Drainage routes of bronchial blood flow in anaesthetized sheep.

The systemic circulation to the lung supplies the trachea and airway walls and may be important in the pathophysiology of asthma and pulmonary oedema. An understanding of the venous drainage pathways of this bronchial blood flow may be therapeutically important. The purpose of this study was to understand the normal drainage pathways in sheep. In seven anaesthetized, ventilated sheep we injected echo contrast agents into a systemic vein or into the bronchial artery while performing echocardiography to determine whether the drainage could be observed to the right heart and/or to the left heart. During transoesophageal echo (n=5) or heart surface echo (n=2), cephalic vein injection of <8 microm diameter gelatin microballoons promptly opacified the right but never the left-sided circulation. Air in agitated saline in the seven animals showed the same result. By contrast, injection into the bronchial artery promptly opacified the left atrium, left ventricle, and aorta but not the right-sided circulation in all seven microballoon injections and all but one of the air in agitated saline injections. The failure of the echo agents to pass through the pulmonary circulation may be related to sheep pulmonary intravascular macrophages or the surface forces on air bubbles of small size promoting collapse. The main conclusion is that there are bronchopulmonary anastomoses that connect the bronchial circulation to the pulmonary venous circulation connecting distal to the pulmonary capillaries. Any bronchial venous drainage to the right-sided circulation must have been below the detection level of the instruments and would in any case appear to be much less that the post-pulmonary capillary anastomoses noted. Pulmonary venous hypertension would be expected to have a direct effect on the bronchial circulation.

Miltefosine (Impavido): the first oral treatment against leishmaniasis.

Miltefosine is a novel antileishmanial drug that has significant selectivity in both in vitro and in vivo models. Clinical efficacy was demonstrated for the treatment of visceral leishmaniasis with the advantage of oral administration over the currently recommended antileishmanial drugs that require parenteral administration. Miltefosine produces high cure rates also in patients resistant to the standard antimonial therapy.

Contrast microbubbles improve diagnostic yield in ICU patients with poor echocardiographic windows.

OBJECTIVE: To determine the value of contrast echocardiographic studies in patients admitted to ICUs who have poor echocardiographic windows secondary to COPD, ventilator use, or inability to obtain optimal positioning for the echocardiogram. DESIGN: A prospective comparison study of technically difficult patients in the ICU. OUTCOME MEASURE: The total scores for the left ventricle (LV) in the two-chamber and four-chamber views were calculated at baseline and following injection of 1 to 2 mL of a contrast agent. The mean numbers of segments visualized in all patients at baseline and after injection of contrast agent were compared to assess the effect on improved visualization. RESULTS: Forty consecutive patients underwent echocardiography in the ICU for evaluation of LV function. Of these, 25 patients (63%) had poor visualization of the endocardium and required IV contrast agent. In these 25 patients, the average baseline segmental score was 4.5, compared to 11.6 in patients who received an IV contrast agent. Nineteen patients had an average baseline segmental score of 3.9 and were deemed to have a nondiagnostic study. After administration of IV contrast, all patients converted to a diagnostic study, with an average score of 11.6 segments visualized. CONCLUSIONS: Use of echocardiographic contrast agents in selected patients with poor baseline echocardiographic windows in the ICU setting significantly enhances segmental LV visualization and yielded 100% conversion from nondiagnostic to diagnostic studies.

M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study).

Previous studies have identified a number of echocardiographic variables that predict cardiovascular disease (CVD) events and mortality, but have not focused on a large elderly cohort. The purpose of this study was to determine whether M-mode echocardiographic variables predicted all-cause mortality, incident coronary heart disease (CHD), congestive heart failure (CHF), and stroke in a large prospective, multicenter, population-based study. In the Cardiovascular Health Study, a biracial cohort of 5,888 men and women (mean age 73 years) underwent 2-dimensional M-mode echocardiographic measurements of left ventricular (LV) internal dimensions, wall thickness, mass and geometry, as well as measurement of left atrial dimension and assessment for mitral annular calcium. Participants were followed for 6 to 7 years for incident events; analyses excluded subjects with prevalent disease. One or more echocardiographic measurements were independent predictors of all-cause mortality and incident CHD, CHF, and stroke. After adjustment for anthropometric and traditional CVD risk factors, LV mass was significantly related to incident CHD, CHF, and stroke. The highest quartile of LV mass conferred a hazards ratio of 3.36, compared with the lowest quartile, for incident CHF. Furthermore, incident CHF-free survival was significantly lower for participants with LV mass in the highest versus the 2 lowest quartiles (86% vs 97%, respectively, at 2,500 days). Eccentric and concentric LV hypertrophy, respectively, conferred adjusted hazards ratios, compared with normal LV geometry, of 2.05 and 1.61 for incident CHD, and 2.95 and 3.32 for incident CHF. Thus, in an elderly biracial population, selected 2-dimensional M-mode echocardiographic measurements were important markers of subclinical disease and conferred independent prognostic information for incident CVD events, especially CHF and CHD.

