Doppler microembolic signals in children with prosthetic cardiac valves

BACKGROUND AND PURPOSE: The aim of this study was the evaluation of the prevalence and counts of Doppler microembolic signals (MES) in children with prosthetic cardiac valves and their comparison to those obtained in corresponding adult patients. PATIENTS AND METHODS: Nine children and 43 adults with ATS valves implanted in the aortic position were monitored over both middle cerebral arteries with transcranial Doppler ultrasound. MES were identified on-line according to standard criteria. Heart rate and rhythm, valve type, size and duration, patients' height, International Normalized Ratio, and prevalence of neurological complications were obtained from all study participants. RESULTS: MES prevalence and counts were significantly higher in children compared with adult patients (100% versus 25.5% and 58 [18.5 to 115.5] versus 55 [2 to 10.5], median, 95% CI, respectively). No corresponding differences in valve duration of valve implant were evident, but children has heart rates and were significantly smaller compared with adults. A positive correlation between patients' size, heart rate, and MES counts was noted. CONCLUSIONS: MES counts in children with mechanical prosthetic valves are significantly higher compared with those in corresponding adults. We hypothesize that this is due to (1) the shorter distance between aortic valve and middle cerebral artery, since cavitation bubbles have a short life span and are bound to dissolve with time, and (2) the faster heart rate in children, resulting in a higher number of valve closures per minute.     

Identification of Doppler microembolic signals with a bigate probe in patients with prosthetic heart valves

BACKGROUND AND PURPOSE: The applicability of a bigate probe, simultaneously harvesting two spatially separated vessel segments, in the identification of Doppler microembolic signals (MES) was evaluated. METHODS: One hundred and ninety-seven patients with artificial heart valves were bilaterally monitored over two segments of each middle cerebral artery, with a minimal distance of 5 mm between them, using 2 MHz probes. Time delay in the appearance of high intensity transients between the two segments was calculated off-line, using dedicated software, integrated in the Doppler device. RESULTS: Bigate monitoring was feasible in 96% of patients. MES prevalence and counts were 37% and 26 (18-44) respectively. All but 8.8% of the 2932 MES signals recorded appeared in both Doppler channels, with a time delay of 4.4 (4.2-4.7) msec (range between 0 and 34 msec). Time delay in 97% of artifact signals was under 1 msec. Application of 1 msec as low and 20 msec as high cut-off point between MES and artifacts resulted in the correct identification of 97% of artifacts and 89.6% of MES. CONCLUSIONS: The multigate approach is a reliable method for identification of Doppler microembolic signals in patients with prosthetic heart valves. The value of this technique in other patient groups remains to be evaluated.     

Detection of asymptomatic cerebral embolic signals with Doppler ultrasound

Can asymptomatic cerebral emboli be detected? With transcranial Doppler ultrasonography of the middle cerebral artery, short-duration high-intensity asymptomatic embolic signals were detected in 6 of 25 patients with carotid stenosis and in 9 of 24 with prosthetic cardiac valves, but not in 20 normal controls. In carotid stenosis the signals were usually unilateral and ipsilateral to the stenosis. Embolic signals were significantly more common in patients with mechanical valves than with pig xenografts (8/13 vs 1/11). With mechanical valves embolic signals were usually bilateral. Detection of asymptomatic emboli may allow identification of and preventive treatment in at-risk patients.     

Hemodynamic performance of four mechanical bileaflet prosthetic valves in the mitral position: an echocardiographic study

Plasma methadone concentrations and its main metabolite D,L-2-ethylidiene-1,5-dimethyl-3,5-diphenylpyrrolidine (EDDP) were determined in 93 patients under methadone maintenance treatment to assess their relationship with heroin use and opioid withdrawal symptoms. Neither plasma concentrations of methadone nor EDDP were significantly different when patients that used heroin in last 3 months were compared with those testing negative for this drug (methadone, 355 +/- 217 versus 369 +/- 216 ng/ml, t = 0.29, P = NS; EDDP, 49 +/- 28 versus 54 +/- 40 ng/ml, t = 0.51, P = NS). No correlation between opioid withdrawal scale scores and plasma concentrations of methadone (r = 0.02, P = NS) and EDDP (r = -0.14, P = NS) was found. Therapeutic drug monitoring during methadone maintenance seems to be useful for assessing compliance with treatment but not for predicting heroin use and subjective withdrawal symptoms.     

