High-dose streptokinase therapy with three million units in one hour significantly improves early coronary patency rates in acute myocardial infarction.

In a prospective, randomized open trial, significantly higher patency rates were observed 60 minutes after beginning fibrinolytic therapy for acute myocardial infarction after administration of 3 million U streptokinase as compared to 1.5 million U (Thrombolysis in Myocardial Infarction [TIMI] grade 2 and 3 in 52% vs 26%; p = 0.04). Adverse events were observed with similar frequency in both groups.

Beneficial effects of a single dose of quinapril on left ventricular performance in chronic mitral regurgitation.

To evaluate the effect of a single dose of the angiotensin-converting enzyme inhibitor quinapril on left ventricular (LV) performance and size in patients with moderate to severe chronic mitral regurgitation (MR), 12 patients with angiographically proven isolated MR grade II to III and no evidence of coronary artery disease were studied. In all patients a baseline right heart catheterization and simultaneous radionuclide angiogram were performed at rest and during supine exercise (maximum 100 W) as well as 2 hours after oral administration of 10 mg of quinapril. Quinapril reduced heart rate slightly and lowered mean blood pressure at rest and during maximal exercise (p < 0.05). Systemic vascular resistance at rest was decreased from 1,484 +/- 505 to 1,150 +/- 427 dynes s cm-5 and with maximal exercise from 999 +/- 455 to 734 +/- 395 dynes s cm-5 (p < 0.005). Pulmonary capillary arterial pressure at rest decreased from 13 +/- 6 to 10 +/- 4 mm Hg (p = 0.01) and during maximal exercise from 29 +/- 10 to 20 +/- 7 mm Hg (p = 0.001). LV end-diastolic volume at rest (146 +/- 26 ml/m2) decreased after administration of quinapril to 128 +/- 24 ml/m2 (p = 0.001) and was also reduced during exercise (p = 0.001). LV end-systolic volume decreased from 63 +/- 43 to 49 +/- 35 ml/m2 at rest (p = 0.001) and with maximal exercise from 56 +/- 49 to 44 +/- 39 ml/m2 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes in infectious endocarditis--analysis of a disease picture in the last decade]. / Die infektiöse Endokarditis im Wandel--Analyse eines Krankheitsbilds im letzten Jahrzehnt.

The following retrospective study analyzes 51 patients aged 45.8 +/- 11 years with infective endocarditis diagnosed from January 1, 1980-December 31, 1989. The aortic valve was mainly affected (59%). 92% of patients showed predisposing factors or a directly related incident. Positive blood cultures were found in 63% of patients. The dominating bacterium was streptococcus viridans (31%) with decreasing tendency compared to the previous decade, followed by staphylococcus aureus (22%) with significantly increasing tendency. Clinical and laboratory findings were not different from those of the previous decade. Main complications in the early period of disease turned out to be acute heart failure (69%) and arterial embolism (41%) which was dependent on the severity of disease. Mortality within the initial 6 months was significantly lower than in the previous decade (16% vs 31%). Patients undergoing heart-valve replacement within the first 6 months of disease (59%) had a mortality rate of 10%, which was significantly smaller than the 24% mortality rate of patients not being operated during the same period. Furthermore, patients with staphylococcus aureus endocarditis demonstrated a markedly worse early prognosis (6 month survival rate 28.6 +/- 17.2% vs 80.0 +/- 6.1% in patients with infective endocarditis other than staphylococcus aureus-related). Late mortality was not different in the above-mentioned subgroups with a 5-year survival of more than 80%. However, surgically treated patients significantly improved their functional class in the follow-up period over medically treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability of amiodarone in serum samples under various storage conditions.

The present study was intended to examine the stability of amiodarone (Cordarex, CAS 1951-25-3) and its metabolite desethylamiodarone. For this purpose 20 ml of blood were taken from each of 12 patients treated with amiodarone and were stored, after centrifuging, at room temperature, +5 degrees C, -18 degrees C and -38 degrees C. The amiodarone and desethylamiodarone concentrations were determined by the HPLC method 30 min, 24 h, 48 h, 72 h, one and two weeks after blood-taking. It turned out that the serum levels decreased continuously as of the first day regardless of the storage temperature. Correction factors were therefore calculated for the amiodarone concentration: if the blood level determination takes place after 24 h one should add 8% to the obtained value, after 48 h 16%, after 72 h 19%, after one week 23% and after two weeks 32%.

