Effects of exercise training on common femoral artery blood flow in patients with intermittent claudication.

Exercise training is a commonly used rehabilitative therapy for patients with intermittent claudication (IC). However, it is not known whether blood flow through the major conduit vessel of the leg, the common femoral artery (CFA), increases with exercise training. We tested the hypothesis that peak CFA blood flow will increase with a supervised, lengthy, and individualized exercise training program. Subjects were 10 IC patients (eight men, two women) with a mean age of 61 +/- 7 (mean +/- SD) years who had either aortoiliac (n = 7) or femoropopliteal (n = 3) stenosis. Using noninvasive Doppler flowmetry, we measured CFA blood flow and ankle pressure at rest and after a maximum symptom-limited graded treadmill test before (T1) and after 3 (T2) and 5 (T3) months of exercise training. Variables were measured in the supine and upright postures at rest and during recovery. Total walking distance and claudication distance on the treadmill were determined for T1, T2, and T3. After training, CFA blood flow and ankle pressure were not significantly higher at rest or at 1 minute after exercise compared with pretraining despite significant increases in claudication and total walking distances. The rate of CFA blood flow recovery was slower at T3, suggesting the accrual of a larger metabolic debt during exercise due to more work performed. We conclude that changes in CFA blood flow are not responsible for measured changes in performance with exercise training in IC patients.

Noninvasive evaluation of aortic stenosis severity utilizing Doppler ultrasound and electrical bioimpedance.

Aortic valve area was calculated noninvasively in 30 patients with aortic stenosis undergoing cardiac catheterization. Continuous wave Doppler ultrasound was employed to estimate the mean transvalvular pressure gradient. The mean left ventricular outflow tract flow velocity and cross-sectional area were determined from pulsed Doppler and two-dimensional ultrasound recordings. Electrical transthoracic bioimpedance cardiography performed simultaneously with the ultrasonic study and repeated at the time of catheterization measured heart rate, systolic ejection period and cardiac output. These noninvasive data permitted calculation of aortic valve area using the Gorlin equation (range 0.21 to 1.75 cm2) and the continuity equation (range 0.25 to 1.9 cm2). Subsequent cardiac catheterization showed valve area to range from 0.21 to 1.75 cm2. The mean Doppler pressure gradient estimate was highly predictive of the gradient measured at catheterization (r = +0.92, SEE = 10). Bioimpedance cardiac output measurements agreed with the average of Fick and indicator dye estimates (r = +0.90, SEE = 0.52). Valve area estimates utilizing continuous wave Doppler ultrasound and electrical bioimpedance were superior (r = +0.91, SEE = 0.12) to estimates obtained utilizing the continuity equation (r = +0.76, SEE = 0.29) and were more reliable in the detection of patients with severe aortic stenosis (9 of 11 versus 6 of 11). These data show that 1) electrical bioimpedance methods accurately estimate cardiac output in the presence of aortic stenosis; 2) the hybridized bioimpedance-Doppler ultrasound method yields accurate estimates of aortic stenosis area; and 3) the speed, accuracy and cost-effectiveness of aortic stenosis evaluation may be improved by this hybridized approach.

Isosorbide-5-mononitrate in angina pectoris: plasma concentrations and duration of effects after acute therapy.

In a double-blind, randomized, crossover study, the duration of effects of single oral doses of 20 and 40 mg isosorbide-5-mononitrate (IS-5MN) and matching placebo were studied in 12 male patients with angina pectoris. Plasma IS-5MN concentrations (mean +/- SD) 2 and 6 hours after administration were 300 +/- 60 and 144 +/- 43 ng/ml after 20 mg IS-5MN and 551 +/- 191 and 376 +/- 129 ng/ml after 40 mg IS-5MN. Exercise time to the onset of angina 2 and 6 hours after administration increased after 20 mg IS-5MN (5.88 +/- 1.85; P less than 0.001 and 5.08 +/- 1.97 minutes; P less than 0.002) and 40 mg IS-5MN (6.17 +/- 1.88; P less than 0.001 and 5.78 +/- 1.72 minutes; P less than 0.001) in comparison to placebo (4.57 +/- 1.22 and 4.15 +/- 1.22 minutes). Similarly, total exercise duration increased at 2 (P less than 0.001) and 6 hours (P less than 0.002) after both doses of IS-5MN. Compared with placebo, ECG ST segment depression during exercise was less (P less than 0.05) 2 hours after both doses of IS-5MN. Thus single oral doses of 20 and 40 mg IS-5MN exert antianginal and anti-ischemic effects for at least up to 6 hours.