Ultrasound-enhanced thrombolysis at 20 kHz with air-filled and perfluorocarbon-filled contrast bispheres.

BACKGROUND: Ultrasound (US) at low frequencies has been shown to enhance clot lysis by itself and in the presence of urokinase (UK). The comparative effects of air-filled versus perfluorocarbon-filled polymer bispheres in enhancing this effect have not been previously demonstrated. METHODS: Freshly drawn human blood was incubated at 37 degrees C for 2 hours, and the subsequent formed clot was dried and weighed. It was then exposed to saline control, saline + UK (10,000 IU), saline + UK + US, saline + UK + US + low shell-strength polymer bispheres (PB1), saline + UK + US + high shell-strength polymer bispheres (PB2), and perfluorocarbon-filled high shell-strength polymer bipsheres (PB3) for a total of 6 minutes. Clots were removed and weighed to determine the percentage of thrombolysis. RESULTS: The percentage of clot lysis for each study group was as follows: saline 18.5% +/- 4%, US alone 22.2% +/- 5%, UK alone 21.9% +/- 4%, US+UK 32.2% +/- 8% (P <.05 compared with UK alone), US+UK+PB1 36.9% +/- 8%, US+UK+PB2 34.3% +/- 8%, and US+UK+PB3 45.0% +/- 11% (P <.05 compared with US+UK, P <.05 compared with US+UK+PB2). CONCLUSION: Ultrasound at 20 kHz significantly enhances clot lysis. The addition of perfluorocarbon-filled bispheres increased this effect more significantly than did the addition of air-filled polymer bispheres.

Prognostic value of 12-lead electrocardiogram during dobutamine stress echocardiography.

The aim of this study was to assess the prognostic value of the 12-lead electrocardiogram (ECG) obtained during dobutamine stress echocardiography (DSE) in predicting subsequent cardiac events. We retrospectively analyzed 345 patients undergoing DSE in 1992-1994 and selected those patients with negative echo results for ischemia. Of the 200 patients with negative DSE results, a separate analysis of their ECG data was performed with results reported as either positive, negative, or nondiagnostic for ischemia. Follow-up was performed through a physician chart review and direct telephone contact. Event rates were determined for hard (myocardial infarction or cardiac death) and soft (hospitalization for angina and/or congestive heart failure, coronary angioplasty, or coronary artery bypass graft surgery) cardiac events occurring after the negative DSE for up to 6 years after the test. Death was also determined by referencing the patients' data with mortality data available on the Internet. There were 143 patients with ECG data reported as negative and 40 patients with ECG data reported as positive for ischemia. The hard and soft event rates were 1.5% and 9% per patient per year in the ECG negative group and 2% and 11% in the ECG positive group. There were no statistical differences in event rates between the two groups during the 5-year follow-up period. Our results suggest that the ECG result obtained during DSE does not confer any incremental prognostic value over the echo result.

Incidence and significance of profound hypotension during dobutamine stress echocardiography.