Ubiquinone (coenzyme Q10) in the long-term treatment of idiopathic dilated cardiomyopathy.

Using a placebo-controlled, double-blind cross-over study the potential therapeutic effect of ubiquinone (coenzyme Q10) was investigated in 25 patients suffering from idiopathic dilated cardiomyopathy (New York Heart Association functional classification I, II and III). Over an initial period of 4 months, 15 patients were administered verum (3 x 33.3 mg coenzyme Q10 x day-1 p.o.) and subsequently given a placebo during the ensuing 4 months (V/P). The sequence of treatment was reversed within the remaining 10 patients (P/V). Therapeutic efficacy was assessed by means of echocardiogram, chest X-ray, radionuclide ventriculography in combination with exercise test and impedance cardiography. Control values for left ventricular function parameters were similar in both groups; left ventricular ejection fraction: 39.5 +/- 11.5% (P/V), 37.6 +/- 17.0% (V/P); left ventricular end-diastolic diameter: 65 +/- 9 mm (P/V), 67 +/- 8 mm (P/V); and cardiac output: 5.1 +/- 1.41 x min-1 (P/V), 5.1 +/- 1.11 x min-1 (V/P). Chronic treatment with ubiquinone had no influence on haemodynamic parameters, electrocardiogram, incidence of ventricular arrhythmias or on exercise tolerance. It was therefore impossible to demonstrate any therapeutic effect of ubiquinone in patients suffering from idiopathic dilated cardiomyopathy.

[Initial studies of the possibility of selective ablation of arteriosclerotic vascular changes using laser-induced shock waves]. / Erste Untersuchungen zur Möglichkeit einer selektiven Ablation arteriosklerotischer Gefässveränderungen mit Hilfe laserinduzierter Stosswellen.

We studied the effect of laser-induced shock waves in 94 arterial segments from freshly obtained autopsy material. In analogy to the well-established method of shock-wave based lithotripsy, the new principle of our treatment depends on an indirect interaction of the laser energy with the arterial wall via laser-induced mechanical shock waves (angiotripsy). We used a Nd:YAG laser, 1064 nm, 8-20 ns pulse-length to create shock waves that effected smooth craters in arteriosclerotically affected arteries. The histological examination found no thermal damage. Shock waves applied to the healthy and normal arterial wall only resulted in focal intimal ablation and in a minor loosening of the medial structures. The examination of the irrigation solution by means of a laser-guided, high-resolution analysis of the particles revealed that, in 97%, the particles created by our shock wave angiotripsy showed a diameter of less than 5 mm and an area of less than 25 mm2. Based on these first in vitro results, it seems possible to ablate arteriosclerotically affected tissue without significant damage to normal wall segments. Further in vitro and in vivo studies are required to evaluate the clinical implications of this new therapeutic approach.

Limitations of flow detection by color Doppler: in vitro comparison to conventional Doppler.

There is little awareness of the limitations of flow detection with the commercially available color Doppler flow mapping system. The influence of flow velocity, ultrasound attenuation, and penetration depth on flow detection in color Doppler (Toshiba SSH 65A) were therefore studied in vitro and compared with conventional Doppler. The flow model had physiological flow volumes and laminar flow with parabolic velocity profile in a horizontal tube of Lucite with less than 3 degrees of coincidence. Conventional Doppler flow velocity measurements correlated highly with laser Doppler anemometry results (r = 0.99, SEE = 3 cm/sec). Signal strength of color Doppler and pulsed Doppler was semi-quantitatively graded using a scale from 0 to 5. Scale 1 (sparse signals) was useless for any assessment in color Doppler but just allowed velocity measurement in pulsed Doppler. Using 19-dB attenuation, flow velocities greater than 100 cm/sec had good scores with moderate gain, 60-100 cm/sec needed increasing gain, and velocities less than 40 cm/sec were not detectable with color Doppler but readily so with pulsed Doppler. With increasing attenuation (1-29 dB) and also with increasing penetration depth, flow detection was reduced significantly (P less than 0.001) more in color Doppler than in the pulsed technique (P less than 0.01). In conclusion, low flow velocities, high attenuation, and greater than 8 cm penetration depth may hamper flow detection in color Doppler and, thus, diagnostic accuracy. Conventional Doppler with its superior accuracy and sensitivity should therefore consolidate diagnostic ultrasound assessment.

