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Cross-sectional and longitudinal relationships between alcohol consumption and lipids, blood pressure and body weight indices.

OBJECTIVE: Serum lipids, blood pressure and body mass may mediate the U-shaped relationship of alcohol consumption with type 2 diabetes mellitus and coronary heart disease. This study examines the cross-sectional and long-term longitudinal relationships of (changes in) alcohol consumption with (changes in) serum lipids, blood pressure and body mass indices. METHOD: In this prospective, observational cohort study, two measurements of alcohol consumption, serum total and high-density lipoprotein cholesterol, triglycerides, blood pressure, body weight, the thickness of four skinfolds and waist circumference were performed 4 years apart in healthy volunteers (143 men and 174 women, 32 years old at the first measurement). Alcohol consumption from beer, wine and distilled spirits was assessed using an extensive dietary history interview. Linear regression analyses were performed to study the cross-sectional relationships between the amount of alcohol consumed at the age of 32 years and the levels of the lipids, blood pressure and body weight indices, and to study the longitudinal relationships between the changes in the amount of alcohol consumed over the 4 years of follow-up and the concurrent changes in the lipids, blood pressure and body weight indices. Nonlinearity was investigated for the cross-sectional relationships. RESULTS: A 10-g/day difference in alcohol consumption was positively related with a 0.05 mmol/L (1.9 mg/dl) difference in high-density lipoprotein cholesterol in both cross-sectional (p = .004), and longitudinal (p < .0001) analyses. This relationship did not differ for men and women or for the consumption of beer, wine or distilled spirits. Relationships with changes in total cholesterol, triglycerides, systolic, diastolic, and pulse pressure, body weight and the sum of four skinfolds were not significant. A borderline significant inverse longitudinal relationship was found with waist circumference. The other lifestyle behaviors (tobacco smoking, physical activity and dietary habits) were major confounders of most cross-sectional relationships between alcohol and serum lipids, blood pressure and body mass indices. The longitudinal relationships, however, were not confounded by changes in the other lifestyle behaviors. A significant nonlinear relationship was found for systolic blood pressure, in which drinkers of about 30 g/day had the lowest values. CONCLUSIONS: Moderate alcohol consumption and moderate long-term changes in alcohol consumption are positively related with the levels and changes in high-density lipoprotein cholesterol in healthy adult men and women. A moderate inverse association between alcohol and waist circumference may be expected. No relationships were found with triglycerides, blood pressure, body weight and the sum of the thickness of four skinfolds. Other lifestyle behaviors confound the cross-sectional, but not the longitudinal, relationships between alcohol consumption and serum lipids, blood pressure and body mass indices. Gender and type of beverage do not modify the relationships between alcohol consumption and these indices.

Adult↗

Alcohol consumption, alcoholics anonymous membership, and suicide mortality rates, Ontario, 1968-1991.

OBJECTIVE: The goal of this study is to identify alcohol-related factors that influence mortality rates from suicide. Specifically, we examine the impact of per capita consumption of total alcohol, distilled spirits, and beer and wine; unemployment rate; and Alcoholics Anonymous (AA) membership rate on total and male and female suicide mortality rates in Ontario between 1968 and 1991. METHOD: We studied the impact of alcohol consumption levels, AA membership rates, and unemployment rates on suicide mortality rates in Ontario from 1968 to 1991. Time series analyses with Auto Regressive Integrated Moving Average (ARIMA) modeling were applied to total and male and female suicide rates. The analyses performed included total alcohol consumption, distilled spirits consumption, beer consumption, and wine consumption. Missing AA membership data were interpolated with cubic splines. RESULTS: Total alcohol consumption and consumption of each of beer, distilled spirits, and wine were significantly and positively related to total and female suicide mortality rates. AA membership rates were negatively related to total and female suicide rates. Although data for males did not reach significance (except for the relationship between wine consumption and suicide rate), the direction of effects was consistent with that observed for female and total suicide rates. Unemployment rates were positively related to male and total suicide rates in some models. CONCLUSIONS: These data confirm the important relationships between per capita consumption measures and suicide mortality rates seen by previous investigators. Additionally, the results for AA membership rates are consistent with the hypothesis that AA membership and treatment for misuse of alcohol can exert beneficial effects observable at the population level.

Adolescent↗

Involvement of GABA-A receptor chloride channel complex in isolation stress-induced free choice ethanol consumption in rats.

