Thiosulfate oxidation by Thiomicrospira thermophila: metabolic flexibility in response to ambient geochemistry.

Previous studies of the stoichiometry of thiosulfate oxidation by colorless sulfur bacteria have failed to demonstrate mass balance of sulfur, indicating that unidentified oxidized products must be present. Here the reaction stoichiometry and kinetics under variable pH conditions during the growth of Thiomicrospira thermophila strain EPR85, isolated from diffuse hydrothermal fluids at the East Pacific Rise, is presented. At pH 8.0, thiosulfate was stoichiometrically converted to sulfate. At lower pH, the products of thiosulfate oxidation were extracellular elemental sulfur and sulfate. We were able to replicate previous experiments and identify the missing sulfur as tetrathionate, consistent with previous reports of the activity of thiosulfate dehydrogenase. Tetrathionate was formed under slightly acidic conditions. Genomic DNA from T. thermophila strain EPR85 contains genes homologous to those in the Sox pathway (soxAXYZBCDL), as well as rhodanese and thiosulfate dehydrogenase. No other sulfur oxidizing bacteria containing sox(CD)2 genes have been reported to produce extracellular elemental sulfur. If the apparent modified Sox pathway we observed in T. thermophila is present in marine Thiobacillus and Thiomicrospira species, production of extracellular elemental sulfur may be biogeochemically important in marine sulfur cycling.

Deconvolving microbial and environmental controls on marine sedimentary pyrite sulfur isotope ratios.

Reconstructions of past environmental conditions and biological activity are often based on bulk stable isotope proxies, which are inherently open to multiple interpretations. This is particularly true of the sulfur isotopic composition of sedimentary pyrite (δ34Spyr), which is used to reconstruct ocean-atmosphere oxidation state and track the evolution of several microbial metabolic pathways. We present a microanalytical approach to deconvolving the multiple signals that influence δ34Spyr, yielding both the unambiguous determination of microbial isotopic fractionation (εmic) and new information about depositional conditions. We applied this approach to recent glacial-interglacial sediments, which feature over 70‰ variations in bulk δ34Spyr across these environmental transitions. Despite profound environmental change, εmic remained essentially invariant throughout this interval and the observed range in δ34Spyr was instead driven by climate-induced variations in sedimentation.

Relations among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease.

Invasive Doppler catheter-derived coronary flow reserve, echocardiographic measurements of left ventricular hypertrophy and intravenous dipyridamole-limited stress thallium-201 scintigraphy were compared in 48 patients (40 were hypertensive or diabetic) with clinical ischemic heart disease and no or minor coronary artery disease. Abnormal vasodilator reserve (ratio less than 3:1) occurred in 50% of the study group and markedly abnormal reserve (less than or equal to 2:1) occurred in 27%. Coronary vasodilator reserve was significantly lower (2.2 +/- 0.8 versus 3.5 +/- 1.3, p = 0.003) and indexed left ventricular mass significantly higher (152.6 +/- 42.2 versus 113.6 +/- 24.0 g, p = 0.0007) in patients with a positive (n = 11) versus a negative (n = 32) thallium perfusion scan. Coronary flow reserve was linearly related in coronary basal flow velocity as follows: y = -0.17x + 4.59; r = -0.57; p = 0.00002. The decrement in flow reserve was not linearly related to the degree of left ventricular hypertrophy. Abnormal vasodilator reserve subsets found in hypertensive patients were defined on the basis of basal flow velocity, indexed left ventricular mass and clinical factors. In this series, diabetes did not cause a detectable additional decrement in flow reserve above that found with hypertension alone. These findings demonstrate that thallium perfusion defects are associated with depressed coronary vasodilator reserve in hypertensive patients without obstructive coronary artery disease. Left ventricular hypertrophy by indexed mass criteria is predictive of which hypertensive patients are likely to have thallium defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Racial differences in myocardial ischemia and coronary flow reserve in hypertension.