BACKGROUND: Mild hypotension (drops of systolic blood pressure of > or = 20 mmHg) occurs in 14-38% of dobutamine stress echo (DSE) and carries a good prognosis for subsequent cardiac events. The incidence and significance of more profound hypotension (PH) (> or = 50 mmHg) is unknown. HYPOTHESIS: The aim of the study was to determine the incidence of PH during DSE and its prognosis for subsequent cardiac events. METHODS: We reviewed 617 DSE performed at our institution between 1992 and 1996 and identified two DSE subgroups. The first group (PH group) consisted of all patients with PH during DSE. A second group was selected with baseline characteristics similar to the PH group but without PH during DSE (non-PH group). Follow-up was by a physician chart review and direct telephone contact. Cardiac event rates were determined for hard [myocardial infarction (MI), or cardiac death] and soft (angina, congestive heart failure, coronary angioplasty, or coronary bypass surgery) events occurring after the DSE. RESULTS: Of the 617 DSE performed, 16 (3%) patients developed PH (PH group) during DSE, with 13 showing no inducible ischemia. The hard and soft cardiac event rate in this 13 PH group was 46% (mean follow-up of 28.7 +/- 18 months). Of the non-PH group, 32 patients had a negative DSE with a coronary event rate of 12.5%. Profound hypotension correlated with a significantly higher cardiac event rate (p < 0.02). CONCLUSIONS: The incidence of PH during DSE is low (3%) and appears to predict a worse prognosis for subsequent cardiac events.

Value of negative dobutamine stress echocardiography in predicting long-term cardiac events.

UNLABELLED: To determine the value of negative dobutamine stress echocardiography (DSE) results in predicting subsequent long-term cardiac event rates, we retrospectively reviewed all dobutamine stress echocardiograms performed at our institution over a 3-year period (1992-1994). Follow-up was accomplished through the completion of a detailed questionnaire compiled from data obtained through chart review and direct telephone contact. Information regarding death also was determined by referencing patient data with mortality data available on the World Wide Web. Event rates were determined for hard (myocardial infarction [MI] or cardiac death) and soft (hospitalization for angina and/or congestive heart failure, coronary angioplasty, or coronary bypass surgery) cardiac events occurring after the negative DSE results for up to 7 years after the test. Negative test results were defined as those showing no new or worsening wall motion abnormalities after either a normal resting echocardiogram (normal-negative [NN]) or an abnormal segmental resting echocardiogram (fixed-negative [FN]). RESULTS: Of the 346 interpretable tests, 224 were negative for inducible wall motion abnormalities, with 171 NN and 53 FN. In the NN group, the MI rate was 1.5% per patient/year, and the mortality rate was 0.13% per patient/year. In the FN group, the MI rate was 0.7% per patient/year, and the mortality rate was 0% per patient/year. CONCLUSIONS: DSE results in both NN and FN groups predict a very low subsequent hard event rate and mortality for up to 5 years after the test.

Acute myocardial infarction associated with dobutamine stress echocardiography.

Acute myocardial infarction as a complication of dobutamine stress echocardiography (DSE) is described in two patients during or shortly after undergoing the procedure. Both clinical events resulted in characteristic elevations in cardiac enzymes and the development of new electrocardiographic Q waves in the inferior leads. Subsequent coronary angiography was performed in both cases; one patient required two-vessel coronary artery bypass grafting to his first obtuse marginal and posterior descending arteries, and the other underwent successful angioplasty of an occluded proximal right coronary artery. Only two cases of DSE-associated myocardial infarction have been reported previously in the literature.

Meta-analysis of the relationships between Kerr and Jermier's substitutes for leadership and employee job attitudes, role perceptions, and performance.

A meta-analysis was conducted to estimate more accurately the bivariate relationships between leadership behaviors, substitutes for leadership, and subordinate attitudes, and role perceptions and performance, and to examine the relative strengths of the relationships between these variables. Estimates of 435 relationships were obtained from 22 studies containing 36 independent samples. The findings showed that the combination of the substitutes variables and leader behaviors account for a majority of the variance in employee attitudes and role perceptions and a substantial proportion of the variance in in-role and extra-role performance; on average, the substitutes for leadership uniquely accounted for more of the variance in the criterion variables than did leader behaviors.

Tamponade in patients undergoing cardiac surgery: a clinical-echocardiographic diagnosis.

