Subcortical vascular dementia: survey of treatment patterns and research considerations

OBJECTIVE: The purpose of this study was to evaluate retrospectively the efficacy of a proposed panel of three cardiac markers (myoglobin, creatine kinase-MB mass [CK-MB], and cardiac troponin I) in the diagnosis of acute myocardial infarction (AMI) in patients with atraumatic chest pain. DESIGN: A total of 110 patients admitted for the evaluation of atraumatic chest pain were examined. Forty-one of these patients were diagnosed with AMI. RESULTS: Five of the 41 patients with AMI had abnormally elevated myoglobin levels, whereas values of CK-MB and/or cardiac troponin I remained negative. Creatine kinase-MB mass alone had a sensitivity of 92.7%, a specificity of 89.9%, a positive predictive value of 84.4%, and a negative predictive value of 95.0% for the diagnosis of AMI. Cardiac troponin I alone had a sensitivity of 90.2%, a specificity of 95.7%, a positive predictive value of 92.5%, and a negative predictive value of 94.3% for the diagnosis of AMI. Cardiac troponin I is a more specific marker for the diagnosis of AMI than CK-MB, particularly in patients with chronic renal failure who are evaluated for chest pain. The combination of CK-MB and cardiac troponin I increased the sensitivity to 100% and the negative predictive value to 100% and had a specificity of 88.4% and a positive predictive value of 83.7%. The panel was diagnostic for all patients with AMI within 12 hours after admission. CONCLUSIONS: Our preliminary results indicate that this panel is highly effective for evaluation of AMI in patients with atraumatic chest pain. Elevated myoglobin levels were useful in detecting patients at high risk for AMI who initially were not detected with other markers. The combination of CK-MB and cardiac troponin I provided much higher sensitivity and had a much higher negative predictive value for the evaluation of AMI than cardiac troponin I or CK-MB alone. The 100% negative predictive value is particularly important because it indicates that patients with negative CK-MB and cardiac troponin I values 12 hours after admission have a negligible likelihood of AMI.     

Quantum chemical studies of methadone

To clarify the association between chest pain and significant coronary artery disease in patients who have aortic valve disease, 76 consecutive candidates for aortic valve replacement were evaluated prospectively with use of a historical questionnaire and coronary arteriography. Of the 76 patients, 19 (25 percent) had no chest pain, 21 (28 percent) had chest pain that was not typical of angina pectoris and 36 (47 percent) had chest pain typical of anigina pectoris. In 18 of 19 patients the absence of chest pain correlated with the absence of coronary artery disease. The single patient without chest pain who had coronary artery disease had evidence of an inferior myocardial infarction in the electrocardiogram. Thus, absence of chest pain and the absence of electrocardiographic evidence of infarction predicted the absence of coronary disease in all cases. The presence of chest pain did not predict the presence of coronary artery disease, but the more typical the pain of angina pectoris the more likely were patients to have significant coronary artery disease. Of the 21 patients with atypical chest pain, 6 (29 percent) had coronary artery disease, but of the 36 patients with typical angina pectoris 23 (64 percent) had significant coronary artery disease. In addition, when patients with chest pain not typical of angina pectoris also had coronary artery disease, the diseased vessels usually supplied smaller areas of the left ventricle than when the pain was typical of angina pectoris. In 21 of 23 patients (91 percent) with typical angina pectoris and significant coronary artery disease, lesions were present in the left coronary artery. There was no systolic pressure gradient across the aortic valve that excluded the presence of coronary artery disease, although all patients with a calculated aortic valve area of less than 0.4 cm2 were free of coronary artery disease. Patients with severe left ventricular dysfunction were more likely to have normal coronary arteries.     

