Regional myocardial perfusion : experimental and clinical studies in patients with coronary artery disease

Doctoral Thesis


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University of Cape Town

Coronary artery disease has become a world wide medical problem. There is an overwhelming association between coronary atherosclerosis, angina pectoris, acute myocardial infarction and sudden death. The narrowing of coronary arteries is thought to damage the heart by limiting appropriate changes in coronary blood flow and by causing myocardial ischemia. This thesis attempts to examine the coronary circulation in patients who present with chest pain with and without coronary artery disease. One of the aims of this thesis is to validate the use of a short-lived radionuclide to study changes in regional myocardial perfusion. This technique has been applied in clinical medicine in an attempt to describe the disturbances of regional myocardial perfusion that occur in patients with coronary artery disease. These disturbances of perfusion have been related to the patients' symptoms, the electrocardiogram and the stenosed arteries seen in the arteriogram. Krypton-81m in solution is an inert freely diffusible gas (half-life 13 seconds) which emits a single 190 kev gamma ray. This tracer, a special catheter and a gamma camera have been developed in experiments to measure changes in regional myocardial perfusion. The systematic and rand-Om errors of the method have been defined in experiments. The results show that the mixing and delivered arterial concentration of krypton-81m are stable within a useful physiological range of changes in heart rate, blood pressure and coronary blood flow. Correlations with a reference technique have shown that the method can measure changes in regional myocardial perfusion between O and 3 ml/ml/min. The invasive method, the planar imaging and the need for calibration with washout at high levels of perfusion are investigated and described as limitations that must be considered. Eighty patients presenting with chest pain have been investigated by routine clinical methods, precordial mapping of the electrocardiogram during exercise and coronary arteriography. Changes in regional myocardial perfusion at rest and during atrial pacing has been measured using krypton-81m. The results have shown that stable mixing and delivered arterial concentration of krypton-81m can be achieved in the patients. Fifteen patients with negative exercise tests all demonstrated uniform increases in regional myocardial perfusion with pacing. The remaining 65 patients with positive exercise tests and significant coronary artery disease all showed both regional increases and decreases in myocardial perfusion during atrial pacing. In 16 of the 65 patients the jeopardized segment of ventricular myocardium showed significant increases in perfusion during the first 4 to 7 minutes of pacing. Th e increase stopped and regional perfusion in the affected segment then decreased progressively until the pacing was stopped. In 23 of the 65 patients the affected segment showed no changes in perfusion for 5 to 7 minutes of atrial pacing and then showed progressive decreases in regional myocardial perfusion until the pacing was stopped. Finally, in 26 of the 65 patients the affected segment showed immediate and progressive decreases of regional myocardial perfusion starting with the commencement of atrial pacing. In all the patients with disturbed perfusion ST segment depression in the electrocardiogram appeared after (140 ± 14 sec) the regional decrease of myocardial perfusion in the affected segment. Chest pain always appeared later at 220 ± 19 sec after the appearance of disturbed myocardial perfusion. Regional myocardial perfusion returned to normal in all the patients after the atrial pacing was stopped. There was a spatial relationship between the region of the ventricles affected by disturbed perfusion and the region of the precordium showing abnormal electrocardiographic signs during the exercise test. In conclusion, this clinical study has shown that patients with chest pain who have coronary artery disease suffer decreases of regional myocardial perfusion in affected segments of the ventricles during episodes of angina pectoris induced by atrial pacing. Regional perfusion may increase, remain stable or decrease in the affected segment following the onset of a stress test such as atrial pacing. This probably represents the amount of reserve function and adaptation left in the diseased coronary circulation and may be a useful physiological indicator of the severity of coronary disease and of patients at high risk. ST segment depression and pain have a close temporal relationship to the decreases of regional myocardial perfusion that occur in these patients. These studies suggest that there is a close relationship between myocardial perfusion and metabolism in health and disease. Both myocardial perfusion and metabolism will have to be affected by any rational therapy for angina pectoris and ischemic heart disease.