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Histological characterization of microlesions induced by myocardial contrast echocardiography
Douglas L Miller1, Peng Li, David Gordon
1Department of Internal Medicine (Cardiology), University of Michigan, Ann Arbor, Michigan 48109-0553, USA. douglm@umich.edu
Background:
Myocardial contrast echocardiography (MCE) has been shown to have a potential for apparently reversible side effects related to the interaction of ultrasound with the contrast microbubbles, including premature ventricular contractions and microvascular leakage. We investigated the potential for high-dose MCE to induce histologically definable microlesions.
Methods:
Myocardial contrast echocardiography with 1:4 end-systolic triggering was performed at 1.5 MHz and 1.7 mechanical index in a short axis view of the left ventricle in rats. Two high doses (500 microl/kg) of Optison agent were given 5 minutes apart during 10 minutes of echocardiography. For histology, the hearts were perfused and fixed in 10% neutral-buffered formalin. Slides from rats sacrificed 1 day after MCE were scored blind by a pathologist, and, in addition, photomicrographs in the anterior half were evaluated by digital image analysis.
Results:
In rats sacrificed 10 minutes after MCE, microvascular leakage and petechiae were highly significant. However, lesions displaying necrotic debris associated with inflammatory infiltrates were not histologically evident at this time. Heart samples 24 hours after MCE showed microlesions with inflammatory infiltrates scattered primarily over the anterior half of the sections. Pathologically, there was inflammatory cell infiltration in areas of 0.6 +/- 0.5% for shams and 3.6 +/- 3.6% for MCE (P < 0.01). Analysis of photographs from the anterior wall found microlesion areas of 0.5 +/- 0.8% for shams and 7.4 +/- 5.0% for MCE (P < 0.02). For rats sacrificed 1 week and 6 weeks after MCE, the microlesions healed to form small fibrous regions interspersed with normal myocytes.
Conclusion:
High-dose MCE has a potential for causing microscale lesions in the myocardium and the possibility of therapeutic applications.
Insights
High-dose myocardial contrast echocardiography (MCE) can cause temporary microscale lesions in the heart. These myocardial microlesions heal over time, suggesting potential therapeutic applications for MCE.
Area of Science:
- Cardiology
- Medical Imaging
- Ultrasound Technology
Background:
- Myocardial contrast echocardiography (MCE) may cause reversible side effects like premature ventricular contractions and microvascular leakage.
- The interaction between ultrasound and contrast microbubbles is implicated in these MCE side effects.
- This study investigates the potential for high-dose MCE to induce histologically observable microlesions in the myocardium.
Purpose of the Study:
- To assess the histological impact of high-dose myocardial contrast echocardiography (MCE) on myocardial tissue.
- To determine if MCE can induce microlesions in the myocardium.
- To explore potential therapeutic applications of MCE based on observed effects.
Main Methods:
- Myocardial contrast echocardiography (MCE) was performed on rats using Optison agent at high doses (500 microl/kg) with specific ultrasound parameters (1.5 MHz, 1.7 MI).
- Hearts were collected at various time points (10 minutes, 1 day, 1 week, 6 weeks) post-MCE for histological analysis.
- Histological slides were evaluated by a pathologist and through digital image analysis to quantify microlesions and inflammatory infiltrates.
Main Results:
- Significant microvascular leakage and petechiae were observed 10 minutes after high-dose MCE.
- Histologically evident microlesions with inflammatory infiltrates appeared 24 hours post-MCE, with significantly higher inflammatory cell infiltration and microlesion areas in MCE-treated rats compared to shams (P < 0.01 and P < 0.02, respectively).
- By 1 week and 6 weeks post-MCE, microlesions healed into small fibrous regions interspersed with normal myocytes.
Conclusions:
- High-dose myocardial contrast echocardiography (MCE) can induce microscale lesions in the myocardium.
- These induced myocardial microlesions demonstrate a healing process over several weeks.
- The findings suggest potential therapeutic applications for MCE, warranting further investigation.
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