Reproducibility of Doppler aortic blood flow measurements: studies on intraobserver, interobserver and day-to-day variability in normal subjects

Doppler aortic flow velocity measurements have been used to assess quantitatively left ventricular performance at rest and after pharmacologic and other hemodynamic interventions. To permit more meaningful interpretation of Doppler data, 10 normal subjects were studied to establish the intraobserver, interobserver and day-to-day variability in Doppler aortic flow velocity measurements. In each subject, pulsed Doppler recordings of ascending aortic flow velocity were obtained from the suprasternal notch on 2 different days (mean interval 6 days), with the same technician performing and same physician reading both Doppler studies to evaluate day-to-day variability of measurements. Interobserver variability was assessed by having 2 observers read each Doppler study. Both observers read the Doppler records from both days again at a second session to determine intraobserver variability. Intraobserver variability ranged from 1.9 +/- 1.8 to 3.2 +/- 2.9% for ejection time, peak flow velocity and flow velocity integral, but was higher for acceleration time (7.9 +/- 6.6%). Interobserver variability ranged from 3.5 +/- 2.2 to 5.4 + 3.4% for peak flow velocity, ejection time and flow velocity integral, but was notably higher for acceleration time (17 +/- 9%). Day-to-day variability was higher for acceleration time (7.0 +/- 5.2%) than for ejection time, peak flow velocity and flow velocity integral (range from 3.6 +/- 3.1 to 5.2 +/- 4.0%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Superiority of two-dimensional measurement of aortic vessel diameter in Doppler echocardiographic estimates of left ventricular stroke volume

Attempts to measure left ventricular stroke volume utilizing the Doppler aortic flow method have found varying correlations between invasive thermodilution and non-invasive Doppler methods. Because stroke volume is the product of the Doppler flow velocity integral (that is, the area under the flow velocity curve) and the cross-sectional area of the vessel through which blood flows, both variables are potential sources of error. Previous studies have shown that the Doppler flow velocity integral can be measured with acceptable reproducibility in the ascending aorta. Consequently, in this study an attempt was made to determine empirically the optimal method for measuring aortic diameter and area. The diameter of the ascending aorta was measured utilizing four M-mode and seven two-dimensional echocardiographic conventions. Doppler aortic flow velocity patterns were recorded with a 2.25 MHz M-mode echocardiographic transducer from the suprasternal notch by mapping the ascending aorta until aortic peak flow velocity was recorded. In 19 adult patients undergoing cardiac catheterization for clinical indications, Doppler stroke volume estimates utilizing the various echocardiographic conventions for measuring aortic root diameter and area were compared with simultaneous measurements of stroke volume by the thermodilution technique. The best correlation (r = 0.87) with thermodilution stroke volume was obtained by estimating aortic area from the two-dimensional parasternal long-axis images with the aortic dimension measured distal to the aortic sinuses from the inner to inner wall. The data were related by the equation: Thermodilution stroke volume = (0.73) X (two-dimensional Doppler stroke volume) + 17 cc.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pseudoischemic “false positive” S-T segment changes induced by hyperventilation in patients with mitral valve prolapse

Hyperventilation-induced S-T segment changes that simulate myocardial ischemia have previously been noted, but the origin of this electrocardiographic finding has never been defined. To investigate further the basis for this response, the records were reviewed of 1,678 consecutive patients who underwent forced hyperventilation for 90 seconds and treadmill exercise testing. Twenty-eight patients (1.7 percent) were identified in whom hyperventilation resulted in ischemic-appearing S-T segment changes, and follow-up was possible in 21 (17 women, 4 men). Of the 21 patients, 16 (76 percent), including 15 (88 percent) of the 17 women, had evidence of mitral valve prolapse, 6 on auscultation alone, 2 on echocardiography alone and 6 with a combination of studies. Ten of the 21 patients had a negative exercise test; of the 11 patients who had a positive exercise test, only 1 had angiographic evidence of coronary arterial narrowing. The finding of ischemic-appearing S-T segment changes in response to forced hyperventilation has a high predictive value for the presence of mitral valve prolapse, particularly in women. The possible association of autonomic factors and mitral valve prolapse in the patho-genesis of an abnormal response to hyperventilation is discussed.     

