Why do we need new treatments for rheumatoid arthritis?

It is being increasingly appreciated that a substantial number of patients with congestive heart failure (CHF) have relatively preserved systolic function. Although these individuals appear to have a somewhat better prognosis than those with low ejection fractions, they experience significant symptoms and frequently require hospitalization. In these patients, CHF is often attributed to left ventricular diastolic dysfunction, but this represents a potentially misleading over-simplification. In contrast to CHF associated with left ventricular systolic dysfunction, little is known about how to treat patients with preserved systolic function. Perhaps the major point of consensus has been that the use of digitalis glycosides is inappropriate in this group. Unexpectedly, however, in the recently completed Digitalis Investigators Group trial, a subgroup of nearly 1,000 patients with radionuclide ejection fractions > or = 45% experienced a similar reduction in heart failure endpoints with digoxin therapy as patients with 25% to 44% ejection fractions. The purpose of this article is to review the diverse causes of CHF with preserved systolic function and to examine the potential mechanisms by which digoxin may be producing beneficial effect in this setting.     

Validations of time-resolved fluoroimmunoassays for urinary estrone 3-glucuronide and pregnanediol 3-glucuronide

OBJECTIVE: In this study, we determined the effect of age, sex, and body size on left ventricular mass. DESIGN: Two-dimensional-guided M-mode echocardiography was used in an assessment of 111 healthy, normal adults. MATERIAL AND METHODS: Left ventricular mass was calculated with the cube function formula corrected by a regression equation to agree with autopsy estimates of left ventricular mass. Calculated left ventricular mass, indexed by body surface area and by height, was analyzed on the basis of sex and age of the study participants. Age was analyzed as a dichotomous, trichotomous, and continuous variable. The effects of age, sex, and obesity, as well as interactions, were tested within a multiple linear regression model framework. RESULTS: Left ventricular mass, when indexed for either body surface area or height, was greater in men than in women. For women, but not men, we found a small but significant increase in left ventricular mass with advancing age. Body mass index, an indicator of obesity, increased with aging in women but not in men and affected left ventricular mass. No significant changes were noted in left ventricular cavity size with advancing age, and the increase in left ventricular mass in women was due to increased ventricular wall thickness. CONCLUSION: The findings in this study suggest that left ventricular mass, as assessed by two-dimensional-guided M-mode echocardiography, is affected not only by sex and body size but also by age in women. This phenomenon may be related to an increase in body mass index with advancing age in women. In clinical studies that use echocardiographic left ventricular mass to diagnose left ventricular hypertrophy, these observations should be considered.     

Comparative efficacy of three indexes of left ventricular performance derived from pressure-volume loops in heart failure induced by tachypacing

OBJECTIVES: The purpose of this study was to serially evaluate the response and variability of the end-systolic pressure-volume relation, the left ventricular end-diastolic volume-peak positive first derivative of left ventricular pressure (dP/dt) relation and the left ventricular end-diastolic volume-stroke work relation in the development of progressive left ventricular dysfunction. BACKGROUND: Evaluation of systolic performance of the failing left ventricle may be enhanced by using relatively load-insensitive measures of left ventricular performance. The end-systolic pressure-volume, left ventricular end-diastolic volume-peak positive dP/dt and left ventricular end-diastolic volume-stroke work relations adequately define left ventricular performance under multiple loading conditions, but efficacy has not been fully assessed in the failing heart, particularly in the intact circulation. METHODS: Fourteen dogs underwent instrumentation and rapid pacing to heart failure. Variably loaded pressure-volume beats were produced by inferior vena cava occlusion. The dogs were evaluated at baseline and at three progressively more severe levels of left ventricular dysfunction. RESULTS: There was a progressive increase in left ventricular volumes at end-diastole ([mean value +/- SE] 60 +/- 28 to 73 +/- 29 ml, p < 0.001) and end-systole (39 +/- 19 to 61 +/- 27 ml, p < 0.001) during the 3 weeks of rapid pacing and a progressive decline in peak positive dP/dt (1,631 +/- 410 to 993 +/- 222 mm Hg/s, p < 0.001) and ejection fraction (37 +/- 8% to 16 +/- 11%, p < 0.001). There was a corresponding decline in the slope of each of the three relations: for end-systolic pressure-volume, 6.3 +/- 2.2 to 2.8 +/- 0.7 (p < 0.05); for left ventricular end-diastolic volume-stroke work, 61.9 +/- 9.1 to 26.5 +/- 2.4 (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 47.1 +/- 13.6 to 20.31 +/- 6.8 (p < 0.05). There was also a corresponding increase in position volumes: for end-systolic pressure-volume, 33.6 +/- 3.9 to 61.2 +/- 6.6 ml (p < 0.05); for left ventricular end-diastolic volume-stroke work, 46.2 +/- 3.6 to 89.3 +/- 7.6 ml (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 29.1 +/- 19.1 to 68.6 +/- 25.9 ml (p < 0.05). The relative degree of change in each of the three relations was similar as more severe heart failure developed. The coefficients of variation for position were significantly less than the variation for slopes. The response of volume intercepts was heterogeneous. For left ventricular end-diastolic volume-stroke work, the intercept increased as ventricular performance decreased. The intercept of the end-systolic pressure-volume relation was significantly more variable than the left ventricular end-diastolic volume-stroke work relation and did not change with progressive heart failure. The intercept for left ventricular end-diastolic volume-peak positive dP/dt was highly variable and showed no consistent changes as left ventricular function declined. CONCLUSIONS: All three relations consistently describe changes in left ventricular performance brought about by tachypacing. Evolution of left ventricular dysfunction causes a decline in slope and a rightward shift of these relations. The position of the relation is the most sensitive and least variable indicator of left ventricular systolic performance.     

