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Right-to-left-shunts detected by transesophageal echocardiography and transcranial Doppler sonography.

BACKGROUND: Transesophageal echocardiography (TEE) and transcranial Doppler sonography (TCD) can identify right-to-left-shunts that predispose to paradoxical embolism. In a large cohort we compared the results of both techniques. METHODS: 222 patients were investigated by both techniques using the contrast agent Echovist-300 and performing each test once without and once with the Valsalva maneuver (VM). RESULTS: TEE-proven right-to-left-shunts were detected by TCD with a high sensitivity of 94%. In addition, TCD revealed shunts not noted during TEE in about 20% of all patients studied. These shunts are in general smaller than those concordantly identified; however, 9% of the patients without a TEE-proven shunt presented with a shunt that allows a considerable amount of contrast medium to pass. There were 12% more microbubbles detected in the right middle cerebral artery than in the left middle cerebral artery during the TCD test performed with VM, but not during the TCD test performed without VM. CONCLUSIONS: Contrast-enhanced TEE and TCD are complementary methods in the assessment of stroke and stroke-prone patients. The side difference of microbubbles may indicate a selective streaming of cardiac emboli during VM.

Adolescent↗

Bubbles and computer-aided image analysis for evaluation of surfactant inhibition.

Surfactant (Curosurf, diluted to 5 mg/ml) was suspended in normal saline with 3 mM CaCl2 and mixed with different concentrations of albumin or fibrinogen. The samples were vortexed to generate microbubbles, and the equivalent circle diameter of these bubbles was determined with computer-aided image analysis. Bubbles in the original surfactant suspension had an average diameter of 27 microns after 2 min, and their size increased only little during a 15-min period of observation. The diameter of bubbles generated in the presence of albumin (4 or 40 mg/ml) or fibrinogen (4 mg/ml) was 4-5 times larger, indicating surfactant inhibition. We conclude that evaluation of microbubble stability with image analysis provides an objective and rapid assessment of surfactant inhibition, and we speculate that the method could also be used for quantification of surfactant activity in airway samples.

Animals↗

Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications.

BACKGROUND: The objective of this study was to assess the impact of intracardiac echocardiography (ICE) on the long-term success and complications in patients undergoing pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). METHODS AND RESULTS: Three hundred fifteen patients underwent PVI for treatment of AF. Each patient underwent ostial isolation of all PVs using a cooled-tip ablation catheter. PVI was performed using circular mapping (CM) alone (group 1, 56 patients), CM and ICE (group 2, 107 patients), and CM and ICE with titration of radiofrequency energy based on visualization of microbubbles by ICE (group 3, 152 patients). After a mean follow-up time of 417+/-145 days, 19.6% (11 of 56), 16.8% (18 of 107), and 9.8% (15 of 152) of patients in groups 1, 2, and 3 experienced recurrence of AF, respectively. Moreover, whereas no group 3 patient experienced severe (>70%) PV stenosis, severe PV stenosis was documented in 3 (3.5%) of 56 patients in group 1 and in 2 (1.8%) of 107 patients in group 2 (P<0.05). No embolic events were detected in group 3 patients. CONCLUSIONS: Intracardiac echocardiography improves the outcome of cooled-tip PVI. Power adjustment guided by direct visualization of microbubble formation reduces the risk of PV stenosis and improves long-term cure.

Atrial Fibrillation↗

Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection.

BACKGROUND: The purpose of this study was to determine whether myocardial perfusion can be quantified with myocardial contrast echocardiography using left atrial (LA) injection of contrast. METHODS AND RESULTS: Based on a series of in vitro and in vivo experiments, the optimal dose of sonicated albumin microbubbles injected into the LA for establishing a linear relation between video intensity and blood volume in the anterior myocardium was determined. In 10 open-chest dogs, myocardial blood flow (MBF) was augmented by increasing myocardial blood volume (MBV) with an intravenous infusion of phenylephrine HCl. In the presence of this drug, left anterior descending artery stenosis was produced, followed by release of stenosis, to change MBF within the anterior myocardium. MBV was calculated by dividing radiolabeled microsphere-derived MBF by microbubble transit rate. There was close coupling between MBF and MBV in the anterior myocardium during LA injection of contrast (y = 1.0x-0.03, SEE = 1.07, r = .92, P < .001). An excellent correlation was also noted between background-subtracted peak video intensity and MBV (y = 0.24x + 0.73, SEE = 0.36, r = .88, P < .001). On multivariate analysis, background-subtracted peak video intensity correlated best with MBV. CONCLUSIONS: Myocardial perfusion can be quantified from time-intensity curves derived from the anterior myocardium after LA injection of contrast. Background-subtracted peak video intensity in this situation correlates closely with MBV. When MBV and MBF are closely coupled, such as during inotropic stimulation of the heart, background-subtracted peak video intensity also correlates closely with MBF. Since there are similarities in the models of LA and venous injections, these data indicate that it may be feasible to quantify myocardial perfusion with myocardial contrast echocardiography after venous injection of contrast.