Correlation of 10-milliliter digital subtraction ventriculograms compared with standard cineangiograms

Left ventriculograms were obtained with the use of 10 ml of contrast media by passing fluoroscopic video images through a video image processor. The low concentration of dye in the left ventricle was enhanced by the technique of mask mode subtraction, and the images were postprocessed to increase visibility by manipulation of the gray scale and contrast levels. These digital subtraction angiograms were compared to standard cineangiograms by means of 40 ml of contrast media. Of 30 patients studied, six (20%) had runs of ventricular tachycardia during the cineangiogram and had to be excluded. In the remaining 24 patients, there was a good correlation between the two techniques for left ventricular end-diastolic volume (r = 0.77, end-systolic volume (r = 0.95), and ejection fraction (r = 0.97). Spatial resolution in the digital studies was adequate to appreciate wall motion abnormalities that were visualized on the cineangiograms. Left ventricular end-diastolic pressure (LVEDP) did not change after the 10 ml injection, but the mean LVEDP rose 6.0 mm Hg after the 40 ml cineangiograms (p < 0.01). Digital subtraction angiography can be used to obtain left ventriculograms with one-fourth the amount of contrast media and one-fourth the x-ray exposure compared to standard cineangiograms. This technology will permit multiple left ventriculograms to be obtained which, in turn, will allow intervention studies to be performed in the catheterization laboratory.     

Influence of aging on the surface area of the small intestine in the rat

The conflicting reports regarding the influence of aging on intestinal absorption are due in part to the lack of a valid measurement of the intestinal surface area. The surface area of the small intestine in male Sprague-Dawley rats (2.5 to 92 weeks of age) was measured by determination of the volume required to fill the bowel under standardized conditions of stretch and pressure, and by calculating the surface area using the volume and length of the bowel. The intestinal surface area of rats of differing ages varied from 82 to 171 cm². The intestinal surface area increased linearly with the age of the animals during the first 6 weeks of life. No further increase was noted in the intestinal surface area during the following 86 weeks of life. A strong linear correlation was found between the intestinal length and surface area in rats of all ages. In contrast, no relationship was found between the intestinal surface area and its dry weight or the animal's body weight. It is concluded that assessment of the intestinal surface area is simple and can be used interchangeably with intestinal length to express the absorptive data in the rat. This parameter is preferred to indirect measurements like intestinal dry weight or animal body weight. Moreover, both the surface area and the length fluctuate at their 6-week values and do not change significantly with the increasing age of the rats.     

Measurement of left ventricular ejection fraction by videodensitometric analysis of digital subtraction angiograms

Left ventricular ejection fraction (LVEF) was calculated from 25 first-pass digital subtraction angiograms using a densitometric analysis. Digital subtraction angiograms are obtained in a computerized format; therefore, they can be readily analyzed with computer software to measure the density of the iodine signal within the image. The video signals from the image intensifier were logarithmically amplified so that there was a linear correlation between the video signal intensity and the depth of the iodine contrast material represented by that video signal. LVEF was also calculated by the area-length method from the same digital subtraction angiograms. There was close correlation between these two techniques (r = 0.94, standard error of the estimate = 5.04%). The videodensitometric EF technique is simple to perform, it correlates well with the standard area-length method, and is not dependent on geometric assumptions of LV geometry.     

Percutaneous transluminal angioplasty of congenital coarctation of the aorta

Two cases of successful dilatation of congenital coarctation of the aorta using the Grüntzig technique are reported. In a 3-week-old boy and an 11-month-old girl, systolic gradients across the narrowed areas were lowered from 50 to 8 mm Hg and from 23 to 8 mm Hg. Although the femoral pulses later disappeared in the younger patient, surgery was avoided. The second patient's gradient has remained minimal for 8 months and no surgery has been performed.     

