Coronary Obstructive Research Articles

Advances in Kawasaki disease bypass surgery for coronary artery obstructions

Coronary bypass surgery for the sequelae of Kawasaki disease is effective in improving cardiac function during exercise and probably in preventing sudden deaths and myocardial infarction in children, although surgical efficacy was initially questioned because the disease is inflammatory vasculitis in origin. The operation utilizing the pedicled arterial grafts is now established as a reliable treatment for severe inflammatory coronary obstructive disease due to Kawasaki disease (Kitamura Operation). Results of the surgery and long-term follow up are quite satisfactory up to 20 years. The postoperative quality of life is also markedly improved allowing over 85% of children with surgery to take full exercise at school, although all of them were prohibited from exercise before operation. The pedicted internal thoracic artery graft is not only excellent in its long-term patency but also is capable of growing with the child and meeting the perfusion demand of the myocardium. Thus, it is an ideal graft material for coronary artery reconstruction in children. Use of bilateral internal thoracic arteries is also safe in growing children. Moreover, right gastroepiploic artery grafts are useful in children with distal coronary artery lesions. The use of vein grafts should be avoided in children, because the patency rate is significantly poorer than arterial grafts. The benefits of surgical treatment for severe coronary artery lesions due to Kawasaki disease have now been recognized not only in Japan but all over the world.

Effects of vesnarinone, a novel orally active inotropic agent with an immunosuppressive action, on experimental cardiac transplantation in rats.

Vesnarinone (VES) has been used for treatment of patients with congestive heart failure. In addition to inotropic effects, it seems to have immunosuppressive action. We tested the hypothesis that VES suppresses graft rejection, inotropic dysfunction caused by early rejection, and chronic coronary obstruction in a heterotopic rat cardiac transplantation model. (1) To study acute rejection, hearts from Lewis-Brown Norway (LBN) rats were transplanted into Lewis rats, which were treated with or without VES (50 or 100 mg/kg/day orally). (2) In a functional study, LBN hearts with or without VES (100 mg/kg/ day) were isolated and perfused on day 3 after transplantation to assess inotropic response to isoproterenol (3 x 10(-8) M). (3) To study chronic rejection, Lewis hearts were transplanted into Fisher 344 rats, which were treated with or without VES (50 mg/kg/day) for 90 days. Coronary obstructive disease was assessed by morphometric analysis. There were five to six animals in each group. (1) VES (100 mg/kg/day) prolonged LBN heart survival (11.7 +/- 0.7 vs. 9.6 +/- 0.7 days in control; P < 0.05). (2) Left ventricular developed pressure was depressed in transplanted hearts regardless of VES treatment (84 +/- 12, 90 +/- 8 vs. 144 +/- 16 mmHg in untransplanted hearts; P < 0.01). The developed pressure after administration of isoproterenol in VES-treated hearts (184 +/- 20 mmHg) was higher than transplanted hearts without VES (118 +/- 16 mmHg; P < 0.05), and similar to untransplanted hearts (203 +/- 27 mmHg; P = NS). (3) Transplanted hearts treated with or without VES showed similar grades of rejection (2.0 +/- 0.3 vs. 2.6 +/- 0.2; P = NS), intimal area (6,996 +/- 3,186 vs. 13,441 +/- 5,165 microns2; NS), and coronary luminal obstruction (45 +/- 16% vs. 67 +/- 14%; NS). VES produces mild prolongation in survival of rat heart grafts, but has no significant effect on chronic graft atherosclerosis. VES preserves the positive inotropic effects of isoproterenol that are otherwise deteriorated by early acute rejection.

Intracoronary cyclic-GMP and cyclic-AMP during percutaneous transluminal coronary angioplasty

We investigated intracoronary cyclic-guanosine monophosphate (c-GMP) levels during percutaneous transluminal coronary angioplasty (PTCA) since experimental studies have shown the endothelial origin of c-GMP production. Intracoronary c-GMP and cyclic adenosine monophosphate (c-AMP) were measured during coronary angioplasty in 24 patients with chronic coronary artery disease. Four coronary blood samples were taken through a catheter from the coronary artery the first sample before coronary angiography and the other three from distal to coronary obstruction, as follows: before the balloon inflation, at the maximum inflation and 5 min after restoration of coronary flow. c-GMP increased from 7.9 ± 1.0 pmol/ml and 7.5 ± 0.9 pmol/ml before angiography and balloon inflation to 11.1 ± 1.3 pmol/ml at the maximum inflation ( P < 0.01), with a trend to decrease 5 min after the end of the intervention (9.5 ± 1.0 pmol/ml, P: NS). Intracoronary c-AMP levels remained almost unchanged. Five venous samples were taken to measure c-AMP before coronary angiography, before PTCA, and 5 min, 2 h and 24 h after PTCA. c-AMP values 2 and 24 h after PTCA (17.8 ± 1.7 pmol/ml and 17.5 + 1.7 pmol/ml, respectively) were lower than the highest value (22.1 ± 2.1 pmol/ml) found 5 min after PTCA, ( P < 0.001). c-GMP increases distal to coronary obstructive lesion during PTCA at the time of balloon inflation, while c-AMP remains unchanged. c-AMP rises in venous circulation only. PTCA stimulates the mechanism of c-GMP release, while systemic c-AMP increase seems to be related to the stress occurring during catheterisation and PTCA.