Microemboli in cerebral circulation and alteration of cognitive abilities in patients with mechanical prosthetic heart valves

BACKGROUND AND PURPOSE: It has been shown previously that cerebral microemboli may occur frequently in patients with a normal mechanical heart valve (MHV) without prior history of stroke. Some arguments strongly suggest that these microemboli have a gaseous origin. In other circumstances such as extracorporeal circulation or decompression in divers, it has been demonstrated that cerebral microbubbles could lead to some deterioration in cognitive functions. Therefore, we have studied attention and memory, which are among the most impaired cognitive functions as demonstrated in previous studies, in patients with an MHV. METHODS: Three groups of 12 volunteers each were composed of patients with an MHV and embolic signals in the cerebral circulation (group 1), patients with biological prostheses (group 2), and healthy subjects (group 3). Groups were carefully matched for age and verbal intellectual abilities. For each group, a transcranial Doppler examination was performed and a set of cognitive tests assessing sustained and selective attention and episodic and working memory was administered. RESULTS: The mean embolic rate was 29 per hour in patients with an MHV. No embolus was detected in the other 2 groups. Episodic memory was significantly modified in both groups 1 and 2 compared with the control group for tasks that required high-processing resources. Working memory performance was significantly decreased in MHV patients. No between-groups differences were observed for the other parameters. CONCLUSIONS: Alteration of episodic memory can be attributed to a long-term effect of the surgical procedure. Deterioration of working memory can be related to the presence of cerebral microemboli in MHV patients.     

Simplified method of evaluating dysfunction in St. Jude medical prosthetic heart valves

The St. Jude medical valve is one of the most common heart valve prostheses used. More than 450,000 have been implanted. Patients with these prosthetic valves need full anticoagulation and close follow-up for life. Without adequate oral anticoagulation, thrombotic complications may develop. A simple method of evaluating the full range of motion of the valve leaflets can be attained by fluoroscopy. Fluoroscopy is easily available, non-invasive, and diagnostic. This article demonstrates early recognition of valve dysfunction due to thrombosis with fluoroscopy leading to prompt treatment.     

Comparative study of in vitro flow characteristics between a human aortic valve and a designed aortic valve and six corresponding types of prosthetic heart valves

A model of a pulsatile cardiovascular system is described including an electronic control, a hydraulic driving unit, a volume storage, a peripheral resistance and measuring equipment. Six different artificial heart valves, a designed aortic valve (Aachen pockett valve II) and a human aortic valve have been tested in the outflow position of the pump. Three of them are presently being used in clinical applications. Measurements of pressure and volume flow have been obtained for different frequencies n, pump volumes Vp and time ratios between pressure and suction phase. From the experimental results a comparative evaluation was deducted for different working conditions. In comparison to natural human aortic valve (NK) large volume flow is verified by the Aachen pocket valve II (AT), the Gott-Dagget value (GD), the Starr-Edwards valve (SE) and the Lillehei-Kaster valve (LK). The Gott-Daggett valve has the smallest back flow volume. The Smeloff-Cutter and in particular the Wada-Cutter valve have the largest regurgitation. This is to be expected since the Cutter valves are purposely so designed that they do not close tightly in order to avoid blood sedimentation. The human aortic valve, the Gott-Daggett valve and the Aachen pocket valve demonstrate the most favourable opening-closing characteristics. The human aortic valve achieves a negligible pressure loss, followed by the Bj?rk-Shiley and the Lillehei-Kaster valve.     

Effects of pulsed ultrasound on embryonic development: an in vitro study

Precursor CD4+ T cells develop into effector Th1 and Th2 cells that play a central role in the immune response. We show that the JNK MAP kinase pathway is induced in Th1 but not in Th2 effector cells upon antigen stimulation. Further, the differentiation of precursor CD4+ T cells into effector Th1 but not Th2 cells is impaired in JNK2-deficient mice. The inability of IL-12 to differentiate JNK2-deficient CD4+ T cells fully into effector Th1 cells is caused by a defect in IFNgamma production during the early stages of differentiation. The addition of exogenous IFNgamma during differentiation restores IL-12-mediated Th1 polarization in the JNK2-deficient mice. The JNK MAP kinase signaling pathway, therefore, plays an important role in the balance of Th1 and Th2 immune responses.     

