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We have reviewed some of the voluminous literature on the effects of aspirin combined with dipyridamole on coronary thrombosis. There is clear evidence that aspirin is partially effective in preventing platelet aggregation and subsequent thrombosis in experimental constricted and damaged coronary arteries of dogs. Clinical studies show a clear reduction in myocardial infarction in male human subjects who are given aspirin as therapy for unstable angina, or as prophylaxis in asymptomatic individuals. In many studies aspirin and dipyridamole have been combined and are effective. We have not found dipyridamole to be effective in the dog with coronary artery constriction and find no substantial evidence that it is effective in preventing myocardial infarction in man. Until definitive studies show that combining dipyridamole with aspirin is more effective than aspirin alone, we do not recommend its use for prevention of coronary thrombosis.

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In 18 anesthetized dogs with a 70% mechanically produced coronary artery stenosis, blood flow measured with an electromagnetic flowmeter showed cyclical reductions in flow due to periodic acute platelet thrombus formation. These were abolished in eight of nine dogs with 2.5 mg/kg of aspirin given intravenously and in nine of nine dogs with 5 mg/kg of aspirin. However in 14 of 18 dogs the cyclical flow reductions were temporarily renewed with the infusion of epinephrine 0.4 microgram/kg/min. Human platelets inhibited with aspirin can be reactivated with physiologic amounts of epinephrine. We postulate that in patients with atherosclerotic stenotic lesions the use of aspirin to inhibit arterial thrombus formation may be less effective when they have elevated catecholamines.

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A retrospective analysis of 38 patients undergoing cardiac catheterization with the diagnoses of hypothyroidism and chest pain revealed 23 to be euthyroid while receiving replacement therapy and 15 to be hypothyroid. Cardiac index was significantly reduced (p less than 0.01) in hypothyroid and euthyroid patients with thyroxine values between 4 and 7 micrograms/dl (2.8 +/- 0.7 and 3.0 +/- 0.9 L/min/m2, respectively), compared to euthyroid patients with thyroxine values greater than 7 micrograms/dl with or without coronary artery disease (4.0 +/- 1.2 and 4.0 +/- 0.7 L/min/m2, respectively). Ten hypothyroid patients underwent coronary artery bypass. There were no deaths, and only one patient required prolonged postoperative intubation. With a mean follow-up of 36 months, there have been no myocardial infarctions and one late death, which occurred at 7 years secondary to stroke. We conclude that preoperative thyroid replacement therapy is theoretically dangerous and may not significantly improve hemodynamics until full replacement is achieved. Coronary bypass grafting can be performed safely despite hypothyroidism with excellent early results.

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The sensitivity and specificity of pulsed Doppler echocardiography (PDE) in diagnosis and estimation of the severity of mitral regurgitation in the presence of rheumatic mitral stenosis was studied in 34 patients (18 women and 16 men) ranging in age from 33 to 70 years (mean 55). Definitive diagnosis of mitral regurgitation was confirmed in all patients by angiography and in 20 patients also by indicator dilution technique. Mitral regurgitation was detected by PDE in all patients with angiographically proven severe mitral regurgitation and in 7 of 8 patients with moderate mitral regurgitation. In patients with trace to mild mitral regurgitation, PDE was positive in only 7 of 13 patients. When subdivided for mild, moderate and severe mitral regurgitation, PDE sensitivity for diagnosis was 54, 88, and 100%, respectively; overall accuracy was 79% and specificity was 100%. Average systolic dispersion on time-interval histogram was 59% for mild, 89% for moderate, and 100% for severe mitral regurgitation. Groups of patients with mild mitral regurgitation could be differentiated from those with moderate (p less than 0.05) and severe (p less than 0.01) mitral regurgitation. A significant overlap of individual values, however, occurred. In 7 of 11 patients with moderate to severe mitral regurgitation, systolic turbulence also was detected in the left atrium. PDE was sensitive and specific in diagnosing moderate to severe mitral regurgitation in the presence of mitral stenosis. Assessment of precise severity of mitral regurgitation is still a problem in individual patients.

