Reduced nitrogen in ecology and the environment.

Since the beginning of the 19th century humans have increasingly fixed atmospheric nitrogen as ammonia to be used as fertilizer. The fertilizers are necessary to create amino acids and carbohydrates in plants to feed animals and humans. The efficiency with which the fertilizers eventually reach humans is very small: 5-15%, with much of the remainder lost to the environment. The global industrial production of ammonia amounts to 117 Mton NH(3)-Nyear(-1) (for 2004). By comparison, we calculate that anthropogenic emissions of NH(3) to the atmosphere over the lifecycle of industrial NH(3) in agriculture are 45.3 Mton NH(3)-Nyear(-1), about half the industrial production. Once emitted ammonia has a central role in many environmental issues. We expect an increase in fertilizer use through increasing demands for food and biofuels as population increases. Therefore, management of ammonia or abatement is necessary.

Ultrafast three-dimensional contrast-enhanced magnetic resonance angiography and imaging in the diagnosis of partial anomalous pulmonary venous drainage.

OBJECTIVES: The purpose of our study was to evaluate patients with suspected anomalous pulmonary veins (APVs) and atrial septal defects (ASDs) using fast cine magnetic resonance imaging (MRI) and ultrafast three-dimensional magnetic resonance angiography (MRA). BACKGROUND: Precise anatomic definition of anomalous pulmonary and systemic veins, and the atrial septum are prerequisites for surgical correction of ASDs. Cardiac catheterization and transesophageal echocardiography (TEE) are currently used to diagnose APVs, but did not provide complete information in our patients. METHODS: Twenty consecutive patients with suspected APVs were studied by MRA after inconclusive assessment by catheterization, TEE or both. The MRI images were acquired with a fast cine sequence and a novel ultrafast three-dimensional sequence before and after contrast injection. RESULTS: Partial anomalous pulmonary venous drainage was demonstrated in 16 of 20 patients and was excluded in four patients. Magnetic resonance imaging correctly diagnosed APVs and ASDs in all patients (100%) who underwent surgery. For the diagnosis of APVs, the MRI and catheterization results agreed in 74% of patients and the MRI and TEE agreed in 75% of patients. For ASDs, MRI agreed with catheterization and TEE in 53% and 83% of patients, respectively. CONCLUSIONS: Fast cine MRI with three-dimensional contrast-enhanced MRA provides rapid and comprehensive anatomic definition of APVs and ASDs in patients with adult congenital heart disease in a single examination.

Effect of very early angiotensin-converting enzyme inhibition on left ventricular dilation after myocardial infarction in patients receiving thrombolysis: results of a meta-analysis of 845 patients. FAMIS, CAPTIN and CATS Investigators.

OBJECTIVES: We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition <9 h after myocardial infarction (MI) on left ventricular (LV) dilation in patients receiving thrombolysis. BACKGROUND: The ACE inhibitors reduce mortality after MI. Attenuation of LV dilation has been suggested as an important mechanism. METHODS: The data of 845 patients with three-month echocardiographic follow-up after MI were combined from three randomized, double-blind, placebo-controlled studies. The criteria for these studies included: 1) thrombolytic therapy; 2) ACE inhibition within 6 to 9 h; and 3) evaluation of LV dilation as the primary objective. RESULTS: The ACE inhibitor was started 3.2+/-1.7 h after the patients' first (mainly, 85%) anterior MI. After three months, LV dilation was not significantly attenuated by very early treatment with an ACE inhibitor. The diastolic volume index was attenuated by 0.5 ml/m2 (95% confidence interval [CI] -1.5 to 2.5, p = 0.61), and the systolic volume index by 0.5 ml/m2 (95% CI -1.0 to 1.9, p = 0.50). Subgroup analysis demonstrated that LV dilation was significantly attenuated by ACE inhibitor treatment for patients in whom reperfusion failed. In contrast, LV dilation was almost unaffected by ACE inhibitor treatment in successfully reperfused patients. CONCLUSIONS: We could not demonstrate attenuation of LV dilation in patients receiving thrombolysis by ACE inhibitor treatment within 6 to 9 h after MI. We speculate that very early treatment with an ACE inhibitor has a beneficial effect on LV remodeling only in patients in whom reperfusion failed. Other mechanisms may be responsible for the beneficial effects of ACE inhibitors in successfully reperfused patients after MI.

Ten weeks of rapid ventricular pacing creates a long-term model of left ventricular dysfunction.