The present study revealed the effect of diazepam, a benzodiazepine, and progesterone, a pregnane precursor of neurosteroids, which act via modulating GABA-A chloride channel complex on the isolation stress-induced free choice ethanol consumption in adult rats. Isolation stress for 24 hr over a period of 6 days produced a significant increase in ethanol consumption, which persisted during the 6-day recovery period. Pretreating the animals with diazepam (5 mg/kg, i.p.), or progesterone (5 mg/kg, i.p.), blocked the isolation stress-induced increase in ethanol consumption. Bicuculline (2 mg/kg, i.p.), a GABA-A receptor antagonist significantly attenuated the effect of both diazepam and progesterone on stress-induced modulation of ethanol consumption. Isolation stress also caused an increase in total fluid consumption, which was antagonised by both diazepam and progesterone. Like ethanol consumption, this effect of diazepam and progesterone on isolation stress-induced increase in total fluid consumption was attenuated by bicuculline. Neither diazepam nor progesterone produced an increase in ethanol consumption in non-stressed rats. However, unlike diazepam, progesterone administration to non-stressed rats caused a significant increase in total fluid consumption. Results of the present study thus show that GABAergic mechanisms may be playing an important role in isolation stress-induced increase in ethanol consumption.

Animals↗

[Transpiration water consumption of young Platycladus orientalis and Robinia pseudoacacia trees and their correction functions under different water supply].

Through artificial water control in the shed of rain-free, this paper studied the physiological water requirement patterns of 2-3 years old Platycladus orientalis and Robinia pseudoacacia trees during their growth period, and the relationships between their transpiration water consumption and soil water supply. The results showed that the transpiration water consumption of Robinia pseudoacacia was increased with increasing soil water supply within the range of 40%-100% of field water-holding capacity. Its maximum transpiration water consumption was at the early and accelerating growth stages, accounted for 80.5% of total annual water consumption. The transpiration water consumption of Robinia pseudoacacia was 5.13 times as much as that of Platycladus orientalis. Platycladus orientalis had a peak value of transpiration water consumption when the soil moisture content was 40%-100% of field water-holding capacity. Its transpiration water consumption was the maximum at accelerating growth stage, accounted for 46.27% of total annual water consumption, next at later growth stage, and relatively small at early growth stage. The correction functions of transpiration water consumption to soil water supply and the time-soil moisture functions of practical transpiration water consumption under insufficient water supply for two test species were put forward for the first time.

Ecosystem↗

[Antibiotic consumption between 1996 and 2003: national survey and international comparison].

AIMS: To describe the qualitative and quantitative changes of antibiotic consumption in Hungarian hospitals and in the primary care setting between 1996 and 2003. METHODS: Sales data relating to community and hospital care antibiotic consumption were obtained for the 8 years period of 1996-2003. The 2003 version of the world health organisation (WHO) anatomical therapeutic chemical (ATC)/ defined daily dose (DDD) system was used for calculations and the 2005 version for classifications. The final expression units were DDD/100 bed-days and DDD/1000 inhabitants/day for hospital and community care utilization, respectively. Trend analysis was applied to assess the annual changes in antimicrobial consumption. RESULTS: The total antibiotic consumption in the community setting and in the hospitals remained relatively stable during the study period. The average antibiotic consumption in the community setting (20.20 +/- 1.42 DDD/1000 inhabitants/day was in line with the European average, while the national average hospital antibiotic consumption (24.81 +/- 1.69 DDD/ 100 bed-days) was very low in international benchmark. Changes in the pattern of antibiotic consumption was observed in both settings. Internationally outstanding consumption of penicillins plus beta-lactamase inhibitor combinations (J01CR) and sulphonamides and extremely low utilisation of beta lactamase resistant penicillins (J01CF) were detected. The hospital antibiotic consumption was characterized by extended use of sulphonamides, tetracyclines, and second generation cephalosporins. CONCLUSIONS: The low hospital consumption of antibiotics and the internationally extreme usage of certain antibiotic groups needs further pharmacoepidemiologic analysis.

Ambulatory Care↗

[Follow-up examination of former recruits regarding their alcohol, tobacco, drug and medicine consumption].

