The value of ECG and echocardiography during stress testing for identifying systemic endothelial dysfunction and epicardial artery stenosis.

BACKGROUND: In the stress imaging era, ECG positivity is regarded as a frequent source of false-positive responses. However, it is known that normal coronary arteries frequently coexist with abnormal endothelial function in patients with chest pain. AIM: To evaluate the anatomical coronary epicardial, and functional systemic endothelial determinants of wall motion and electrocardiographic responses during stress testing. METHOD: Sixty-eight in-hospital patients with chest pain syndrome, no previous myocardial infarction, and off nitrate therapy at the time of testing underwent, on different days, in random order and within 1 month: (1) stress ECG echo testing (with dipyridamole in 43, dobutamine in 3, and exercise in 22 patients); (2) coronary angiography; (3) endothelium-dependent, flow-mediated dilation of the brachial artery during reactive hyperaemia using high-resolution ultrasound. Criteria of positivity were: ST segment depression >0.1mm in the stress ECG; regional dysfunction >2 segments demonstrated by stress-echo; diameter reduction >50% on coronary angiography; and <5% flow-mediated dilation as revealed by endothelial function. RESULTS: Significant coronary artery disease was present in 39 patients, and was predicted on multivariate analysis by stress-induced wall motion abnormalities (OR=108.8; 95% CI=8.5-1,389.4, P=0.0003), but not by either ST segment depression (P=0.13; OR=0.47; 95% CI=0.7-1.3) or reduced flow-mediated dilation (P=0.81; OR=0.87; 95% CI=0.27-2.8). Abnormal flow-mediated dilation was present in 53 patients (78%), and was predicted by stress-induced ST segment depression (P=0.023; OR=6.2; 95% CI=1.3-30.5), but not by either stress echo positivity (P=0.66; OR=0.77; 95% CI=0.23 to 2.5) or angiographically assessed coronary artery disease. There was no correlation between flow-mediated dilation and extent of coronary artery disease as assessed by the angiographic Duke score (from 0=normal to 100=most severe disease): r=-0.13, P=0.91. CONCLUSION: Epicardial coronary artery anatomy affects wall motion abnormalities, and systemic endothelial dysfunction affects ST segment depression during stress. However, echocardiographic positivity is unrelated to endothelial dysfunction, and electrocardiographic positivity is an inaccurate predictor of coronary stenosis. An integration of ECG and functional markers is warranted in the stress testing lab.

Diagnosis of myocardial ischemia in hypertensive patients.

Arterial hypertension can provoke a reduction in coronary flow reserve through several mechanisms that are not mutually exclusive (i.e. epicardial coronary artery disease (CAD), left ventricular hypertrophy and structural and/or functional microvascular disease). These different targets of arterial hypertension should be explored with different diagnostic markers. In fact, stress-induced wall motion abnormalities are highly specific for angiographically assessed epicardial CAD, whereas ST segment depression and/or myocardial perfusion abnormalities are frequently found with angiographically normal coronary arteries associated with left ventricular hypertrophy and/or microvascular disease. Exercise-electrocardiography stress test can be used to screen patients with negative maximal test due to its excellent negative predictive value, which is high and comparable in normotensives and hypertensives. When exercise-electrocardiography stress test is positive (or uninterpretable or ambiguous), an imaging stress-echo test is warranted for a reliable identification of significant, prognostically malignant epicardial CAD in view of an ischemia-guided revascularization.

Effect of coronary bypass and cardiac valve surgery on systemic endothelial function.

Seventeen patients scheduled for a cardiac procedure necessitating cardiopulmonary bypass underwent serial perioperative assessment of brachial artery flow-mediated dilation. Patients who underwent coronary bypass surgery had a sustained systemic endothelial dysfunction in the perioperative period, whereas those undergoing cardiac valve surgery experienced transient postoperative systemic endothelial dysfunction.

Clinical experience with SonoVue in myocardial perfusion imaging.