OBJECTIVES: Using invasive measurements of endothelium-independent coronary flow reserve and stress thallium testing with or without dipyridamole, this study investigated racial differences in ischemia and coronary reserve in hypertensive left ventricular hypertrophy. BACKGROUND: African Americans compared with Caucasian Americans appear to have a higher case fatality from coronary heart disease but lesser amounts of atherosclerotic coronary artery disease. This paradox may be explainable by intrinsic or acquired racial differences in coronary arteriolar autoregulation and vasoreactivity. METHODS: The study enrolled 91 African and 81 Caucasian Americans referred for cardiac catheterization because of suspected myocardial ischemia but found to have no significant coronary stenosis. Patients were stratified by degree of left ventricular hypertrophy for comparison purposes after calculation of indexed left ventricular mass by means of echocardiographic M-mode measurements. Coronary flow reserve measurements were made using the intracoronary Doppler catheter and hyperemic doses of intravenous dipyridamole in 100 patients and intracoronary papaverine and adenosine in 72 patients. Seventy-seven percent of patients underwent adequate stress thallium testing with or without dipyridamole. RESULTS: In African Americans, mean (+/- SD) coronary flow reserve decreased from 4.4 +/- 2.3 for 38 without mass hypertrophy to 3.2 +/- 1.3 for 53 with hypertrophy (p = 0.005) to 2.7 +/- 1.1 for 12 with severe hypertrophy (p = 0.02). Thallium testing was abnormal in 31% of those without mass hypertrophy and 59% of those with hypertrophy. In Caucasian Americans, coronary flow reserve decreased from 4.1 +/- 2 for 58 without hypertrophy to 3.6 +/- 1.5 for 23 with hypertrophy (p = NS) to 3 +/- 1.5 for 6 with severe hypertrophy (p = NS). Thallium testing was abnormal in 36% without mass hypertrophy and in 39% with hypertrophy. CONCLUSIONS: This study establishes that development of left ventricular hypertrophy in hypertension carries greater physiologic morbidity for African compared with Caucasian Americans, typified by marked reduction in endothelium-independent coronary flow reserve and increased frequency of abnormal thallium tests.

Heterogeneous vasomotor responses of coronary conduit and resistance vessels in hypertension.

OBJECTIVES: The purpose of our study was to investigate the relation between conductance and resistance coronary vasomotor responsiveness in hypertensive patients without atherosclerosis. BACKGROUND: Although similar in morphology, conduit and resistance coronary vessels differ importantly in size, function and local environment and appear to be differentially affected in certain disease processes, such as atherosclerosis and hypertension. However, little is known about the effect of hypertension on contiguous coronary conduit and resistance vessels in humans. METHODS: Changes in coronary blood flow (a measure of resistance vessel reactivity) and coronary artery diameter (a measure of conduit vessel reactivity) were investigated in response to graded infusion of the endothelium-dependent agonist acetylcholine (ACh) in 98 patients with normal coronary arteries. RESULTS: In 31 normotensive, euglycemic patients, conduit and resistance coronary artery responses to intracoronary infusion of ACh were significantly correlated (r = 0.73, p = 1 x 10[-6]), although eight patients (26%) had constriction of conduit but dilation of resistance arteries at peak effect. In 28 hypertensive patients without left ventricular hypertrophy (LVH), conduit and resistance artery responses to ACh remained significantly correlated (r = 0.5, p = 0.006), although 12 patients (43%) had discordant findings. Finally, in 39 hypertensive patients with LVH, conduit and resistance artery responses to ACh displayed the lowest correlation (r = 0.38, p = 0.02), with 22 patients (56%) demonstrating conduit artery constriction and resistance artery dilation. CONCLUSIONS: Despite angiographically normal coronary arteries, heterogeneous vasomotor responses (dilation and constriction) were demonstrated in contiguous conduit and resistance arteries in normotensive and hypertensive patients referred for cardiac catheterization because of chest pain. In addition to more severe endothelial dysfunction among conduit and resistance arteries, a greater frequency of discordant conduit and resistance artery responses and resistance vessel constriction was found with increasing severity of hypertension. Our study suggests differing mechanisms of endothelium responsiveness to ACh among conduit and resistance coronary arteries.