Animals↗

Temporal changes in myocardial perfusion patterns in patients with reperfused anterior wall myocardial infarction. Their relation to myocardial viability.

BACKGROUND: Several studies demonstrated ischemic microvascular damage in patients with acute myocardial infarction (AMI). In this study, myocardial contrast echocardiography (MCE) was used to assess the temporal changes in myocardial perfusion after reflow and to investigate the relation between MCE findings and myocardial viability. METHODS AND RESULTS: MCE was performed with the intracoronary injection of sonicated microbubbles before and shortly after coronary reflow and 1 month later in 45 patients with anterior wall AMI. MCE before reflow was analyzed to determine the risk area as an area of contrast defect in the apical long-axis view. MCE images after reperfusion were analyzed to determine peak contrast intensity, which should be in proportion to the concentration of microbubbles within the microvasculature and in the infarcted and normal myocardium, and the ratio of these (PI ratio) was used to assess microvascular integrity. Areas of residual contrast defect were expressed as a ratio to those of left ventricular myocardial (RCD ratio) to assess the spatial extent of the MCE "no reflow." Regional wall motion (RWM, SD per chord) in the territory of the left anterior descending coronary artery was determined by the centerline method in both the acute and late stages. Although the PI ratio was extremely low shortly after coronary reflow, it increased in the late stage of AMI with the improvement in regional contractile function (RWM, -3.2 +/- 0.5 versus -2.6 +/- 1.0, P < .01; PI ratio, 0.44 +/- 0.25 versus 0.60 +/- 0.29, P < .01). Reduction in the RCD ratio was observed even in 15 patients with MCE no reflow in the acute stage (0.33 +/- 0.09 versus 0.16 +/- 0.11, P < .01). Then we investigated the relation between residual contractile function and microvascular integrity in the late stage. A significant correlation was found between the PI ratio and RWM (r = .73, P < .001) in the late stage of the AMI. CONCLUSIONS: (1) Recovery from ischemic microvascular damage is generally observed in the late stage of AMI in association with improvement in myocardial contractile function. The degree of improvement in contractile function and microvascular integrity, however, varies among patients. (2) Contrast peak intensity in the late stage of infarction may provide a useful estimate of myocardial viability.

Adult↗

Detection of coronary stenoses and quantification of the degree and spatial extent of blood flow mismatch during coronary hyperemia with myocardial contrast echocardiography.