On behalf of the Swiss Federal Commission Against Alcoholism, 1103 former military recruits were surveyed in 1979 with regard to consumption of alcohol, tobacco, and illicit and psychotropic drugs. The men had been surveyed for the first time with regard to the same factors when under military training in 1972-73 (Battegay, Mühlemann et al.). With regard to alcohol consumption, the 1979 results showed a larger number of consumers than in 1972/73, i.e. an increase of 6.1% from 88.5% in 1972/73 to 94.6% in 1979. In 1979 the men, aged approximately 26 years, in the main (73.8% of subjects) mentioned only low alcohol consumption (10-150 g alcohol 100% a week). Heavy consumption of alcoholic beverages (greater than 350 g alcohol 100% a week) was indicated in a lower .e. an increase of 6.1% from 88.5% in 1972/73 to 94.6% in 1979. In 1979 the men, aged approximately 26 years, in the main (73.8% of subjects) mentioned only low alcohol consumption (10-150 g alcohol 100% a week). Heavy consumption of alcoholic beverages (greater than 350 g alcohol 100% a week) was indicated in a lower .e. an increase of 6.1% from 88.5% in 1972/73 to 94.6% in 1979. In 1979 the men, aged approximately 26 years, in the main (73.8% of subjects) mentioned only low alcohol consumption (10-150 g alcohol 100% a week). Heavy consumption of alcoholic beverages (greater than 350 g alcohol 100% a week) was indicated in a lower number of cases than in 1972/73. In 1972/73, 6% of the men, aged approximately 20 years, indicated this level of alcohol consumption, compared with 3.2% in 1979. With regard to tobacco consumption, no major changes were found between the two investigation periods. The proportion of nonsmokers had risen from 43.8% in 1972/73 to 46.4% in 1979, whereas the proportion of heavy consumers (more than 24 g tobacco a day) remained almost unchanged at 13% in 1979 against 13.5% in 1972/73. There was a major fall in the number of drug consumers. In 1979, 85.8% said they had been drug abstainers since 1972/73. In 1972/73, only 75.2% had said they had never taken drugs. The fall in the number of subjects who consumed drugs can be explained by a reduction in the number of "drug experimenters" (1--8 drug intakes) in the period from 1972/73 to 1979 compared with the years before 1972/73. The number of those reporting more than 48 drug intakes remained virtually unchanged (1.6% in 1979 against 1.3% in 1972/73).

Adult↗

Some remarks on the current morphine consumption in Italy.

AIM: To analyse therapeutic morphine consumption in Italy and explain the current trend. ENVIRONMENT: Morphine consumption was examined at Santa Croce Hospital, Cuneo, a general provincial hospital. METHOD: The overall annual consumption of morphine was used as a starting point from which to evaluate the "average daily consumption of set doses", both in general and using a number of methods of administration. From these figures it was possible to calculate the average number of patients receiving full doses of the drug daily; this finding was compared every 10,000 days of hospitalisation. RESULTS: The analysis of consumption over the two-year period 1991-92 shows a 98.41% increase in mean morphine consumption compared to the period 1988-89. Over the five-year period the average number of patients receiving full doses of morphine daily through a variety of methods of administration was 9.89, equivalent to 3.79 patients every 10,000 days of hospitalisation. CONCLUSIONS: Useful information can be derived regarding the trend of morphine consumption from the "mean daily consumption of set doses" of morphine and, above all, from monitoring consumption per 10,000 days of hospitalisation. At present we are not aware of similar data relating to other hospitals. We hope that this lacuna will soon be filled so as to evaluate and monitor morphine consumption trends in Italy.

Drug Utilization↗

[Trends in alcohol consumption in relation to liver diseases in Slovakia 1973-1994].

The World Health Organisation warns before the increase in alcohol consumption and the proportional increase in ethyltoxic diseases which have taken place in past decades. Slovakia is included into the countries with the highest consumption of alcohol in Europe. The authors present a retrospective analysis of alcohol consumption from 1973 to 1994 in Slovakia according to the kinds of alcohol beverages, in a selected district and according to profession and family status. The epidemiologic analysis of the situation of alcohol consumption that is currently present in Slovakia is based on the data from wholesale and retail sale in relation to the prevalence and the mortality due to hepatic cirrhosis. The presented data was investigated by the Slovak Statistical Institute and the Institute of Medical Statistics of the Slovak Republic. Mortality due to hepatic cirrhosis has increased during the past 40 years 10-fold in men, and 4-fold in women. A severely increasing trend in alcohol consumption which had taken place prior to 1990 was succeeded by an abrupt decrease in pure alcohol consumption after 1990 (as much as by 21.2%). This decrease corresponds with the proportional decrease in the prevalence of chronic hepatopathies (by 35%) and with the decrease in mortality due to hepatic cirrhosis (by 20%). This phenomenon may be explained by the proportional increase in prices of alcoholic beverages. According to average yearly consumption of pure alcohol (p.a.) per capita, the consumption of spirits dominates when compared with the consumption of beer and wine. It is desirable to continue in the begun decreasing trend in alcohol consumption which is crucial in the procurement of primary, secondary as well as of tertiary preventions on both individual and population levels. (Tab. 1, Fig. 6, Ref. 19.)