Noninvasive Doppler assessment of human postprandial renal blood flow and cardiac output.

We compared the effects of protein, carbohydrate, or water ingestion on human renal blood flow (RBF) and cardiac output (CO). We validated and applied a noninvasive ultrasonic Doppler method to measure blood velocities and lumen diameters in the right renal artery and the ascending aorta of five healthy adults. From these measurements, we calculated the average RBF and CO over five cardiac cycles. Normalizing to body surface area, renal blood flow index to one kidney (RI) and cardiac index (CI) were calculated. The percentage of the CI distributed to a single kidney was determined as %CI = RI/CI. Subjects were studied randomly on three separate days after ingestion of each of the following equivolume (500 ml) meals: 1) 150 g protein, 30 g fat, and 30 g carbohydrate (P); 2) 150 g carbohydrate, 30 g fat, and 30 g protein (C); and 3) water. Data were obtained after 12 h of fasting and at 30, 60, 90, 120, 180, and 240 min postprandially. Analysis of covariance revealed significant (P less than 0.05) increases from fasting levels in postprandial RI at 90 to 240 min after P. Postprandial RI with P was significantly higher than with C at 180 and 240 min. Postprandial %CI with P and C decreased significantly from the fasting value at 30 to 180 min. Heart rate and mean arm cuff blood pressure did not change significantly with any diet. Results suggest that the protein-rich meal evokes a more sustained increase in postprandial RI than the carbohydrate rich meal. Despite the increase in postprandial RI, the percentage of cardiac output perfusing a kidney declines similarly with both diets.

Doppler predictions of pulmonary artery pressure, flow, and resistance in adults.

We examined the accuracy of noninvasive predictions of pulmonary artery pressure (P), flow (Q), and resistance (R) by means of main pulmonary artery blood velocities and diameters measured with Doppler echocardiography (DE). The ratio of noninvasive acceleration time to ejection time (An) was correlated to invasively determined mean pulmonary artery pressure (Pl) and resistance (Rl). Noninvasive flows were correlated to thermodilution flows (Ql). Simultaneous invasive and noninvasive measurements were made in nine adult patients (ages = 22 to 73 years). The results were: Pl = 87 - 152An, r = 0.90, SEE = 7 mm Hg, p less than 0.05; Rl = 899 - 1722An, r = 0.79, SEE = 121 dynes X sec X cm-5, p less than 0.05; and Ql = -0.3 + 1.21Qn, r = 0.95, SEE = 0.81 L X min-1, p less than 0.05. We then used these equations prospectively to predict Pl, Rl, and Ql in 21 of 25 (83% technically adequate) consecutive patients. Pl, Rl, and Ql ranged from 10 to 35 mm Hg, 39 to 456 dynes X sec X cm-5, and 3.51 to 8.39 L X min-1, respectively. Results were: Pl = 0.80P + 3, r = 0.72, SEE = 6 mm Hg, p less than 0.05; Rl = 0.75R - 12, r = 0.64, SEE = 77 dynes X sec X cm-5, p less than 0.005; and Ql = 0.87Q + 0.38, r = 0.83, SEE = 0.86 L X min-1, p less than 0.05. These results suggest that DE predictions of pulmonary artery pressure, flow, and resistance correlate significantly with values subsequently obtained at catheterization.

Doppler echocardiographic profiles in obstructive right and left atrial myxomas.