Ultrasound-enhancing agents have the potential to evaluate myocardial perfusion, adding a new dimension to echocardiography. This article summarizes the clinical studies involving SonoVue, a new intravenous ultrasound contrast agent, in assessing myocardial perfusion. Safe and well tolerated, SonoVue coupled with echocardiography has the capability to identify perfusion abnormalities, as confirmed by scintigraphic imaging. While the optimal modalities for ultrasound perfusion assessment are not yet determined, numerous technical advances have been introduced: continuous infusion or slow intravenous administration of the agent, harmonic intermittent imaging, pulse inversion, background subtraction, color coding, and others. SonoVue is a promising new agent in the booming field of myocardial contrast echocardiography.

Contrast echocardiography for myocardial perfusion imaging using intravenous agents: progress and promises.

AIMS: This article is a convenient overview to assist the interested echocardiographist towards acquiring his own experience in the field of myocardial perfusion imaging using intravenous contrast agents. This goal is now pursued in many centres, since contrast echo holds the advantages of cardiac ultrasound (non-invasiveness, high spatial and temporal resolution, wide availability, use of non-ionizing radiation), and because a variety of transpulmonary agents-together with a spectrum of imaging modalities-are becoming available. METHODS AND RESULTS: Many technical considerations need to be addressed for optimal myocardial perfusion imaging: characteristics of the contrast medium (air-filled or perfluorocarbon filled and/or encapsulated agents), modality of administration (bolus injection or continuous infusion) and interaction between microbubbles and ultrasound (dependency on power output). Moreover, intermittent harmonic imaging, intermittent harmonic power Doppler, pulse inversion and amplitude modulation imaging have all been developed to enhance microbubble detection over myocardial tissue. These new acquisition modalities also yield specific artifacts impacting on myocardial perfusion assessment. Finally, acute myocardial infarction and chronic ischaemic heart disease (at baseline and during stress) are the most studied clinical models for perfusion imaging with contrast echo, and are reviewed in this article. CONCLUSION: Perfusion imaging with intravenous contrast agents has never been as close to widespread clinical use as it is today, but many methodological issues remain unsettled before the wish of the contrast echocardiographist comes true: that is, a cheap, user-friendly and widely available technology that would disclose new information in echocardiography.

Mitral valve repair: Intermediate to long-term echocardiographic follow-up.

OBJECTIVE: To review intermediate to long term echocardiographic follow-up after mitral valve repair for mitral regurgitation. DESIGN: Nonrandomized, retrospective and prospective observational study. SETTING: Sacré-Coeur Hospital, University of Montreal, Montreal, Quebec. PATIENTS: Echocardiographic findings in 37 patients (mean age 62.1 +/- 10 years) three to 197 months (median 45) after mitral valve repair were reviewed. INTERVENTIONS: Preoperative data were collated from hospital records. Between October 1994 and March 1995, all patients had a clinical evaluation and a complete transthoracic echocardiogram done by a cardiologist. RESULT: There was a significant reduction in the dimensions of the left-sided cavities compared with preoperative data. Left atrial diameter decreased from from 50.9 +/- 7.7 to 46.3 +/- 8.1 mm (P = 0.01), left ventricular end-diastolic diameter from 59.6 +/- 7.1 to 51.2 +/- 6.3 mm (P < 0.001) and left ventricular end-systolic diameter from 35.3 +/- 7.9 to 32.8 +/- 7.8 mm (P = 0.07). On colour Doppler echocardiography, nine patients had no mitral regurgitation, 25 had mitral regurgitation grade I to II/IV, and three had grade III/IV. The mean mitral valve gradient was 4.2 +/- 1.8 mmHg and the pressure half-time 121.9 +/- 48 ms. There was no difference in gradient, mitral valve area and mitral regurgitation in patients with degenerative (29) compared with rheumatic (five) mitral valve disease. CONCLUSIONS: Mitral valve repair is highly effective in reducing mitral regurgitation in the long term and is associated with a reduction in the dimensions of the left atrium and the left ventricle. However, it leaves a mild degree of mitral valve obstruction.