OBJECTIVE: Rapid ventricular pacing produces a reliable model of heart failure. Cessation after 4 weeks of rapid ventricular pacing results in rapid normalization of left ventricular function, but the left ventricle remains persistently dilated. We present novel data that show that prolonged rapid ventricular pacing (10 weeks) creates a model of chronic left ventricular dysfunction. METHODS: In 9 dogs undergoing 10 weeks of rapid ventricular pacing, left ventricular function and volumes were serially assessed by using 2-dimensional echocardiography and pressure-volume analysis for 12 weeks after cessation of pacing. RESULTS: Increased end-diastolic volume and decreased systolic and diastolic function were seen at the end of pacing. By 2 weeks of recovery from rapid ventricular pacing, end-diastolic volume and ejection fraction were partially recovered but did not improve further thereafter. Load-independent and load-sensitive indices of function obtained by pressure-volume analysis at 8 and 12 weeks of recovery confirmed a persistence of both systolic and diastolic dysfunction. In addition, left ventricular mass increased with pacing and remained elevated at 8 and 12 weeks of recovery. Four of these dogs studied at 6 months of recovery showed similar left ventricular abnormalities. CONCLUSION: Ten weeks of rapid ventricular pacing creates a long-term model of left ventricular dysfunction.

Detailed examination of fenfluramine-phentermine users with valve abnormalities identified in Fargo, North Dakota.

Although several studies have reported on valve abnormalities among users of fenfluramine or dexfenfluramine, detailed information on these subjects has not been provided, limiting the ability to understand who may be at risk for valve abnormalities and to generate hypotheses about the etiology and pathogenesis of these abnormalities. This study was a detailed medical record review of 18 previously reported users of fenfluramine and phentermine, all with valve abnormalities on echocardiogram and 2 with surgical pathology. Both clinical characteristics and medication use were recorded by trained abstracters using a standardized data collection form. Two subjects (11%) had other possible etiologies of valve disease: a history of rheumatic fever and prescribed ergotamine. Three subjects (17%) had a history of migraine headaches and 4 (22%) had murmurs noted before using fenfluramine. Use of medications that may affect serotonin receptors was common: ergotamine (1 subject, 5%), selective serotonin reuptake inhibitors (6, 33%), sumatriptan (2, 11%), and mirtazapine (1, 5%). Prior medication and nonmedication allergies were recorded in 6 (33%) and 3 (17%) subjects, respectively. All subjects had symptoms possibly due to fenfluramine or phentermine side effects. This study raises the hypotheses that valvular heart disease among fenfluramine users may be less common than previously estimated, that serotonin excess may play a role in valve pathology, and that a patient's response to anorexigens and other medications may serve as a marker for increased risk. Further study is needed to test these hypotheses.

Homocysteine: evidence for a causal relationship with cardiovascular disease.

Elevated plasma homocysteine levels are associated with vascular disease and thrombosis. Premature atherosclerosis and thromboembolism are seen in children who are homozygotes for defects in enzymes responsible for the metabolism of homocysteine. Adults with heterozygous defects have less marked elevations of homocysteine, and onset of atherosclerosis and vascular disease are delayed into the fourth and fifth decade of life. Homocysteine can damage vascular endothelium, cause proliferation of vascular smooth muscle, activate platelets, promote lipid peroxidation, and activate the coagulation cascade. Epidemiologic studies have linked elevations in plasma homocysteine with coronary artery disease, cerebrovascular disease, and thromboembolism. Folic acid, in combination with vitamins B6 and B12, can normalize homocysteine levels in most patients. Although randomized trials assessing the efficacy of homocysteine reduction have yet to be completed, treatment with vitamin supplementation should be considered in all patients at risk for vascular disease.

Effect of dobutamine on regional left ventricular function measured by tagged magnetic resonance imaging in normal subjects.

The effect of inotropic stimulation on the pattern and magnitude of regional left ventricular contraction was studied using tagged magnetic resonance imaging to assess whether dobutamine exacerbates variation in regional contraction at rest. Dobutamine stress testing defines a normal response as a homogeneous increase in regional wall motion. In 8 normal subjects, 4 equally spaced left ventricular short-axis levels were imaged through systole using tagged magnetic resonance imaging. The baseline imaging sequence was repeated with 5-, 10-, 15-, and 20-microg/kg/min dobutamine infusion. Regional myocardial displacement, radial thickening, and circumferential shortening were measured. The left ventricle was analyzed by level (base to apex) and wall (septum, inferior, lateral, anterior). Dobutamine did not alter baseline regional functional heterogeneity. Dobutamine infusion resulted in a uniform increase in displacement, radial thickening, and circumferential shortening from baseline to 10-microg/kg/min infusion without additional increases at higher doses.

Long-term dynamic cardiomyoplasty improves chronic and acute myocardial energetics in a model of left ventricular dysfunction.