BACKGROUND: We hypothesized that the degree and spatial extent of blood flow mismatch in beds supplied by stenoses that are not flow-limiting at rest can be quantified with myocardial contrast echocardiography (MCE) using left atrial (LA) and right atrial (RA) injections of contrast during pharmacologically induced coronary hyperemia. METHODS AND RESULTS: In 12 open-chest dogs, MCE was performed and myocardial blood flow (MBF) was measured by use of radiolabeled microspheres at baseline and during phenylephrine-induced coronary hyperemia. In the presence of this drug, stenoses were placed during different stages on the left anterior descending (LAD) and left circumflex (LCx) coronary arteries, and MCE and MBF assessments were performed. LA injections of 2 mL of 0.5 billion/mL microbubbles (mean diameter, 4.3 microns) were performed at each stage in all 12 dogs, and RA injections of 10 mL of 6 billion/mL microbubbles (mean diameter, 3.7 to 5.3 microns) were administered in 7 dogs. MCE images in which the contrast disparity between the LAD and LCx beds was maximal were digitally subtracted from precontrast images, and mean videointensities in these beds were measured after the dynamic range of gray-scale intensities was increased in the subtracted image and the image was color coded. The region showing hypoperfusion during LAD stenosis was planimetered and expressed as a percentage of the myocardial area in the short-axis slice. There was an excellent correlation between the LAD/LCx bed videointensity ratio and LAD/LCx bed MBF ratio (y = 0.5x + 0.44, r = .91, P < .001) during 57 LA injections. There was also an excellent correlation between the hypoperfused bed size on MCE during LA injection of contrast in the presence of LAD stenosis and the hypoperfused myocardium as determined by radiolabeled microspheres (y = 0.8x + 4.2, r = .90, P < .001, SEE = 2.4, n = 11). The anterior myocardium was opacified in 6 dogs receiving RA injections of contrast, and the hypoperfused area during LAD stenosis correlated closely with that determined by radiolabeled microspheres (y = 0.86x + 3.4, r = .93, P < .01). CONCLUSIONS: Coronary stenoses, which are not flow limiting at rest, can be detected and the degree and spatial extent of blood flow mismatch during pharmacologically induced coronary hyperemia can be quantified with MCE using LA and RA injections of contrast. Thus, it is possible that the severity of coronary stenoses and the quantum of myocardium in jeopardy could be quantified in the future with MCE using venous injection of contrast.

Animals↗

Myocardial contrast echocardiography can be used to quantify intramyocardial blood volume: new insights into structural mechanisms of coronary autoregulation.

BACKGROUND: Changes in intramyocardial blood volume (IBV) mediate autoregulatory adaptations to coronary stenosis. This study investigated whether (1) myocardial contrast echocardiography (MCE) can quantify changes in IBV during coronary stenosis and (2) the relation between coronary resistance- and MCE-derived IBV could yield insight into structural mechanisms of IBV change. METHODS AND RESULTS: A circulating in vitro model with constant flow and varying volume was used to determine whether indicator dilution theory could be applied to MCE. Contrast echo was performed with albumin microbubbles, and time-intensity data were fit to a gamma-variate function. With six different volumes, bubble transit time was linearly related to volume (r=.91). To determine whether changes in IBV could be quantified in vivo, the left anterior descending coronary artery in 12 dogs was instrumented with a flow probe, occluder, and intracoronary pressure catheter, and non-flow-limiting stenoses were created. IBV was derived by use of coronary resistance measurements applied to models that assumed autoregulation to occur via vasodilatation or microvascular recruitment. MCE-IBV was calculated from microbubble transit rates. At constant flow, MCE and resistance IBV increased with stenosis. Although MCE and resistance IBV were linearly related, MCE overestimated IBV derived from the vasodilatation model and underestimated IBV calculated from the recruitment model. CONCLUSIONS: MCE can quantify autoregulatory increases in IBV that maintain resting myocardial perfusion. These data suggest that both microvessel vasodilatation and recruitment are dual mechanisms of IBV change. MCE thus may be a clinically useful technique for the detection and quantification of coronary artery disease at rest.

Animals↗

Characteristics of patent foramen ovale associated with cryptogenic stroke. A biplane transesophageal echocardiographic study.

BACKGROUND AND PURPOSE: Patent foramen ovale is associated with ischemic stroke in patients without a clearly identifiable etiology for stroke (cryptogenic stroke). Paradoxical embolization is thought to be a potential mechanism. However, patent foramen ovale is also found in patients with known cause of stroke. Therefore, using contrast transesophageal echocardiography, we characterized the patent foramen ovale in cryptogenic stroke patients to assess morphological factors that may contribute to paradoxical embolization. METHODS: Contrast transesophageal echocardiographic studies of 74 consecutive patients referred for ischemic stroke were reviewed. Twenty-three patients with patent foramen ovale were identified. These patients were classified as having strokes of determined origin or cryptogenic strokes according to criteria developed for the Stroke Data Bank of the National Institute of Neurological Disorders and Stroke. Separation of septum primum from secundum and the number of microbubbles appearing in left atrium were then quantitated. These parameters were compared between patients with cryptogenic stroke and those with known cause of stroke. RESULTS: The patent foramen ovale dimension was significantly larger in patients with cryptogenic stroke compared with patients with an identifiable cause of stroke (2.1 +/- 1.7 mm versus 0.57 +/- 0.78 mm [mean +/- SD]; P < .01). The number of microbubbles was also greater in patients with cryptogenic stroke compared with patients with an identifiable cause of stroke (13.9 +/- 10.7 versus 1.6 +/- 0.8 [mean +/- SD]; P < .0005). CONCLUSIONS: Patients with cryptogenic stroke have larger patent foramen ovale with more extensive right-to-left interatrial shunting than patients with stroke of determined cause. Transesophageal echocardiographically identifiable characteristics of patent foramen ovale may be important in defining the clinical significance of individual patent foramina.