[Quebec spirometry reference values]. / Valeurs de références spirométriques québécoises.

Lung volumes forced expiratory flow rates and carbon monoxide diffusing capacity (apnea) were measured in 397 non-smoking, nonatopic, asymptomatic subjects (219 women, 178 men). The equipments and methods for measurements met the ATS criteria. The linear regression of the different variables according to age and height allowed the elaboration of a new set of predictive equations (Quebec). When comparing the different reference values used in North America and Europe, it is found that those of Miller and associates as well as those recommended by the CECA provide the best description of the Quebec situation. However, we would eventually prefer the reference values of Miller and associates over those of the CECA, because they better fit the current ATS criteria and also provide references for smokers. Lung volumes and forced expiratory flow rates of 97 non-smoking, nonatopic, asymptomatic manual workers were measured in the same conditions and submitted to the same comparisons. Quebec predictive values as well as those of Miller and associates isolated the same individuals in the so called abnormal zone. We therefore conclude that Quebec's standards should be preferred in the Province of Quebec pulmonary function laboratories.

Salmonella endocarditis of a ventricular aneurysm: a case report and review of the literature.

A 63-year-old man with salmonella endocarditis of a ventricular aneurysm is presented. The patient had a documented apical aneurysm with mural thrombus and left ventricular dysfunction following a previous myocardial infarction. His condition was unresponsive to maximal medical therapy and was cured by surgery. A review of the English-language literature revealed that only two other published cases of nonvalvular salmonella endocarditis resulted in patient survival. This report underscores the importance of suspecting a cardiovascular origin in cases of salmonella bacteremia to avoid delay in diagnosis and surgical intervention in this deadly condition.

Monitoring changes in lung air and liquid volumes with electrical impedance tomography.

Electrical impedance tomography (EIT) uses electrical measurements at electrodes placed around the thorax to image changes in the conductivity distribution within the thorax. This technique is well suited to studying pulmonary function because the movement of air, blood, and extravascular fluid induces significant conductivity changes within the thorax. We conducted three experimental protocols in a total of 19 dogs to assess the accuracy with which EIT can quantify changes in the volumes of both gas and fluid in the lungs. In the first protocol, lung volume increments from 50 to 1,000 ml were applied with a large syringe. EIT measured these volume changes with an average error of 27 +/- 6 ml. In the second protocol, EIT measurements were made at end expiration and end inspiration during regular ventilation with tidal volume ranging from 100 to 1,000 ml. The average error in the EIT estimates of tidal volume was 90 +/- 43 ml. In the third protocol, lung liquid volume was measured by instilling 5% albumin solution into a lung lobe in increments ranging from 10 to 100 ml. EIT measured these volume changes with an average error of 10 +/- 10 ml and was also able to detect into which lobe the fluid had been instilled. These results indicate that EIT can noninvasively measure changes in the volumes of both gas and fluid in the lungs with clinically useful accuracy.

Comparison between dipyridamole and adenosine as pharmacologic coronary vasodilators in detection of coronary artery disease with thallium 201 imaging.

