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Nitrogen microbubbles induce a disappearance of single platelets (aggregation) with porcine platelets: a comparative study of the effects of anticoagulants and blood collection methods.

The pathogenesis of decompression illness (DCI) is uncertain. DCI involves all parts of the organism where gas bubbles are produced. They have both primary and secondary effects and have been classified as an agonist aggregating human platelets. In vitro effects of N2 bubbles on porcine platelets were investigated. Comparative studies using two different anticoagulants and three different sampling methods were performed. A disappearance of single platelets interpreted as platelet aggregation was observed in the presence of N2 bubbles in all studied groups. Aggregatory responses were more profound with platelets in heparinized plasma than in citrated plasma. In citrated plasma the aggregatory responses were more profound when blood was obtained from nonanaesthetized (awake) animals than from slaugtherhouse animals. Adrenaline (1 microM) had an inhibitory effect on N2 bubble induced platelet aggregation in vitro. The pig could be useful to investigate possible gas bubble effects in vivo.

Animals

Contrast agents for diagnostic ultrasound: development and evaluation of polymer-coated microbubbles.

Although the concept of an ultrasound contrast agent dates from Gramiak's work in 1968 in which indocyanine green was injected into the ascending aorta and heart, no universally accepted contrast agent for ultrasound now exists. This is primarily due to problems with stability, size and/or toxicity of the agents which have been investigated. Development of an effective ultrasound contrast agent would be highly significant for the health care industry, since it would greatly expand the scope of ultrasound (a noninvasive and safe procedure) as a diagnostic technique. While encapsulated gas bubbles offer particular advantages in stability over hand-agitated systems, they frequently present problems with size. Capsules larger than 10 microns in diameter become entrapped in the capillary bed of the lung. This paper describes the use of ionotropic gelation of the naturally occurring polysaccharide, alginate, for microencapsulation of air. Two procedures have been investigated. A novel jet head has been developed which allows co-extrusion of a solution of sodium alginate and air to produce nascent microencapsulated air bubbles which fall into a hardening solution of calcium ions. A second method employs ultrasound to introduce cavitation-induced bubbles into the alginate before capsule formation by spraying. Power spectra of these preparations demonstrate echogenicity (that is strong scatter of the incident ultrasound wave back to the emitting transducer, which also acts as a receiver), with resonant peaks that are a function of capsule size and wall characteristics.

Alginates

Echocardiographic contrast agents: effect of microbubbles and carrier solutions on left ventricular contractility.

Recently, there has been a resurgence of interest in the use of contrast-enhanced echocardiography as a means of noninvasively assessing myocardial perfusion. However, if injections of echocardiographic contrast agents are to be used for this purpose it is essential that they are not intrinsically toxic to the heart. In this study, the left ventricular end-systolic wall stress-rate-corrected velocity of fiber shortening relation, a load independent index of contractility, was studied in nine dogs. Two-dimensional and targeted M-mode echocardiographic as well as central aortic pressure tracings were made during echocardiographically gated, pressure- and volume-controlled aortic root injections of nonsonicated and sonicated Renografin-76, saline and dextrose 70% (n = 6), and sonicated and hand-agitated Renografin-76/saline mixture (n = 5). Two of nine dogs received all agents. Off-line computer videodensitometric analysis documented myocardial perfusion. In all cases, data were obtained at control and 5 and 15 seconds after injection. Additional data were collected at 25 seconds after injection for the Renografin-76/saline mixture. Alterations in contractility were measured relative to control as changes in rate-corrected velocity of fiber shortening after afterload (measured as end-systolic wall stress) was eliminated as a confounding variable. Under no condition did saline or Renografin-76 cause alterations in left ventricular contractility. Nonsonicated and sonicated dextrose 70% increased left ventricular contractility at 15 seconds but not at 5 seconds after injection. Hand-agitated Renografin-76/saline mixture induced a negative inotropic effect at 5 and 15 seconds after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Myocardial contrast echocardiography in acute myocardial infarction using aortic root injections of microbubbles in conjunction with harmonic imaging: potential application in the cardiac catheterization laboratory.

