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Objectives: To validate absolute measurement of myocardial blood flow (MBF) with 1.5 Tesla (T) and 3T cardiovascular magnetic resonance (CMR) using positron emission tomography (PET) as the gold standard. Methods: 21 healthy subjects and 44 patients with coronary artery disease (CAD) were randomised to undergo PET scanning using oxygen 15-labeled water and CMR scanning at either 1.5T or 3T, using a saturation recovery fast-gradient echo sequence and 0.04 mmol/kg gadolinium bolus. MBF was assessed at rest and during adenosine stress. CMR MBF was determined by model independent deconvolution Results: There was no significant difference in rest and stress rate pressure product during PET and CMR scanning at either field strength. Agreement between the two methods was tested by Bland Altman plots The mean difference between PET MBF and 3T CMR MBF was 0.30 ml/g/min, limits of agreement of -1.23 and 1.89 ml/g/min. For the 3T cohort the sensitivity and specificity for the detection of coronary stenoses ≥50 % was 87% and 81 % for PET (threshold 1.93 ml/g/min) and 61% and 78% (threshold 1.73 ml/g/min) for 3T CMR. The mean difference between PET and 1.5T CMR was 0.05 ml/g/min, limits of agreement of -1.75 and 1.84 ml/g/min. For the 1.5T cohort the sensitivity and specificity for the detection of coronary stenoses ≥50 % was 84% and 94% for PET (threshold 1.98 ml/g/min) and 81% and 78% (threshold 2.29ml/g/min) for CMR. Conclusion: This study demonstrates there is no significant difference in mean MBF as measured by PET and CMR at either 1.5T or 3T CMR. However there is marked variation in values of MBF between different segments as demonstrated by the wide limits of agreements.

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Current pharmacological therapies fail to address the final end-point of cardiac ischaemia — the death and dysfunction of cardiomyocytes. Advances in stem cell biology have provided hope, for the first time, of addressing this underlying pathology. The work performed here was designed to further understanding of the mechanisms by which bone marrow derived cells improve damaged myocardium. In situ hybridisation was used to detect sex chromosomes within ex-planted, human, sex-mismatch hearts. Host derived cells were found at low frequency in donor hearts, suggesting ongoing post-natal cardiac tissue repair. Human mesenchymal stem cells were examined in vitro and in a rat model of ischaemia-reperfusion injury. Cardiomyocytes were not formed when cultured with either 5-azacytidine or ascorbic acid, and the cells failed to home to the ischaemic heart or improve cardiac function. In the same model, rat mononuclear cells significantly reduced infarct size when administered immediately upon reperfusion. Cells were rarely identified within the myocardium. No functional improvement was seen acutely, but at seven days cardiac function had improved. The low frequency of cells retained in the heart suggested that a process other than transdifferentiation accounted for the observations. Hence, evidence for paracrine actions was sought. In the same model, apoptosis and necrosis in cardiomyocytes were found to be significantly reduced. Western blots demonstrated activation of the reperfusion salvage kinase pathway, analogous to that seen in ischaemic pre- and post-conditioning. Blocking this pathway abolished the infarct size reduction. Global proteomic analysis confirmed alterations in protein expression consistent with known cardioprotective pathways. In conclusion, endogenous myocardial repair processes are inadequate to compensate for pathological insults. Supplementation with mononuclear cells in an ischaemia-reperfusion model produced significant benefit to infarct size and cardiac function. The mechanism of benefit appears to be induced by paracrine effects activating pro-survival pathways.