BACKGROUND: Both dipyridamole and adenosine are widely used as pharmacologic stressors with 201Tl imaging for detection of coronary artery disease. The purpose of this study was to compare dipyridamole and adenosine 201Tl imaging directly in patients with angiographically proved coronary artery disease. METHODS AND RESULTS: Fifty-four patients were submitted to two planar 201Tl studies: one with dipyridamole and the other with adenosine. The interval between the two studies varied from 2 to 7 days and the order was assigned randomly. Three standard planar views were obtained 10 minutes and 4 hours after the injection of 3.0 mCi 201Tl. Administration of dipyridamole was as follows: 0.142 mg/kg/min during 4 minutes, followed by a slight exercise and 201Tl injection. The infusion of adenosine was as follows: 0.140 mg/kg/min during 6 minutes with injection of 201Tl after the third minute of infusion. Patients were asked to give their preference considering the number, type, severity, and duration of side effects on a scale from 0 (worst) to 5 (best). Reading was done by two experienced observers. The heart was divided into three segments per view. The change in systolic blood pressure was -12 +/- 11 mm Hg for adenosine and -5 +/- 10 mm Hg for dipyridamole (p < 0.001), and the change in heart rate was 18 +/- 10 beats/min for adenosine and 8 +/- 7 beats/min for dipyridamole (p < 0.001). With regions of interest, ischemic/normal wall ratios were determined: 0.78 +/- 0.06 for adenosine and 0.83 +/- 0.08 for dipyridamole (p < 0.001). Adenosine detected 295 normal, 170 ischemic, and 21 scar segments, whereas dipyridamole detected 326, 135, and 25 segments, respectively. Patients preferred adenosine (4.3 +/- 1.0 for adenosine vs 3.8 +/- 1.5 for dipyridamole; p < 0.04) mainly because of the short duration of side effects. CONCLUSION: This study shows that the use of adenosine with 201Tl imaging may have some advantages over dipyridamole.

Effect of intravenous atrial natriuretic peptide on gas exchange in humans.

The aim of this work was to establish whether a physiological increase in atrial natriuretic peptide (ANP) plasma levels affects pulmonary gas exchange in humans. Ten volunteers received an infusion of either ANP (4 pmol.kg-1.min-1) or physiological saline, for 60 min. Baseline measures of the alveolar-arterial PO2 difference and of the physiological dead space were within normal limits and remained stable during and after the infusion of ANP or saline, although plasma ANP and cGMP rose significantly (p < 0.01) (mean +/- SEM: ANP: 13.4 +/- 3.9 to 56.0 +/- 10.4 pmol/l; cyclic GMP: 3.8 +/- 0.3 to 17.0 +/- 3.8 nmol/l). We conclude that a physiological increase in plasma ANP does not affect pulmonary gas exchange significantly in humans.

Effect of salbutamol on gastroesophageal reflux in healthy volunteers and patients with asthma.

The aim of this work was to establish whether beta-adrenergic agonists promote or increase gastroesophageal reflux in patients with asthma. Ten healthy individuals and eight patients with asthma were studied on 2 different days. One day they received a placebo, and the other day they received 4 mg of salbutamol by mouth. Complete measurements of esophageal manometry were performed before and every 30 minutes for 210 minutes after the administration of the drugs. Esophageal pH was measured continuously for the duration of the experiment. The results demonstrate that (1) salbutamol had no effect on the lower esophageal sphincter pressure gradient, the peak esophageal contraction pressure, or the number and duration of reflux episodes in patients with asthma and normal individuals, and (2) patients with asthma have a resting lower esophageal sphincter pressure higher than healthy subjects. We conclude that the administration of salbutamol does not affect esophageal function.

Release of atrial natriuretic factor (ANF) induced by acute airway obstruction.

The aim of this study was to measure the effects of an increase in negative intrathoracic pressure on the release of ANF. With the subjects seated comfortably, 3 control blood samples were obtained over 30 minutes. Eight subjects then breathed for 30 min. through an inspiratory resistance in such a way that maximal inspiratory pleural pressures were between -30 to -40 cmH2O. Three blood samples were withdrawn after 20, 25, and 30 min., with the subject still breathing against the artificial resistance. Plasma concentrations of ANF were analysed by RIA. They measured: control value 24.6 +/- 3.7 pg ANF/mL (X +/- SE); with resistance 37.1 +/- 8.1 pg/mL (p less than or equal to .05). These results suggest that ANF could be released during an asthma attack.

Reflex decrease of histamine-induced bronchoconstriction after laryngeal stimulation in asthmatic patients.