Previous reports have suggested that atrioventricular (AV) flow disturbances accompanying atrial myxomas mimic mitral stenosis. Two patients complaining of orthostatic syncope and positional intolerance had a large right and left atrial myxoma, respectively. Doppler flow records showed abrupt early diastolic flow cessation and normal velocity half-times, unlike AV valve stenosis. Large, obstructing atrial myxomas may behave as ball valves.

Sleep apnea and autonomic cerebrovascular dysfunction.

Changes in common carotid blood flow (CCF) and resistance index (RI), calculated from velocity waveforms by a noninvasive pulsed Doppler technique, were measured during apneic episodes and voluntary breath holding in five sleep apnea patients (SA) and during breath holding in five normal subjects (N). During apneic episodes averaging 27 s, CCF was reduced by 9% and RI increased by 4%, both trends being related to apneic duration. Internal carotid artery measurements in one SA indicated more dramatic changes in blood flow and RI than noted in CCF. During breath holding, CCF decreased significantly in SA but not in N, and RI showed a smaller reduction in SA. These changes in CCF and RI during sleep apnea are similar to those noted in anesthetized dogs where vasomotor waves and associated apneas were induced by elevating intracranial pressure. Previously reported recordings of ventilatory and systemic cardiovascular responses in SA are similar to these recordings in dogs, and it is therefore proposed that vasomotor responses to intermittent cerebral ischemia and hypercapnia may be the principle event in SA and periodic breathing only a secondary consequence of the prevailing autonomic dysfunction.

Clinically silent atrial septal defects with evidence for cerebral embolization.

The cause of stroke in young patients frequently cannot be established. Eleven consecutive patients, age 50 and younger, had clinical evidence of cerebral embolization. Results of physical, radiographic, electrocardiographic, and two-dimensional echocardiographic examinations were normal in all patients. During normal respiration, eight of the patients had right-to-left shunts at the atrial level shown by microcavitation contrast two-dimensional echocardiography. Six of the eight patients with positive contrast studies had cardiac catheterization. Five of six patients had an atrial septal defect, normal right and left heart pressures, and small right-to-left shunts during a Valsalva strain. Four patients had surgical closure of the defect, which ranged in size from 5 to 10 mm. The remaining patients received anticoagulants. Interatrial communications appear to be common in young patients with stroke, suggesting paradoxical embolization as a possible mechanism. Contrast two-dimensional echocardiography should be done in such patients because it is the only noninvasive technique that reliably finds these defects.

Quantification of aortic regurgitation utilizing continuous wave Doppler ultrasound.

Aortic regurgitation and mitral stenosis are hemodynamically similar, insofar as both result in passive ventricular filling across a narrow orifice driven by a declining pressure gradient. Because mitral stenosis is successfully characterized by Doppler ultrasound determination of the velocity half-time, or time constant, aortic regurgitation might be quantified in an analogous fashion. Eighty-six patients with diverse causes of aortic regurgitation underwent continuous wave Doppler examination before cardiac catheterization or urgent aortic valve replacement. The Doppler velocity half-time was defined as the time required for the diastolic aortic regurgitation velocity profile to decay by 29%, whereas catheterization pressure half-time was calculated as the time required for transvalvular pressure to decay by 50%. Doppler velocity and catheterization pressure half-times were linearly related (r = 0.91). Doppler velocity half-times were inversely related to regurgitant fraction (r = -0.88). Angiographic severity (1+ = mild to 4+ = severe) was also inversely related to pressure and velocity half-time; a Doppler half-time threshold of 400 ms separated mild (1+, 2+) from significant (3+, 4+) aortic regurgitation with high specificity (0.92) and predictive value (0.90). The Doppler velocity half-time was independent of pulse pressure, mean arterial pressure, ejection fraction and left ventricular end-diastolic pressure. Estimation of transvalvular aortic pressure half-time utilizing continuous wave Doppler ultrasound is a reliable and accurate method for the noninvasive evaluation of the severity of aortic regurgitation.

Noninvasive Doppler flowmetry for measuring regional blood flow.