Regional differences in cardiac effects of pituitary adenylate cyclase-activating polypeptide-27 in the isolated dog heart

Recent observations indicate that several neuropeptides may be involved in the regulation of cardiac function, but the effects of these peptides on the atrium are not always the same as those on the ventricle. To compare the effect of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 on the atrium with that on the ventricle, we investigated the effects of PACAP-27 on the sinus rate and atrial and ventricular contractility in isolated, blood-perfused dog heart preparations. PACAP-27 (0.01-0.3 nmol) caused transient positive followed by negative chronotropic and inotropic responses in a dose-dependent manner in the isolated right atrium, whereas it caused only a dose-dependent positive inotropic response in the left ventricle. After atropine treatment, PACAP-27 caused only positive cardiac responses in isolated atria. The order of the increase in response to PACAP-27 was atrial contractile force > sinus rate > or = ventricular contractile force. Tetrodotoxin blocked the negative chronotropic and inotropic responses to PACAP-27 in isolated atria. Propranolol did not affect the positive response. PACAP-(6-27), a type I PACAP receptor antagonist, attenuated the positive responses similarly in the atropine-treated right atrium and the left ventricle. Thus, we demonstrated that (1) PACAP-27 caused negative cardiac effects in the atrium and sinoatrial node by activation of intracardiac parasympathetic nerves, but had no negative effect on the ventricle; (2) PACAP-27 had positive effects in the atrium, sinoatrial node and ventricle mediated by type I PACAP receptors, but PACAP-27 was more effective in the atrium and sinoatrial node than in the ventricle of the dog heart.     

Difficult weaning from mechanical ventilation: a graduated approach and teamwork

Weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease (COPD) or left ventricular failure may be difficult. At the time of intubation and initiation of mechanical ventilatory support, this treatment is usually life-saving in the short term. Only later on, the condition which necessitated such support may prove irreversible. COPD patients often require positive end-expiratory pressure to enable them to trigger the ventilator comfortably. Patients with left ventricular failure need pharmacological support to reduce the circulating volume and to reduce left ventricular afterload because the ventilatory support itself reduces both left ventricular preload and afterload. Gradual withdrawal of pressure support and gradually increasing periods of T-piece weaning are probably equally effective. New methods have been described but have not yet been tested in randomized controlled trials. More important than the method of weaning is the presence of qualified and dedicated nursing support. Not all patients can be weaned; for most of those who cannot, prospects are grim. These patients require optimal palliative support with recognition of their autonomy.     

