delivery-cardioactive-therapeutics-porcine-myocardial-infarction

Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model

Myocardial infarction is one of the leading causes of death and disability worldwide, and there is an urgent need for novel cardioprotective or ...

The University of Sydney

Westmead hospital

Bone marrow transplantation (BMT) has significantly improved survival rates in various hematological malignancies. However, this has led to an increased prevalence of long-term cardiotoxicity, particularly in those with prior anthracycline (AC) therapy.

Left atrial strain in cardiac surveillance of bone marrow transplant patients with prior anthracycline exposure.

Breath-held (BH) cardiac magnetic resonance imaging (CMR) is the gold standard for volumetric quantification. However, large animals for pre-clinical research are unable to voluntarily breath-hold, necessitating general anaesthesia and mechanical ventilation, increasing research costs and affecting cardiovascular physiology. Conducting CMR in lightly sedated, free-breathing (FB) animal subjects is an alternative strategy which can overcome these constraints, however, may result in poorer image quality due to breathing motion artefact. We sought to assess the reproducibility of CMR metrics between FB and BH CMR in a porcine model of ischaemic cardiomyopathy. FB or BH CMR was performed in 38 porcine subjects following percutaneous induction of myocardial infarction. Analysis was performed by two independent, blinded observers according to standard reporting guidelines. Subjective and objective image quality was significantly improved in the BH cohort (image quality score: 3.9/5 vs. 2.4/5; p < 0.0001 and myocardium:blood pool intensity ratio: 2.6-3.3 vs. 1.9-2.3; p < 0.001), along with scan acquisition time (4 min 06 s ± 1 min 55 s vs. 8 min 53 s ± 2 min 39 s; p < 0.000). Intra- and inter-observer reproducibility of volumetric analysis was substantially improved in BH scans (correlation coefficients: 0.94-0.99 vs. 0.76-0.91; coefficients of variation: < 5% in BH and > 5% in FB; Bland-Altman limits of agreement: < 10 in BH and > 10 in FB). Interstudy variation between approaches was used to calculate sample sizes, with BH CMR resulting in greater than 85% reduction in animal numbers required to show clinically significant treatment effects. In summary, BH porcine CMR produces superior image quality, shorter scan acquisition, greater reproducibility, and requires smaller sample sizes for pre-clinical trials as compared to FB acquisition.

Comparative assessment of motion averaged free-breathing or breath-held cardiac magnetic resonance imaging protocols in a porcine myocardial infarction model.

Tejas Deshmukh

Centre for Heart Research,
The Westmead Institute for Medical Research,
Centre for Heart Research, The Westmead Institute for Medical Research

The University of Sydney

Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model

Tejas Deshmukh

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The University of Sydney

Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model

Centre for Heart Research,
The Westmead Institute for Medical Research,
Centre for Heart Research, The Westmead Institute for Medical Research