Alcohol Drinking↗

[Validity of alcohol consumption records: comparison of clinical history and telephone survey].

OBJECTIVES: To compare primary care clinical records (PCCRs) and a telephone survey of the population group seeking health care, for the prevalence of alcohol consumption. To determine factors linked to screening and observation of alcohol consumption, and to analyse the perception and recording of medical counselling on alcohol and tobacco consumption. DESIGN: Descriptive, crossover study. SETTING: Urban Health Centre. PARTICIPANTS: Random sample of 320 patients with PCCRs, aged between 15 and 75. MEASUREMENTS AND MAIN RESULTS: The PCCR was reviewed for age, sex, educational level, profession, frequency of attendance, chronic illnesses, alcohol and tobacco consumption, pathologies linked to alcohol consumption, screening and observance of this consumption as recommended by the preventive activities and health promotion programme (PAHPP), and the recording of counselling to smokers and at-risk drinkers. Later a standard questionnaire on the patients' alcohol and tobacco consumption and their perception of medical counselling was filled in by phone, 36.1% of patients consumed alcohol, according to the PCCR, which rose to 51.1% in the questionnaire (95% CI variation, 6.2-23.8). Initial screening of alcohol consumption was recorded in 67.4% of the PCCRs, with a significant association to age of 20 or over (OR = 20.5; CI, 2.9-142.6), and to education beyond primary level (OR = 8; CI, 1.7-38.5). The observation recommended by the PAHPP was correctly followed for 24.8% of patients, and was associated with being a smoker (OR = 2; CI, 1.2-3.4) and male (OR = 1.9; CI, 1.1-3.3). No significant differences were found when the under-recording in the PCCRs of alcohol counselling to at-risk drinkers (27.8% PCCRs and 35.7% questionnaire) was studied: but there were significant differences for tobacco dependency (20.7% PCCRs and 55.7% questionnaire; CI of variance: 23.6-46.4). CONCLUSIONS: We found considerable under-recording of alcohol consumption in the clinical records, along with little medical counselling. Preventive activities should be given priority, especially among young people, since consumption starts in adolescence, and young people, along with women and patients of low educational level, are more susceptible to medical counselling.

Adolescent↗

Oxygen consumption in myoglobin-rich and myoglobin-poor isolated fish cardiomyocytes.

The function of myoglobin at the cellular level was investigated by comparing O2 consumption in isolated myoglobin-rich cardiac myocytes from the sea raven (Hemitripterus americanus) and myoglobin-poor myocytes from the ocean pout (Macrozoarces americanus). O2 consumption by sea raven myocytes, 0.21 +/- 0.04 microM O2/10(6) cells.min-1, was significantly higher than O2 consumption by ocean pout myocytes, 0.10 +/- 0.07 microM O2/10(6) cells.min-1 at high PO2. O2 consumption in sea raven myocytes treated with sodium nitrite was not significantly different than that in untreated myocytes at high PO2, but it was significantly lower than controls at low PO2. O2 consumption of sea raven myocytes treated with the mitochondrial uncoupler CCCP was not significantly different from that of control myocytes at high PO2, but it was significantly greater than untreated controls at low PO2. In ocean pout preparations, O2 consumption by nitrite-treated myocytes was significantly higher than that of untreated myocytes at high PO2, but it was not different from that of controls at low PO2. CCCP-treated ocean pout myocytes had a significantly higher oxygen consumption than that of untreated myocytes at high PO2, but oxygen consumption was not different from that of controls at low PO2. The CCCP-activated O2 consumption at low PO2 was myoglobin-dependent in that CCCP alone resulted in a threefold increase in sea raven cells over controls but had no impact on sea raven cells in the presence of nitrite or ocean pout cells treated with CCCP alone. This study further supports the contention that myoglobin only plays an important role in oxygen metabolism at low extracellular PO2's.