The aim of this work was to determine if the nonadrenergic noncholinergic nervous system can be reflexly activated in asthmatic patients by stimulating the vocal cords. The stimulation was produced by a cytology brush passed through a bronchoscope previously introduced transnasally and positioned just above the epiglottis. The subjects were premedicated with cholinergic blockers, and bronchoconstriction was induced by inhalation of histamine. In 11 experiments performed on six patients, vocal cords stimulation resulted in a decreased RL from 8.4 +/- 1.0 to 6.3 +/- 0.8 cm H2O.L-1.s (mean +/- SE) (p less than 0.01). To assess the possible contribution of circulating catecholamines to this decrease, plasma epinephrine and norepinephrine levels were measured in six experiments, before and 30 s, 1, 3, and 5 min after the stimulation. Pulmonary resistance fell from 10.0 +/- 1.3 to 7.6 +/- 0.9 cm H2O.L-1.s (mean +/- SE) (p less than 0.05) 30 s and to 7.9 +/- 0.9 cm H2O.L-1.s (p less than 0.05) 60 s after stimulation. Epinephrine and norepinephrine levels increased slightly but not significantly throughout the experiment. We conclude that in asthmatic patients, as in normal subjects, stimulation of the vocal cords produces a reflex decrease in histamine-induced bronchoconstriction which is modulated by the nonadrenergic noncholinergic nervous system.

Sampling technique and rheology of human tracheobronchial mucus.

The aims of this work were: (1) to establish a technique for the sampling of human tracheobronchial mucus not contaminated by saliva or topical anesthesia, and (2) to measure its viscoelastic properties. After local anesthesia of the hypopharynx by topical application of 4% xylocaine, a double-sleeve microbiology specimen brush was introduced into a flexible bronchoscope placed in the trachea. The brush was left in direct contact with the bronchial mucosa for 20 to 30 s to allow mucus to collect on it. The mucus sample was then scraped from the brush and immediately covered with paraffin oil. Its viscoelastic properties were determined by the magnetic microrheometer technique. Excluding the time to anesthetize, the whole procedure took less than 1 min (thus minimizing the effect of cough) and resulted in sufficient mucus for rheologic analysis in approximately 90% of trials, i.e., 2.1 +/- 1.5 (SD) mg. Mucus specimens were collected from 20 fasting healthy nonsmoking subjects; 17 of them returned for a second collection several days later. Values for mucus mechanical impedance (vector sum of elasticity and viscosity) at 1 rad/s were: Control 1, 141 +/- 41 (SE); Control 2, 155 +/- 58 dyn/cm2. There was a large variation in mucus viscoelasticity, both between subjects (CV, 130%) and within the same subject (CV, 55%) on different days. In 7 subjects, mucus samples were collected 15 min after intravenous injection of 0.6 mg atropine. Viscoelasticity in these samples was 708 +/- 147 dyn/cm2, a value significantly different from Control 1 (p less than 0.05) and Control 2 (p less than 0.05) values.(ABSTRACT TRUNCATED AT 250 WORDS)

Reflex decrease of histamine-induced bronchoconstriction after laryngeal stimulation in humans.

