Oxygen Inhalation Can Differentiate Gaseous From Nongaseous Microemboli Detected by Transcranial Doppler Ultrasound
Background and Purpose Clinically silent circulating microemboli can be detected by transcranial Doppler sonography. The composition of these emboli in different clinical conditions is unclear.
Methods We performed 1-hour transcranial Doppler sonographic recordings from the middle cerebral or posterior cerebral artery in 20 patients with mechanical prosthetic heart valves, in 78 patients with an arterial embolic source, and in 20 control subjects. During 30 minutes of this recording, the patients inspired room air and 6 L of oxygen per minute via a loosely fitting facial mask; during the remaining 30 minutes, they breathed room air only.
Results There was a significant decline of embolic signals (ES) under oxygen in the patients with mechanical prosthetic cardiac valves (144 ES without oxygen versus 63 ES with oxygen; P=.002) but not in the patients with arterial embolic sources (145 ES without oxygen versus 135 ES with oxygen; P=NS). In the control subjects, no ES were found.
Conclusions ES in patients with mechanical prosthetic cardiac valves correspond mainly to gas bubbles. Oxygen inhibits the cavitation process of mechanical prosthetic heart valves or speeds up redissolution of gas bubbles generated by cavitation. In contrast, solid microemboli originating from thrombus or atheroma cannot be suppressed by oxygen inhalation. This simple method of oxygen inhalation should help to clarify the composition of microemboli in various clinical and experimental settings.
The detection of circulating emboli by TCD is of increasing interest in clinical neurology, cardiothoracic surgery, and cardiology. Solid emboli such as thrombus and atheroma originating from carotid and aortic plaques or cardiac sources are generally accepted to be the main cause of cerebral ischemic events. Circulating cerebral microemboli produce a characteristic visible and audible short-duration, high-intensity signal within the TCD frequency spectrum.1 2 From physical considerations, tube and animal models, and the presence of microemboli in patients with active embolic sources and their absence in normal subjects, evidence has accumulated that these signals truly correspond to gaseous or solid microemboli.3 4 5 The overwhelming majority of these microemboli remain clinically asymptomatic. Detection of such, however, proves the presence of an active embolic source (“smoking guns”), helps to localize the source, and provides information on the frequency of embolization. The final goal of such investigations is to select patients for prophylactic treatment. The composition of these microemboli, however, is still unclear. Some investigators believe that circulating microemboli are mainly gaseous in patients with mechanical prosthetic cardiac valves.6 7 8 9
In a previous communication, we described a prompt decrease of the number of ES under the inhalation of oxygen in six patients with mechanical prosthetic cardiac valves, and we suggested that microemboli in these patients are predominantly gaseous.10 In this report we want to validate these findings in an additional larger cohort and to demonstrate that microemboli from arterial sources are predominantly nongaseous.
Subjects and Methods
After having given informed consent, all subjects received a full-color duplex investigation of their neck arteries and a continuous-wave Doppler investigation of the periorbital arteries. Subjects were also examined by TCD, including the intracranial segments of the ICAs, the MCAs, the anterior cerebral arteries and PCAs, and the basilar artery. In 24 patients, the result of an echocardiogram was also available.
The MCA or the PCA (P1or P2 segment, PCA) was continuously insonated through the temporal window for 1 hour. A 2-MHz probe was mounted on the temporal plane and secured in a head ribbon. A small sample volume of 4 mm in length and a low gain provided a setting guaranteeing optimal ES discrimination from the background spectrum.4 This setting was maintained throughout the recordings. The investigations were well tolerated by the subjects without side effects. The sametranscranial pulsed Doppler ultrasound device (TC4040, Nicolet-EME) was used for all studies and for the blinded off-line evaluation of the data. The machine employed a 128-point FFT analysis and used a graded color scale to display the intensity of the received Doppler signal. FFT time frame overlap was 67%. The Doppler signal was recorded onto DAT with normal speed for documentation and off-line control. The tapes were given numbers. No patient details could be deduced from these tapes. An experienced observer’s analysis of ES comprised (1) listening to each signal and (2) watching each signal on the screen at highest speed. This analysis was done blinded off-line by reintroducing the DAT signal into the FFT processor. The following definition for ES was used: typical visible and audible (click, chirp, whistle) short-duration, high-intensity signal within the Doppler flow spectrum with its occurrence at random in the cardiac cycle, and an intensity increase of 3 dB or more above the background signal.1 2 11 Interobserver and intercenter validations were performed to guarantee reproducibility and stability of assessment. In a randomized way, oxygen was applied at a dose of 6 L/min by a loosely fitting facial mask during either the first 30 minutes or the last 30 minutes of the recording time. We also assessed off-line from the DAT tapes in a period of 20 seconds sampled at random between the 10th and the 20th and between the 40th and 50th minute of the recording the mean peak systolic and end-diastolic velocity from each heart beat as well as the heart rate from each subject over 20 seconds. We then calculated the mean maximal peak systolic and the mean maximal end-diastolic blood flow velocity from all the heart beats in these 20 seconds. The heart rate per 20 seconds was tripled to obtain the heart rate per minute.
