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Silent MI occurred in 8.2% of patients presenting with first AMI and was independently related to poorer long-term clinical outcome, with a more than 3-fold risk of mortality and MACE. Silent MI holds prognostic value over important traditional prognosticators in the setting of AMI, indicating that these patients represent a high-risk subgroup warranting clinical awareness.

Exenatide did not reduce myocardial infarct size expressed as a percentage of AAR in ST elevated myocardial infarction patients successfully treated with percutaneous coronary intervention.

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Coronary intervention for myocardial infarction often results in microvascular embolization of thrombus. Sonoreperfusion therapy (SRP) using ultrasound and microbubbles restored perfusion in our in vitro flow model of microvascular obstruction. In this study, we assessed SRP efficacy using whole blood as the perfusate with and without tissue plasminogen activator (tPA). In a phantom vessel bearing a 40-μm pore mesh to simulate the microvasculature, microthrombi were injected to cause microvascular obstruction and were treated using SRP. Without tPA, the lytic rate increased from 2.6±1.5 mmHg/min with 1000 cycles to 7.3±3.2 mmHg/min with 5000 cycles ultrasound pulses (p<0.01). The lytic index was similar between tPA-only [(2.0±0.5)×10−3 mmHg−1min−1] and 5000 cycles without tPA [(2.3±0.5)×10−3 mmHg−1min−1] (p=0.5) but increased [(3.6±0.8)×10−3 mmHg−1min−1] with tPA in conjunction with 5000 cycles ultrasound (p<0.01). In conclusion, SRP restored microvascular perfusion in whole blood and SRP lytic rate in experiments without tPA increased with ultrasound pulse length and efficacy increased with the addition of tPA.

a b s t r a c tIntroduction: Current treatment of patients with an acute occlusion of a cranial or a coronary artery, in for example ST segment elevation myocardial infarction (STEMI), consists of either thrombolysis or percutaneous intervention. Various thrombolytic agents (tissue plasminogen activators) are used for reperfusion therapy in patients with STEMI. However, their use may be associated with an increased risk of bleeding which is inherent to their action mechanism. Therefore, new methods of coronary clot resolution are being studied in an attempt to potentiate the efficacy and reduce the side effects of thrombolytics. A new method is ultrasound mediated thrombus dissolution, or sonothrombolysis. The current literature exploring sonothrombolysis is diverse in size and quality. In this systematic review of the current literature, we describe cardiovascular applications of sonothrombolysis in patients. A comparison to the neurovascular application in ischemic stroke is made, as more research has been performed on patients suffering from stroke. Methods: A systematic search was performed following the PRISMA guidelines using EMBASE and MEDLINE databases regarding sonothrombolysis in human ischemic stroke and acute myocardial infarction patients. Results: 12 original case-control or randomized controlled trials using a combination of ultrasound and microbubbles were found. 6 trials studied ischemic stroke, and 6 trials studied acute myocardial infarction. Conclusion: This systematic review provides up to date information on the subject of sonothrombolysis.

Purpose: Intra-arterial administration of microbubbles (MBs) through an ultrasound (US) catheter increases the local concentration of MBs into the thrombus and may further enhance outcomes of contrast-enhanced sonothrombolysis (CEST). The objective of this study was to evaluate the feasibility and lytic efficacy of intra-arterial infusion of MBs during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models. Materials and Methods: SonoVue and Luminity MBs were infused at a flow rate of 20 mL/h through either the drug delivery lumen of the US catheter (DDC, n=20) or through the tube lumen of the vascular phantom (systematic infusion, n=20) during thrombolysis with a low-dose urokinase (UK) protocol (50 000 IU/h) with(out) US application to assess MB survivability and size by pre-treatment and post-treatment measurements. A human thrombus was placed into a vascular phantom of the flow system to examine the lytic effects of CEST by post-treatment D-dimer concentrations measurements of 5 treatment conditions (saline, UK, UK+US, UK+US+SonoVue, and UK+US+Luminity). Thrombolytic efficacy of localized MBs and US delivery was then investigated in vivo in 5 porcine models by arterial blood flow, microcirculation, and postmortem determined thrombus weight and remaining length. Results: US exposure significantly decreased SonoVue (p=0.000) and Luminity (p=0.000) survivability by 37% and 62%, respectively. In vitro CEST treatment resulted in higher median D-dimer concentrations for the SonoVue (0.94 [0.07–7.59] mg/mL, p=0.025) and Luminity (0.83 [0.09–2.53] mg/mL, p=0.048) subgroups when compared with thrombolysis alone (0.36 [0.02–1.00] mg/mL). The lytic efficacy of CEST examined in the porcine model showed an improved median arterial blood flow of 21% (7%–79%), and a median thrombus weight and length of 1.02 (0.96–1.43) g and 2.25 (1.5–4.0) cm, respectively. One allergic reaction and 2 arrhythmias were observed due to the known allergic reaction on lipids in the porcine model. Conclusion: SonoVue and Luminity can be combined with an US catheter and could potentially accelerate thrombolytic treatment of peripheral arterial occlusions. Clinical Impact Catheter-directed thrombolysis showed to be an effective alternative to surgery for acute peripheral arterial occlusions, but this technique is still associated with several limb and life-threatening complications. The effects of thrombolysis on clot dissolution may be further enhanced by intra-arterial administration of microbubbles through an ultrasound catheter. This study demonstrates the feasibility and lytic efficacy of intra-arterial infusion of microbubbles during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models.

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