Animals↗

Use of ventriculography in assessing performance and oxygen consumption of the left ventricle: response to altered afterload.

Using ventriculography, we assessed the relationship between performance, blood flow, and oxygen consumption of the left ventricle in seven anesthetized dogs. Ventricular loading was varied between increased and decreased afterload by intraaortic infusion of angiotensin and acetylcholine. Intact ventricular performance was measured by computer-based analysis of biplane left ventriculograms. Myocardial blood and flow distribution was determined by radioactive microspheres, and oxygen consumption was measured by coronary arteriovenous oxygen difference times blood flow. When left ventricular systolic pressure rose, tension-time index, stress-time index, stroke work, and minute work derived from the ventriculogram increased significantly; end diastolic volume increased; and ejection fraction decreased. Inverse responses occurred to a smaller degree when left ventricular pressure was reduced. With increased pressure, myocardial blood flow and oxygen consumption changed proportionately to minute work. Correlation coefficients between oxygen consumption and stroke work (0.782), oxygen consumption and minute work (0.769), oxygen consumption and tension-time index (0.792), and between oxygen consumption and stress-time index (0.740) all indicate that performance measures obtained from ventriculograms can be used to estimate changes in oxygen consumption during acute afterload changes. These measurements can be applied to data obtained from clinical catheterization studies in man and suggest that changes in myocardial performance and oxygen consumption can be estimated from ventriculographic data.

Angiotensin II↗

Canine coronary microvessel NO production regulates oxygen consumption in ecNOS knockout mouse heart.

We have previously shown that NO production by tissues following stimulation with bradykinin or other agonists can regulate oxygen consumption in skeletal muscle, heart and kidney. From those studies and from those using agonists, which classically release NO from blood vessels and which are unable to regulate tissue oxygen consumption in heart from ecNOS knockout mice, we concluded that vascular NO production is capable of regulating tissue oxygen consumption. The goal of these studies was to directly address the concept that NO production by blood vessels can regulate tissue oxygen consumption using a classical transfer paradigm. Microvessels, capable of producing NO, were prepared from canine hearts using a sieving technique, cardiac tissue was taken from mice lacking the ability to produce NO from ecNOS (ecNOS -/- mice) and tissue oxygen consumption measured in vitro using a Clark type electrode in a sealed chamber. Bradykinin (10(-7)to 10(-4)M) had no effect on tissue oxygen consumption when administered to heart from ecNOS -/mice as expected and no effect on oxygen consumption by isolated canine coronary microvessels (0+/-5% at 10(-5)M). However when coronary microvessels were co-incubated with heart from ecNOS -/- mice, bradykinin caused a dose dependent reduction in tissue oxygen consumption reaching a maximum of 44+/-10% at 10(-4)M. The effects of bradykinin were entirely abolished by L -NAME. The calculated concentration range for NO in these studies was 2.9 to 293 n M, within estimated physiologic range for the activity of NO on cytochrome oxidase. These data indicate that coronary microvessels can regulate cardiac oxygen consumption through a NO dependent mechanism.

Animals↗

Myocardial oxygen consumption during dobutamine infusion in endotoxemic pigs.

PURPOSE: Dobutamine infusion is used to increase whole-body oxygen delivery in septic patients to satisfy unmet oxygen demand of hypoxic tissues. However, dobutamine infusion also increases myocardial work and myocardial oxygen consumption. Our goal was to determine the importance of this effect as a fraction of the increase in whole-body oxygen consumption, in a porcine model of septic shock. MATERIALS AND METHODS: Four hours after a 50 microg/kg infusion of Escherichia coli endotoxin (0111: B4, Sigma) in eight anesthetized pigs, whole-body oxygen delivery and myocardial oxygen delivery and consumption were calculated from blood flow and arterial and venous oxygen content measurements. We directly measured whole-body oxygen consumption by analysis of inhaled and exhaled gases using a metabolic cart. Then dobutamine 10 and 20 microg/kg/min was infused and measurements were repeated. RESULTS: Dobutamine infusion increased whole-body oxygen delivery but did not increase metabolic cart measured whole-body oxygen consumption. Dobutamine infusion of 10 and 20 microg/kg/min increased myocardial oxygen consumption by 7.0 +/- 0.6 (80 +/-10%) and 12.0 +/- 2.0 mL O2/min (142 +/- 30%), respectively (P < .01). CONCLUSIONS: In this porcine model of sepsis, dobutamine infusion significantly increases myocardial oxygen consumption. Because whole-body oxygen consumption does not change, dobutamine infusion may fail to increase and may decrease oxygen consumption by other organs.

