This thesis describes the development of new magnetic resonance imaging (MRI) methods to characterize cardiac tissue with myocardial infarction (MI). Wall motion imaging (for visualizing myocardial contraction) and viability imaging (to identify MI) are two components of cardiac tissue characterization used for prognosis and treatment planning. MRI-based wall motion and viability methods are considered the gold standard in imaging, and characterization of MRI viability images has been correlated with inducibility for ventricular tachycardia (VT). However, viability imaging with MRI has limitations such as difficulty visualizing the blood-infarct border. Wall motion and viability images are acquired separately, each requiring cardiac gating and breath holds, leading to long scan times. A novel multi-contrast delayed enhancement (MCDE) sequence was developed that simultaneously acquires wall motion and viability images. In a patient study, the MCDE sequence was demonstrated to provide improved visualization of MI compared to the conventional inversion-recovery gradient echo (IR-GRE) sequence, particularly for small infarcts adjacent to the blood pool. MCDE images also provided accurate wall motion images that could be used to calculate the left ventricular ejection fraction. An image processing algorithm was developed to analyze MCDE images to segment and classify the infarct gray zone, which is hypothesized to represent heterogeneous infarct responsible for causing VT. In a study of 15 patients with MI, the MCDE-derived gray zone was shown to be less sensitive to image noise than the IR-GRE-derived gray zone, and did not require manual contours of the blood pool which contributes to additional variability in the IR-GRE gray zone analysis. Finally, a real-time delayed enhancement (RT-DE) method was developed to provide black-blood viability images without requiring cardiac gating or breath holds. RT-DE imaging was shown to have a high sensitivity for detecting MI in a study of 23 patients. The methods described in this thesis help expand the patient population that can undergo a cardiac viability exam and help improve the visualization of myocardial infarct. Further modifications in the pulse sequences to improve the temporal and spatial resolutions are proposed with the goal of predicting and guiding treatment of ventricular tachycardia resulting from myocardial infarct.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 206-224).

Thesis--Columbia University. / Photocopy of typescript. Ann Arbor, Mich. : University Microfilms International, 1977. -- 21 cm. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 160-168).

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Objectives: When used as a cardioplegic solution, Custodiol® HTK solution is typically administered in a single-dose, allowing the operation to be performed continuously. This is an advantage over alternative cardioplegic solutions that may have to be re-administered every 20-30 minutes. Although Custodiol is widely used as a cardioplegic solution in Europe, its use for myocardial protection remains an off-label indication in the United States. Thus, the aim of this study is to compare the efficacy of Custodiol to standard 4:1 blood cardioplegia in adult cardiac cases. METHODS: This study was a single-center retrospective review of prospectively collected data. Adult cardiac cases performed between November 2011 and August 2013 using Custodiol® were compared to cases using standard Plegisol® 4:1 blood cardioplegia. Twenty-six primary intra-operative and post-operative endpoints were compared including 30-day mortality, 30-day hospital readmission, prolonged mechanical ventilation time, and renal failure. RESULTS: Of the 229 cases identified, 63 cases used Custodiol and 166 used 4:1 blood cardioplegia. Demographics were similar in both groups with a mean patient age of 65.27±15.07 years for Custodiol and 66.72±12.85 years for 4:1 blood cardioplegia. The average cardiopulmonary bypass time for Custodiol and 4:1 blood cardioplegia was 124.76±61.45 and 137.93±54.05 minutes respectively. The Custodiol group had a greater incidence of prolonged ventilation (>24 hours), 20.6% versus 15.1% respectively, and this approached statistical significance with a p value of 0.052. Intra-operative blood usage was significantly higher in the Custodiol group compared to the blood cardioplegia group, with 44.4% of patients receiving fresh frozen plasma during the operation compared to only 25.3% in the blood cardioplegia group (p=0.005). The results revealed no statistically significant difference in 30-day mortality, 30-day hospital readmission, renal failure, and stroke. CONCLUSION: Despite the distinct advantage of long-term ischemic tolerance, Custodiol use was associated with an increased requirement for fresh frozen plasma during the perioperative period when compared to blood cardioplegia.

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This thesis is concerned with the influence of acute and long-term beta-adrenergic blockade on myocardial infarction in man. An original statistical evaluation of all published and some available unpublished clinical trials is presented in Chapter I. Chapter III and TV concern the measurement and evolution of infarct size in man. In Chapter III, praecordial ECG mapping and the standard 12 lead ECG have been correlated with cumulative release of the MB isomer of creatine kinase. Using these techniques, I have found that approximately 50% of eventual infarction is complete in 6 hours; implying that interventions designed to salvage ischaemic myocardium may be feasable (Chapter IV). In Chapter V, I have demonstrated delayed beta-adrenergic blockade after oral administration of atenolol and that an initial intravenous dose is essential to achieve early and effective beta-blockade. In a randomised control trial of 215 patients, atenolol administered intravenously within 12 hours of pain, prevented infarction in treated patients with initial threatened infarcts and reduced infarct size and morbidity in those with initial definite infarcts (Chapter VI). Patients with anterior myocardial infarction, randomised to receive atenolol for a year, showed significantly greater R wave recovery and Q wave disappearance on serial praecordial maps compared to placebo patients. In a further study, this was demonstrated to be due to lowering the heart rate. This phenomenon of improved EGG recovery with atenolol was reproduced in experimental infarction and was shown to be due to improved scar shrinkage (Chapter VII). The implications of these studies are discussed. It is likely that both early and long-term beta-blockade will be beneficial to patients with myocardial infarction.

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