Spontaneous angina in the coronary care unit. 2. Electrocardiographic changes during and after chest pain

Serial ECGs of 16 patients with repetitive attacks of spontaneous angina in the CCU were studied from admission to the hospital to the follow-up phase at the cardiac clinic. Transient repolarization ECG changes occurring during unprovoked angina included ST-segment elevation and ST-segment depression, alterations of T-wave amplitude and polarity, and pseudonormalization of previously inverted T-waves. In addition, QRS complexes were altered transiently during chest pain. Such changes comprised augmentation or reduction of amplitude of R and S waves, widening of QRS complexes and a merging of R waves with the elevated ST-segments. Occasionally the ECG during attacks of angina did not show any change. During asymptomatic periods, between attacks of spontaneous angina, the ECG either returned to baseline, or displayed minor ST-segment shifts, and/or T-wave alterations of varying durations. However, such changes became either persistent or were replaced in the late course of hospitalization by ECG alterations diagnostic of transmural or nontransmural myocardial infarction. Twelve patients suffered an acute myocardial infarction. Four patients died within one month of admission. During follow-up of the 12 surviving patients in the cardiac clinic, amelioration of T-wave changes was noted in the ECGs of patients who remained asymptomatic, but new ischemic alterations were seen in the ECG of patients who had recurrent angina, or were readmitted to the hospital for evaluation. Increase in the amplitude of R-waves, disappearance of Q-waves, or reduction of Q-wave depth were noted at follow-up, in comparison with the discharge ECG, in some patients who had suffered primarily an anterior myocardial infarction.     

The effect of ischemic preconditioning on early death in acute Q-wave myocardial infarction

Ischaemic preconditioning is still a laboratory-based phenomenon, not conclusively documented in patients. In this study it was of interest whether there is any beneficial influence of ischemic preconditioning on 30-day in-hospital mortality in patients undergoing acute Q-wave myocardial infarction. All men and women admitted to our ward between December 1994 and July 1996 with their first acute Q-wave myocardial infarction were divided into two groups. I group--29 patients with prodromal angina, defined as chest pain episodes in the 24-hour period before myocardial infarction. II group--25 patients who showed no chest pain before infarction onset. Both groups did not differ statistically in view of age, sex, smoking habits and adjunctive therapy. The use of streptokinase in the I and II group was also similar--in 58.6% and 56% of patients respectively in the first and second group. In the I group there was no fatal outcome, all 5 death cases occurred in the II group. The results are statistically significant and suggest lower in-hospital mortality in Q-wave myocardial infarction patients with previous ischaemic preconditioning.     

The effect of the suture-induced delay phenomenon on skin flap survival and lipid peroxidation in rats

To assess the prognostic significance of a normal dobutamine-atropine stress echocardiogram in relation to the pretest probability of coronary artery disease (CAD), 200 consecutive patients (86 men and 114 women, mean [SD] age 59 [13] years) with a stable chest pain syndrome and a normal dobutamine-atropine stress echocardiogram were followed-up for 21 +/- 16 months. Outcome events were cardiac death, non-fatal myocardial infarction, and coronary revascularization procedures. Low (<10%), intermediate (10% to 80%), and high (>80%) pretest probabilities of CAD were present in 27 (14%), 108 (54%), and 65 (33%) patients, respectively. During follow-up, 2 patients (annual event rate 0.6%) had cardiac death, none had nonfatal myocardial infarction, and 4 patients (annual event rate 1.1%) underwent a coronary revascularization procedure. All patients with cardiac events had high pretest probabilities of CAD. Patients with cardiac death (but unproven significant CAD) had maximal tests without angina or ischemic electrocardiographic changes. In contrast, all patients with subsequent coronary revascularization had dobutamine-induced angina or ischemic electrocardiographic changes, and all except one study were submaximal. We conclude that patients with a stable chest pain syndrome and normal findings on dobutamine-atropine stress echocardiograms have an excellent cardiac prognosis. However, patients with typical angina, high pre-test probabilities of CAD, and stress-induced angina or ischemic electrocardiographic changes, and in particular those with submaximal stress, still appear to be at risk for functionally important CAD despite a normal dobutamine-atropine stress echocardiogram.     