Sex hormone concentrations in men with angiographically assessed coronary artery disease--relationship to obesity and body fat distribution.

The relationship between circulating sex hormone levels and the occurrence of coronary artery disease (CAD) was studied in a group of 274 men undergoing coronary angiography. Hormone levels in men with CAD (n = 200) were compared to those in men found to be free of coronary lesions (n = 74). No significant differences were found for serum concentrations of estradiol, total testosterone, sex-hormone-binding globulin, free androgen index, dehydroepiandrosterone sulfate, or cortisol between the two groups. Serum androgens were negatively correlated to age in both groups, whereas estradiol was weakly associated with total cholesterol in the group of men without CAD. No consistent associations were detected between sex hormone levels and the degree of obesity or the distribution of body fat, the latter being assessed by the ratio of waist-to-hip circumferences. The results of this study do not support a significant role of sex steroid hormones in coronary artery disease in men.

Evaluation of antiarrhythmic drug effects with simultaneous analysis of single ventricular premature contractions, couplets and salvos.

To improve the clinical value of ambulatory Holter electrocardiographic (ECG) monitoring as a tool of antiarrhythmic therapy control, a new statistical model was developed. In a patient group at increased risk of sudden cardiac death, the spontaneous variability of ventricular arrhythmias was assessed, with simultaneous consideration of single ventricular premature complexes, couplets and salvos. The study included 100 patients who suffered from coronary heart disease or idiopathic dilated cardiomyopathy and for whom greater than 30 ventricular premature complexes/h and couplets had been demonstrated on the last Holter ECG before the study. Between 3 and 12 Holter recordings were made for each patient in a drug-free state; the mean follow-up period was 260 days (maximum 1,403). The mean hourly values of the ectopic events (EE) were assessed separately for ventricular premature complexes, couplets and salvos. The spontaneous variability (SV) was calculated for single ventricular premature complexes, couplets and salvos as SV = log (EEday 2 + 0.01/EEday 1 + 0.01) and linked in one, two and three dimensions. Compared with the consideration of only one type of arrhythmia (one-dimensional model), the simultaneous use of two or three types of arrhythmia (two- or three-dimensional model) resulted in considerably lower reduction and aggravation rates as sufficient proof of drug effects. With control intervals up to 1 week, the one-dimensional model yielded reduction rates for ventricular premature complexes, couplets and salvos of -63%, -90% and -95%, respectively. In contrast, with the three-dimensional model, the rates were -28%, -72% and -88%. The corresponding aggravation values were +370, +1,114% and +2,189% versus +38%, +256% and +747%.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of histamine H1-receptor blockade on respiratory and cardiac manifestation of systemic anaphylaxis.

In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced an initial increase of left ventricular pressure which was followed by a rapid decrease 5 min after antigenic challenge. Enddiastolic left ventricular pressure increased within 3 min, thus indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, heart rate steadily decreased. All animals died within 15 min. Simultaneously with cardiac anaphylactic malfunction, severe arterial hypoxia and carbon dioxide retention occurred, revealing respiratory distress. Histamine is known as a potent bronchoconstrictor via histamine H1-receptor stimulation. Administration of H1-receptor antagonists to improve respiration may therefore provide further information on the contribution of pulmonary malfunction to anaphylactic cardiovascular shock. Therefore, additional experiments were performed with sensitized guinea pigs pretreated with the histamine H1-receptor blocker mepyramine. In these experiments the antigenic challenge induced a dissociation of cardiac and respiratory manifestation of anaphylaxis. Despite inhibition of hypoxia and carbon dioxide retention, left ventricular pump failure and occurrence of myocardial ischemia were delayed but not suppressed. It is concluded that histamine is an important mediator of anaphylactic respiratory distress. However, vasoactive anaphylactic mediators other than histamine are primarily involved in anaphylactic cardiac malfunction occurring during the later phase of systemic anaphylaxis.

[Effect of amiodarone on signal-averaged and long-term ECG]. / Einfluss von Amiodaron auf Signalmittelungs- und Langzeit-EKG.