Analysis of Variance↗

The relationship between oxygen delivery and consumption in the conscious rat before and after expansion of body fluid volumes.

Oxygen consumption and delivery (defined as the product of cardiac output, haemoglobin concentration and arterial oxygen saturation) and haemodynamic variables were examined in the conscious resting rat throughout the day and after the expansion of body fluid volumes. Cardiac output was measured in arbitrary units by electromagnetic flowmetry and oxygen consumption by respirometry. The variability of blood pressure in the basal state was significantly less than that of cardiac output. Oxygen consumption was significantly correlated with cardiac output and oxygen delivery. In studies undertaken throughout the day, both oxygen consumption and delivery fell in the afternoon and there was evidence that the relationship between these two variables was curvi- rather than recti-linear. During oral sodium chloride administration for 7 days, blood pressure rose and some evidence was found for an alteration in the relationship between oxygen consumption and delivery, with an excess of delivery relative to consumption, particularly on the first day of salt loading. Intravenous injection of sodium chloride solution (0.171 mol/l) did not alter the relationship between oxygen consumption and delivery. Expansion of blood volume, while the packed cell volume was maintained nearly constant, raised oxygen delivery transiently and evidence was obtained that the relationship between oxygen consumption and delivery was altered, with oxygen delivery rising relatively more than oxygen consumption. The findings are discussed in relation to the autoregulatory hypothesis of circulatory control and for the role of autoregulation in hypertensive states. The importance of relating oxygen delivery to metabolic requirements in studies of the role of autoregulation is emphasized.

Animals↗

Arterial oxygen consumption after hemorrhagic shock: the effect of beta-adrenergic agonist.

Oxygen consumption of the rabbit femoral artery after hemorrhagic shock was studied. Hemorrhagic shock was initiated and maintained at 60 mm Hg of systolic blood pressure for 2 hours. A significant reduction in femoral artery oxygen consumption was observed after hemorrhagic shock (1.64 +/- 0.14 microliter/g/hr) when compared to oxygen consumption in the normal condition (2.52 +/- 0.22 microliter/g/hr). Application of the beta-agonist isoproterenol significantly increased oxygen consumption in the isolated femoral artery after hemorrhagic shock (2.66 +/- 0.20 microliter/g/hr), but did not exceed the normal values recorded without stimulation. Also, isoproterenol significantly increased oxygen consumption in the femoral artery of nonhemorrhagic condition (4.84 +/- 0.42 microliter/g/hr). The increase in oxygen consumption conditioned by isoproterenol was significantly lower after hemorrhagic shock compared with values in the nonhemorrhagic state. The data suggest that oxygen consumption is regulated by beta-adrenergic receptors, and the phenomenon of diminished oxygen consumption after hemorrhagic shock probably occurs because of changes in beta-adrenergic receptors, causing the appearance of change in the mechanism of oxygen consumption.

Animals↗

Effects of 2,4-dinitrophenol amylobarbitone and certain other drugs on the rate of oxygen consumption and force of contraction of isolated curarized diaphragm muscle of the rat.

1 A technique has been developed for studying over periods of 10 min or longer the effects of drugs on both the force of electrically-induced contractions and the oxygen consumption of an isolated, curarized, mammalian, skeletal muscle preparation.2 The resting oxygen consumption of the muscle was increased substantially by 2,4-dinitrophenol in concentrations (0.02 mM and higher) that eventually produced contracture. Two other uncoupling agents, 4,6-dinitro-o-cresol and carbonylcyanide-p-trifluoromethoxyphenylhydrazone, behaved similarly.3 The oxygen consumption over 10 min of the stimulated muscle was also increased by 2,4-dinitrophenol (0.05 mM), although the strength of the ;maximal' contractions was lessened.4 Amylobarbitone increased the strength of contraction at a concentration (0.2 mM) that did not affect oxygen consumption significantly. Amylobarbitone and pentobarbitone also increased it at a concentration (1 mM) that depressed oxygen consumption. They decreased both strength of contraction and oxygen consumption at a concentration of 5 mM. Phenobarbitone had a weaker action.5 S-n-decyl-thiouronium increased oxygen consumption when given at a concentration (1 mM) that diminished strength of contraction and eventually produced contracture of the muscle.6 Both S-methyl-thiouronium (1 mM) and 4-aminopyridine (0.1 mM and 0.5 mM) increased strength of contraction without increasing oxygen consumption. Neither strength of contraction nor oxygen uptake was affected by ouabain (up to 0.01 mM) or by phenformin (0.1 mM).7 It is concluded that the response to 2,4-dinitrophenol is due mainly, if not wholly, to its known ability to uncouple oxidative phosphorylation; that the response to the barbiturates is due to a combination of a known metabolic action (viz., blocking of the respiratory chain) and a stimulant action on muscle; and the response to S-n-decyl-thiouronium to a disruptive action on cell membranes. The disproportionate actions of 4-aminopyridine and S-methyl-thiouronium on strength of contraction relative to oxygen consumption are also attributed to a non-metabolic action.