The purpose of this study was to evaluate the sensitivity of current echocardiographic criteria in detecting cardiac tamponade in the patient who has undergone cardiovascular surgery. Because the current echocardiographic criteria for tamponade were initially developed and studied predominantly in patients with medical problems, relatively less information is available in patients who have undergone cardiac surgery. Of 848 consecutive patients who underwent cardiovascular surgery, patients were selected for the study if they had clinical or hemodynamic deterioration and had undergone an echocardiogram just before a successful pericardiocentesis or a surgical evacuation of pericardial blood or clot. The echocardiograms were evaluated for evidence of chamber collapse, cardiac motion, Doppler flow variations, and the location and width of pericardial separation. Fourteen patients were identified who met the inclusion criteria (clinical or hemodynamic deterioration, recent echocardiogram, and successful intervention) for cardiac tamponade. The clinical and hemodynamic findings were hypotension (13 patients), low cardiac output (7), low urine output (3), cardiopulmonary arrest (1), elevated central venous pressure (1), and shortness of breath (1). In these patients current echocardiographic criteria were seen infrequently: chamber collapse in the right atrium (6 of 14 patients) and right ventricle (4 of 14); Doppler flow variation (2 of 5); and swinging heart (0 of 15), whereas increased pericardial separation (> or = 10 mm) was seen in all (14 of 14) the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine in chronic stable angina: results of a multicenter double-blind crossover trial.

The efficacy and safety of amlodipine, 10 mg, a new long-acting calcium antagonist, was compared with placebo in 103 patients with stable angina pectoris in a multicenter double-blind crossover study. The trial consisted of an initial 2-week single-blind placebo period followed by a first period of 4 weeks of double-blind therapy, which was followed by a 1 week washout period and then a second 4-week double-blind period after treatments were crossed over. Twenty-four-hour Holter electrocardiographic monitoring was carried out in 12 patients at three centers. In the first double-blind period amlodipine produced a significantly greater increase in symptom-limited exercise duration (amlodipine 478.5 to 520.6 vs placebo 484.6 to 485.2 seconds; change +8.8% vs +0.1%, respectively; p = 0.0004) and total work (amldipine 2426 to 2984 vs placebo 2505 to 2548 kilopondmeters; change +24% vs +1.7%, respectively; p = 0.0006) and a decrease in angina attack frequency (from 3 to 1 per week; p = 0.016) and nitroglycerin consumption (from 2 to 0.5 tablets/wk; p = 0.01) compared with placebo. Holter monitoring revealed significant reductions in numbers (amlodipine 4.65 to 2.22 vs placebo 1.84 to 1.54; change -52% vs +84%, respectively; p = 0.06), absolute total area (amlodipine 87.66 to 11.43 vs placebo 5.76 to 35.24; change -87% vs +513%, respectively; p = 0.02), and duration (amlodipine 12.29 to 2.95 vs 1.66 to 7.74 seconds; change -76% vs +367%, respectively; p = 0.008) of ST-segment depressions after treatment with amlodipine compared with placebo. After the treatments were crossed over changes continued to favor amlodipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex, age, and disease affect echocardiographic left ventricular mass and systolic function in the free-living elderly. The Cardiovascular Health Study.

BACKGROUND: Left ventricular (LV) hypertrophy, as measured by M-mode echocardiography, is an independent predictor of mortality and/or morbidity from coronary heart disease (CHD). LV global and segmental systolic dysfunction also have been associated with myocardial ischemia and cardiovascular morbidity and mortality. Echocardiographic data, especially two-dimensional, have not been available previously from multicenter-based studies of the elderly. This report describes the distribution and relation at baseline of echocardiographic LV mass and global and segmental LV wall motion to age, sex, and clinical disease category in the Cardiovascular Health Study (CHS), a cohort of 5201 men and women (4850 white) 65 years of age and older. METHODS AND RESULTS: M-mode LV mass adjusted for body weight increased modestly with age (P < .0001), increasing less than one gram per year increase in age for both men and women. After adjustment for weight, LV mass was significantly greater in men than in women and in participants with clinical CHD compared with participants with neither clinical heart disease nor hypertension (both P < .001). Across all CHS age subgroups, the difference in weight-adjusted LV mass by sex was greater in magnitude than the difference related to clinical CHD. M-mode measurements of LV mass could not be made in 34% of CHS participants, and this was highly related to age (29% in the 65 to 69 year versus 50% in the 85+ year age group, P < .001) and other risk factors. In participants with clinical CHD and with neither clinical heart disease nor hypertension, LV ejection fraction and segmental wall motion abnormalities were more prevalent in men than women (all P < .001). Of interest, 0.5% of men and 0.4% of women with neither clinical heart disease nor hypertension had LV segmental wall motion abnormalities, suggesting silent disease, compared with 26% of men and 10% of women in the clinical CHD group (P < .0001). Multivariate analyses revealed male sex and presence of clinical CHD (both P < .001) to be independent predictors of LV akinesis or dyskinesis. CONCLUSIONS: Significant baseline relations were detected between differences in sex, prevalent disease status, and echocardiographic measurements of LV mass and systolic function in the CHS cohort. Age was weakly associated with LV mass measurements and LV ejection fraction abnormalities. These relations should be considered in evaluating the preclinical and clinical effects of CHD risk factors in the elderly.