Intracoronary artery thrombus formation in unstable angina: a clinical, biochemical and angiographic correlation

OBJECTIVES: We examined the relation between the level of urinary fibrinopeptide A and the presence of angiographic intracoronary thrombus in patients with unstable angina to determine whether this marker predicts active thrombus formation. BACKGROUND: Although it is known that thrombus plays a role in acute ischemic syndromes, a noninvasive method to predict its presence in individual patients with unstable angina has not been determined. Fibrinopeptide A is a polypeptide cleaved from fibrinogen by thrombin and thus is a sensitive marker of thrombin activity and fibrin generation. METHODS: Angiographic thrombus, graded 0 to 4, and the presence of ST segment depression or T wave inversions, or both, on the electrocardiogram (ECG) were related to fibrinopeptide A levels in 24 patients with rest angina of new onset, 18 with crescendo angina, 19 with stable angina and 9 with chest pain but without coronary artery disease. All patients had chest pain within the 24 h of sample acquisition. RESULTS: The angiographic incidence of thrombus was significantly higher in patients with new onset of rest angina (67%, p < 0.001) and crescendo angina (50%, p < 0.001) as were fibrinopeptide A levels (p = 0.002). Fibrinopeptide A levels correlated significantly (p < 0.001) with the presence of a filling defect (grade 4 intracoronary thrombus) or contrast staining (grade 3). All patients with fibrinopeptide A > or = 8 ng/mg creatinine showed grade 3 to 4 thrombus and 15 of 16 patients with levels > or = 6.0 ng/mg creatinine exhibited angiographic evidence of thrombus (13 with grades 3 to 4). Patients with reversible ST changes on the ECG had significantly higher levels of fibrinopeptide A (p < 0.001), and ST changes correlated significantly with the presence of angiographic thrombus (p < 0.001). Nonetheless, a significant minority of patients with unstable angina had neither angiographic nor biochemical evidence of thrombus. CONCLUSIONS: Elevated fibrinopeptide A levels in unstable angina reflected active intracoronary thrombus formation and were present in patients with angina of new onset as well as crescendo angina. Reversible ST changes are accompanied by thrombin activity and angiographic thrombus formation. However, a sizable percentage of patients with unstable angina had no evidence of thrombus and these patients may have had transient platelet aggregation without fibrin thrombus formation.     

Accumulation of amphotericin B in human macrophages enhances activity against Aspergillus fumigatus conidia: quantification of conidial kill at the single-cell level

Several cardiac serum markers such as cardiac myosin light chain, creatine kinase MB, and cardiac troponins have been shown to be elevated in patients with acute myocardial infarction. These markers are well utilized as clinical indicators for diagnosis and prognosis of myocardial necrosis. Recent studies have strongly indicated that cardiac structural protein troponin T and I are predictive of future cardiac events in patients with acute coronary syndromes including unstable angina pectoris. Immunoassays have also been developed to measure serum levels of cardiac troponins in recent years. These biochemical markers may be useful as a guide for intervention in the near future.     

Transfemoral repositioning of malpositioned central venous catheters

Sumatriptan, a 5-hydroxytryptamine1, (5-HT1) receptor agonist is an effective abortive agent for migraine headaches. A common side effect in 3% to 7.9% of patients is chest pain. Although most cases of chest pain are not thought to be of cardiac origin, its mechanism is not entirely understood. Rare examples of electrocardiogram changes consistent with transient ischemia have been reported. Isolated instances of angina, arrhythmia, myocardial infarction, and death have been temporally associated with sumatriptan administration. In most cases, it is unclear whether underlying cardiovascular disease existed or contributed to this adverse event. We report the history of a 56-year-old female patient with migraine who experienced a myocardial infarction shortly after using sumatriptan, despite having had a normal cardiovascular evaluation. As she had a normal cardiac catheterization after the event, we find it probable that sumatriptan induced coronary vasospasm and myocardial infarction.     