A new in vitro test method for calcification of bioprosthetic heart valves

To investigate the calcification behavior of different bioprosthetic heart valves and verify possible hypotheses of the etiology of valve calcification, an accelerated pulse tester for bioprostheses was developed, whereby up to ten valves can be tested under identical test conditions. Each valve was mounted in a separate compartment on a piston and cyclically moved through a calcifying solution at frequencies of up to 800/min at 37 degrees C: An appropriate calcifying solution was evaluated by incubation tests of bovine and porcine tissue. Calcification was confirmed by measuring Ca and phosphate depletion by atomic absorption spectroscopy, von Kossa staining, EDAX, and microradiography. The first tests were successfully carried out on porcine valves that had been nondestructively assessed for tissue/stress anomalies by holographic interferometry prior to the calcification test. The tests showed that 75% of irregular fringe pattern areas corresponded to the calcification areas.     

Warfarin, aspirin and microembolic signals in the acute phase of stroke in a patient with mechanical heart valves

We report the case of a 54-year-old woman, with atrial fibrillation and mechanical heart valves, who suffered a left-hemispheric stroke while she was under warfarin. Daily bilateral simultaneous transcranial Doppler monitoring of the middle cerebral arteries showed the presence of microembolic signals (MES), whose number remained unchanged after adding aspirin 100 mg daily. We conclude that anticoagulant plus antiplatelet therapy does not influence the number of MES in the acute phase of stroke in patients with prosthetic heart valves, suggesting the gaseous origin of MES in these patients.     

Transcranial Doppler and cortical microcirculation at increased intracranial pressure and during the Cushing response: an experimental study on rabbits

The effect of increased intracranial pressure on the flow velocity of the basilar artery was measured with transcranial ultrasonic Doppler in New Zealand White rabbits under alpha-chloralose anesthesia and artificial respiration. Laser Doppler flowmetry served to study changes of the cortical microcirculation. The results confirm a high inverse correlation of the diastolic flow velocity, the pulsatility index, and the resistance index with the cerebral perfusion pressure (CPP). During acute intracranial hypertension, however, these parameters do not show a good correlation with the local cortical blood flow. The absence of a correlation was evident over a wide CPP range down to values of 35 mm Hg. Only at CPP values below this critical threshold is the microcirculation impaired. The threshold is reached at pulsatility index values of more than 2.0 and at resistance index values of more than 0.8. Therefore, transcranial Doppler indices permit the detection of critical reductions of microcirculatory blood flow. The Cushing reaction occurred with a constant time lag of 5.5 +/- 0.7 seconds after the loss of CPP. The Cushing reaction did not establish systolic blood flow, which remained below the functional threshold, as concluded from the temporary loss of somatosensory evoked potentials.     

The effect of cortical endplates on ultrasound velocity through the calcaneus: an in vitro study

Ultrasound velocity has been reported as a good predictor of bone strength measured in vitro using standard mechanical testing techniques. Such mechanical investigation of bone strength cannot be carried out in vivo, because of the invasive nature of the testing. Therefore to be able to extrapolate the in vitro findings to the clinical situation, the effect of cortex on ultrasound transmission velocity through the calcaneus is required. This was investigated in vitro by measuring ultrasound velocity through samples of different modification using a CUBAResearch ultrasound machine. The different sample modifications were: "whole" (soft tissue removed), "core" (cylindrical sample), "can" (cancellous sample without the cortex) and "def" (defatted cancellous sample). Ultrasound transmission velocity for the various sample modification were highly correlated with each other (r = 0.80-0.97). Coring resulted in a 0.77% increase in the mean velocity. Substituting bone marrow (defatting) with water at room temperature had no measurable effect on the ultrasound velocity. The velocity in the whole samples and the cancellous samples were statistically different with the cortex introducing only a 2% increase in the ultrasound velocity. Therefore the in vivo ultrasound velocity measured at the calcaneus is determined mainly by the cancellous bone component which is more sensitive to osteoporotic changes. Hence the reported ability of ultrasound velocity in vitro to predict bone strength could be expected in vivo.     