Effect of African-American race and hypertensive left ventricular hypertrophy on coronary vascular reactivity and endothelial function.

Excess cardiovascular morbidity and mortality among African (black) Americans remains an important yet unexplained public health problem. One possible explanation proposes that intrinsic or acquired abnormalities in coronary vascular reactivity and endothelial function result in excess ischemia among black Americans. To examine this hypothesis, we subjected 80 individuals with normal coronary arteries to invasive testing of coronary artery and microvascular relaxation using intracoronary infusions of acetylcholine and adenosine, a Doppler tipped intracoronary guide wire, and quantitative coronary angiography. We measured the percent increase in coronary blood flow and epicardial diameter after graded infusion of intracoronary acetylcholine and in coronary blood flow after intracoronary adenosine in 31 normotensive subjects (10 black, 21 white) and 49 hypertensive subjects with left ventricular hypertrophy (25 black, 24 white). Categorical and multivariate analyses revealed that in response to intracoronary adenosine and acetylcholine, the depression in endothelium-independent and -dependent microvascular relaxation during peak agonist effect was largely related to the presence of chronic hypertension and left ventricular hypertrophy. Normotensive subjects demonstrated no intrinsic racial differences in conduit and resistance vessel vasoreactivity. In response to maximal infusion of acetylcholine, epicardial coronary arteries constricted similarly in black and white subjects with hypertensive left ventricular hypertrophy and dilated similarly in normotensive black and white subjects. Thus, our study shows that in a cohort of black and white subjects referred for coronary arteriography because of chest pain, African American race is not associated with excess intrinsic or acquired depression in coronary vascular relaxation during the peak effect of the endothelium-dependent and -independent agonists acetylcholine and adenosine, after adjustment for the presence of left ventricular hypertrophy.

Coronary vasomotor reactivity among normotensive African and white American subjects with chest pain.

BACKGROUND AND OBJECTIVES: Excess cardiovascular morbidity and mortality among African (black) Americans is the subject of intensive investigation but the etiology remains speculative. One hypothesis proposes that inherent, or intrinsic, differences in coronary vascular reactivity and endothelial function predispose African Americans to enhanced vasoconstriction and/or depressed vasodilation, resulting in excess ischemia. The objective of this study was to establish whether coronary vasoreactivity differs among normotensive, nondiabetic African and white Americans with normal arteries referred for coronary arteriography because of chest pain. PATIENTS AND METHODS: Eleven African American (8 female, 3 male) and 28 white American (9 female, 19 male) normotensive, euglycemic patients with normal coronary arteries were prospectively recruited for invasive testing of coronary artery and microvascular relaxation using the endothelium-dependent and -independent agents, acetylcholine and adenosine; a Doppler tipped intracoronary guidewire; and quantitative coronary angiography. RESULTS: The study cohort consisted of 17 women (44%) and 22 men (56%) with a mean age of 46 +/- 10 yrs. Of 8 African American women, 6 were premenopausal and 2 were postmenopausal on estrogen replacement therapy. Of 9 white American women, 2 were premenopausal, 1 was 46-year old with a previous history of hysterectomy without ovariectomy, 2 were postmenopausal on estrogen replacement therapy, 2 were perimenopausal and 44- and 54-year old, and 2 were postmenopausal without estrogen replacement therapy. In response to maximal infusion of acetylcholine, epicardial coronary arteries and resistance vessels dilated similarly in black and white subjects. Dose-response curves revealed no significant racial differences during submaximal graded infusion of acetylcholine. In response to peak effect of adenosine, there were no racial differences in dilation of the microcirculation. CONCLUSIONS: In the absence of hypertension, diabetes mellitus, and angiographic evidence of coronary artery disease, African American women demonstrate no evidence of intrinsic predisposition to enhanced coronary conduit vasoconstriction or depressed microcirculatory dilation in response to the endothelium-dependent and -independent vasodilator agonists-acetylcholine and adenosine-when compared with responses of similar white men and women. Because of low enrollment of black males, definitive conclusions cannot be drawn regarding this group.