Hemodynamic evaluation in acute myocardial infarct. Application to the treatment of contractile insufficiency syndromes of the left ventricle

Even though the coronary care units have reduced to a minimum the mortality due to arrhythmias, the syndromes of left ventricular failure are responsible for the greatest part of hospital deaths in patients with acute myocardial infarction. The poor results depend upon the extensive destruction of left ventricular mass. The management in these cases should be directed to improve the performance of viable muscle as well as to preserve thejeopardized ischemic myocardium that is potentially viable. These goals may be adequately pursued by continuous hemodynamic characterization of left ventricular function. The experience of the Coronary Care Unit of the Instituto Nacional de Cardiología de México in the study of 30 of these patients is presented. Hemodynamic evaluations were performed by means of a Swan-Ganz catheter and cardiac output determinations by the thermodilution technique. The studies may be performed with a minimum of risk. Central venous pressure measurements do not adequately indicate the status of the left ventricle. Its function may be evaluated by the use of end diastolic pulmonary artery pressure which reflects, quite accurately, the left ventricular filling pressure in these patients. Continuous hemodynamic monitorization facilitates the proper manipulation of the determinants of ventricular performance (preload, afterload, cardiac rate and contractility) and permits an attempt to improve the balance between available oxygen and myocardial oxygen requirements. Hemodynamic studies and ventricular function curves are presented in selected patients with acute myocardial infarction. The mortality due to left ventricular failure and cardiogenic shock in patients with acute myocardial infarction remains extremely high. However, it is only through the early recognition by continuous hemodynamic monitorization and the aggressive management of the patient with incipient left ventricular failure that the number of survivors may be increased.     

Analysis of the structure of cardiac rhythm during treatment of auricular fibrillation with digitalis

The structure of cardiac rhythm was studied with the help of specialized computers during digitalization in 60 patients with atrial fibrillation of different etiology. The reduction of the heart contractions rate under digitalization is accompanied by certain changes in the structure of cardiac rhythm: the arrhythmic pattern of the ventricular contractions increases with a predominant growth of the number of long R--R intervals, the transitions from short intervals to longer ones become sharper, and portions of a relatively stable ventricular rhythm appear. Three main types of dynamics of the rhythm structure were distinguished on the basis of the changes in the interval R--R histogram. The described changes in the structure of cardiac rhythm are not specific, but when Digitalis drugs are used alone they can be used as additional criteria for digitalization.     

Prognosis of heart failure and factors influencing mortality

According to the recent concept, heart failure has been regarded as the syndrome in which left ventricular function is associated with shortened life expectancy. Thus, an understanding of heart failure is of the utmost importance in understanding the mortality. Five primary factors that appear to influence prognosis in heart failure are an etiology of heart failure, the severity of ventricular dysfunction, the degree of impairment of exercise capacity, the activation of neurohumoral factors, and high incidence of ventricular arrhythmias. Both left ventricular ejection fraction and exercise tolerance bear a close relationship to survival in heart failure but there is only weak correlation between these two parameters indicating that each factor may be an independent determinant of survival. Sympathetic stimulation could certainly increase the likelihood of lethal ventricular arrhythmias and contribute to sudden death in heart failure. However, the result of recent large scale trials have indicated that reduction of mortality in patients with chronic heart failure and low ejection fraction by medical treatment was not necessarily a result of the reduced mortality due to an arrhythmia but that due to progressive heart failure. Establishing the prognosis of a patient with heart failure may be of considerable importance in patient management.     

Relationship between left ventricular mass and serum cholesterol level in the untreated hypertensive

OBJECTIVE: To study the relationship between serum cholesterol level and left ventricular mass for a population of untreated hypertensive patients. DESIGN: A cross-sectional study. PATIENTS: We studied 273 untreated hypertensive patients without associated diseases consecutively referred for evaluation of blood pressure. All patients underwent M-mode echocardiographic assessment of left ventricular mass, office blood pressure measurement and 24 h ambulatory blood pressure monitoring. Fasting plasma glucose and total cholesterol levels were measured on the same day. RESULTS: We found a weak but significant correlation (r = 0.20-0.26, P < 0.01) between serum cholesterol level and left ventricular wall thickness or left ventricular mass irrespective of the mode of indexation used (height, height2.7 and body surface area). In multivariate analysis this relation remained significant after introduction of sex, age, weight, height, blood pressure and blood glucose level. When data for men and women were analysed separately the relationship between left ventricular mass and cholesterol remained significant for men only. CONCLUSION: There is a significant and independent positive relationship between serum cholesterol level and left ventricular mass that could contribute to the prognostic value of left ventricular hypertrophy.     

