14.7 +/- 1.6 to 13.5 +/- 1.6 units). at submaximal exercise (300 kilopond-meters/min), however, cardiac index after treatment increased in group 1 (0.51 +/- 0.18 l/min/m2, p less than 0.05) and systemic vascular resistance decreased (-3.3 +/- 1.3 units, p less than 0.05), but were unchanged in group 2. Thus, although vasodilators do not improve maximal exercise capacity acutely, they can improve hemodynamics at lower work loads which may, therefore, be better tolerated in patients with CHF.

Adult↗

Synergistic action of myocardial oxygen and carbon dioxide in controlling coronary blood flow.

A two-part experiment was designed to test the hypothesis that myocardial oxygen and carbon dioxide tensions, as measured by coronary venous oxygen and carbon dioxide tensions, determine coronary blood flow during increases in myocardial oxygen consumption. The left main coronary artery was pump-perfused at constant pressure in closed-chest, anesthetized dogs. Oxygenators in the perfusion circuit permitted control of coronary arterial gas tensions. The steady-state relation between coronary venous oxygen and carbon dioxide tensions and coronary flow at a constant myocardial oxygen consumption was determined by locally altering coronary arterial oxygen and carbon dioxide tensions. Values of coronary venous oxygen and carbon dioxide tensions and coronary flow were also obtained at normal coronary arterial gas tensions during pacing-induced increases in myocardial oxygen consumption. The data yielded a hyperbolic relation among coronary venous oxygen and carbon dioxide tension and coronary flow during constant myocardial metabolism, suggesting a synergistic interaction between myocardial oxygen and carbon dioxide tensions in determining coronary flow. This relation was then used to predict the coronary flow change during pacing-induced increases in myocardial metabolism. Approximately 40% of the flow response during pacing-induced increases in myocardial oxygen consumption was predicted. In conclusion, coronary venous oxygen and carbon dioxide tensions synergistically interact to produce steady-state changes in coronary flow at a constant myocardial oxygen consumption. Changes in myocardial oxygen and carbon dioxide tensions can account for about 40% of the change in coronary flow during moderate changes in myocardial oxygen consumption.

Animals↗

Amiodarone. Haemodynamic profile during intravenous administration and effect on pacing-induced ischaemia in man.

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti-ischaemic properties are mainly based on a reduction of myocardial oxygen demand, rather than on an improvement in coronary flow. It is concluded then, that amiodarone has significant haemodynamic effects as manifested by an early reduction in vascular resistance and a late negative inotropic effect. Although vasodilatation of short duration caused by its solvent, polysorbate 80, also occurs, the overall cardiovascular changes are caused by the direct, intrinsic haemodynamic effects of amiodarone alone. The important anti-ischaemic properties of amiodarone appear to result primarily from these cardiovascular actions and the inherent reduction in myocardial oxygen demand.

Amiodarone↗

Effect of dietary zearalenone on reproduction of chickens.

Variable quantities of zearalenone (0, 10, 25, 50, 100, 200, 400, or 800 mg/kg diet) were incorporated into a practical laying hen diet and fed to 30-week-old White Leghorn females in egg production. During the 3 week pretest and 8 week experimental periods hens were inseminated weekly with .05 ml of pooled semen from males fed normal diets. Zearalenone was without effect on egg production, egg size, feed consumption, change in body weight, fertility, hatchability of fertile eggs, growth of progeny to 3 weeks of age, comb, weight, oviduct weight, heart weight, liver weight, spleen weight, egg shell thickness, Haugh units, blood hematology, serum calcium, serum inorganic phosphorus, and serum alkaline phosphatase. Zearalenone above 50 mg/kg of diet caused reduced serum cholesterol. In a reciprocal study, adult male New Hampshire chickens were fed diets containing 0, 100, or 800 mg/kg zearalenone for an 8 week period. Semen was collected and inseminated into White Leghorn females fed normal diets. Zearalenone was without effect on fertility or hatch of fertile eggs resulting from matings of these males. Zearalenone resulted in reduced serum inorganic phosphorus, serum cholesterol, and serum alkaline phosphatase in males. Histological examination of a number of tissues in both males and females revealed no changes due to zearalenone feeding. It is concluded that zearalenone up to 800 mg/kg of diet is without effect on reproductive performance of mature chickens.

Animal Feed↗

[Artificial hyperventilation in head injury. I. Spontaneous hyperventilation and assisted ventilation (author's transl)].

The present study was desined to clarify the roles of artificial hyperventilation in management of the patients with cerebral injury. Here reported is the first part of the serial studies and concerned with general informations about hyperventilation. The measurements of PaCO2, minute ventilation volume (VE), dead space (VD), tidal volume (VT), cardiac output (by dye dilution method), oxygen consumption (by Fick' principle) and oxygen equilibrium were performed in the patients suffering from acute, severe head injury. And the effect of assisted ventilation on them were investigated (using pressure-limited respirator). 1. There was a common finding that marked and sustained increase in VE, VA (alveolar ventilation), and decrease in PaCO2 existed during the first week of injury. 97% of both VE and VA were above normal and mean value of PaCO2 was 29-33 mmHg. The syndrome of spontaneous hyperventilation was evidently more prominent in the nonsurvived group of patients. It was noteworthy that increased VE (or VA) was dependent neither on VD or pulmonary dysfunction nor on metabolic acidosis of arterial blood. The relation of VA to base excess in head injury was well contrasted to that of acute CO poisoning. 2. Assisted ventilation resulted in increased VT and decreased respiratory rate, and little change in VE. Consequently, PaCO2 changed only from 33.0 to 29.4 mmHg as a mean of entire series of patients. But when the influence affected by hypoxemic drive was subsided, a significant reduction of PaCO2 was disclosed following assisted ventilation. The assisted ventilation with pure oxygen was also associated with reduced cardiac output (from 6.0l/min to 5.3l/min), though the oxygen consumption changed variedly among the patients. 3. The fact was confirmed that both hypocapnea and alkalosis produced the left-sised shift of oxygen dissociation curve, decrease in P50 (P02 at 50% saturation of oxygen), and in addition, narrowed arterio-mixed venous oxygen difference. The changes of artero-mixed venous oxygen saturation difference which were calculated at 100 mmHg of PaO2 and 40mmHg of mixed venous PO2 were in a linear fashion with those of P50. Apart from the problems on injured brain, the beneficial and non-beneficial effects of hyperventilation were further discussed. The availability and inidcation of artificial hyperventilation should be precisely evaluated later, in a comprehensive manner with the subsequent studies (Part 2 and 3) on cerebral metabolism and intracranial pressure.

Brain Injuries↗

[Neutral peptide hydrolases in the blood serum and lungs in hypoxia].

In rats exposed to hypoxia (breathing 11% O2-N2 for 15 min), activity of neutral peptide hydrolases in lungs and serum was measured before and after altitude chamber training. When exposed to normal air breathing, activity of lung neutral peptide hydrolases was markedly higher in Group 1 rats, i.e. those in whom O2 consumption changed insignificantly in response to the hypoxic test, than in Group 2 rats, i.e. those in whom O2 consumption increased in response to the hypoxic test. After altitude chamber training activity of lung and serum neutral peptide hydrolases decreased in Group 1 rats and increased in Group 2 rats. The potential correlation between lung and blood neutral proteolysis is discussed. Its contribution to the biochemical control of oxygen transport via blood rheological properties and vascular tone is considered.

Animals↗

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↗