Leaf water stable isotopes and water transport outside the xylem.

How water moves through leaves, and where the phase change from liquid to vapour occurs within leaves, remain largely mysterious. Some time ago, we suggested that the stable isotope composition of leaf water may contain information on transport pathways beyond the xylem, through differences in the development of gradients in enrichment within the various pathways. Subsequent testing of this suggestion provided ambiguous results and even questioned the existence of gradients in enrichment within the mesophyll. In this review, we bring together recent theoretical developments in understanding leaf water transport pathways and stable isotope theory to map a path for future work into understanding pathways of water transport and leaf water stable isotope composition. We emphasize the need for a spatially, anatomically and isotopically explicit model of leaf water transport.

A single-substrate model to interpret intra-annual stable isotope signals in tree-ring cellulose.

The carbon and oxygen stable isotope composition of wood cellulose (delta(13)C(cellulose) and delta(18)O(cellulose), respectively) reveal well-defined seasonal variations that contain valuable records of past climate, leaf gas exchange and carbon allocation dynamics within the trees. Here, we present a single-substrate model for wood growth to interpret seasonal isotopic signals collected in an even-aged maritime pine plantation growing in South-west France, where climate, soil and flux variables were also monitored. Observed seasonal patterns in delta(13)C(cellulose) and delta(18)O(cellulose) were different between years and individuals, and mostly captured by the model, suggesting that the single-substrate hypothesis is a good approximation for tree ring studies on Pinus pinaster, at least for the environmental conditions covered by this study. A sensitivity analysis revealed that the model was mostly affected by five isotopic discrimination factors and two leaf gas-exchange parameters. Modelled early wood signals were also very sensitive to the date when cell wall thickening begins (t(wt)). Our model could therefore be used to reconstruct t(wt) time series and improve our understanding of how climate influences this key parameter of xylogenesis.

Effects of intravenous theophylline on exercise-induced myocardial ischemia. I. Impact on the ischemic threshold.

OBJECTIVES: Theophylline has been shown to delay the onset of myocardial ischemia and to prolong exercise duration. The present study was done to evaluate the mechanisms and actions of intravenous theophylline on the onset of ischemia and exercise duration. BACKGROUND: The ischemic threshold may be altered by the differential coronary vasodilation induced by endogenous adenosine. Theophylline is a competitive receptor antagonist of adenosine and may have a potential as an anti-ischemic medication. METHODS: A double-blind, placebo-controlled crossover trial using an infusion of intravenous theophylline (8.0 +/- 2.0 mg/liter) or placebo before exercise in 12 patients was done. Oxygen uptake, heart rate, blood pressure and heart rate-blood pressure product were determined at the onset of > or = 0.1-mV ST segment depression and angina pectoris, as well as at peak exercise. The extent of myocardial ischemia was evaluated by electrocardiographic criteria and quantitation of thallium-201 images at peak exercise. RESULTS: When compared with placebo, theophylline significantly delayed time to the onset of exercise-induced ischemia. Ischemia occurred at a higher heart rate-blood pressure product and oxygen uptake. Exercise duration was prolonged but was not associated with greater ischemia, as determined by oxygen uptake, ST segment depression, angina pectoris and size of thallium-201 defect. CONCLUSIONS: It is concluded that theophylline favorably alters myocardial ischemia not only by delaying its onset but also by enabling it to occur at a higher threshold without causing deleterious effects during exercise. The mechanism for the increased ischemic threshold may be through the inhibition of adenosine and the coronary steal phenomenon.

Effects of intravenous theophylline on exercise-induced myocardial ischemia: II. A concentration-dependent phenomenon.

OBJECTIVES: The effects of varying concentrations of theophylline on exercise-induced myocardial ischemia were evaluated in patients with stable coronary artery disease. BACKGROUND: Theophylline is a competitive antagonist of adenosine and may have potential as an anti-ischemic medication. It is not known whether these effects on myocardial ischemia are concentration dependent. METHODS: In a double-blind, randomized, crossover manner, 11 patients received, at 1-week intervals, placebo and each of three theophylline doses by intravenous infusion for 45 min. Graded exercise testing was performed before randomization and immediately after each infusion. Concurrent anti-ischemic medications were withheld for 24 h before each exercise test. Serum theophylline concentrations achieved were 3.9 +/- 1.0 mg/liter (low), 8.2 +/- 1.8 mg/liter (medium) and 13.2 +/- 2.3 mg/liter (high). RESULTS: Compared with placebo, none of the three theophylline infusions produced a significant alteration in rest heart rate, blood pressure, mean frequency or severity of ventricular ectopic activity or noncardiac symptoms. The time to onset of ischemia was progressively increased, with medium and high concentrations achieving statistical significance. Similar patterns were observed for oxygen uptake and the heart rate-systolic blood pressure product at the onset of ischemia. Total exercise duration was significantly prolonged with the medium and high concentrations. CONCLUSIONS: It is concluded that administration of varying doses of theophylline before exercise produces a clinically significant and concentration-dependent improvement in the indicators of myocardial ischemia in patients with chronic stable coronary artery disease.