BACKGROUND: We present the first long-term evaluation of myocardial energetics after dynamic cardiomyoplasty (CMP) in a model of left ventricular (LV) dysfunction. METHODS AND RESULTS: Seventeen dogs underwent rapid ventricular pacing (RVP) to create heart failure. Eight dogs were randomly selected to undergo cardiomyoplasty. All dogs continued RVP for 6 additional weeks, whereas the CMP dogs underwent a simultaneously delivered synchronized muscle wrap conditioning protocol. After termination of RVP at 10 weeks in all dogs, myoplasty dogs continued to receive muscle wrap stimulation until the terminal study. Pressure-volume analysis to assess LV energetics was conducted at baseline and 4 weeks and 3 months after termination of RVP (6 months after baseline). At 6 months, CMP dogs displayed enhanced contractility, lower volumes, and more optimal energetics compared with control animals. Acute muscle wrap stimulation further increased effective contractility and myocardial efficiency compared with unassisted beats. CONCLUSIONS: The decrease in NYHA functional class that occurs in patients after dynamic cardiomyoplasty may be secondary to its beneficial effects on long-term myocardial function, volume, and energetics.

Transmyocardial laser revascularization fails to prevent left ventricular functional deterioration and aneurysm formation after acute myocardial infarction in sheep.

OBJECTIVE: Transmyocardial laser revascularization is an investigational technique for revascularizing ischemic myocardium in patients with inoperable coronary arterial disease. This study tests the hypothesis that laser revascularization prevents left ventricular functional deterioration and aneurysm formation after acute anteroapical myocardial infarction. METHODS: An ultrasonic ascending aortic flow probe and snares around the distal left anterior descending and second diagonal coronary arteries were placed in 26 Dorsett hybrid sheep. Ten to 14 days later, snared arteries were occluded to produce an anteroapical infarction of 23% of left ventricular mass. Before infarction 14 animals had 34 +/- 4 transmyocardial perforations in the area of the anticipated infarction made with a carbon dioxide laser. Twelve animals served as controls. Hemodynamic measurements and transdiaphragmatic quantitative echocardiograms were obtained before, immediately after, and 2, 5, and 8 weeks after infarction. Eighteen sheep completed the protocol. RESULTS: All animals had large anteroapical left ventricular aneurysms with massive ventricular enlargement. Immediately after infarction the anterior wall became thinner and dyskinetic in all sheep. At 8 weeks aneurysmal size and shape were indistinguishable between groups. Two days after infarction, laser holes were filled with fibrin. At 5 and 8 weeks the infarct consisted of dense collagen, fibroblasts, scattered calcifications, myocyte fragments, neutrophils, macrophages, and no laser holes. There were no significant differences at any time between groups for cardiac pressures or output, ventricular volumes, ejection fraction, stroke work, and the stroke work-left ventricular end-diastolic pressure index. CONCLUSION: Transmyocardial laser perforations do not revascularize acute myocardial infarction in sheep.

Dynamic cardiomyoplasty: its chronic and acute effects on the failing heart.

OBJECTIVES: Dynamic cardiomyoplasty is an alternative therapy for end-stage heart failure. We investigated the mechanisms, both acute and chronic, by which a synchronously stimulated conditioned muscle wrap affects left ventricular function in a chronic canine model of dilated cardiomyopathy. METHODS: Nineteen dogs underwent rapid ventricular pacing at a rate of 215 beats/min for 4 weeks to create a model of heart failure. Eight dogs were then randomly selected to undergo cardiomyoplasty, and all dogs received 6 additional weeks of rapid ventricular pacing. The cardiomyoplasty group also received a graded muscle conditioning protocol of synchronized burst stimulation to transform the muscle wrap. All dogs were studied with pressure-volume analysis and echocardiography at baseline and after 4 and 10 weeks of rapid ventricular pacing. Data in the cardiomyoplasty group were analyzed with the stimulator off, with it augmenting every beat (1:1), and with it augmenting only every other beat (1:2). RESULTS: Stimulator "of" data at 10 weeks of rapid pacing demonstrated chronic effects by enhanced ventricular function (end-systolic elastance = 1.80 after myoplasty vs 1.17 for controls, p = 0.005) and a stabilization of volumes and composite end-systolic and end-diastolic pressure-volume relations in the cardiomyoplasty group when compared with controls. Myoplasty stimulation increased apparent contractility (preload recruitable stroke work = 31.3 for stimulator "of" vs 40.6 for stimulator 1:2 assisted beats [p < 0.05] and vs 45.4 for stimulator 1:1 [p < 0.05]). CONCLUSIONS: Benefits from dynamic cardiomyoplasty are by at least two mechanisms: (1) the girdling effects of a conditioned muscle wrap, which halts the chronic remodeling of heart failure, and (2) active systolic assistance, which augments the apparent contractility of the failing heart.

