Chronic heart failure is the major contributor to today's mortality and morbidity. It forms the final pathway for most heart disease forms among which coronary heart disease is the common contributor. The advent of revascularization along with the advances in pharmacologic treatments including beta-blockers, angiotensin-converting enzyme, also called as ACE inhibitors, and spironolactone have not been able to curb the impact of chronic heart failure on mortality and morbidity.
New therapies such as cell transplantation for the replacement or repair of damaged tissue following cardiac arrest are becoming increasingly popular in the battle to hinder post-infarct congestive heart failure (CHF). In addition, the imbalance in the supply and demand of transplant organs has made cellular therapy a welcome choice to organ transplantation and problems pertaining to chronic immunosuppression.
Assessing Viability of Cell with PET
The common protocol used for tissue viability evaluation with PET includes various assessments of regional myocardial Rubidium or [O]-water, perfusion with [N]-ammonia followed by the glucose uptake with [F]-FDG, thus providing an indicator of myocardial metabolism and cell viability.
Normal myocardium employs several energy-producing substrates in order to satisfy its energy requirements. Free Fatty Acids (FFA), in the fasting state, are mobilized in large quantities from the triglycerides that are stored in the adipose tissue. Thus, the FFA availability in plasma has made them as myocardium's most preferred energy-producing fuel. The increase in plasma glucose level and insulin level, in the fed state, tend to reduce the release of FFA from the adipose tissue. Glucose transporters (example, GLUT 4) are mobilized by the increased insulin levels onto the cell membrane. This results in an increased utilization and transportation of exogenous glucose by myocardium.
The metabolism of FFA through beta-oxidation in the mitochondria depends on the availability of oxygen and thus, suffers a sharp decline during myocardial ischemia. Studies in human and animal experiments, under this condition, have shown that there is an increased uptake and glucose metabolism by the ischemic myocardium. This glucose uptake plays an important role in the survival of compromised myocytes as high-energy phosphates maintain the basic cellular functions.
Non-invasive approaches that assess exogenous glucose utilization play a critical role in the tissue viability evaluation in patients suffering from myocardial dysfunction because of CAD. These adaptations require sufficient nutrient perfusion to supply energy-rich substrates (example, glucose) and oxygen, and for the removal of glycolysis byproducts (example, hydrogen ion and lactate). A stern and prolonged reduction in the myocardial blood flow quickly precipitates the depletion of high-energy phosphate, cell membrane disruption, and subsequent death of the cells.
Since dysfunctional myocardial improves in function after the process of revascularization and must retain substantial blood flow and metabolic activity in order to sustain myocyte viability, the combined assessment of glucose metabolism and regional blood flow appear the most attractive option for myocardial viability. In this approach, the evaluation of myocardial perfusion is done following the administration of Rubidium or [O]-water, [N]-ammonia; the FDG assess the regional glucose uptake thereby providing an indicator of myocardial metabolism and cell viability. Following the intravenous administration, FDA traces the glucose transport across the myocyte membrane and the phosphorylation mediated by hexokinase to FDG-6-phosphate.
Preparing Patients for FDG Imaging
The utilization of energy-rich substrates by the heart muscle is a function based on their concentration in the hormone levels (insulin/glucagon ration, catecholamines, plasma insulin, and growth hormone) and plasma and also the availability of oxygen for oxidative metabolism. The approaches for FDG imaging include:
• Glucose Loading
• Hyperinsulinemic-Euglycemic Clamp
PET Patterns- Myocyte Viability
With the help of FDG-sequential approach, four separate metabolism-perfusion patterns are observed in dysfunctional myocardium:
• Normal FDG uptake associated with normal perfusion
• Reduced perfusion associated with improved or preserved FDG uptake thereby reflecting myocardial viability
• Reduction in FDG and perfusion uptake thereby reflecting non-viable myocardium
• Normal perfusion with decreased FDG uptake
The metabolism and normal perfusion pattern or of a PET mismatch identifies cell viability, while the PET match pattern recognizes irreversible myocardial dysfunction. The FDG-reversed perfusion mismatch is often described in patients with left-bundle branch block and in repetitive myocardial stunning. Quantitating the FDG-tracer uptake and regional myocardial perfusion along with their difference is helpful in assessing the viability magnitude.
PET imaging has provided insights into the success and failure of cell therapy; aiming at improving the therapy for patients under this difficult group.
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