Comparison of chest pain, electrocardiographic changes and thallium-201 scintigraphy during varying exercise intensities in men with stable angina pectoris.

This study was performed to evaluate the presence of angina pectoris, electrocardiographic changes and reversible thallium-201 defects resulting from 2 different levels of exercise in 19 patients with known coronary artery disease and evidence of exercise-induced ischemia. The exercise protocols consisted of a symptom-limited incremental exercise test (Bruce protocol) followed within 3 to 14 days by a submaximal, steady-state exercise test performed at 70% of the maximal heart rate achieved during the Bruce protocol. The presence and time of onset of angina and electrocardiographic changes (greater than or equal to 0.1 mV ST-segment depression) as well as oxygen uptake, exercise duration and pressure-rate product were recorded. Thallium-201 (2.5 to 3.0 mCi) was injected during the last minute of exercise during both protocols, and the images were analyzed using both computer-assisted quantitation and visual interpretations. Incremental exercise resulted in anginal symptoms in 84% of patients, and electrocardiographic changes and reversible thallium-201 defects in all patients. In contrast, submaximal exercise produced anginal symptoms in only 26% (p less than 0.01) and electrocardiographic changes in only 47% (p less than 0.05), but resulted in thallium-201 defects in 89% of patients (p = not significant). The locations of the thallium-201 defects, when present, were not different between the 2 exercise protocols. These findings confirm the sequence of the ischemic cascade using 2 levels of exercise and demonstrate that the cascade theory is applicable during varying ischemic intensities in the same patient.

Effect of dipyridamole therapy on myocardial ischemia in patients with stable angina pectoris receiving concurrent anti-ischemic therapy.

The effects of oral dipyridamole on exercise performance and anginal symptoms were evaluated in 15 men with stable angina pectoris. In a double-blind, randomized, crossover design, patients received 75 mg of dipyridamole or placebo every 8 hours for 2 weeks in addition to their previously prescribed cardiac medications. Graded exercise tolerance testing was performed twice before randomization, at the end of each treatment period, and after single-blind placebo washout. When compared with baseline tests, the time to onset of 0.1 mV ST-segment depression was similar between dipyridamole and placebo treatments (316 +/- 89 vs 345 +/- 102 seconds, respectively, p = not significant). No significant differences existed between treatments in the peak systolic blood pressure-heart rate product or in the duration of exercise. Angina pectoris occurred during all 3 baseline exercise tests in 7 of the 15 subjects; the time to onset of angina was unchanged by either treatment. Analysis of symptom diaries conducted in 13 patients revealed no significant alteration in reported anginal symptoms during dipyridamole treatment compared with placebo treatment (0.6 +/- 0.9 vs 0.3 +/- 0.4 episodes per week). Ambulatory electrocardiographic monitoring in 12 patients revealed few episodes of ischemia during daily activities with no alteration in frequency of episodes during treatment periods. Plasma concentrations of dipyridamole did not correspond with the outcomes of exercise testing. It is concluded that chronic oral dipyridamole therapy given in its usual clinical dose does not adversely affect exercise performance, daily anginal episodes or ambulatory ischemia in patients receiving concurrent anti-ischemic medication.

Comparison of dobutamine and exercise using technetium-99m sestamibi imaging for the evaluation of coronary artery disease.