Amobarbital↗

Influence of temperature on the response time of mitochondrial oxygen consumption in isolated rabbit heart.

1. In this study we determined the temperature dependence of the mean response time of cardiac mitochondrial oxygen consumption following steps in metabolic demand. Metabolic demand was altered by stepwise changes in heart rate or in left ventricular volume at 20 and 28 degrees C. 2. Ten isolated rabbit hearts were perfused with Tyrode solution at constant oxygen tension and constant arterial flow. A balloon was inserted in the left ventricle and developed pressure was measured. Coronary venous oxygen tension was measured continuously with a Clark-type oxygen electrode. 3. The mean response time of mitochondrial oxygen consumption is defined as the first statistical moment of the impulse response function. This mean response time of mitochondrial oxygen consumption, following the change in metabolic demand, is calculated from the measured mean response time for the change in coronary venous oxygen tension by subtracting the transport time resulting from diffusion and convective transport in the blood vessels. The transport time is obtained from a model for oxygen transport developed previously. Experimental data, necessary for the model calculation, were obtained from measurement of the coronary venous oxygen tension transients following stepwise changes either in arterial oxygen tension or perfusion flow. 4. The calculated mean response times of mitochondrial oxygen consumption were 26.9 +/- 3.0 s (mean +/- S.E.M.) at 20 degrees C and 14.9 +/- 1.0 s at 28 degrees C. The mean response times of mitochondrial oxygen consumption did not differ significantly for steps in heart rate and in left ventricular volume and between upward and downward steps. 5. We suggest that intracellular calcium concentration is not the sole regulator of mitochondrial oxygen consumption in the isolated rabbit heart, since steps in heart rate and in left ventricular volume showed the same time course of oxygen uptake. 6. The mean response time of mitochondrial oxygen consumption obtained in the isolated rabbit heart at 20 degrees C did not differ significantly from the mean response time of mitochondrial oxygen consumption of isolated rabbit papillary muscle. After combining our data with previously published data on empty beating hearts at 37 degrees C, a Q10, which is the factor by which the mean response time of mitochondrial oxygen consumption increases per 10 degrees C decrease in temperature, of 2.1 was calculated.

Animals↗

Extrapolated maximal oxygen consumption: a new method for the objective analysis of respiratory gas exchange during exercise.

Respiratory gas exchange was measured during maximal treadmill exercise testing in six healthy volunteers and 20 patients with chronic heart failure. A curve of equation y = ax-bx2 was used to model the relation between the rate of oxygen consumption (y axis) and the rate of carbon dioxide production (x axis). The constants "a" and "b" were used to calculate the maximal value of the expression ax-bx2. This value was termed the "extrapolated maximal oxygen consumption". For all subjects a close fit between experimental data and mathematical model was obtained and the values of the measured maximal rate of oxygen consumption and "extrapolated maximal oxygen consumption" were similar. Respiratory gas exchange was reanalysed using only those values obtained during the first 90%, 75%, and 66% of exercise. In contrast with the value for the measured rate of oxygen consumption, the value of "extrapolated maximal oxygen consumption" was effectively independent of exercise duration. Extrapolated maximal oxygen consumption provides an objective measure of cardiorespiratory functional reserve that, within limits, is independent of exercise duration. Extrapolated maximal oxygen consumption is complementary to the direct measurement of the maximal rate of oxygen consumption and increases the amount of information derived from a single exercise test.

Adult↗