Effect of valve holder flexibility on cavitation initiation with mechanical heart valve prostheses: an in vitro study

The records of 98 patients with 160 hypoplastic thumbs seen between 1923 and 1993 were reviewed to determine the salient characteristics of this population. Physical findings, photographs, and x-ray films were studied. Sixty-three percent of patients were male, and 63% had bilateral thumb hypoplasia, 59% had radial dysplasia, and 86% had other anomalies. An associated syndrome, most commonly the vertebral, anal, tracheosophageal, renal, and radial limb anomalies association or Holt-Oram syndrome, was present in 44%. Patients with spine, genitourinary, or gastrointestinal anomalies were most likely to have the vertebral, anal, tracheosophageal, renal, and radial limb anomalies association, those with cardiac anomalies were most likely to have Holt-Oram syndrome, and those with lower extremity anomalies were most likely to have a different syndrome. One hundred thirty-nine thumbs were classifiable, using a modification of Blauth's classification; 19% were types 1 and 2, 23% were type 3, and 58% were types 4 and 5. One hundred seven operations were performed on 63 upper limbs, including 24 thumb reconstructions and 35 pollicizations. These patients must be carefully examined for bilaterality, other anomalies, and syndromes. Classification using a modification of Blauth's criteria is useful and helps the surgeon determine a treatment plan.     

Evaluation of breast tumors with color Doppler imaging: a comparison with image-directed Doppler ultrasound

Preclinical experience has shown that it is possible to maintain and expand hematopoietic cells in liquid culture systems by provision of optimal combinations of colony-stimulating factors (CSF). Ex vivo hematopoietic cell expansion (HCE) would be expected to reduce harvesting time and effort and could also decrease the infusion dose necessary for hematopoietic reconstitution after bone marrow transplantation. In addition, ex vivo expanded cells might be of value for therapeutic gene transfer. The central question in ex vivo HCE is whether the CSF combinations employed provide not only amplification of the late progenitor pools, but also maintenance or expansion of the stem cell compartment to ensure long term engraftment. Choice of CSF and experimental parameters in the culture system appear to be the most critical factors influencing the outcome of strategies for ex vivo HCE. Moreover, it is essential to define the goal of HCE and to adapt the experimental conditions to obtain the required cell populations. In future work, it remains to test the potential applicability of ex vivo expanded cells and to carefully monitor the possibility of the expansion of tumoral cells in ex vivo proliferation systems.     

Color Doppler ultrasound pulsatile flow signals of thoracic lesions: comparison of lung cancers and benign lesions

Color Doppler ultrasound (US) was performed in 153 patients (including 102 with lung cancer and 51 with benign lesions) to assess pulsatile flow signals in thoracic lesions. The values of resistive index (RI) and pulsatility index (PI) of color Doppler US pulsatile flow signals in lung cancers and benign lesions were measured, analyzed, and compared. In the enrolled 153 patients with thoracic lesions, 61 lung cancers and 34 benign lesions had detectable color Doppler US pulsatile flow signals, and lung cancers had lower RI and PI values than benign lesions (RI: 0.70+/-0.03 vs. 0.79+/-0.04, p < 0.05; PI: 1.61+/-0.15 vs. 2.44+/-0.25, p < 0.005). However, overlapping RI and PI values in lung cancers and benign lesions somewhat limited color Doppler US pulsatile flow signals to differentiate lung cancers from benign lesions. Further analysis of RI and PI values in subgroups of lung cancers [squamous cell carcinoma (SCC, n = 34), adenocarcinoma (AC, n = 18), and small-cell lung cancer (SCLC, n = 6)] and benign lesions [cavitary benign lesions (CBL, n = 8), and noncavitary benign lesions (NCBL, n = 26)] revealed that all different cell types of lung cancers (SCC, AC, and SCLC), indeed, had lower RI and PI values than NCBL (for RI, all p < 0.01; for PI, all p< or =0.001). Moreover, the mean RI and PI values showed a significant incremental decrease from NCBL (mean RI, PI = 0.88, 2.94) toward SCC and AC (for SCC, mean RI, PI = 0.71, 1.68; for AC, mean RI, PI = 0.68, 1.67) and, finally, to SCLC (mean RI, PI = 0.62, 1.05). In contrast, CBL had relatively lower RI and PI values than AC and SCLC (for CBL, mean RI, PI = 0.53, 0.80; both p > 0.05 for RI and PI), and even a significant difference from SCC (p < 0.05 for RI and PI). We conclude that color Doppler US pulsatile flow signal is somewhat limited to differentiate lung cancers from benign lesions, but provides a noninvasive in vivo model to assess the neovascularity intensity of lung cancers.