OBJECTIVES: The aim of this study was to evaluate myocardial contrast echocardiography using aortic root injections with harmonic imaging in experimental acute myocardial infarction to determine the potential of this approach in the cardiac catheterization laboratory. BACKGROUND: It would be desirable to have an adjunctive procedure that could evaluate myocardial perfusion at the time of cardiac catheterization in patients with acute myocardial infarction. A single injection of contrast medium in the aortic root would provide complete information on myocardial perfusion in a cross section of the heart. High quality images would provide on-line assessment of myocardial perfusion without recourse to image processing. These data could be very valuable for determining patient management. METHODS: Perfusion defects on myocardial contrast echocardiography were measured during coronary occlusion and reflow, using fundamental and harmonic imaging in both continuous and intermittent modes in nine open chest dogs. These defects were compared with risk area on technetium-99m autoradiography and infarct size on tissue staining. RESULTS: Whereas harmonic imaging increased myocardial video intensity by more than twofold (p < 0.001) compared with fundamental imaging after aortic root injection of contrast medium, intermittent imaging was not superior to continuous imaging. The improved signal to noise ratio of harmonic imaging allowed on-line definition of risk area (r = 0.98) and infarct size (r = 0.93) without recourse to off-line processing. Similar results could be obtained with fundamental imaging only after off-line processing. CONCLUSIONS: Aortic root injection of contrast medium coupled with harmonic imaging can be used to provide accurate on-line assessment of risk area and infarct size during acute myocardial infarction. These results have important implications for the catheterization laboratory.

Adenosine

Reduction in left ventricular cavitary attenuation and improvement in posterior myocardial contrast with higher molecular weight intravenous perfluorocarbon-exposed sonicated dextrose albumin microbubbles.

Although intravenous perfluoropropane-exposed sonicated dextrose albumin (C3SDA) produces myocardial contrast, the posterior myocardium cannot be visualized with epicardial or transthoracic imaging because of excessive left ventricular cavitary contrast. We hypothesized that higher molecular weight, less diffusible gases such as perfluoropentane-exposed sonicated dextrose albumin (C5SDA) would produce equivalent anterior myocardial contrast at lower intravenous doses with less cavitary attenuation. To test this hypothesis, we compared the anterior and posterior peak myocardial videointensity after 0.06 ml/kg intravenous injections of C3SDA and 0.015 to 0.030 ml/kg intravenous injections of C5SDA in seven open-chest dogs. The ability of C5SDA to detect posterior myocardial perfusion abnormalities was also tested. Despite the lower dose, intravenous C5SDA produced equivalent anterior myocardial contrast but significantly higher posterior myocardial contrast (2.6 +/- 1.9 units peak myocardial videointensity C5SDA versus 0.6 +/- 0.9 units C3SDA; p < 0.0001) because of less acoustic shadowing. The visual detection of posterior ischemia with intravenous C5SDA was also significantly improved. We conclude that increasing the molecular weight of the perfluorocarbon gas in sonicated dextrose albumin will significantly improve the detection of posterior perfusion abnormalities.

Animals

In vivo microbubble detection in decompression sickness using a second harmonic resonant bubble detector.

A resonant bubble detection method based on a second harmonic technique has been used to monitor the femoral vascular system of dogs subjected to rapid decompression. For this study, the detector consisted of two acoustic transducers mounted at right angles to each other that were packaged in a perivascular cuff configuration. This detector responds selectively only to bubbles near resonant size (4.2 mum in diameter); solid particles and large bubbles produce no response. The detector was used to monitor a total of 15 dogs. Eleven dogs were subjected to a series of simulated underwater dives until acute symptoms of decompression sickness occurred; 4 dogs served as controls. In the dived group, either the femoral vein or the femoral artery was monitored. Resonant bubbles were observed in the femoral veins of all 6 dogs monitored at this location. During arterial monitoring, most dogs showed no response, but an occasional weak response was observed in 2 of the dogs. No resonant bubbles were detected in the femoral artery or the femoral vein in any of the controls. The data suggest that this bubble detection method is feasible for in vivo use. Furthermore, 4 mum diameter bubbles are much more prevalent in the veins of dogs suffering from decompression sickness than they are in dog arteries, presumably because they are filtered out effectively by the pulmonary circulation. Modifications of this method are discussed to enhance its accuracy and applicability for quantifying bubble size, location, and number.

Animals