Morphologic, hemodynamic and coronary perfusion characteristics in severe left ventricular hypertrophy secondary to systemic hypertension and evidence for nonatherosclerotic myocardial ischemia.

Patients with the clinical diagnosis of ischemic heart disease who were found to be free of significant coronary artery atherosclerotic disease (n = 150) underwent coronary vasodilator reserve testing, 2-dimensional echocardiography, and dipyridamole limited-stress thallium testing. After exclusions (predominantly for technically poor coronary artery Doppler signals or suboptimal echocardiography), 100 patients formed the study population. The purpose was to characterize typical cardiac and coronary artery findings in hypertensive patients with severe left ventricular (LV) hypertrophy (n = 15) and to investigate the evidence for myocardial ischemia unrelated to coronary atherosclerosis in early and advanced hypertensive heart disease. Normotensive and hypertensive control groups without LV hypertrophy (n = 12 and 34, respectively) were used for comparison. Severe LV hypertrophy was defined as LV mass index greater than or equal to 50% above established gender specific norms using 2-dimensional-directed M-mode echocardiography and the cube equation corrected to agree with necropsy estimates of mass. Clinical characteristics more often associated with severe LV hypertrophy were black race (67%), diabetes mellitus (33%), proteinuria (47%) and elevated creatinine (1.5 +/- 0.9 mg/dl). Baseline electrocardiograms and dipyridamole limited-stress thallium scans were highly likely to be abnormal (94 and 73%, respectively). Both eccentric and concentric cardiac hypertrophies were found in the severe group. Ejection fraction was significantly lower (0.51 vs 0.68, p = 0.002) and basal coronary flow velocity higher (12.0 vs 5.0 cm/s, p = 0.0004) among these patients when compared with normotensive control patients. Coronary flow reserve did not differ between control groups but was significantly depressed in patients with severe LV hypertrophy (2.5 vs 3.9, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vasomotor function in a normotensive, nondiabetic referral population with normal coronary arteriograms.

In a referral normal cardiac population, endothelium-independent coronary relaxation is nearly always normal, but endothelium-dependent relaxation may be depressed in a significant proportion of patients. Further study of the natural history of referral subjects with endothelial dysfunction is necessary to assess the potential cardiovascular risk of this finding in a presumed low-risk population.

Long-term severe pulmonary hypertension associated with right atrial myxoma.

An 18-year-old black woman presented with marginally compensated right heart failure, severe pulmonary hypertension, tricuspid incompetence, and right atrial myxoma. Catheterization suggested a substantial reactive component to her P-HTN, especially to nifedipine. Initial management consisted of excision of two right atrial myxomas and tricuspid annuloplasty, and postdischarge management with nifedipine, 30 mg four times daily. Emergency pulmonary thromboendarterectomy was required two weeks later for acute cor pulmonale. It is suggested that concomitant procedures are mandatory in this setting because of the otherwise accelerated adverse pathophysiology of obliterative pulmonary vascular obstructive disease.

Cholesterol lowering with pravastatin improves resistance artery endothelial function: report of six subjects with normal coronary arteriograms.

STUDY OBJECTIVES: Improvement in coronary artery endothelial function has been demonstrated after cholesterol lowering in hypercholesterolemic patients with significant atherosclerosis. However, to our knowledge, no previous study has shown improvement in resistance artery function in subjects with normal coronary arteries after cholesterol lowering. The purpose of our study was to investigate the effect of cholesterol lowering with pravastatin on coronary resistance artery endothelial function in the setting of angiographically normal coronary arteries. METHODS: Invasive testing of coronary endothelial and vasomotor function was performed at baseline and after 6 months of pravastatin treatment in six patients with normal coronary arteriograms. RESULTS: After 6 months of pravastatin treatment, low-density lipoprotein cholesterol level dropped from 157+/-11 to 117+/-8 mg/dL (p = 0.02) and percent increase in coronary blood flow after acetylcholine improved from 97+/-13% to 160+/-16% (p = 0.01). There was a trend (p = 0.17) toward enhanced epicardial dilation in response to acetylcholine after pravastatin treatment when compared with the baseline study. CONCLUSIONS: Our study demonstrates significant improvement in coronary resistance artery endothelial function after 6 months of cholesterol lowering with pravastatin in six subjects presenting with chest pain who were found to have normal coronary arteriograms. A trend toward improved epicardial vasomotion was also observed.