Coronaviruses in Balkan nephritis

Phenothiazines have significant electrophysiologic and cardiocirculatory effects. The electrophysiologic effect of these drugs is similar to that reported for quinidine. Phenothiazines decrease the rate of rise of phase 0 of the action potential, decrease the duration and amplitude of phase 2, and prolong phase 3. The surface ECG changes produced by phenothiazines are lengthening of the QTC interval, ST-T wave changes, increased size of U waves, and prolongation of the PR interval. The degree of repolarization abnormalities secondary to phenothiazines seems to be dose-related.Various arrhythmias have been attributed to the effect of phenothiazine therapy and numerous cases of sudden death as a result of fatal arrhythmia have been described. Paradoxically, phenothiazines such as chlorpromazine and thioridazine also have been shown to have significant antiarrhythmic properties. Chlorpromazine shows a powerful vasodilatory effects which is caused by alpha-adrenergic receptor blockade, a central action, and a direct effect on the vascular wall. In addition, the drugs also have a direct depressant effect on the myocardium. As a result of peripheral vasodilatation and negative inotropic effects, hypotension is the most common adverse reaction of phenothiazines in patients with no evidence of congestive heart failure.Experimental studies have demonstrated significant reductions in systemic and pulmonary vascular resistance as well as systemic blood pressure following intravenous administration of chlorpromazine. These hemodynamic changes were accompanied by significant increase in cardiac output in one study and by no change in cardiac output in another study. The vasodilatory effect of chlorpromazine resulted in increased renal and mesenteric blood flow and prolongation of survival time in dogs following hemorrhagic hypotension. Chlorpromazine was found effective in relieving abnormal vascular tonus and improving the circulation in patients undergoing cardiopulmonary bypass surgery. In patients with myocardial infarction complicated by congestive heart failure, intravenous administration of chlorpromazine caused significant hemodynamic improvement and a considerable degree of sedation. The drug was found effective in reducing the vasoactive response in patients with cardiogenic shock which resulted in improved tissue perfusion and metabolism.     

Marked early attenuation of hemodynamic effects of oral prazosin therapy in chronic congestive heart failure.

Prazosin, in a single oral dose has been shown to induce balanced reduction in left ventricular preload and arteriolar resistance and therefore has been advocated as a potential agent of choice for the long-term treatment of patients with heart failure. However, preliminary reports have questioned the persistence of these beneficial effects. The effects of the first and the fifth consecutive administration of oral prazosin at Its maximal dose (3 to 10 mg every 6 hours) were compared in 11 patients with chronic congestive heart failure. Oral administration of the first dose resulted in a significant reduction in systemic vascular resistance (from 2,062 ± 498 to 1,560 ± 639 dynes sec cm^?5, P < 0.05), mean pulmonary wedge pressure (from 23.5 ± 6.2 to 13.7 ± 6.2 mm Hg, P < 0.05) and mean systemic blood pressure (from 88.8 ± 10.4 to 79.8 ± 11.1, P < 0.05). The drug also produced a significant increase in cardiac index (from 1.96 ± 0.3 to 2.53 ± 0.6, liters/min per m², P < 0.05), stroke volume index (from 22.2 ± 4.5 to 28.8 ± 6.4 ml/m², P < 0.05) and stroke work index (from 19.4 ± 4.2 to 26 ± 7.1, g-m/m², P <0.05), whereas the heart rate did not change significantly (87.7 ± 17 versus 88.4 ± 16 beats/ min).In contrast to the significant favorable effect demonstrated initially with prazosin, no significant hemodynamic changes were noted after the administration of the fifth consecutive dose. A comparison between the values at the peak response elucidated a complete abolishment of the effect on left ventricular filling pressure (13.7 ± 6.2 versus 22.5 ± 4.2 mm Hg, P < 0.05) with a greatly attenuated effect of the drug on systemic vascular resistance (1,560 ± 639 versus 1,816 ± 544 dynes sec cm^?5, P < 0.05). These data suggest an early development of tolerance to the beneficial hemodynamic effects mediated by oral prazosin and raise doubt regarding the value of this agent in the ambulatory treatment of patients with chronic congestive heart failure.     

A search for heterogeneity in insulin dependent diabetes mellitus (IDDM): HLA and autoimmune studies in simplex, multiplex and multigenerational families

HLA antigens (A, B, C and DR loci), serum islet cell antibodies, thyrogastric antibodies, and insulin antibodies were studied in 77 families (25 simplex, 42 multiplex, and 10 multigenerational). In order to test for intrafamilial constancy and intergroup variation, we compared simplex with multiplex families, HLA identical and non identical siblings within families, as well as groups of families characterized by different DR alleles (DR3, DR4, and DR3/DR4) for various immunologic and clinical characteristics. These comparisons did not reveal all the distinct subgroups suggested by different cross-sectional population studies, but did provide evidence for a compound form having an aggregation of different high risk alleles. This study suggests that in many cases (and possibly especially in families with multiple affected individuals), there are several different genetic influences leading to IDDM.     