Patients With Mechanical Prosthetic Cardiac Valves
Three women and 17 men aged 25 to 81 years (mean age, 56 years) were investigated. All of them had received aortic valve prostheses, and 7 of them had an additional mitral valve prosthesis (Edwards Tekna, models 3200 A and 9200 mol/L; 1 patient had a St Jude medical aortic valve). The time between the operation and the ultrasound investigation varied from 37 to 1358 days (mean, 702 days). In 13 patients the right MCA was insonated; in the remaining 7 the left MCA was the artery of interest. Insonation depths varied from 44 to 56 mm. Seven patients were in atrial fibrillation during the embolus detection. Two patients had minor plaques, and 1 patient had a 60% stenosis of the extracranial ICA proximal to the artery under investigation. Two patients had cerebral or retinal ischemic events 881 and 902 days, respectively, before the recording. Three patients were smokers, 2 were diabetic, 5 had arterial hypertension, and 5 had hyperlipidemia. All patients were on oral anticoagulation.
Patients With Arterial Embolic Sources
Twenty-one women and 57 men, aged 39 to 84 years (mean age, 57 years) were investigated in a vessel downstream to a proven arterial embolic source. None of these patients had an artificial cardiac valve. In 7 patients we recorded from the right PCA, in 3 patients from the left PCA, in 38 patients from the right MCA, and in 30 patients from the left MCA. Insonation depths varied from 44 to 56 mm for the MCA insonation (in 1 patient 58 mm) and from 60 to 66 mm for investigating the PCA. In the MCA recorded group, patients 1 to 61 had ipsilateral extracranial carotid artery disease (47 ICA or CCA stenoses ≥60%, 6 severe plaques, 5 ICA occlusions, 3 ICA dissections). Patients 62 to 68 had a corresponding MCA or carotid siphon stenosis, and 1 had a proximal MCA occlusion. In the PCA group, patients 69 to 71 had high-grade basilar artery stenosis, patients 72 and 73 had a corresponding high-grade PCA stenosis, patient 74 had a proximal subclavian artery stenosis, patient 75 had an intracranial vertebral artery occlusion on one side and an extracranial vertebral artery stenosis on the other side, patients 76 and 77 had vertebral artery dissection, and patient 78 had an extracranial vertebral artery stenosis. Two patients were in atrial fibrillation during the recording. Of all 78 patients, 35 had experienced cerebral or retinal ischemic events in the corresponding arterial territory in the past. Twenty-one patients were smokers, 13 were diabetic, 44 had arterial hypertension, and 38 suffered from hyperlipidemia. Thirteen patients were on oral anticoagulation, 45 on antiaggregants, and 24 on intravenous heparin.
Twenty subjects without any ischemic retinal or cerebrovascular events and a normal ultrasound examination served as a control group (9 men and 11 women; age range, 19 to 77 years; mean age, 26 years). Four subjects were smokers, 1 was diabetic, none were hypertensive, and 1 suffered from hyperlipidemia. No subject was in atrial fibrillation during the recording. In 11 subjects we recorded from the left MCA and in 9 subjects from the right MCA. Insonation depths varied from 46 to 54 mm.
For the statistical analysis, the numbers of ES as well as the systolic and end-diastolic blood flow velocity and the heart rate with or without oxygen inhalation were compared with the nonparametric Wilcoxon test. Three groups were considered separately: (1) 20 patients with mechanical prosthetic cardiac valves, (2) 78 patients with arterial embolic sources, and (3) the control group (n=20). We also compared the heart rate and the maximal systolic and end-diastolic blood flow velocity using the Wilcoxon test for the each group. Statistical significance was declared at the .05 level.
Patients With Mechanical Prosthetic Cardiac Valves
All but 3 of these patients showed ES varying from 1 to 53/h. There were a total of 144 ES without oxygen inhalation (mean±SD, 7.2±10.7; range, 1 to 34/30 min in the individual patients), and 63 ES were seen with oxygen inhalation (mean±SD, 3.2±5.7; range, 0 to 20/30 min in the individual patients). The Figure⇓ presents the mean number of ES per 30 minutes for the three groups.