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In 67 dogs with a 60-80% coronary stenosis produced by an external constricting plastic ring, blood flow measured with an electromagnetic flowmeter showed cyclical flow reductions of varying magnitude and duration, and then an abrupt return to control flow. In 45 dogs, heparin did not prevent these flow reductions, but ibuprofen (Motrin) or indomethacin abolished them. With incremental doses of each of these drugs, the cyclical flow reduction and the platelet function in vitro were diminished proportionately. In 10 more dogs, during low flow, pinching or poking the narrowed vessel suddenly restored normal flow. Topical application of papaverine and nitroglycerin proximal to the stenosis did not abolish the cyclic flow reduction, although a transient fall in systemic pressure indicated that they had been absorbed. Seven dogs had the constricting cylinder and flow probe chronically implanted for 4-6 weeks. A single oral dose of aspirin, 20 mg/kg, abolished their cyclic flow reductions for 2-4 days. In five dogs with 70% stenosis in the circumflex coronary artery, coronary arteriography was performed before coronary flow reduction and when coronary blood flow was low. This showed that there was a considerable additional reduction in the size of the mechanically constricted lumen during spontaneous flow reduction. In one dog, a nonopacified mass was dislodged from the area of constriction in 67 msec and this restored the lumen to its control diameter. Similar rapid clearing was filmed in two more dogs. In no case was vasospasm observed. These results suggest that obstruction from platelets aggregated in the narrowed lumen caused the cyclic flow reductions.

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A computerized fluoroscopy system has been developed on the basis of real-time digital processing of x-ray transmission data from traditional image-intensified fluoroscopy equipment. High-quality visualization of any part of the arterial system is obtained following intravenous injection of 0.5 to 0.75 ml/kg of iodinated contrast materials. This report describes the use of this technique to evaluate the aortic arch, left ventricular function, and coronary artery bypass graft patency. Fifty intravenous studies were performed in 25 patients. Among 20 patients with coronary artery bypass grafts, computerized fluoroscopy correctly identified 11 of 15 patent grafts and 11 of 11 occluded grafts as confirmed by standard coronary arteriography in 11 of these patients. Unlike computerized tomography, our technique gives a longitudinal view of the bypass graft much like direct coronary angiography. Aortic arch studies included demonstration of a right aortic arch with a small left subclavian artery, a coarctation, and a normal aortic arch in a trauma patient with a wide mediastinum. Segmental wall motion abnormalities were clearly identified by a modification of the technique which produces a negative outline on the ventriculogram in dyskinetic segments. Ejection fractions may be calculated by determining the amount of iodine in the ventricle in systole and diastole. This technique may also be used to evaluate carotid disease and peripheral vascular disease in patients undergoing coronary artery bypass procedures. Computerized fluoroscopy, therefore, allows evaluation of the entire cardiovascular system by the relatively noninvasive technique of intravenous angiography.

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A new surgical technique using perfusion of the circumflex coronary artery with retrograde blood flow of the internal mammary artery (IMA) is described. This project was undertaken because the IMA is uniquely well supplied with blood: proximally through is attachment to the subclavian artery, along the sternum by the intercostal arteries to the aorta, and distally from the iliac artery by the epigastric and musculophrenic arteries. In this experimental study, the IMA in 16 dogs was ligated and divided at the subclavian artery, then dissected free down along the sternum to obtain sufficient length. The large subclavian end was then anastomosed to the circumflex coronary artery using a metal cannula technique to perfuse the circumflex bed while the anastomosis was being done. In all 16 dogs, the retrograde flow of the IMA was adequate to maintain the circumflex bed. It is postulated that this technique may have some limited use in man.

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A computerized fluoroscopy system which was recently developed in our laboratories permits image contrast increases of 8-16 relative to conventional image intensifer fluoroscopy and permits study of canine and human ventricular wall motion using peripheral intravenous injections. Two time-dependent image subtraction algorithms are illustrated in connection with observation of artificially infarcted dog hearts. The first algorithm produces a display analogous to direct ventriculography using catheterization. The second displays regions of dyskinetic motion as anomalous image grey shades.

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We have shown previously that acute aortic insufficiency in chronically instrumented dogs reverses the normally high ratio of diastolic to systolic coronary blood flow. Phasic blood flow in the dominant right coronary artery was measured directly with an electromagnetic flow meter during surgery in eight patients with severe aortic insufficiency before and after relacement of the aortic valve. Before the insufficiency was eliminated, right coronary flow average 116 +/- 37 ml./minute and the diastolic to systolic flow ratio was 0.88 +/- 17. Mean arterial blood pressure averaged 106 +/- 17 mm. Hg, heart rate 84 +/- 19 beats/minute, and mean diastolic pressure averaged 67 +/- 10 mm. Hg. After the aortic valve was replaced with an average heart rate of 90 +/- 15 and mean blood pressure of 103 +/- 13 mm. Hg, the average right coronary blood flow increased to 180 +/- 40 ml./minute with a D/S ratio of 2.18 +/- 0.8. In all cases the right coronary blood flow increased after the aortic insufficiency was eliminated surgically. Right coronary flow probably increased because of the improved diastolic perfusion pressure and the change from predominantly systolic to diastolic coronary flow.

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