Adult↗

A novel technique for identification of doppler microembolic signals based on the coincidence method: in vitro and in vivo evaluation.

BACKGROUND AND PURPOSE: The applicability of a novel differentiation technique in embolus detection based on the coincidence principle and using a multigate probe was evaluated in this study. METHODS: According to the coincidence method, high-intensity transients should only be classified as microembolic signals if they appear sequentially in the two sample volumes monitored and within a defined time window calculated from the blood velocity and the spatial distance between the insonation depths. Part A: microbubbles were introduced in a continuous flow bench model of the middle cerebral artery to evaluate the accuracy of the multigate probe in embolus detection. Part B: in the subjects and patients, the minimal and maximum time delays in the appearance of microembolic signals in the two middle cerebral artery sample volumes were calculated as 0.01 second and set at 0.1 second, respectively. The multigate probe was used to monitor (1) 5 normal volunteers in whom 1008 artifact signals were produced,(2) 2 patients undergoing aortic valve replacement surgery, and (3) 12 patients with potential cardiac or carotid embolic sources. RESULTS: In the bench model, 95.5% of microembolic signals produced by microbubbles appeared in the two sample volumes with a time delay between 0.02 and 0.05 second, while in the remaining 4.5% a shorter passage time of 0.01 second was measured. A total of 1968 high-intensity signals were recorded in subjects and patients. All but 20 of these (99%) appeared in both monitoring channels within the above time frame. To summarize, 996 (98.8%) of the 1004 artifact signals and 943 (98.1%) of the 961 microembolic signals were correctly classified. CONCLUSIONS: Application of the coincidence theory to distinguish microembolic signals from artifacts provides a promising new technique with high sensitivity and specificity that could decisively improve the validity of embolus detection.

Adult↗

Second harmonic imaging In acute middle cerebral artery infarction. Preliminary results.

BACKGROUND: Second harmonic imaging (SHI) is a new ultrasound technique that is able to detect microbubbles in the tissue vascular space. The aim of this pilot study was to prove that this technique may detect focal abnormalities of cerebral echo-contrast enhancement in acute hemispheric stroke. CASE DESCRIPTIONS: Two male patients (aged 72 and 64 years) were included who presented with acute onset of severe hemiparesis and no established demarcation of the ischemic area in CT scans. After bolus application of galactose-based microbubbles, axial SHI examinations in a diencephalic plane of sections were performed using the transtemporal approach. Ultrasound investigations were recorded and evaluated offline. In both individuals demarcated focal abnormalities of cerebral contrast enhancement were detectable: in patient 1 the region of the lentiform nucleus and the adjacent parts of the temporoparietal lobe was affected, and in patient 2 a large region including the lentiform nucleus and cortical white matter was involved for at least 24 hours. Follow-up CT scans demonstrated a striatocapsular infarct in patient 1 and complete MCA infarction in patient 2, correlating with the presumed ischemic area in acute ultrasound examinations. The patient with complete MCA infarction showed missing contrast enhancement in the entire hemisphere of the affected side in follow-up SHI examinations. He died of malignant space-occupying brain edema. In the patient with the striatocapsular infarction, reappearance of echo-contrast enhancement in the ischemic area was assessable after 1 week. CONCLUSIONS: SHI may identify focal abnormalities of cerebral echo-contrast enhancement in acute hemispheric stroke. Furthermore, this technique helps to determine size, localization, and prognosis of the ischemic region and could be useful for bedside assessment of echo-contrast agent distribution related to brain tissue perfusion.

