The relationship between disease-related characteristics and conduction disturbances in ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is associated with an increased cardiovascular (CV) risk. Conduction disturbances (CD) may explain the CV burden, as they are independently associated with cardiac disease. The aim of this study was (i) to determine the prevalence of CD in AS, and (ii) to evaluate the relationship between CD and demographic and AS-related characteristics. METHODS: A rheumatological evaluation assessing demographic and AS-related characteristics and a resting standard 12-lead electrocardiogram (ECG) were performed in 131 consecutive AS patients. RESULTS: A first-degree atrioventricular (AV) block was found in six (4.6%) patients. One (0.8%) patient suffered from a complete right bundle branch block (RBBB) and one (0.8%) patient had a left anterior hemiblock. A prolonged QRS (pQRS) interval was observed in 38 (29.2%) patients, including those with a complete or incomplete BBB. Age, disease duration, and body mass index (BMI) were significantly associated with the PR interval, and male gender, disease duration, and the Bath Ankylosing Spondylitis Metrology Index (BASMI) with the QRS interval. In multivariate analyses, disease duration remained independently associated with both the PR and the QRS intervals. CONCLUSION: Intraventricular CD is highly prevalent in AS, particularly in patients with long-standing disease. Further research is needed to determine whether intraventricular CD contribute to the increased CV risk and long-term CV mortality in AS.

Safety and feasibility of real time adenosine myocardial contrast echocardiography with emphasis on induction of arrhythmias: a study in healthy volunteers and patients with stable coronary artery disease.

INTRODUCTION: Some studies reported an increased incidence of premature ventricular complexes (PVCs) during triggered myocardial contrast echocardiography (MCE) using high-intensity ultrasound destruction. Whether PVCs are also induced by real time MCE using low emission power, is unknown. The aim of the study was to assess the occurrence of arrhythmias during real time adenosine MCE in healthy volunteers and patients with stable coronary artery disease (CAD). METHODS: Fifty healthy volunteers and 26 patients with stable CAD underwent real time MCE using Sonovue and power pulse inversion (ATL 5000) at rest and during adenosine stress. The occurrence of premature atrial complexes (PAC) and PVCs was analyzed before and during MCE using ECG-tracings from videotapes. RESULTS: In healthy subjects, the occurrence of PVCs at baseline (0.04 +/- 0.23 PVCs/min) was similar at rest (0.04 +/- 0.23 PVCs/min, P = NS), and adenosine stress (0.03 +/- 0.14, P = NS). In CAD patients, the occurrence of PVCs at baseline was 0.30 +/- 0.76 PVC/min, compared to 0.29 +/- 0.74 at rest (P = NS), and 0.34 +/- 0.74 during adenosine stress (P = NS). The number of subjects demonstrating PVCs did not increase during MCE. The occurrence of PACs during MCE was not increased compared to baseline. CONCLUSION: Real time MCE using low emission power does not increase the occurrence of premature complexes in healthy volunteers or CAD patients.

Transient permeabilization of cell membranes by ultrasound-exposed microbubbles is related to formation of hydrogen peroxide.

In the present study, we addressed the interactions among ultrasound, microbubbles, and living cells as well as consequent arising bioeffects. We specifically investigated whether hydrogen peroxide (H(2)O(2)) is involved in transient permeabilization of cell membranes in vitro after ultrasound exposure at low diagnostic power, in the presence of stable oscillating microbubbles, by measuring the generation of H(2)O(2) and Ca(2+) influx. Ultrasound, in the absence or presence of SonoVue microbubbles, was applied to H9c2 cells at 1.8 MHz with a mechanical index (MI) of 0.1 or 0.5 during 10 s. This was repeated every minute, for a total of five times. The production of H(2)O(2) was measured intracellularly with CM-H(2)DCFDA. Cell membrane permeability was assessed by measuring real-time changes in intracellular Ca(2+) concentration with fluo-4 using live-cell fluorescence microscopy. Ultrasound, in the presence of microbubbles, caused a significant increase in intracellular H(2)O(2) at MI 0.1 of 50% and MI 0.5 of 110% compared with control (P < 0.001). Furthermore, we found increases in intracellular Ca(2+) levels at both MI 0.1 and MI 0.5 in the presence of microbubbles, which was not detected in the absence of extracellular Ca(2+). In addition, in the presence of catalase, Ca(2+) influx immediately following ultrasound exposure was completely blocked at MI 0.1 (P < 0.01) and reduced by 50% at MI 0.5 (P < 0.001). Finally, cell viability was not significantly affected, not even 24 h later. These results implicate a role for H(2)O(2) in transient permeabilization of cell membranes induced by ultrasound-exposed microbubbles.

Adverse reactions to ultrasound contrast agents: is the risk worth the benefit?

The introduction of ultrasound contrast agents has led to a marked improvement in diagnostic capabilities in echocardiography. As no serious adverse events were seen during the preclinical development phase, ultrasound contrast agents were thought to be safe. Recently, three fatal and 19 severe, non-fatal adverse reactions were reported in a post marketing analysis of more than 150,000 studies of Sonovue, which has led to the addition of several contra-indications for the use of this ultrasound contrast agent. Although a strong relationship was established between the non-fatal cases and administration of Sonovue, a causal relationship between the fatal cases and the use of Sonovue is debatable. Therefore, the risk associated with the use of this ultrasound contrast agent should be judged carefully, taking into consideration the prevalence of adverse effects of other contrast media and diagnostic procedures used in cardiology.

Microbubbles and ultrasound: from diagnosis to therapy.

The development of ultrasound contrast agents, containing encapsulated microbubbles, has increased the possibilities for diagnostic imaging. Ultrasound contrast agents are currently used to enhance left ventricular opacification, increase Doppler signal intensity, and in myocardial perfusion imaging. Diagnostic imaging with contrast agents is performed with low acoustic pressure using non-linear reflection of ultrasound waves by microbubbles. Ultrasound causes bubble destruction, which lowers the threshold for cavitation, resulting in microstreaming and increased permeability of cell membranes. Interestingly, this mechanism can be used for delivery of drugs or genes into tissue. Microbubbles have been shown to be capable of carrying drugs and genes, and destruction of the bubbles will result in local release of their contents. Recent studies demonstrated the potential of microbubbles and ultrasound in thrombolysis. In this article, we will review the recent advances of microbubbles as a vehicle for delivery of drugs and genes, and discuss possible therapeutic applications in thrombolysis.

Local drug and gene delivery through microbubbles and ultrasound.

Although gene therapy has great potential as a treatment for diseases, clinical trials are slowed down by the development of a safe and efficient gene delivery system. In this review, we will give an overview of the viral and nonviral vehicles used for drug and gene delivery, and the different nonviral delivery techniques, thereby focusing on delivery through ultrasound contrast agents. The development of ultrasound contrast agents containing encapsulated microbubbles has increased the possibilities not only for diagnostic imaging, but for therapy as well. Microbubbles have been shown to be able to carry drugs and genes, and destruction of the bubbles by ultrasound will result in local release of their contents. Furthermore, ligands can be attached so that they can be targeted to a specific target tissue. The recent advances of microbubbles as vehicles for delivery of drugs and genes will be highlighted.