Correction of left ventricular ischemia in blacks with hypertensive heart disease.

Among hypertensive patients, blacks are more likely than whites to have ischemia by electrocardiographic and 201Tl-myocardial stress imaging, possibly due to racial differences in the regulation of coronary blood flow or velocity. This investigation was undertaken to determine whether intensive antihypertensive therapy with two or more drugs can correct or reduce ischemia in black hypertensive patients. Thallium myocardial stress imaging and electrocardiographic and echocardiographic studies were performed on 13 black patients with essential hypertension and ischemic heart disease due to hypertensive heart disease (without significant obstructive epicardial coronary artery disease). The studies were made at baseline and after 4 to 48 months of intensive treatment, with a calcium antagonist and an angiotensin converting enzyme (ACE) inhibitor as the main components of the antihypertensive drug regimen. The majority of the patients with abolition or reversal of myocardial ischemia documented by 201Tl-myocardial imaging also had a significant reduction in left ventricular mass (LVM). However, some patients either did not have LV hypertrophy at baseline or had changes in LVM beyond the precision of the echocardiographic M-mode mass calculations. The finding indicated that factors other than reduction of LVM were involved in the reversal of the ischemia. The most likely factor was a change in the regulation of coronary blood flow. Reduction in LVM and reversal of myocardial ischemia determined either by electrocardiography or by thallium myocardial imaging studies may be considered indicators of the effectiveness of treatment.

A negative thallium (+/- dipyridamole) stress test excludes significant obstructive epicardial coronary artery disease in hypertensive patients.

The operating characteristics of thallium stress testing for detection of significant epicardial coronary artery disease (CAD) in hypertensive subjects with chest pain or electrocardiographic (ECG) ischemia have not been previously defined. This becomes important because of the high prevalence of both hypertensive heart disease and CAD. Ninety-two hypertensives with a history of typical or atypical chest pain or ECG myocardial ischemia underwent coronary arteriography, 2D-guided echocardiography, and thallium-201 stress testing, combined with intravenous dipyridamole if the rate-pressure product was less than 20,000. Patients with myocardial infarction, prior revascularization procedure, valvular heart disease, and chronic ethanol abuse were excluded. The mean age was 54.8 +/- 9.9 years with 55% blacks and 46% women. Eighteen patients (19.6%) had significant (greater than or equal to 50% luminal diameter narrowing) epicardial CAD at catheterization, of whom 17 had positive thallium scans. Overall, there were 17 true positives, 47 true negatives, 27 false positives, and one false negative resulting in 94.4 +/- 5.4% sensitivity (95% confidence limits [95% CL] 71 to 100%), 63.5 +/- 5.6% specificity (95% CL 51 to 74%), 38.6 +/- 7.3% positive predictive value (95% CL 25 to 54%), 97.9 +/- 2.1% negative predictive value (95% CL 88 to 100%), and 69.6 +/- 4.8% overall accuracy (95% CL 59 to 79%). For hypertensive patients with chest pain or ECG myocardial ischemia, the high sensitivity and negative predictive value and low false negative rate support the role of thallium stress testing +/- dipyridamole as an exclusion test for significant CAD.

Postpartum myocardial infarction treated by balloon coronary angioplasty.