Acute Disease↗

Contrast transcranial Doppler ultrasound in the detection of right-to-left shunts: comparison of different procedures and different contrast agents.

BACKGROUND AND PURPOSE: Cardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound (TCD) with the use of different contrast agents and different provocation procedures. Currently, data on an appropriate time window for the appearance of contrast bubbles in the TCD recording after the injection of the contrast medium and the comparison of different provocation maneuvers to increase right-to-left shunting are insufficient. METHODS: Forty-six patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with 6 injection modes was applied in a randomized way: (1) injection of 10 mL of agitated saline without Valsalva maneuver, (2) injection of 10 mL of agitated saline with Valsalva maneuver, (3) injection of 10 mL of a commercial galactose-based contrast agent (Echovist) without Valsalva maneuver, (4) injection of 10 mL of Echovist with Valsalva maneuver, (5) injection of 10 mL of Echovist with standardized Valsalva maneuver, and (6) injection of 10 mL of Echovist with coughing. RESULTS: In 20 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt-positive). Sixteen patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 10 patients were only positive on at least 1 TCD investigation but negative during TEE. The amount of microbubbles detected in the various tests decreased in the following order: Echovist and Valsalva maneuver, Echovist with coughing, Echovist and standardized Valsalva maneuver, saline with Valsalva maneuver, Echovist, and saline. With a time window of 20 to 25 seconds for the bubbles to appear in the TCD recording and with a sequence of first Echovist and Valsalva maneuver and then Echovist with coughing, all shunts were reliably identified with a specificity of 65% compared with TEE as the traditional gold standard. The time of first microbubble appearance was not helpful to distinguish between shunts detected on TEE and other shunts. CONCLUSIONS: TCD performed twice with 2 provocation maneuvers using Echovist is a sensitive method to identify cardiac right-to-left shunts also identified by TEE.

Adult↗

Stimulated acoustic emission detected by transcranial color doppler ultrasound : a contrast-specific phenomenon useful for the detection of cerebral tissue perfusion.

BACKGROUND AND PURPOSE: Experimental and clinical data suggest that insonation of echo-contrast agents with high acoustical power produces disintegration of microbubbles, resulting in a pseudo-Doppler phenomenon called stimulated acoustic emission (SAE). The purpose of this study was to investigate whether SAE might be detected by transcranial color Doppler imaging and whether these signals might be used for cerebral tissue perfusion measurements. METHODS: Nonmoving microbubbles (SHU 563 A) were insonated in vitro through the temporal parts of a human cadaver skull, and contrast signals were detected by velocity-coded color Doppler and power Doppler recordings. Transcranial color as well as power Doppler investigations were performed in 10 healthy volunteers with the echo-contrast agent Levovist (SHU 508 A). RESULTS: Color Doppler signals indicating SAE were observed in vitro and in transcranial human investigations. These signals were characterized by a mosaic of color Doppler pixels ranging over the full color scale. Apparent velocity information and spatial distribution of SAE signals changed from image frame to image frame. In the experimental model, the intensity of SAE signals decreased exponentially over time. With an increase of acoustic power, there was a significant increase of the maximum signal intensity (P<0.01) and a significantly shortened signal duration (P<0.01), consistent with stronger and more rapid disintegration. In humans, SAE signals were clearly detected in cerebral tissue regions. The intensity of SAE signals in those regions (eg, temporal cortex, 3.7+/-1.2 dB) was approximately 8 times lower than the signal enhancement in the major cerebral arteries (eg, in the MCA, 29.5+/-5.6). CONCLUSIONS: Echo-contrast specific color Doppler signals known as SAE are detectable by transcranial color and power Doppler sonography. Signals due to SAE might represent tissue perfusion, thereby providing a method for imaging flow with transcranial ultrasound.

Adult↗

Noninvasive prediction of ultimate infarct size at the time of acute coronary occlusion based on the extent and magnitude of collateral-derived myocardial blood flow.