C-reactive protein as a marker for acute coronary syndromes

BACKGROUND: For several years, acute coronary syndromes have been perceived as causing the most hospital admissions, and even hospital mortality. The syndrome of unstable angina frequently progresses to acute myocardial infarction but its pathogenesis is poorly understood, and prognosis determination is still problematic. We tested the hypothesis that measurement of the C-reactive protein in patients admitted for chest pain could be a marker for acute coronary syndromes. METHODS AND RESULTS: We studied 110 patients admitted with suspected ischaemic heart disease, but without elevated serum creatine-kinase levels at the time of hospital admission. Patients were subsequently divided into two groups based on their final diagnosis: group 1 comprised patients with unstable angina; group 2 patients with acute myocardial infarction. We measured the C-reactive protein at the time of hospital admission. The concentration of C-reactive protein was elevated in 59% of the patients with a final diagnosis of acute myocardial infarction, and in 5% of the patients with a final diagnosis of unstable angina, (P < 0.001). CONCLUSION: This study indicates that C-reactive protein levels measured at the time of admission in patients with suspected ischaemic heart disease could be a marker for acute coronary syndromes, and helpful in identifying patients at high risk for acute myocardial infarction. Measurement of C-reactive protein may have practical clinical significance in the management of patients hospitalized for suspected acute coronary syndromes.     

Clinical profile of patients admitted to the coronary care unit with possible myocardial infarction without diagnostic ECG and/or enzyme changes

Concern has been expressed about the cost-effectiveness of the Coronary Care Unit (CCU) and solution options offered on account of the large number of patients admitted to the CCU who turn out not to have acute myocardial infarction. In a prospective study over four years, we studied a group of patients admitted to the CCU with suspected myocardial infarction but who did not have diagnostic ECG and/or enzyme changes for the causes of their chest pain. We compared the clinical profile of these patients (Group A) with that of a random sample of patients with confirmed myocardial infarction (Group B). Gastrointestinal disorders, musculoskeletal chest pain, panic and anxiety disorders were the major causes of chest pain in Group A patients. A normal ECG and a normal creatine phosphokinase (CPK) within the first 24 hours, a normal initial random blood sugar, a younger age and absence of coronary risk factors effectively separated Group A patients as low risk from Group B patients as high risk for acute myocardial infarction. These simple parameters will assist physicians providing CCU care in most hospitals in early decision making and in the judicious use of the CCU.     

Growth hormone stimulates the tyrosine kinase activity of JAK2 and induces tyrosine phosphorylation of insulin receptor substrates and Shc in rat tissues

Each year, acute myocardial infarctions (AMI) account for more than half a million deaths in the United States. Complicating treatment of AMI is the difficulty in accurately diagnosing the event, for patients have nondiagnostic electrocardiograms (ECG) more than 50% of the time. In this population, cardiac markers are essential to confirm the diagnosis. The new bedside cardiac markers, which use eight drops of whole blood and require 15 minutes to be read negative, make it possible to shorten time needed to diagnose AMI. One hundred twenty-seven consecutive patients presented to the emergency department complaining of atypical chest pain. All had ECGs that were nondiagnostic for myocardial infarction. Serial cardiac markers were performed: myoglobin, troponin I, rapid myoglobin, and rapid troponin I. One hundred eighteen patients with negative serial cardiac markers had exercise treadmill tests in the emergency department. Nine patients with positive serial cardiac markers received emergent primary angioplasty. Six of the nine patients were treated based on the positive results of the rapid bedside cardiac markers. A 100% correlation existed between the quantitative serum results and the rapid bedside markers. With the availability of rapid bedside assays, dependency on the laboratory can be minimized, since quantitative cardiac markers require at least 1 hour of turnaround time. Rapidly and correctly diagnosing AMIs in patients with ECGs nondiagnostic for AMI has always been a dilemma. Rapid bedside assays enable the physician to accurately diagnose myocardial infarction and safely decrease the time in evaluating chest pain, thus maximizing the benefits of early reperfusion.     