Ventricular dysfunction and the risk of stroke after myocardial infarction.

BACKGROUND: In patients who have had a myocardial infarction, the long-term risk of stroke and its relation to the extent of left ventricular dysfunction have not been determined. We studied whether a reduced left ventricular ejection fraction is associated with an increased risk of stroke after myocardial infarction and whether other factors such as older age and therapy with anticoagulants, thrombolytic agents, or captopril affect long-term rates of stroke. METHODS: We performed an observational analysis of prospectively collected data on 2231 patients who had left ventricular dysfunction after acute myocardial infarction who were enrolled in the Survival and Ventricular Enlargement trial. The mean follow-up was 42 months. Risk factors for stroke were assessed by both univariate and multivariate Cox proportional-hazards analysis. RESULTS: Among these patients, 103 (4.6 percent) had fatal or nonfatal strokes during the study (rate of stroke per year of follow-up, 1.5 percent). The estimated five-year rate of stroke in all the patients was 8.1 percent. As compared with patients without stroke, patients with stroke were older (mean [+/-SD] age, 63+/-9 years vs. 59+/-11 years; P<0.001) and had lower ejection fractions (29+/-7 percent vs. 31+/-7 percent, P=0.01). Independent risk factors for stroke included a lower ejection fraction (for every decrease of 5 percentage points in the ejection fraction there was an 18 percent increase in the risk of stroke), older age, and the absence of aspirin or anticoagulant therapy. Patients with ejection fractions of < or = 28 percent after myocardial infarction had a relative risk of stroke of 1.86, as compared with patients with ejection fractions of more than 35 percent (P=0.01). The use of thrombolytic agents and captopril had no significant effect on the risk of stroke. CONCLUSIONS: During the five years after myocardial infarction, patients have a substantial risk of stroke. A decreased ejection fraction and older age are both independent predictors of an increased risk of stroke. Anticoagulant therapy appears to have a protective effect against stroke after myocardial infarction.

Quantitative echocardiography in left ventricular remodeling after myocardial infarction.

Two-dimensional transthoracic echocardiography has been used to study patients during and after myocardial infarction. Quantitative studies have revealed that progressive increase in left ventricular size is associated with a poor prognosis. When pre-defined echocardiographic criteria were used to stratify infarction patients for adverse cardiovascular outcome, the efficacy of combined thrombolysis and angiotensin-converting enzyme inhibitor therapy could be shown in those who developed left ventricular enlargement. Other descriptors of left ventricular architecture and function, such as cavity shape and the ratio of short-axis left ventricular muscle to cavity area, may predict cardiovascular death and severe heart failure.

QT interval and dispersion in primary autonomic failure.

OBJECTIVE: To investigate the role of the autonomic nervous system in determining QT interval and dispersion. PATIENTS AND METHODS: 32 patients with chronic primary (idiopathic) autonomic failure (19 men, mean age 60 years) and 21 normal controls (11 men, mean age 59) without symptoms of ischaemic heart disease were studied retrospectively. Autonomic failure was diagnosed by a combination of symptomatic postural hypotension, subnormal plasma noradrenaline response to head-up tilt, and abnormal cardiovascular responses to standing, Valsalva manoeuvre, mental stress, cutaneous cold, isometric exercise, and deep breathing. QT intervals were measured from surface electrocardiograms and QT dispersion was defined as maximum QT--minimum QT occurring in any of the 12 leads. RESULTS: Mean heart rate (RR intervals) was similar in patients with autonomic failure and controls (S2 lead: 865 (132) v 857 (108) ms, P = NS; V2 lead: 865 (130) v 868 (113) ms, P = NS). QT intervals measured from electrocardiogram leads S2 and V2 were significantly longer in patients than in controls (401 (40) v 376 (16) ms, P < 0.01; and 403 (41) v 381 (20) ms, P < 0.05 respectively). The mean maximum QT interval in any lead, which is the best estimate of the maximum duration of electrical systole, was significantly longer in the patients than in controls (417 (48) v 388 (23) ms, P < 0.005). Linear regression analysis of QT and RR intervals for both groups showed a significant difference between the slopes of the two regression lines (F = 8.4, P < 0.001). However, QT dispersions were similar between patients and controls. CONCLUSIONS: Patients with primary autonomic failure have prolongation of QT intervals, indicating that the autonomic nervous system is an important determinant of QT interval. However, QT dispersion does not seem to be affected by chronic primary autonomic denervation.