BACKGROUND: We hypothesized that by detecting regions with adequate collateral-derived myocardial blood flow (MBF) within the risk area (RA), we could predict ultimate infarct size (IS) at the time of coronary occlusion. METHODS AND RESULTS: Group 1 dogs (n=15) underwent coronary occlusion without reperfusion, whereas group 2 dogs (n=6) underwent both occlusion and reperfusion. RA was measured with aortic root injections of microbubbles. Myocardial contrast echocardiography (MCE) was performed with high mechanical index intermittent harmonic imaging at pulsing intervals (PIs) of <1 to 30 cardiac cycles during an intravenous infusion of microbubbles (Sonozoid). MBF was measured with radiolabeled microspheres, and postmortem tissue staining was used to determine IS. Perfusion defect size (PDS) on MCE varied with the PI and was largest at a PI of 2.6+/-0.4 seconds, where it correlated well with RA (r=0.82). PDS was smallest at a PI of >/=10.6+/-1.5 seconds, where it correlated closely with IS (r>/=0.92). Areas that underwent necrosis could be identified early after coronary occlusion as having the lowest microvascular flow velocity (beta) and MCE-derived MBF (Axbeta). The results were similar with or without reperfusion. Because of variability in collateral-derived MBF, there was no correlation between RA and ultimate IS (P=0.37). The extent of regional dysfunction also correlated poorly with IS (r=0.31). CONCLUSIONS: MCE can be used immediately after coronary occlusion to define ultimate IS by measuring the magnitude and spatial extent of collateral-derived residual MBF within the RA. Thus, it could help individualize risk and management in acute myocardial infarction.

Animals↗

Reversal of meconium inhibition of pulmonary surfactant by ferric chloride, copper chloride, and acetic acid.

Meconium inhibits pulmonary surfactant function. We investigated the in vitro effect of meconium on three different commercial surfactants. The dynamic surface properties of these surfactants were evaluated at the concentration of 5 mg/ml with a pulsating bubble system. The inhibitory effect of 2.75 mg/ml meconium was significantly less on Alveofact than on Curosurf and Survanta. Ferric chloride and copper chloride completely reversed the inhibitory effect of meconium. Meconium also prevented effective spreading of surfactant in a Wilhelmy balance system, and this inhibitory effect was counteracted by addition of ferric chloride. Image analysis of Curosurf demonstrated that meconium reduced the total number of microbubbles in 15 light-microscopic fields (4.35 mm(2)) from 1,748 +/- 481 to 180 +/- 166. Ferric chloride restored the number of microbubbles. Addition of ferric chloride or copper chloride to surfactant/meconium lowers pH, and pH adjustment by acetic acid also reversed the inhibitory effect of meconium. Together with the fact that the iron-chelator deferoxamine did not attenuate the effect of ferric chloride this suggests that the observed contrainhibition is caused by lowering of pH, and that meconium inhibition of surfactant is pH-dependent. Lowering pH from 6.2 to 5-5.5 abolished the inhibitory effects of meconium on surfactant. Inhibition of 2.5 mg/ml of Curosurf with plasma could also be reversed by increasing amounts of ferric chloride. We conclude that the inhibitory effect of meconium on surfactant in vitro can be abolished by addition of ferric chloride, copper chloride, or acetic acid.

Acetic Acid↗

Vortex pumping for routine cardiac surgery: a comparative study.

Vortex pumping has become popular for mechanical assist applications, but has only recently received serious consideration for use as the arterial pump of choice for routine open-heart surgery. We report on a prospective randomized study designed to evaluate this pump in routine use. Sixteen patients undergoing routine coronary artery surgery were randomized into two groups in which the only difference in equipment and technique was the use of a Stockert roller pump in group S and a Biomedicus vortex pump in group B. The groups were compared with respect to haematology, perioperative fluid balance, transfusion requirements, complement activation, haemolysis and microbubble transmission. The groups were reasonably well matched, with slightly longer mean bypass and ischaemic times in group S (94.8 vs 105.5 minutes and 75.7 and 83.8 minutes respectively). Group B patients showed significant improvements over group S patients with respect to preservation of platelet numbers, decreased complement activation and reduced microbubble transmission. The afterload sensitivity of the vortex pump did not present the perfusionist with any practical problems although a different technique is required for initiating and terminating bypass. We conclude that vortex pumping would seem to offer better blood handling for routine use. More extensive testing is required to establish whether or not this would be reflected in clinically measurable improved patient outcome.

Adult↗

Behavior of gaseous microemboli in extracorporeal circuits: air versus CO2.