Sixteen patients with ES had more ES without oxygen inhalation than with oxygen inhalation, and only 1 patient had more ES with oxygen inhalation (P=.002). Mean±SD peak systolic and end-diastolic blood flow velocity and heart rate were 72.8±9.2 cm/s, 31.4±6.7 cm/s, and 72.3±11.6/min, respectively, without oxygen inhalation and 71.6±6.8 cm/s, 29.9±5.8 cm/s, and 72.3±11.4/min, respectively, with oxygen inhalation. None of these differences were significant.
Patients With Arterial Embolic Sources
ES were detected in 22 of 78 patients varying from 1 to 71/h in the individual patients. There were a total of 145 ES without oxygen (mean±SD, 1.9±5.3; range, 1 to 33/30 min in the individual patients) and 135 ES with oxygen (mean±SD, 1.7±5.3; range, 1 to 38/30 min in the individual patients). Twelve patients had more ES without oxygen, and 9 had more ES with oxygen. One patient had the same amount of ES under the two conditions. When the Wilcoxon test was performed, the comparison showed no significant difference (P=.34) between the number of ES under baseline conditions and under oxygen inhalation. Mean±SD peak systolic and end-diastolic blood flow velocity and heart rate were 65.6±20.9 cm/s, 30.0±10.9 cm/s, and 70.9±13.5/min, respectively, without oxygen inhalation and 65.9±21.6 cm/s, 29.7±10.8 cm/s, and 68.4±12.4/min, respectively, with oxygen inhalation. None of these differences were significant.
None of these subjects showed ES. Mean±SD peak systolic and end-diastolic blood flow velocity and heart rate were 90.0±20.3 cm/s, 44.1±12.7 cm/s, and 72.7±10.7/min, respectively, without oxygen inhalation and 87.5±20.9 cm/s, 41.9±13.3 cm/s, and 70.0±10.6/min, respectively, with oxygen inhalation. None of these differences were significant.
Our results suggest that the majority of clinically silent circulating microemboli in patients with mechanical prosthetic cardiac valves are gaseous in nature. This confirms preliminary data from our group.10 Oxygen inhibits the cavitation process of mechanical prosthetic heart valves or speeds up redissolution of gas bubbles generated by cavitation. Cavitation, ie, formation of bubbles from a gas dissolved in the blood, in patients with mechanical prosthetic cardiac valves is a well-known phenomenon.12 13 14 15 16 It was found that cavitation is generated primarily by the deceleration of the closing body of the valve. The pressure drop produced thereby is overlapped by the pressure drop in accelerated or turbulent flow regions produced by design characteristics at outlet struts, stop faces, or sealing lips during backflow through the closing disk.12 15 Smaller valves have higher cavitation thresholds than larger ones.14 Some of these bubbles persist and are washed out into the cerebral circulation where they can be detected by TCD. Patients with mechanical prosthetic cardiac valves have an increased risk of arterial thromboembolism.17 18 Our findings suggest that the majority of clinically silent circulating microemboli in these patients mainly reflect valve cavitation properties.8 9 Only 44% of the ES persist under oxygen inhalation. These ES may either correspond to solid microemboli or to gaseous microemboli not affected by oxygen, which was only supplied at a medium dose through a loosely fitting facial mask.
Moreover, our data strongly support the view that clinically silent circulating microemboli in patients with arterial thromboembolic sources are predominantly nongaseous. Whether these signals correspond to reversible platelet aggregates, thrombus, or plaque debris remains unclear.
Differences in blood flow velocity or heart rate due to oxygen inhalation did not exist and therefore cannot account for the above observations.19
The simple application of oxygen described in this report may be used not only in patients with different cardiac valves but also in other thromboembolic sources such as cardiac assist devices. Oxygen may also be helpful in tube models to better define the nature and potential concomitant risk of microemboli.20
Selected Abbreviations and Acronyms
|CCA||=||common carotid artery|
|FFT||=||fast Fourier transform|
|ICA||=||internal carotid artery|
|MCA||=||middle cerebral artery|
|PCA||=||posterior cerebral artery|
|TCD||=||transcranial Doppler sonography|
We are very grateful to Nicolet-EME, Kleinostheim, Germany, for technical support.
- Received March 20, 1007.
- Revision received July 11, 1997.
- Accepted August 28, 1997.
- Copyright © 1997 by American Heart Association
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