Quantitation of organ symmetry by diagnostic ultrasonic imaging: a group theoretical approach.

A method based on group theory is proposed to quantify the shape of an organ. It is proposed that a complex shape is characterized by a basic set of symmetry operations involving rotation about the center axis. Based on this concept, partial symmetry elements (PSE) were determined by stepwise rotation of the images and measurement of overlap area between the original and rotated images. These measurements were used to define a symmetry index (SI) and to "decompose" the complex shape into simpler shapes with regular geometry such as a circle, an ellipse, an equilateral triangle, a square, etc. Computer simulations and two-dimensional (2-D) ultrasonic images of the prostate were used to demonstrate the feasibility of the method. The method was also applied to a series of clinical ultrasonic cardiac images to determine the dynamic shape changes in left ventricle (LV) of a normal heart and an heart with infarction. The results of this study show that SI increased with an increase in the symmetry of the simulation models and the prostate. Cross-sectional images of prostate with triangular and ellipsoidal shapes exhibited larger proportion of three-fold and two-fold symmetries, respectively. Symmetry index of the LV changed during the cardiac cycle and exhibited a loop-like structure when plotted as a function of size. Quantitative measurements of SI indicated that the left ventricular chamber is rounder during the diastolic phase of the cardiac cycle. The loop-like structure was considerably reduced in the heart with infarction. Also, larger distortions in cardiac shape were observed over cardiac cycle in the heart with infarction, as compared to the normal heart. In conclusion, it is feasible to quantitatively characterize 2-D shapes of the organs by symmetry operations based on group theoretical analysis.

Acute systolic and diastolic indices of left ventricular function after cardiomyoplasty in a chronic model of heart failure.

Recent experimental studies have suggested that the initial nonstimulated stage of dynamic cardiomyoplasty acutely impairs ventricular function. Those investigations were performed on normal hearts and primarily examined diastolic alterations as a result of the passive muscle wrap. The purpose of this study was to assess the acute systolic and diastolic effects of a nonstimulated muscle wrap in chronic heart failure induced by rapid ventricular pacing in canines. Pressure-volume analysis of ventricular function based on conductance catheter volume and micromanometer pressure data was used. Each animal was studied before rapid pacing, before cardiomyoplasty, and immediately after wrap. By the end of the pacing period and before wrap, left ventricular dysfunction developed in all dogs, manifested by significant deterioration of both systolic and diastolic indices of ventricular function, as well as progressive increases in left ventricular volumes. However, no further deterioration with load insensitive indices of systolic or diastolic indicators of ventricular function was found as a result of the passive muscle wrap. These results suggest that the cardiomyoplasty procedure can be safely performed on failing hearts without prohibitive acute impairment of ventricular function.

Effects of type 1 diabetes mellitus on cardiac function: a study of monozygotic twins.

OBJECTIVE: To investigate left ventricular size and function in type 1 diabetes and their relation with diabetes duration, glycaemic control, autonomic dysfunction, and complications of diabetes. DESIGN: Cross sectional study using a pulsed wave Doppler echocardiogram to assess left ventricular dimensions, wall thickness, and transmitral blood flow velocity signals. PATIENTS: 40 monozygotic twin pairs (23 male, mean age 26 years) discordant for type 1 diabetes and 40 non-diabetic singleton controls with no clinical evidence of cardiac ischaemia. RESULTS: For all Doppler echocardiographic measurements there were strong correlations between monozygotic twins but not between twins and control subjects. Left ventricular dimensions, wall thickness and systolic function, peak E velocity, and the velocity integrals of early left ventricular filling were similar in all three groups. Peak A velocity and the velocity integrals of late ventricular filling (mean (SD)) were greater in diabetic twins (45 (12) v 38 (8) cm/s, P = 0.002; and 32 (11) v 26 (6), P = 0.0002). Diabetic twins had lower E/A ratio (1.59 (0.39) v 1.83 (0.39), P < 0.001), greater atrial filling fraction to total diastolic filling (28 (6) v 25 (5)%, P = 0.002), and prolonged isovolumic relaxation time (72 (12) v 63 (9) ms, P < 0.001). The differences in Doppler findings between diabetic and non-diabetic twins were related to disease duration whereas the prolongation of the isovolumic relaxation time was related to cardiac autonomic dysfunction. CONCLUSIONS: These results show that twins with type 1 diabetes have left ventricular diastolic dysfunction related to diabetes duration and cardiac autonomic dysfunction but not to glycaemic control or microvascular complications. In addition, genetic factors contribute to left ventricular dimension and function.