Prolonged haemolytic anaemia in malaria and autoantibodies against triosephosphate isomerase.

Prolonged haemolysis may accompany infection with Plasmodium falciparum. We observed prolonged haemolysis in 4 of 10 patients with this type of malaria after parasitological cure. IgM antibodies specific for the glycolytic enzyme triosephosphate isomerase were detected in these patients' sera. Clinical recovery and a decrease in haemolysis coincided with a fall in these autoantibodies. In vitro, affinity purified autoantibodies isolated from the sera directed against triosephosphate isomerase induced lysis of erythrocytes and activation of complement as shown by the 51Cr release assay. We assume that autoantibodies against triosephosphate isomerase contribute to the development of prolonged haemolysis and anaemia in P falciparum malaria.

Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group.

BACKGROUND AND PURPOSE: This article describes the prevalence of extracranial carotid atherosclerosis assessed by ultrasonography, its association with risk factors, and its relation to symptomatic coronary disease and stroke in men and women aged > or = 65 years. METHODS: Maximum percent stenosis, maximum common carotid artery wall thickness, and maximum internal carotid artery wall thickness were assessed using duplex ultrasound in 5,201 men and women aged > or = 65 years in the Cardiovascular Health Study, a study of the risk factors and natural history of cardiovascular disease in the elderly. Existing coronary disease and stroke were assessed by physical examination and participant history. RESULTS: Detectable carotid stenosis was present in 75% of men and 62% of women, although the prevalence of > or = 50% stenosis was low, 7% in men and 5% in women. Maximum stenosis and maximum wall thickness measurements increased with age and were uniformly greater at all ages in men than in women (p < 0.00001). Established risk factors for atherosclerosis (hypertension, smoking, diabetes) and indications of vascular disease (left ventricular hypertrophy, major electrocardiographic abnormality, bruits, and history of heart disease or stroke) related to all three carotid artery measures in the elderly. Of the three ultrasound measures, the best correlate for a history of coronary disease was maximum internal carotid artery wall thickness. For stroke the best correlate was common carotid artery wall thickness. Multiple logistic regression models of prevalent coronary heart disease and stroke that included the ultrasound findings indicated, after adjustment for age and sex, that maximum internal wall thickness and maximum common carotid wall thickness were significant correlates of both. Maximum stenosis did not add significantly to the correlation. CONCLUSIONS: In the elderly the incidence of carotid atherosclerosis was high, although the frequency of severe disease was low. The prevalence and severity of carotid atherosclerosis continued to increase with age even in the late decades of life, and more disease was found in men than in women at all ages. Known risk factors for atherosclerosis continued to relate to carotid abnormalities in the later decades of life, both in symptomatic and asymptomatic subjects.

Magnetic resonance and other imaging techniques in valvular and cardiac disease.

A number of new magnetic resonance imaging techniques are offering excellent views of the cardiovascular system. These techniques can provide accurate information about chamber sizes, ventricular mass, and wall motion. Blood flow patterns can be analyzed to provide semiquantitative estimates of valvular regurgitation. Accurate measurements of the area and velocity of great vessel flow may provide the first truly quantitative magnetic resonance imaging estimates of shunt flow and regurgitant volumes. Future developments and improvements may lead to coronary artery imaging in clinical patients. In addition to these promising developments in magnetic resonance imaging, several other interesting imaging papers are discussed in this review of magnetic resonance and other imaging techniques.