Studies using dobutamine thallium-201 myocardial perfusion imaging have suggested a high sensitivity and specificity for the detection of coronary artery disease. However, few data are available comparing dobutamine with exercise stress for the detection and localization of perfusion defects. This study compared the effects of dobutamine and exercise stress using technetium-99m sestamibi single-photon emission computed tomographic imaging in the same patients in a prospective crossover trial. Twenty-four patients with a high likelihood of coronary artery disease underwent tomographic myocardial imaging at rest, after symptom-limited treadmill exercise, and after intravenous dobutamine (maximum 30 micrograms/kg/min). Tomograms of the left ventricle were divided into 20 segments and were interpreted without knowledge of patient identity or stress protocol. Dobutamine was well tolerated by all patients. Segment-by-segment concordance between exercise and dobutamine images was highly significant (kappa = 0.56, p < 0.0001). Global first-order agreement (normal vs abnormal) between exercise and dobutamine studies was 96% (kappa = 0.65, p = 0.02); global second-order agreement (normal vs fixed vs ischemic defect) was 88% (kappa = 0.45, p = 0.02). Regional first- and second-order agreement were 96 and 93%, respectively (p < 0.001 for both). Twenty patients underwent coronary angiography. Comparisons between exercise and angiography and between dobutamine and angiography were similar for both global agreement (95 vs 100%, p = NS) and regional agreement (77 vs 72%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacology and pharmacotherapy of cardiovascular drugs in patients with chronic renal disease.

Cardiovascular disease is a common comorbidity and a major cause of mortality in patients with chronic renal disease. Drug regimens in patients with cardiovascular disease are frequently complex and can be significantly affected by alterations in renal function. In addition, several cardiovascular drugs directly affect renal function and the management of patients with renal disease. This article reviews the impact of renal disease on the pharmacokinetics of cardiovascular drugs and identifies clinically important interactions between these and other drugs commonly used in the management of chronic renal disease. Several classes of cardiovascular drugs are also discussed in relationship to their differential effects on the management and progression of renal disease.

Antiischemic therapy in patients with coronary heart disease living in long-term care. Systematic Assessment of Geriatric Drug Use by Epidemiology (SAGE) Group.

We evaluated antiischemic therapy in elderly nursing home residents with a diagnosis of coronary heart disease (CHD) using a population-based data base with over 300,000 residents (1992-1995) of all Medicare/Medicaid-certified nursing homes of five states. We identified 72,263 patients age 65 years or older with a diagnosis of CHD. We examined data collected with the federally mandated Minimum Data Set, drug information, and Medicare hospital claims. Antiischemics were defined as beta-adrenergic blockers, long-term nitrates, and calcium channel blockers. We determined factors associated with use of the drugs by logistic regression. Antiischemic therapy was inversely related to age and cognitive and physical functioning, but positively associated with recent hospitalization and concomitant cardiovascular diseases. beta-Adrenergic blockers were least likely to be administered regardless of age, gender, or cognitive or physical function. We conclude that antiischemic therapy in nursing home residents may not be optimal.

The drug data base of the Pawtucket Heart Health Program: development and description.

Pharmacoepidemiology has become an important tool for identifying patterns of drug use and adverse drug reactions in the general population. Drug data bases derived from population-based samples have been particularly useful in addressing questions such as adherence to national guidelines for the treatment of chronic diseases. As part of the Pawtucket Heart Health Program, a continuing community-based research and demonstration project, detailed information regarding the use of drugs among the general population of two southeastern New England cities was collected using cross-sectional and longitudinal methodologies.

Predictors of future antihypertensive use in patients with mildly elevated blood pressure.

We prospectively identified predictors of future antihypertensive use in untreated persons age 18-65 years who had elevated diastolic blood pressures of 90-104 mm Hg or systolic blood pressures of at least 140 mm Hg. Data were derived from two independent cohorts completing household surveys conducted in 1981-1984 and 8 years later, as part of the Pawtucket Heart Health Program. Demographics, self-reported health behaviors and beliefs, and physiologic measurements were obtained. Drug use was determined through structured interviews. Analysis of covariance and logistic regression were performed. In the 492 subjects, independent baseline predictors of future antihypertensive use (p < 0.05) included female gender, older age, diastolic blood pressure elevation, self-perceived high blood pressure, and self-reported salt limitation. Antihypertensive use for previously untreated mild hypertension is diverse. Older women with diastolic elevations who are health conscious are most likely to be treated.

Is antidepressant use changing? Prevalence and clinical correlates in two New England communities.

We attempted to determine whether the prevalence of antidepressant use had increased in population-based samples between 1981 and 1993, and compared the characteristics of antidepressant users and nonusers. Data were derived from six biennial, random sample, cross-sectional household surveys conducted between 1981 and 1993 in two southeastern New England communities. For each survey, point prevalence estimates were determined for the major antidepressant categories. Antidepressant users were most likely to be women, slightly older, and less likely to be employed than nonusers (p < 0.0001). Comorbid conditions and concurrent drug therapy were present more frequently among users. The overall prevalence of antidepressant use per 1000 population increased from 7.8 (95% confidence interval 4.3, 11.3) in 1981-1982 to 31.4 (95% CI 23.9, 38.9) in 1992-1993, especially among women and respondents between ages 40 and 59 years.