Effects of WB4101 and chloroethylclonidine on the positive and negative inotropic actions of phenylephrine in rat cardiac muscle

This study was designed to determine if the positive and negative inotropic actions of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium are mediated via different alpha-1-adrenergic receptor (AR) subtypes. Inotropic effects of phenylephrine were examined in isolated left atrial and papillary muscle before and after treatment with prazosin, WB4101 (N-[2-(2,6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin+ ++-2-methanamine), chloroethylclonidine (CEC) and WB4101 plus CEC. Phenylephrine (10 microM) elicited a monophasic positive inotropic response in left atrial muscle and a triphasic inotropic action in papillary muscle (transient positive, then negative inotropic components preceding a sustained positive inotropic response). CEC, WB4101 and prazosin each antagonized the monophasic response in isolated left atria and the sustained positive inotropic response in papillary muscle. CEC and prazosin each antagonized the transient negative inotropic component in papillary muscle. The transient positive inotropic response was not affected by CEC, WB4101 or CEC plus WB4101, but was antagonized by higher concentrations of prazosin. These data suggest that the sustained positive inotropic effect of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of alpha-1A and alpha-1B ARs, whereas the transient negative inotropic component of the triphasic response in ventricular preparations is mediated via alpha-1B ARs. However, present data do not exclude the possibility that the CEC-sensitive inotropic responses elicited by phenylephrine may be mediated in part by other recently described alpha-1 subtypes. The receptors involved in the transient positive inotropic action cannot be identified by current results.     

Silent myocardial ischaemia and left ventricle hypertrophy in diabetic patients

The purpose of this study was to evaluate the ability of three noninvasive techniques to detect silent myocardial ischaemia and analyse the factors associated with this condition, particularly left ventricular hypertrophy, in diabetic patients. An ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole intravenous infusion, ambulatory 48 h ECG monitoring and an echocardiographic study were performed in 92 diabetic patients without cardiac symptoms but with > or = 2 additional cardiovascular risk factors. At least one of these tests was positive in 28 patients (30.4%), suggesting silent myocardial ischaemia. Twenty-four of these patients had a coronary angiography which showed significant coronary stenosis in only 9 cases. An accurate echocardiographic tracing was obtained in 79 patients, particularly in 7 of the 9 with coronary stenosis. Left ventricular hypertrophy was detected in 34 patients, 6 of whom had coronary stenosis. In patients with left ventricular hypertrophy, the positive predictive values of myocardial scintigraphy and the ECG stress test were respectively 50% and 100%, as compared to only 33% and 11% in those without hypertrophy. In summary, coronary stenoses were found in < 10% of asymptomatic diabetic patients with > or = 2 cardiovascular risk factors, but more frequently in individuals with left ventricular hypertrophy. Thus, silent myocardial ischaemia should be searched for first in diabetic patients with hypertrophy, for which the stress test was the most accurate detection method in this study.     

Effect of the treatment with amlodipine on left ventricular hypertrophy in hypertensive patients

BACKGROUND: Left ventricular hypertrophy (LVH) is one of the physiopathological effects of hypertension and one of the main risk factors for sudden death, myocardial infarction and congestive heart failure. Drugs to treat hypertension must not only reduce blood pressure, but also modify the facts which lead to ventricular hypertrophy. This study has been designed to assess the effect of amlodipine, a calcium-antagonist, on LVH in hypertensive patients. METHODS: 20 hypertensive patients (mild to moderate, both sexes, mean age 45.0 yr) were included in a single-blind study. After an initial, four weeks placebo period, active treatment was given (amlodipine 5 mg a day). Dose titration was made after 4-8 weeks to 10 mg a day if necessary and continued until the end of the study. Systolic (SBP) and diastolic blood pressure (DBP), as well as pulse rate (PR) and adverse events were recorded at every visit. Blood and urine analysis, catecholamine, plasmatic renin activity and Mode M echocardiography were made at the beginning and the end of the study. RESULTS: Only one patient was excluded. SBP and DBP showed a significantly fall (p < 0.001). In 80% of patients DBP fell under 90 mm Hg. Every echocardiographic parameter, but left ventricular diastolic dimension, showed significantly reductions at the end of the study: septum thickness (p = 0.001), posterior wall thickness (p = 0.001), left ventricular systolic dimension (p = 0.014), wall relative thickness (p = 0.015), shortening fraction (p = 0.009), left ventricular mass (p = 0.001) and corrected left ventricular mass (p = 0.001). Blood parameters did not modify. CONCLUSIONS: Amlodipine has a beneficial effect on LVH and also is an effective and safe drug to treat mild to moderate hypertension.     