BACKGROUND: Open heart surgery is associated with serious risk of cerebral and peripheral organ dysfunction, attributed in part to air microbubbles generated in or not eliminated from the extracorporeal circuit (ECC). Venous air leakage leads to increased arterial bubble load. CO2 replacing air in cardiac chambers show faster resorption times, reducing possible cerebral or peripheral organ damage after heart valve interventions. In two models of ECC the effect of air entering closed circuits was demonstrated and compared to the effect of CO2 entry. METHODS: Fragmentation and dissolution of gas (0.5 mL) was evaluated in an in vitro model of ECC, using ultrasonic bubble detection. Air leakage (10 mL) in the venous line of the ECC was simulated and compared to the effect of the same quantity of CO2 entering the circuit. Both models used whole blood priming and physiological conditions, verified with blood gas analyses. RESULTS: Fragmentation and dissolution of gas bubbles injected into a closed ECC could be demonstrated, complete resorption of CO2 bubbles was observed earlier than complete resorption of room air (5.0+/-0.6 vs. 14.4+/-5.9 min, p=0.0009). CO2 entering the venous line lead to 40% less arterial bubble load as compared to the same amount of room air entering the circuit (2099+/-991 vs. 3555+/-632, p=0.005). CONCLUSIONS: Current ECC systems fail to eliminate gas entering the circuit, leading rather to microbubble dispersion. CO2 is much faster resorbed within the circuit than room air. In open heart surgery as valvular operations, CO2 insufflation into the operative field is protective, as we have demonstrated in our models.

Air↗

The identification of right-to-left shunts using contrast transcranial Doppler ultrasound: performance and interpretation modalities, and absence of a significant side difference of cardiac micro-emboli.

Cardiac and extracardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) as well as by transcranial Doppler ultrasound (TCD) using contrast agents that do not pass the lungs. Currently, the appropriate performance of a Valsalva manoeuvre (VM) to provoke the shunt, the use of different contrast agents and the classification of the TCD results are still under debate. In this study, we looked also at possible side effects of provoked cardiac micro-emboli in the left and right hemisphere. Seventy-one patients were investigated by both TEE and bilateral TCD of the middle cerebral arteries. The following protocol was applied in a randomized way: (1) Echovist-300 without VM; (2) Echovist-300, VM for 5 seconds starting 5 seconds after the beginning of contrast injection; (3) repetitive short VMs in between 2 and 13 seconds after the beginning of Echovist-300 injection; and (4) repetitive short VMs in between 2 and 13 seconds after the beginning of agitated saline injection. Only if one of the tests (2-4) was negative, this particular negative test was repeated. Use of Echovist-300, but not of saline yielded 100% sensitivity in the detection of TEE-proven shunts. The repetitive VM was slightly superior to the conventional VM. Introduction of a threshold of two or even three microbubbles produced less falsely positive TCD results in comparison to the TEE. There was no difference in microbubbles. TCD using Echovist-300 is a sensitive method to identify TEE-proven cardiac right-to-left shunts. Repetitive VM is an alternative to conventional VM.

Adult↗

Characterization of the surface activity of a synthetic surfactant with albumin.

We previously reported that a human analogue of pulmonary surfactant protein-C (SP-C), SP-CL16 (6-28), with 23 residues was the most active analogue in a reconstituted lipid mixture and had the shortest chain among the poly leucine analogues examined. In this study, we verified the influence of albumin, a component of serum, on the surface activity of surfactant. Surface activity was measured using the Langmuir-Wilhelmy surface balance (WSB), pulsating bubble surfactometer (PBS), and stable microbubble test (MBT). The surface activity of synthetic lung surfactant (SLS) was only slightly influenced by albumin (0.1-10 mg/ml) as compared with that of a ternary mixture of phospholipids. The ternary mixture of phospholipids showed a decrease in surface activity due to albumin. In particular, SLS did not show interaction of surface activity with albumin in vitro (WSB, PBS, and MBT). In contrast, dipalmitoylphosphatidylcholine/phosphatidylglycerol/palmitic acid had significantly weaker surface activity in the presence of albumin. Surfactant-TA showed interaction of surface activity with albumin in the MBT. The number of stable microbubble increased in the presence of albumin at a concentration of 0.1 mg/ml.

Humans↗