The aim of this work was to determine whether the nonadrenergic, noncholinergic, inhibitory nervous system can be reflexly activated in humans by laryngeal stimulation. The stimulation was achieved with a cytology brush passed through a bronchoscope previously introduced transnasally and positioned just above the epiglottis. In one series of experiments, subjects were premedicated with beta-adrenergic and cholinergic blockers, and bronchoconstriction was induced by histamine inhalation. The results showed that mechanical irritation of the vocal cords with the cytology brush produced a sharp, short-lasting (less than 1 min) decrease in RL from (mean +/- SE) 6.8 +/- 2.1 to 4.8 +/- 1.5 cm H2O.L-1.s, and in the absence of parasympathetic blockade, laryngeal irritation produced a fall in RL from (mean +/- SE) 9.0 +/- 3.7 to 5.4 +/- 2.0 cm H2O.L-1.s (p less than 0.0001) (ANOVA). This decrease in RL was independent of the slight cough produced by laryngeal stimulation and reflects a change in lower and not upper airway resistance. Adequacy of the beta-adrenergic and cholinergic blockade was checked with an intravenous infusion of isoproterenol and inhaled methacholine, respectively. In 2 subjects, the fall in RL was abolished by a block of the superior laryngeal nerves and direct local anesthesia of the vocal cords. We conclude that mechanical irritation of the larynx produces a partial reversal of histamine-induced bronchoconstriction that is mediated through nervous pathways that are neither beta-adrenergic nor cholinergic in origin. We suggest that this decrease in bronchoconstriction is modulated by the nonadrenergic, noncholinergic, inhibitory nervous system.

Prolonged hyporesponsiveness of airway smooth muscle to histamine following general anesthesia.

The prolonged effect of barbiturates and inhalation anesthesia on airway response to histamine was studied in five groups of dogs. Group B (n = 10), H24 (n = 5), and H72 (n = 5) were anesthetized with sodium thiamylal (B) or halothane and N2O (H24, H72) for 3 h, during which a dose-response curve to histamine was obtained. The animals were then allowed to recover; 24 h (B and H24) or 72 h later, the animals were killed and an in vitro dose-response curve to histamine was obtained on a tracheal smooth muscle (TSM) specimen. Group C (n = 5), the control group, had no prolonged exposure to anesthesia. The dogs were immediately killed and the in vitro histamine response of the TSM was measured. The results (mean +/- SE) showed that the smooth muscle contractile properties (i.e., the maximum contraction to electrical field stimulation) were comparable in all four groups: 111 +/- 12 g (B); 168 +/- 23 g (H24); 106 +/- 32 g (H72); and 107 +/- 31 g (C). The maximum response (mean +/- SE) to histamine (as % of maximum electrical contraction) was: 15 +/- 6% (B), 30 +/- 9% (H24), 32 +/- 12% (H72), and 50 +/- 8% (C). Statistical analysis of the data showed that the histamine response of Group B and Group H24 was significantly decreased compared to Group C (P less than 0.01 and less than 0.05, respectively); in Group H72 the results were not significantly different from Group C (0.1 greater than P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of dopamine on tracheal smooth muscle.

Dose-response curves to dopamine were obtained on guinea-pig, dog and human tracheal smooth muscle. Dopamine produced a relaxation of the guinea-pig tracheal chain, and this relaxation was completely blocked by propranolol. The potency of dopamine as a beta-agonist was 1/10 000 that of isoprenaline, 1/250 that of adrenaline and 1/50 that of noradrenaline. In human and dog tracheal smooth muscle, dopamine induced a contraction which could be entirely abolished by alpha-adrenoceptor antagonists. As an alpha-agonist, the potency of dopamine was 1/20 that of adrenaline and noradrenaline. Our data also show that a dopamine induced contraction is greatly potentiated if the smooth muscle specimen has been previously slightly contracted with histamine. We conclude that there are few, if any, specific dopaminergic receptors in the airways. Dopamine acts on both alpha- and beta-adrenoceptors, but in humans and dogs, its effect is predominantly on alpha-adrenoceptors.

Dopamine effect on bronchomotor tone in vivo.

The effect of increasing doses of dopamine (inhaled or infused) on pulmonary resistance (RL) was measured in 4 normal and in 4 asthmatic subjects. Dopamine, in doses sufficient to raise systolic blood pressure 25 mmHg, did not change RL. However, dopamine, inhaled and infused, significantly decreased histamine-induced bronchoconstriction both in normal and in asthmatic subjects. Thus, we conclude that if dopamine is released by the adrenal medulla during an asthmatic attack, it should have a beneficial rather than a deleterious effect.