This prospective study examined the influence of long-term amiodarone therapy on the parameters of the signal-averaged ECG and their relation to simultaneously derived Holter monitoring data. For this purpose, 23 patients with angiographically confirmed dilated cardiomyopathy or coronary heart disease and high-grade ventricular arrhythmias, in whom an average of four class I antiarrhythmic drugs had proven ineffective, were stabilized on amiodarone. Before the beginning of therapy, as well as after 2 months and, subsequently, every 3 months, a resting ECG, a signal-averaged ECG by Simson's method, and Holter monitoring were performed. Compared to the initial measurement, we found a significant increase in the duration of the total filtered QRS complex from an average of 114 +/- 24 ms to 127 +/- 35 ms, while the change in voltage did not reach the significance level. The incidence of late potentials remained largely constant under amiodarone; 10 patients showed a constant late potential, 12 patients had no late potential, and one patient with coronary heart disease developed a new late potential. In the long-term follow-up, we ascertained a relatively high responder rate under amiodarone between 41% and 81%. No relation could be detected between the results of the signal-averaged ECG and those of 24-h Holter monitoring.

Effects of histamine H1- and H2-receptor antagonists on cardiovascular function during systemic anaphylaxis in guinea pigs.

The heart is a target organ of anaphylaxis. In isolated perfused hearts, an anaphylactic reaction is characterized by arrhythmias, coronary constriction and severe impairment of ventricular contractile force. Various mediators such as PAF, thromboxane A2 and leukotrienes are responsible for anaphylactic coronary constriction and negative inotropic effects. The cardiac effects of anaphylactic histamine release are related to the stimulation of two antagonistic receptor types. Histamine induces atrioventricular conduction delay and constriction of the epicardial coronary vessels via H1-receptor stimulation. H2-receptors, however, mediate coronary vasodilation and an increase in heart rate and myocardial contractility. It may therefore be concluded that administration of histamine H2-receptor antagonists is disadvantageous. During anaphylactic states, the cardiodepressive effects of the other mediators of anaphylaxis are unmasked, resulting in a sustained coronary constriction and impairment of myocardial contractility. To verify this speculation, we investigated the effects of H1- and H2-receptor antagonists on cardiovascular function of guinea pigs during systemic anaphylaxis. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed administration of the antigen induced severe cardiac dysfunction. Within a few minutes, cardiac output markedly decreased and left ventricular end-diastolic pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of an atrioventricular block.(ABSTRACT TRUNCATED AT 400 WORDS)

[Long-term treatment with amiodarone]. / Langzeitbehandlung mit Amiodaron.

The aim of this study was to investigate the efficacy and the side effects of a long-term treatment with amiodarone. We analyzed the data of 41 patients in whom amiodarone therapy had been initiated between 1974 and 1984. Twenty-one patients had dilative cardiomyopathy, 14 patients had chronic myocardial infarction, four patients suffered from WPW syndrome with intermittent atrial fibrillation, one patient had aortic valve surgery, whereas in one patient there was no clinical evidence of a heart disease. All patients had salvos of ventricular extrasystoles, ventricular tachycardia or documented intermittent ventricular fibrillation. There have been seven drop-outs up to the present time. In each patient, the lowest antiarrhythmically effective dose was applied, which was generally higher in patients with low ejection fraction. Effective treatment of the ventricular tachycardia was achieved in 55-92% of patients and did not depend on the duration of treatment. In 10 patients in whom amiodarone therapy had to be stopped for various reasons. Sudden cardiac death was slightly more frequent than in the 24 patients treated with amiodarone, though the difference was not significant. In cases with a history of syncope the prognosis was poor, even with amiodarone therapy. Due to side effects, a dosage reduction or discontinuation of amiodarone treatment became necessary in 14 patients. Amiodarone proved to be an effective drug also for the long-term treatment of ventricular tachycardia, and possibly for the prevention of sudden cardiac death. With the exception of blue skin color, there was no accumulation of side effects, even during long-term treatment of several years.

Body fat distribution in men with angiographically confirmed coronary artery disease.

Body fat distribution and its relationship to coronary artery disease and established cardiovascular risk factors have been studied in a cohort of 286 men aged between 30 and 74 years undergoing coronary angiography. 207 (72.4%) patients showed stenosis (greater than 30%) or occlusion of one or more coronary arteries. whereas the remaining 79 (27.6%) men were free of coronary lesions and served as a control group. 112 men with angiographically defined coronary artery disease had an additional history of myocardial infarction. Body fat distribution was assessed by determining the waist-to-hip circumference ratio. A stepwise logistic regression analysis revealed that in addition to LDL-cholesterol (P = 0.0001) and age (P = 0.0005) an abdominal type of body fat distribution (P = 0.0129) is also a significant risk indicator for the occurrence of coronary artery disease (CAD) independent of body weight and other factors such as total cholesterol, HDL-cholesterol, triglycerides, insulin, systolic and diastolic blood pressure. The results of this study suggest that an abdominal type of fat distribution is associated with an increased risk of coronary artery disease.