Absorptive function following small intestinal transplantation

Detection of cardiac troponin I (cTnI) in patients suspected of having an acute coronary syndrome is highly predictive for an adverse outcome. We evaluated a bedside test for cTnI that uses a polyclonal capture antibody and two monoclonal indicator antibodies. Clinical studies were performed in patients with acute coronary syndrome and patients with chest pain but no evidence of acute myocardial injury. The whole-blood, 15-minute assay had a concordance of 98.9% with an ELISA for cTnI and a detection limit of 0.14 microg/L, and the device tolerated temperatures between 4 degrees C and 37 degrees C. Diagnostic sensitivity for myocardial infarction at arrival (3.5 +/- 2.7 h after onset of symptoms) was 60% [creatine kinase isoenzyme MB (CK-MB) mass, 48%; CK activity, 36%; P < 0.01], and 4 h later, diagnostic sensitivity was 98% (CK-MB mass, 91%; CK activity, 61%; P < 0.01). In 38% of the patients with unstable angina, at least one positive cTnI test was found (CK-MB mass, 4%; CK activity, 2%). No false-positive test results were found in renal failure or injury of skeletal muscle. We conclude that the diagnostic efficacy of the cTnI rapid test was comparable with the cTnI ELISA and superior to CK-MB determination. Therefore, this device could facilitate decision-making in patients with chest pain at the point of care.     

Unstable angina in coronary intensive care units without hemodynamics: is admissible a strategy limiting the indications for coronarography?

In coronary care units (CCU) without cardiac catheterization facilities, coronary angiography is rarely carried out when a successful medical treatment in the acute phase of unstable angina has been obtained. However, the unstable angina still has an uncertain prognosis when the remission of pain is obtained with drugs. This study presents a follow-up of 147 consecutive patients (aged 66.8 +/- 10.4 years) admitted to our CCU in 1991 and 1992 for unstable angina; 33 of them (22.4%) were in Braunwald class I. 2 (1.4%) in class II and 112 (76.2%) in class III. The patients were treated according to the usual therapy protocols and class III patients received i.v. heparin. In selected cases we used thrombolysis (10 patients) and intra-aortic balloon pump (5 patients). During hospitalization 1 patient died (0.7%), 5 patients (3.4%) suffered an acute myocardial infarction and 9 patients (6.1%) had angina. Stabilization of unstable angina was achieved in 132 patients (89.9%): in 113 (76.8%) during the first 48 hours, and in 19 (12.9%) later. Coronary angiography was carried out in non-stabilized patients and in 46 (34.8%) of the 132 with successful treatment (Group I). Eighty-six patients, without indication to coronary angiography were discharged in medical therapy (Group II). During the follow-up (mean of 15.0 +/- 9.0 months) Group I 10 patients (18.2%) had cardiac events (death, myocardial infarction, or recurrent angina) vs 26 of Group II (p < 0.05). In Group I coronary angiography together with clinical criteria of high risk allowed the identification of candidates to coronary revascularization (61.8% of Group I patients while). These data show that the initial success of treatment during the acute phase of unstable angina should not be considered as a favourable prognostic index. Coronary angiography appears to be indicated for clinical evaluation and therapeutical decision.     

Improved risk stratification in unstable angina: identification of patients at low risk for in-hospital cardiac events by admission echocardiography

BACKGROUND: Current protocols for risk stratification of patients with acute chest pain syndromes rely on clinical parameters and are oriented toward identification of patients at high risk for adverse cardiac events; however, this paradigm for risk stratification does not adequately address the observation that adverse cardiac events are relatively uncommon in this population. In an era of cost containment, consideration also should be given to identification of patients at low risk for adverse cardiac events, who may be safely discharged without expensive inpatient hospitalization. HYPOTHESIS: The purpose of this study was to develop echocardiographic predictors that identify unstable angina patients at low risk for adverse cardiac events and that discriminate between low- and high-risk patients. METHODS: The predictive accuracy of retrospectively determined echocardiographic predictors were compared in a population-based sample of 66 consecutive unstable angina patients undergoing echocardiography within 24 h of admission. RESULTS: Echocardiographic predictors of adverse events included wall motion score index > or = 0.2, ejection fraction < or = 40%, and mitral regurgitation severity > 2. One or more echocardiographic predictors of adverse events were present in 32 patients (48%). A composite echocardiographic predictor of adverse events was specific, had a high positive predictive value for the identification of high-risk patients, and discriminated between unstable angina patients at high and low risk for adverse cardiac events. CONCLUSION: Echocardiographic predictors of adverse events are specific and discriminate between unstable angina patients at high and low risk for adverse cardiac events.     