Correlates of oral contraceptive use in two New England communities: 1981-1993.

This study compared the sociodemographic and cardiovascular correlates of oral contraceptive users and nonusers between 1981 and 1993. We also sought to determine changes in the prevalence of oral contraceptive use among older premenopausal women. Using data from six biennial cross-sectional household surveys in a population-based sample of two New England communities, 5239 women between ages 18 and 45 years were identified. Women using oral contraceptives were 5 years younger and better educated than nonusers, and users more frequently reported a per capita income above the median for the survey population than nonusers. Users were more likely to report smoking and have a lower body mass index than nonusers. Little use of oral contraceptives was detected among women ages 40-45 years despite changes in FDA recommendations about their use and increasing evidence of their noncontraceptive benefits in healthy older nonsmoking women.

Drug therapy and prevalence of erectile dysfunction in the Massachusetts Male Aging Study cohort.

STUDY OBJECTIVE: To examine the association of commonly used drugs with erectile dysfunction (ED) at two time points. DESIGN: Population-based, cross-sectional, survey analysis. PARTICIPANTS: Randomly selected cohort of men in the Massachusetts Male Aging Study (MMAS) that included 1476 men for the baseline (1987-1989) and 922 for the follow-up (1995-1997) analyses. INTERVENTION: Crude associations between specific drug categories were examined with chi2 statistics. Logistic regression analysis was used to separate the effect of drugs from the influence of heart disease, hypertension, untreated diabetes, or depressive symptoms. MEASUREMENTS AND MAIN RESULTS: In the MMAS, medical history, current drug use, and erectile function status were ascertained with in-home interviews. In unadjusted analyses, thiazide and nonthiazide diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, benzodiazepines, digitalis, nitrates, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, and histamine2 receptor antagonists were associated with prevalent ED. Adjustment for comorbidities and health behaviors attenuated these associations, with only nonthiazide diuretics and benzodiazepines remaining statistically significant. CONCLUSION: Several common drugs may increase prevalence of ED; however, additional data from larger populations are needed to determine whether these associations are independent of underlying health conditions and to explore the effects of dosage and duration of use.

Changing trends in antihypertensive therapy in two New England communities during the 1980s.

The prevalence rates and correlates of antihypertensive drug use among individuals with hypertension were determined using data derived from five biennial population-based surveys conducted between 1981 and 1990 in two New England communities. Point prevalence estimates were determined for nine categories of antihypertensive agents at five time points, and were analyzed by age and sex using multiple logistic regression. In the first cross-sectional survey, the prevalence of use per 1000 individuals with hypertension was 235.4 for diuretics, 57.1 for beta-blockers, 65.5 for combination products, 29.2 for central alpha-agonists, 2.8 for peripheral alpha-antagonists, and 8.4 each for adrenergic blockers and direct vasodilators. The prevalence rates for calcium channel blockers and angiotensin-converting enzyme inhibitors increased sharply between the third and fourth survey cycles. Significant age- and sex-related differences in antihypertensive use were detected.

Pharmacotherapy of systolic heart failure: emphasis on mortality outcomes.

Mortality outcomes in clinical trials have become the foundation for the evidence-based management of patients with systolic heart failure. This review was intended to give the clinician a better understanding of newer pharmacological strategies in this patient population.

Components of ecosystem evaporation in a temperate coniferous rainforest, with canopy transpiration scaled using sapwood density.

Here we develop and test a method to scale sap velocity measurements from individual trees to canopy transpiration (E(c)) in a low-productivity, old-growth rainforest dominated by the conifer Dacrydium cupressinum. Further, E(c) as a component of the ecosystem water balance is quantified in relation to forest floor evaporation rates and measurements of ecosystem evaporation using eddy covariance (E(eco)) in conditions when the canopy was dry and partly wet. Thermal dissipation probes were used to measure sap velocity of individual trees, and scaled to transpiration at the canopy level by dividing trees into classes based on sapwood density and canopy position (sheltered or exposed). When compared with ecosystem eddy covariance measurements, E(c) accounted for 51% of E(eco) on dry days, and 22% of E(eco) on wet days. Low transpiration rates, and significant contributions to E(eco) from wet canopy evaporation and understorey transpiration (35%) and forest floor evaporation (25%), were attributable to the unique characteristics of the forest: in particular, high rainfall, low leaf area index, low stomatal conductance and low productivity associated with severe nutrient limitation.