Ultrasonic Doppler flowmetry should assume an increasingly important role in the serial evaluation of human cardiovascular physiology. The principal advantages of this method are that it (1) is noninvasive, (2) is nontraumatic, (3) provides anatomic and physiologic data, and (4) provides dynamic measurements. Nevertheless, the equally important limitations of the technique are that it (1) is difficult to apply in some subjects (ie, those who are obese or have anatomic variations), (2) requires operator skill and a thorough knowledge of human anatomy and cardiovascular dynamics, (3) has a finite spatial resolution that may compromise the measurement of small (1 mm) vessel diameters, and (4) has a finite velocity-measuring capability that will affect measurements of blood velocities outside the range of approximately 2 to 200 cm/sec. Full appreciation of the capabilities and limitations of noninvasive ultrasonic Doppler flowmetry makes possible a better understanding of the dynamic interplay of anatomy, pressure, flow, and resistance in the normal and abnormal intact human cardiovascular system.

Doppler ultrasound in noninvasive cardiac evaluation. The growing range of applications.

Ultrasound is of proven clinical utility for imaging cardiac structures. Doppler ultrasonic techniques can be used with or without echocardiography for noninvasive hemodynamic studies. The usefulness of Doppler ultrasonic techniques in the noninvasive laboratory has been shown recently at the Massachusetts General Hospital, Boston. In 61 of 100 consecutive patients in a prospective study, Doppler ultrasound provided clinical information that could not be obtained with echocardiographic studies alone. The advantages of this technique for noninvasive cardiac studies are now being recognized in the general medical community. The results of ongoing clinical investigations will help define the role of Doppler echocardiography as a clinically useful diagnostic tool for cardiac evaluation.

Noninvasive Doppler determination of cardiac output during submaximal and peak exercise.

We compared pulsed Doppler (PD) measurements of stroke volume (SV) and cardiac output (CO) as a function of work load with previously reported values that were obtained by standard invasive methods. Suprasternal notch measurements of Doppler-shifted frequency (delta f) were obtained from the ascending aorta and SV calculated with the Doppler equation and an independent measurement of aortic diameter. Motion artifacts were minimized with the aid of a restraining table cycle ergometer. Signal aliasing was accommodated with manual summation of delta f waveforms. A total of 207 determinations were made in 10 sitting subjects exercising to exhaustion. Linear regression analysis of CO vs. work load was significant (P less than 0.001). The correlation coefficient (r = 0.95) and standard error of estimate value (1.21 1/min) were similar to values from the literature. Absolute values of CO and SV underestimated the literature values across all work loads. Technical reproducibility was assessed by comparing with paired t tests the differences between 65 duplicate serial measurements of CO and SV at rest and exercise. No significant differences (P less than 0.001) were found. We concluded that PD-determined SV and CO are reproducible and correlate linearly with work load in a manner consistent with reported invasive techniques. Thus the PD method appears suitable for use during submaximal and peak exercise.

A comparison of digital and analog methods of Doppler spectral analysis for quantifying flow.

Ultrasonic methods can be used for calculating flow when the mean Doppler frequency is representative of spatial average velocity. We have examined the capabilities of two commercially available methods of Doppler spectral analysis for providing measurements of spatial average velocity and flow. In a steady state flow model, Doppler audio spectra were recorded using a 5-MHz duplex scanner. Fast Fourier transform (FFT) spectral analysis was used to determine mean (M), mode (MO), and maximum (MAX) frequencies. An analog method (offset zero crossing detector = ZC) was used to determine root mean square (RMS) frequencies. The results of comparing Doppler flow estimates (QM, QMO, QMAX and QRMS) with direct flow measurements (n = 10; range = 128-1098 ml/min) were (1) QM = 0.67Q + 23 ml/min (SEE = 36 ml/min); (2) QMO = 0.96Q + 152 ml/min (SEE = 32 ml/min); (3) QMAX = 1.19Q + 171 ml/min (SEE = 23 ml/min); and (4) QRMS = 0.93Q + 76ml/min (SEE = 92 ml/min). Estimates of flow using M and RMS frequencies were adversely affected by experimental conditions likely to result in turbulence. We conclude that application of commercially available FFT determined M frequencies could result in significant errors in calculations of spatial average velocity and flow. Alternatively, FFT determined MO frequencies and ZC determined RMS frequencies resulted in accurate estimates of flow in this model. This study demonstrates the importance of evaluating the capabilities of commercially available methods of Doppler spectral analysis when using ultrasound for determining velocity and flow.