Pathophysiology of antigen 85 in patients with active tuberculosis: antigen 85 circulates as complexes with fibronectin and immunoglobulin G

Antigen 85 (Ag85) complex proteins are major secretory products of Mycobacterium tuberculosis and induce strong cellular and humoral immune responses in infected experimental animals and human beings. We have previously shown that nanogram doses of these 30- to 32-kDa fibronectin-binding proteins inhibit local expression of delayed hypersensitivity by a T-cell fibronectin-dependent mechanism. Circulating levels of Ag85 might be expected to be elevated in patients with active tuberculosis and possibly to play a role in systemic anergy in these patients. To test this hypothesis, Ag85 was measured in serum and urine by a monoclonal antibody-based dot immunobinding assay in 56 patients and controls with known skin test reactivity. Median serum Ag85 levels were 50- to 150-fold higher in patients with active tuberculosis than in patients with active M. avium-intracellulare disease or other nontuberculous pulmonary disease or in healthy controls (P < 0.001). The median and range of serum Ag85 in patients with active tuberculosis was not significantly different between skin test-positive and -negative subjects. Patients with active M. avium disease could be distinguished from those with disease due to M. tuberculosis by monoclonal anti-Ag85 antibodies of appropriate specificities. No increases in urinary Ag85 were detected in any patient, regardless of the Ag85 level in serum. Chromatographic analysis and immunoprecipitation studies of serum revealed that Ag85 existed in the serum of these patients complexed to either fibronectin or immunoglobulin G (IgG). Uncomplexed circulating Ag85 was demonstrable in serum from fewer than 20% of patients with active tuberculosis. In patients with active tuberculosis, Ag85 is therefore likely to circulate primarily as complexes with plasma fibronectin and IgG rather than in unbound form. The existence of Ag85 complexes with plasma proteins would account for its lack of urinary clearance.     

Direct conversion of atrial flutter to sinus rhythm with low-output, short-duration transesophageal atrial pacing

BACKGROUND AND HYPOTHESIS: Transesophageal atrial pacing (TAP) is useful for terminating paroxysmal non-self terminating atrial flutter (PAF); however, high output pacing of long stimulus duration causes severe symptoms such as chest pain. The objective of this study was to investigate the effect of low-output, short-duration TAP on the conversion of PAF. METHODS: We applied low-output (within 15 mA with a pulse duration of 10 ms), short-duration (within 4 s) TAP in 31 patients (50 +/- 19 years) with PAF. Transesophageal pacing was delivered with 10 pulses of burst pacing at intervals that were 20 ms shorter than those of the flutter wave length. When the conversion was unsuccessful, we delivered 20 pulses of burst pacing. RESULTS: Sixteen patients (52%) were converted directly to sinus rhythm and 12 (38%) to atrial fibrillation. Transesophageal pacing was ineffective in 3 (10%) patients. The duration of atrial flutter, maximum flutter wave amplitude, effective pacing intervals, underlying heart diseases, and cardiac function were not different between patients who had direct conversion to sinus rhythm and those converted to atrial fibrillation. The patients who had direct conversion to sinus rhythm had longer flutter wave cycle lengths than those converted to atrial fibrillation (248 vs. 221 ms, p < 0.005). No patient had complications and complained of any symptoms. CONCLUSION: Low-output, short-duration TAP was useful to convert PAF directly to sinus rhythm without side effects.     