Differences between atrial single chamber pacing (AAI) and ventricular single chamber pacing (VVI) with respect to prognosis and antiarrhythmic effect in patients with sick sinus syndrome.

Several studies suggest different effects of atrial (AAI) and ventricular single chamber pacing (VVI) for sick sinus syndrome with respect to the suppression of atrial tachycardias and to the prognosis. With this aspect in mind, we studied 222 patients with sick sinus syndrome, 110 of whom had been supplied with AAI systems, and 112 with VVI systems, in the period from January 1978 to December 1986. The mean observation period was 53 +/- 28 months. The cumulative 5-year survival rate was not significantly different in the two groups. After subgroups with comparable underlying diseases had been differentiated, patients with coronary heart disease showed a significantly higher survival rate (P less than 0.05) under AAI pacing, and the same was shown for patients with no underlying heart disease (P less than 0.02). The incidence of chronic atrial fibrillation was 6% in the AAI group and 19% in the VVI group. Patients with preexisting atrial tachyarrhythmias showed the lowest incidence of chronic atrial fibrillation under AAI pacing. Under VVI pacing this incidence was a function of the basic rate of the pacemaker systems. In conclusion, the pacing mode seems to have a prognostic importance in spite of all methodological difficulties. A suppressive effect of AAI pacing on atrial dysrhythmias can also be assumed.

Amiodarone--efficacy and late potentials during long-term therapy.

This prospective study was intended to examine the influence of long-term amiodarone therapy on the parameters of the signal averaged ECG and their relation to simultaneously derived Holter monitoring data. For this purpose 27 patients with angiographically confirmed dilated cardiomyopathy or coronary heart disease and highgrade ventricular arrhythmias, in whom an average of four class I antiarrhythmic drugs had proven ineffective, were stabilized on amiodarone. Before the beginning of therapy, as well as after two months and subsequently every three months if possible, a resting ECG, a signal averaged ECG by the method of Simson and Holter monitoring were performed. Compared to the initial measurement we found a significant increase in the duration of the total filtered QRS complex, while the change in the voltage did not reach the significance level. The incidence of late potentials remained largely constant under amiodarone. In the long-term follow up Holter monitoring showed a relatively high responder rate of between 46 and 81% under amiodarone. No relation could be detected between the results of the signal averaged ECG and those of 24-h Holter monitoring.

[30 years cardiac pacemaker therapy: a status evaluation]. / 30 Jahre Herzschrittmachertherapie: Eine Standortbestimmung.

Antibradycardiac pacemaker therapy has become established as one of the most effective forms of cardiological therapy for the indications AV-block, sick sinus syndrome, bradyarrhythmia, and hypersensitive carotid sinus. About 220,000 systems are implanted per year worldwide, about 32,000 in West Germany. Of the pacing modes, the fixed-rate ventricular single chamber systems (VVI) dominate with a share of almost 90%. Prognostic importance: For AV-block, the improvement of the prognosis by pacemaker therapy is unquestionable, since it increases the cumulative survival rates to 81% and 95% after 1 year and 50% to 65% after 5 years. For sick sinus syndrome, VVI-pacing proves to be a symptomatic measure, no prognostic importance can be proven. It is not conclusively clarified at present whether physiological pacing modes (AAI, DDD) have any such importance. Pacemaker therapy also has no prognostic importance for bradyarrhythmia. Hemodynamic importance: Numerous hemodynamic studies show that fixed-rate VVI-pacing fails to produce a long-term hemodynamic improvement for either an AV-block or a sick sinus syndrome. In sick sinus syndrome hemodynamic improvement can only be achieved by physiological pacing modes (AAI, DVI, DDD), whereby the increase in cardiac output is between 11% to 30%. For AV-block a long-term hemodynamic improvement can only be obtained by atrial triggered pacing modes (VAT, VDD, DDD); this is higher than the values of fixed-rate VVI-pacing by 7-25% at rest, or 10-40% under exercise. Similar results with improvements of the exercise hemodynamics between 22% and 66% are reported for rate-modulated single-chamber pacing (VVIR) for AV-block. Future trends: In the fourth decade of pacemaker therapy, developments point toward the "smart pacemaker", toward rate-modulated systems with combinations of parameters, toward rate-modulated dual-chamber systems and universal antibradycardiac and antitachycardiac systems.