Acute myocardial infarction in pregnancy is a rare event that carries substantial morbidity and mortality. New technologies have been developed in cardiology to open obstructed vessels during the acute evolution of coronary thrombosis. We present a case of acute postpartum myocardial infarction in a woman with class F/R diabetes. She underwent successful balloon angioplasty but developed chest pain suspicious of angina pectoris 6 weeks after the procedure. A thallium scan demonstrated fixed defects in the inferoposterior and posterolateral segments and minimal apical redistribution. This represents the second case of angioplasty performed in pregnancy and the first for an acute myocardial infarction.

Pharmacotherapy of unstable angina.

All patients with unstable angina should be admitted to a coronary or an intensive care unit. There should be an attempt to classify the patient according to the proposed Braunwald nomenclature. If the patient has a secondary cause for unstable angina (e.g., tachyarrhythmia, heart failure, fever, thyrotoxicosis, severe hypertension, hypoxia, unusual emotional stress, or anemia), this condition should be treated initially with therapy specific for that etiology. If the patient does not have a secondary etiology, therapy should be initiated with nitrates, preferably intravenous nitroglycerin. Heparin should be concomitantly administered. If the patient cannot receive heparin, aspirin should be initiated. All patients should receive beta-blockers. If the patient cannot take a beta-blocker, a calcium antagonist (probably diltiazem) should be initiated. However, if the patient is refractory to beta-blockers, the dihydropyridine nifedipine should be added. Failure to all pharmacologic interventions necessitates a progressive invasive approach dictated by the potential surgical risk of the patient. Long-term aspirin and beta-blockers should be strongly considered.

Case report: acute presentation of pseudo myocardial infarction secondary to metastatic cancer.

Electrocardiographic ST segment changes that mimic myocardial infarction (MI) may occur secondary to metastatic carcinoma. Presented here is a case in which symptomatology suggestive of acute MI occurred with impressive new anterior ST segment elevation in a patient with a history of laryngeal carcinoma. Clinical options in this setting are discussed, including use of thrombolytic agents and acute catheterization.

Possible triggering of paroxysmal atrial fibrillation in normal hearts by psychological stressors: a report of two cases.

Paroxysmal atrial fibrillation was triggered by psychological stress in two patients, both of whom had normal echocardiograms and coronary angiography. Neither patient was alcoholic or had ingested ethanol in relation to the onset of atrial fibrillation and both were free of metabolic derangements. Possible mechanisms involved in the triggering of atrial fibrillation are discussed.

Basal and reserve renal artery blood flow: effect of endothelium-dependent and -independent vasoactive agonists and radiographic contrast medium in two patients.

This manuscript describes the results of invasive testing of renal artery and arteriolar reactivity in two patients using a panel of endothelium-dependent and -independent agents including radiographic contrast medium. We found that the renal artery and microcirculation dilate in response to graded acetylcholine infusions and to bolus nitroglycerin infusion; the renal microcirculation dilates in response to papaverine but constricts after adenosine and after radiographic contrast medium. Future indications for this testing are briefly discussed.

Spontaneous multivessel coronary artery dissection: repeated presentation in a healthy postmenopausal woman.

Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction which is infrequently diagnosed antemortem. Most previously reported cases were found in women of whom a significant proportion presented during pregnancy or the postpartum period. We describe the first antemortem case of spontaneous coronary artery dissection, unrelated to pregnancy or the postpartum state, which ultimately resulted in diffuse involvement of both the left and right coronary arteries over a period of 4 months. Pathophysiology and case management of this disorder are discussed.

Pericarditis and myocarditis. Which is benign and which isn't?

Pericarditis and myocarditis are inflammatory diseases that are often initiated by common viruses. Pericarditis rarely causes serious long-term disability, whereas myocarditis may lead to chronic congestive cardiomyopathy and permanent disability. The pathogenesis of both is proposed to be bimodal, with an early stage characterized by viral replication and a later stage by infiltration of lymphocytes and necrosis of cells secondary to an autoimmune process. Treatment of pericarditis is usually symptomatic. Myocarditis requires bed rest and conventional therapy for congestive heart failure. Efficacy of immunosuppressive therapy for myocarditis is currently being tested in an international multi-center clinical trial.