Effect of di-N-propylacetic acid (valproic acid) on the TSH response to TRH--a presumptive role for gamma aminobutyric acid

The effect of di-n-propylacetic acid (valproic acid), an inhibitor of gamma aminobutyric acid (GABA) transaminase, was studied with reference to its effect on the serum concentration of thyroid hormones, baseline serum TSH concentration and TRH stimulated TSH release, in seven normal controls and six patients with primary hypothyroidism. All volunteers took 250 mg of valproic acid administered orally, four times daily for 3 days. Baseline serum T4 and TSH concentrations were unaffected by valproic acid administration (p less than 0.05) while serum T3 concentrations fell in all volunteers (p less than 0.001). Serum T3 concentration (mean +/- SD) fell from 116.3 +/- 18 ng/dl to 101.7 +/- 15 ng/dl in the control group and from 94.2 +/- 47.9 ng/dl to 81.5 +/- 43.2 ng/dl in the hypothyroid group. Valproic acid produced a decline in stimulated serum TSH concentrations (delta TSH--maximum increment above baseline) in all controls and patients studied (p less than 0.01). delta TSH (mean +/- SD) declined from 16.1 +/- 4.7 microunits/ml to 10.5 +/- 5.8 microunits/ml in the control subjects and from 43.1 +/- 25.4 microunits/ml to 29.7 +/- 18 microunits/ml in the hypothyroid patients. Based on the data presented, it is postulated that GABA plays an inhibitory role either by acting directly on the pituitary gland inhibiting TSH release, or by inducing the secretion of a hypothalamic TSH-inhibitory factor. The data do not exclude a direct pharmacological effect of valproic acid on pituitary TSH release. Decrease in serum T3 following valproic acid may be due to peripheral mechanisms.     

Detection of pulmonary venous flow by pulsed Doppler echocardiography in children

Parasternal pulsed Doppler echocardiographic examinations of the left atrium were prospectively performed in 14 pediatric patients, aged 2 weeks to 8 years, in order to characterize the left atrial flow pattern in children. None of the patients had clinical or cardiac catheterization evidence (9 of 14 patients) of either mitral regurgitation, right-to-left shunts at the atrial level, or anomalies of pulmonary venous drainage. In all 14 patients, a systolic-diastolic positive velocity pattern could be recorded within the left atrium. Furthermore, this pattern was more readily detected in those children with left-to-right shunts. We conclude that continuous positive velocity patterns are commonly recorded in the left atria of children and probably represent pulmonary venous return. Demonstration of this signal is contingent on proper orientation of the transducer with respect to pulmonary venous flow.     

Detection and quantitation of coronary artery stenoses from digital subtraction angiograms compared with 35-millimeter film cineangiograms

To assess the ability to detect coronary artery narrowings from computer-acquired angiograms, a panel of 4 observers independently identified and measured focal coronary narrowings from digital subtraction angiograms and compared the results to those obtained from standard 35-mm cine film angiograms. Both cine and digital angiograms were obtained sequentially using selective intracoronary artery injection of standard amounts of iodinated contrast media. Digital images were obtained at 8 frames/s with a 512 × 512 × 8-bit pixel matrix. Modifications in the imaging chain for computer acquisition included a slower pulsed radiographic mode, a progressive scan camera, and initial storage of the images on an 80-megabyte digital hard disk. Postprocessing computer algorithms were used to enhance the unsubtracted digital images; these included single-frame, mask-mode subtraction, vessel boundary edge enhancement, and 4-fold pixel magnification. In 19 patient studies, 32 arteries were reduced more than 25 % in diameter according to at least 1 of 4 observers on either the digital or cine film angiograms. There was no significant difference in the mean percent diameter narrowing for all the narrowings between the digital angiograms (53 ± 31 %) and the cineangiograms (52 ± 31 %). In addition, a 2-way analysis of variance yielded no significant difference between the amount of variability in the measurements between the cine film and the digital technique. This similar variability persisted when subsets of patients based on the degrees of stenosis were considered (e.g., only narrowings from 50 to 90% diameter reduction). Because digital acquisition permits immediate playback with image enhancement and greater ease of coronary artery quantification, digital angiography may have widespread clinical use for the detection and quantitation of coronary artery disease.