[Acute reduction of increased atrial natriuretic peptide level and cyclic guanosine monophosphate in patients with chronic heart failure caused by beta-adrenergic stimulation with dopexamine hydrochloride. Correlation with hemodynamic parameters]. / Akute Senkung erhöhter Spiegel des atrialen natriuretischen Peptids (ANP) und des zyklischen Guanosinmonophosphats (cGMP) bei Patienten mit chronischer Herzinsuffizienz durch beta-adrenerge Stimulation mit Dopexamin-Hydrochlorid. Korrelation zu hämodynamischen Parametern.

In eight patients (63 +/- 8 years) with dilated cardiomyopathy, the acute effects of positive inotropic stimulation with dopexamine hydrochloride, a beta-2-agonistic and DA1-dopaminergic catecholamine, on the plasma levels of ANP and cGMP were tested. A four-point dose-response curve was prepared for dopexamine from 1 microgram/kg/min to 4 micrograms/kg/min. Each infusion stage lasted 15 min; ANP and cGMP were taken from the mixed venous blood. Hemodynamic parameters were determined by a Swan-Ganz catheter; cardiac output was determined by thermodilution. ANP dropped by 40% from 348 +/- 124 pg/ml to 208 +/- 70 pg/ml (p less than or equal to 0.01), while cGMP dropped by 25% from 4.8 +/- 1.6 pmol to 3.6 +/- 1.3 pmol/ml at the time of maximum hemodynamic effect after 1 h. Linear regression analyses revealed a significant relationship (p less than or equal to 0.01) between ANP as the independent variable and cGMP as the dependent variable. The hemodynamic determinants of the ANP concentration proved to be--independently of each other--the pulmonary capillary wedge pressure (p less than or equal to 0.01) and the mean right atrial pressure (p less than or equal to 0.01). The results show that chronically elevated ANP and cGMP levels can be strikingly reduced within a short time, whereby ANP and cGMP show similar kinetics. The results suggest a use of ANP and cGMP as humoral parameters in the therapy control of chronic heart failure.

[Accuracy of various Doppler technics in recording blood flow velocity. Studies in vitro]. / Genauigkeit verschiedener Dopplertechniken in der Erfassung von Flussgeschwindigkeiten. Untersuchungen in vitro.

Conventional and color-coded Doppler techniques were studied as to their accuracy in displaying flow and velocity using an in vitro model and a Laser-Doppler-anemometer. Furthermore, the estimation of pressure gradients as determined by Doppler ultrasound was compared to measurements by manometers under a variety of hemodynamic conditions. Pulsed and continuous wave Doppler had good reproducibility. There was an excellent correlation for measurements of flow velocity as determined by Doppler ultrasound and by Laser-Doppler anemometer (r = 0.98, SEE = 3 cm/s). The well-known underestimation of flow velocity due to an increasing angle of incidence (greater than 25 degrees) was confirmed in vitro. However this error was smaller than the actual overestimation resulting from angle correction for the apparent cosine. Doppler gradients correlated strongly with manometer gradients for orifice areas 12-80 mm2 and flow volumes 0.9-12.8 l/min (r = 0.98, SEE = 7 mm Hg) using continuous as well as pulsatile flow. Some overestimation of the Doppler gradient occurred with increasing flow rates (r = 0.66). Color-Doppler has poor spatial resolution. Display of velocities was therefore assessed using a qualitative score (0-5), the variability of which was 13 +/- 30% of the initial value. Display of faintest quality (score 1) was useless for clinical assessment in color-Doppler technique, but allowed quantitative measurement of velocity in conventional Doppler. Reduction of flow velocities limited display in color-Doppler (5-20 cm/s) but not in pulsed-Doppler technique. Thus, conventional Doppler has better sensitivity and accuracy of displaying flow when compared to color-Doppler, particularly in conditions of poor imaging. As reproducibility and accuracy of velocity determination are excellent, this technique should be used in all diagnostic procedures involving ultrasound. The Doppler gradient as derived from the modified Bernoulli equation provides accurate results in vitro which may also be concluded for use in the clinical situation.