Directional variability in the R wave response during serial exercise testing in patients with coronary artery disease.

The reproducibility of the direction of R wave amplitude response to exercise was analyzed in patients with coronary artery disease. Forty-three serial exercise tests were performed by 10 patients with exertional angina pectoris and documented coronary artery disease (CAD). Seventeen tests (37%) resulted in no change or an increase in R wave amplitude (abnormal response). Twenty-six tests (63%) resulted in a decrease in R wave amplitude. The direction of the R wave amplitude response was variable in at least one exercise test in 7 of 10 patients with CAD, all of whom had reproducible ischemic ST segment responses during serial testing. The inconsistent R wave response in these patients was unrelated to heart rate, workload, or duration of exercise. Because of the variability in the directional R wave response during serial exercise testing in CAD patients, we conclude that the R wave response during exercise is unreliable for the detection of CAD or ischemia-related myocardial dysfunction.

Noninvasive diagnosis of renal artery stenosis by echo-Doppler velocimetry.

We evaluated the diagnostic accuracy of ultrasonic echo-Doppler velocimetry for the noninvasive diagnosis of renal artery stenosis. Renal artery stenosis was diagnosed if one or more of the following four abnormal hemodynamic parameters were found by Doppler velocimetry: (1) peak blood velocity greater than 100 cm . sec-1 in a focal area along the length of a renal artery, (2) absence of blood velocity during diastole, (3) absence of any detectable blood velocity denoting occlusion, or (4) broad-band Doppler frequency spectra due to focal blood velocity disturbances. With these criteria, the presence or absence of renal artery stenosis was blindly evaluated in 26 patients (52 arteries) who underwent standard or digital subtraction angiography. Compared to arteriography (reduction in diameter greater than or equal to 50%), the sensitivity of Doppler method was 89%, while its specificity was 73%. This noninvasive method may be useful in selecting patients for radiographic evaluation of renal artery stenosis and in the long term follow-up of these patients. Furthermore, echo-Doppler velocimetry may have the unique capability of assessing the hemodynamic consequences of renal artery stenosis.

A comparison of echo-Doppler and electromagnetic renal blood flow measurements.

The linearity and accuracy of noninvasive ultrasonic method of measuring beat-to-beat renal blood flow was evaluated by correlation with standard electromagnetic flowmetry. Using a combined real-time ultrasonic imager and pulsed Doppler velocimeter known as a duplex scanner (DS), lumen diameter (D) and average blood velocity (V) within the imaged renal artery were recorded. Renal blood flow ( QDS ) was calculated offline using a microprocessor from the equation QDS = (pi x D2 x V)/4. This noninvasive method had previously been validated in vitro using a controlled hydraulic system which modeled steady-state flow (QT) where QDS = 0.98 QT + 7.75, SEE = +/- 13.2, r = +0.98, P less than 0.001. In three anesthetized dogs, simultaneous QDS and electromagnetic flow ( QEMF ) measurements (range 44-484 ml x min-1) were made in the proximal left renal artery. Linear regression analysis gave QDS = 0.43 QEMF + 40.5, r = 0.78, SEE = 33.8 ml x min-1, P less than 0.01; QDS = 1.2 QEMF + 2.9, r = 0.86, SEE = 20.8 ml x min-1, P less than 0.01; QDS = 0.86 QEMF + 0.2, r = 0.93, SEE = 53.4 ml x min-1, P less than 0.01. These results suggest that noninvasive QDS measurements of renal blood flow are linear and reasonably accurate compared with invasive QEMF in dogs. The method may have utility in the noninvasive measurement of beat-to-beat blood flow in human renal arteries.