QT dispersion may be a useful adjunct for detection of myocardial infarction in the chest pain center

BACKGROUND: QT dispersion has been proposed as a noninvasive measurement of the degree of inhomogeneity in myocardial repolarization. Increased QT dispersion has been reported after myocardial infarction. We hypothesized that increased QT dispersion may be a useful adjunct for risk stratification in patients being evaluated in a chest pain center. METHODS AND RESULTS: Patients were admitted to the chest pain center for evaluation of chest pain. Exclusion criteria included (1) systolic blood pressure <90 mm Hg, (2) ischemia or infarction on the initial electrocardiograph (ECG), (3) elevated creatine kinase or MB fraction, and (4) chest pain associated with cocaine use. Serial creatine kinase and MB levels and ECGs were obtained at 0, 6, and 9 hours. Patients were monitored for (1) creatine kinase and MB rise, (2) ECG changes for infarction, (3) ST-segment changes, and (4) rest angina. A negative evaluation at the chest pain center led to an exercise stress test. Patients with a positive exercise stress test were admitted for further evaluation and patients with a negative exercise stress test result were discharged home. Patients were divided into 3 groups. Group 1 consisted of patients who were found to have an acute myocardial infarction (AMI), group 2 consisted of patients with prior history of coronary artery disease but no evidence of AMI, and group 3 consisted of patients without prior coronary artery disease or AMI. QT dispersion was measured on the initial ECG in all patients. A total of 586 patients were evaluated. Group 1 consisted of 13 patients with mean QT dispersion of 44.6+/-18.5 ms, group 2 consisted of 267 patients with a mean QT dispersion of 10.0+/-13.8 ms, and group 3 consisted of 303 patients with a mean QT dispersion of 10.5+/-10.0 ms. Analysis of variance showed a significantly higher QT dispersion in patients who had AMI compared with other patients with chest pain (P< .001). CONCLUSIONS: QT dispersion can be a useful diagnostic adjunct for detection of AMI in patients with chest pain with a normal ECG and normal cardiac enzymes.     

Angina pectoris caused by coronary microvascular spasm

BACKGROUND: Microvascular angina can occur during exercise and at rest. Reduced vasodilator capacity of the coronary microvessels is implicated as a cause of angina during exercise, but the mechanism of angina at rest is not known. Our aim was to test the hypothesis that primary hyperconstriction (spasm) of coronary microvessels causes myocardial ischaemia at rest. METHODS: Acetylcholine induces coronary artery spasm in patients with variant angina. We tested the effects of intracoronary acetylcholine at graded doses in 117 consecutive patients with chest pain (at rest, during exertion, or both) and no flow-limiting (>50%) organic stenosis in the large epicardial coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration in 36 of the patients by measurement of lactate in paired blood samples from the coronary artery and coronary sinus vein. FINDINGS: Of the 117 patients, 63 (54%) had large-artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest pain. The 29 patients with microvascular spasm developed angina-like chest pain, ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients) or after administration of acetylcholine (27 patients) without spasm of the large epicardial coronary arteries. Testing of paired samples of arterial and coronary sinus venous blood showed that lactate was produced during angina attack in nine of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer coronary risk factors (p<0.01) in patients with microvascular spasm than in those with large-artery spasm. INTERPRETATION: Coronary microvascular spasm and resultant myocardial ischaemia may be the cause of chest pain in a subgroup of patients with microvascular angina.     

Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis

Blood monocytes from patients with active tuberculosis are activated in vivo, as evidenced by an increase in the stimulated release of proinflammatory cytokines, such as TNF-alpha, and the spontaneous expression of IL-2R. Further, monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro. Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines. In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis. We found a constitutive degradation of I kappa B-alpha, the major cytoplasmic inhibitor of nuclear factor kappa B (NF-kappa B), in freshly isolated PBMC and monocytes from patients with tuberculosis. In contrast, I kappa B-alpha levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact. Further, by electrophoretic mobility shift assay, NF-kappa B was activated in monocytes from tuberculous patients. The expression of I kappa B-alpha gene, which is responsive to activation by NF-kappa B, was up-regulated in PBMC and monocytes from patients, but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases. By contrast, the expression of other adherence-associated early genes, such as IL-8 and IL-1 beta, was not up-regulated in PBMC of tuberculous patients. Further, M. tuberculosis and its tuberculin, purified protein derivative, induced the degradation of I kappa B-alpha and the expression of I kappa B-alpha mRNA, and purified protein derivative induced the activation of NF-kappa B in monocytes.