Isometric handgrip exercise increases endothelin-1 plasma levels in patients with chronic congestive heart failure

This study demonstrated an immediate and short-lasting endothelin-1 release in the circulation of patients with severe chronic congestive heart failure during isometric handgrip exercise, but not in normal subjects. Our data suggest that endothelin-1 levels may increase transiently during daily physical activity, thus contributing to progressive deterioration of left ventricular function.     

Aging and regression of cardiac hypertrophy in the hypertensive patient

OBJECTIVE: This study was aimed at determining factors acting on the regression of left ventricular hypertrophy due to essential hypertension. METHODS: It was a non-randomized, echocardiographic study of 60 previously untreated hypertensive subjects (20 to 75 years of age). RESULTS: Following a 5-year therapy, the decrease in the left ventricular mass was 14%. Normalization of blood pressure and reversal of left ventricular hypertrophy were obtained in 50% and 58% of patients, respectively. Patients of the non-responder group (non-response being defined as a less than 10% decrease in the left ventricular mass) were older and had a longer history of high blood pressure. A positive correlation was observed between age and decrease in the left ventricular mass, the latter being less marked in older patients. Antihypertensive drugs classes had no influence on reversal of left ventricular hypertrophy. CONCLUSION: Ageing may be a factor of resistance to the decrease in left ventricular mass with therapy. These results suggest that early screening and management of hypertension are essential.     

Structure-activity relationships of alkylxanthines: alkyl chain elongation at the N1- or N7-position decreases cardiotonic activity in the isolated guinea pig heart

Relationships between the alkyl substitutions (C1-C6) and cardiac inotropic activities of xanthine derivatives were studied in isolated guinea pig heart muscles. Most of the alkylxanthines exhibited positive inotropic activity on the left atrium, which was increased with an elongation of alkyl chain at the N3-position but decreased by substitution of a long alkyl group at the N1- or N7-position of the xanthine skeleton. Although positive inotropic activity in the right ventricular papillary muscle was also increased by longer alkyl groups at the N3-position, the inotropic activity became negative with an increment in alkyl chain length at the N1- or N7-position. The positive inotropic activity of alkylxanthines was correlated with their inhibitory activity on the phosphodiesterase (PDE) III isoenzyme. Adenosine A1 antagonism and PDE IV inhibitory activity were also partly associated with the inotropic activity because H-89, an inhibitor of cyclic AMP-dependent protein kinase, diminished the positive inotropic action and potentiated the negative inotropic action. These results indicate that the positive inotropic activity of alkylxanthines becomes weak with elongation of alkyl chains at the N1- and N7-positions; In particular, xanthines having two long alkyl chains show a negative inotropic activity on the right ventricular papillary muscle, an effect that could not be elucidated from their cyclic AMP-dependent action.     

In situ detection of DNA fragmentation and expression of bcl-2 in human neuroblastoma: relation to apoptosis and spontaneous regression

In patients with alcoholic cardiomyopathy there is evidence that mild heart failure is reversible if patients abstain from alcohol, but there is no consensus whether the disease is progressive once structural myocardial dilation has evolved. The aim of the present study was to compare the long-term course of congestive heart failure due to alcoholic and idiopathic dilated cardiomyopathy. Of 75 patients with overt congestive heart failure, 23 had alcoholic cardiomyopathy and were compared to 52 patients with idiopathic cardiomyopathy. The mean age was 48 +/- 12 years. Despite medical therapy, heart failure class New York Heart Association III-IV was present in 52% of patients with alcoholic and 47% of patients with idiopathic cardiomyopathy (not significant). Their mean left ventricular ejection fraction was 30 +/- 12% vs 28 +/- 12% and left ventricular end-diastolic volumes were 264 +/- 125 ml and 254 +/- 100 ml respectively (not significant). Overall survival at 1, 5 and 10 years was 100%, 81% and 81% for the group with alcoholic dilated cardiomyopathy and 89%, 48% and 30% for the group with idiopathic cardiomyopathy, respectively (P = 0.041), and the difference was even greater for transplant-free survival P = 0.005). Clinical and invasive signs of left and right heart failure as well as left ventricular dimensions were predictive of a fatal outcome; however, symptom duration and left ventricular volumes were only predictive in patients with idiopathic cardiomyopathy, suggesting that in the two patient groups different mechanisms may lead to death. Mortality in patients with severe congestive heart failure and left ventricular dilatation due to alcoholic cardiomyopathy is significantly lower than that in patients with idiopathic cardiomyopathy and similar degrees of heart failure. Thus, despite structural changes inherent in marked left ventricular dilatation, disease progression in alcoholic dilated cardiomyopathy is different from that in idiopathic cardiomyopathy and thus may have implications for the choice of therapy.     

Important metabolites to measure in pharmacodynamic studies of chlorpromazine

Left ventricular hypertrophy occurs in numerous hypertensive patients. It can be diagnosed by using echocardiography, whose sensibility (93%) and sensitivity (95%) are both excellent, provided the quality of the recordings is good enough (80%). Most often, left ventricular hypertrophy is a concentric one (relative wall thickness greater than 0.45). The determinants of hypertensive left ventricular hypertrophy are of mechanical and hormonal origin; Weber's and Brilla's recent findings suggest that the haemodynamic burden should be responsible for myocytes hypertrophy, whereas hormonal factors stimulate fibrosis proliferation. Although left ventricular hypertrophy is initially an adaptative process, it eventually results in numerous deleterious effects: arrhythmias, myocardial ischemia, left ventricular filling abnormalities. Left ventricular hypertrophy is now recognized as a powerful blood-pressure independent risk factor for cardio-vascular morbidity and mortality. Therefore, antihypertensive therapy must be aimed at reducing not only blood pressure but also left ventricular mass. Most of the published regression studies have however to be criticized from a methodologic standpoint.     

A case of dilated cardiomyopathy caused by myocardial microinfarcts in the course of polycythemia vera

This article presents a case of 45-year-old man with polycythemia vera non diagnosed before. The first symptom of polycythemia vera was acute congestive heart failure which suggested diagnosis of myocarditis. Polycythemia vera was confirmed by raised hematocrit, significantly increased platelet count, normal oxygen saturation, score for leukocyte alkaline phosphatase (LAP)-130 and splemomegaly. Echocardiography revealed left ventricular histological. Coronary arteriography showed normal coronary arteries. Finding of histological examination of the endomyocardial biopsy were described as necrosis of myocytes and abnormal blood flow in very small coronary vessels. It was the main reason of dilated cardiomyopathy caused by microinfarcts in polycythemia vera. Hematological parameters were reduced to normal levels after hydroxyurea treatment. Digitalis and ACE-inhibitor therapy quickly improved cardiovascular status from III to II NYHA class.     

Hemodynamic effects of intravenous prenalterol in severe heart failure

Nine patients with chronic severe low output heart failure (radionuclide left ventricular ejection fraction 17 +/- 5 percent [mean +/- standard deviation], left ventricular filling pressure 26 +/- 6 mm Hg, cardiac index 1.9 +/- 0.4 liters/min per m2, left ventricular stroke work index 18 +/- 6 g-m/m2) from various causes were treated with intravenous prenalterol (a new catecholamine-like inotropic agent) in doses of 1,4 and 8 mg. Significant hemodynamic improvement occurred as measured by increased left ventricular ejection fraction (to 26 +/- 4 percent), decreased left ventricular filling pressure (to 21 +/- 8 mm Hg) and increased cardiac index (to 2.4 +/- 0.6 liters/min per m2) and left ventricular stroke work index (to 25 +/- 8 g-m/m2). Significant increases in heart rate (from 87 +/- 18 to 91 +/- 18 beats/min) and mean systemic arterial pressure (from 87 +/- 8 to 92 +/- 7 mm Hg) also occurred. Peak hemodynamic response occurred at various doses. Significant adverse effects associated with prenalterol consisted of increased ventricular ectopic beats in two patients and asymptomatic ventricular tachycardia in two patients. Thus, intravenous prenalterol produces hemodynamic improvement in patients with a chronic severe low output state but may be associated with increased ventricular ectopic activity.     

Flow in pulmonary veins

Pulmonary venous flow can be evaluated by means of pulsed Doppler echocardiography during a transthoracic or transesophageal echocardiography examination. In most cases a three-peak spectral curve with highest positive wave during ventricular systole, a lower positive wave during ventricular diastole and a small negative wave during the left atrial contraction are recorded. Multiple factors affect the systolic and diastolic components of pulmonary venous flow. Pulmonary venous flow measurement may prove to be an important tool in routine judgment of diastolic left ventricular and atrial function. With regard to clinical importance, the pulmonary venous flow is a useful parameter for left atrial pressure quantification and for differential diagnosis of restrictive cardiomyopathy and constrictive pericarditis.