Assessing the physiologic significance of coronary obstructions in patients: Importance of diffuse undetected atherosclerosis

T HE HALLMARK OF coronary atherosclerosis is an apparently localized obstruction of a conduit coronary vessel. Until Sones introduced the technique of selective coronary angiography,’ for the most part the anatomy of these localized coronary obstructions could only be defined at postmortem. The ability to anatomically define coronary obstructions with a broadly applicable clinical technique has vastly altered our approach to the diagnosis and treatment of coronary atherosclerosis. Each new step forward, however, immediately brings forth new questions. Thus, coronary angiography has forced physicians to develop approaches of defining the physiologic significance of coronary lesions that can be demonstrated angiographically. Accurately assessing the physiologic significance of coronary obstructive lesions is critical to clinical decision making. The need for coronary bypass surgery, percutaneous transluminal coronary angioplasty, the adequacy of prior bypass surgery and percutaneous transluminal coronary angioplasty, and the validation of noninvasive approaches to the diagnosis of coronary disease all critically depend on assessing the physiological significance of coronary obstructive lesions. For more than two decades, the physiological significance of coronary obstructions detected by coronary angiography has been assessed primarily by visual estimates of percent stenosis. To a lesser extent clinicians have used other aspects of the patients’ clinical presentation including symptoms and results of various noninvasive procedures. Because percent stenosis remains the gold standard today in more than 99% of hospitals that perform coronary angiography, this review will examine the advantages and disadvantages of this approach.

Coronary Obstructive Lesions: Assessing Their Physiological Significance in Humans

For more than two decades cardiologists and cardiac surgeons have estimated the physiologic significance of coronary lesions by measuring percent stenosis of the obstructive vascular segment from coronary angiograms. Such measurements, when performed without computer-based analysis, are associated with substantial variability between observers, as well as within a single observer. In addition, recent intraoperative measurements of coronary reserve in individual obstructed vessels of patients with multivessel coronary disease performed with a suction Doppler probe indicate that, in the intermediate range (10% to 90% diameter stenosis), percent stenosis measurements of coronary lesions by angiography correlates poorly with coronary reserve. These studies suggest that the physiologic significance of coronary obstructions cannot be accurately assessed by visual interpretation of coronary angiograms. More sophisticated and accurate approaches are needed for assessing the physiologic significance of coronary obstructions preoperatively.

Exercise digital subtraction ventriculography for the detection of ischaemic wall motion abnormalities in patients without myocardial infarction.

Digital subtraction angiography permits high resolution imaging of the left ventricle after an intravenous injection of contrast medium. The capacity of digital subtraction angiography to detect ischaemic wall motion abnormalities was tested in 150 consecutive patients without myocardial infarction who were referred for coronary angiography. Digital ventriculograms were considered to be abnormal if there was a severe wall motion abnormality at rest or if segmental wall motion deteriorated after exercise. The global ventricular response to exercise was considered to be abnormal if the ventricular ejection fraction computed by the Dodge area length formula was less than 50% at rest or failed to increase after exercise. Seventy eight (52%) of these subjects had stenosis of greater than 50% of at least one major coronary artery. In 36 (24%) more than one major coronary vessel was affected. Sensitivities for the detection of stenoses greater than 50% coronary obstruction were 82% and 69% for an abnormal segmental wall motion response and an abnormal ejection fraction response respectively. The specificity of these test responses was 76% and 68% respectively. No complications resulted from the digital ventriculographic studies. It is concluded that safe adequate digital ventricular imaging at rest and after exercise is possible and that an abnormal wall motion response is a sensitive indicator of important coronary obstructive disease.

Mucocutaneous lymph node syndrome: Clinical, hemodynamic and angiographic features of coronary obstructive disease

Clinical, hemodynamic and angiographic features of coronary obstructive disease (≥ 90% diameter reduction) in Kawasaki disease were evaluated in 30 patients. The mean age at the onset of Kawaski disease was 2.9 ± 1.9 years and that at cardiac catheterization was 6.3 ± 2.8 years. Obstructive lesions were observed in the right coronary artery in 12 patients (group 1), in the left anterior descending coronary artery (LAD) in 6 (group 2), in both right coronary artery and LAD in 10 (group 3) and in the left main coronary artery in 4 (group 4). Twenty-two patients (73%) had cardiac symptoms, including myocardial infarction in 10 (33%). Cardiac symptoms were observed in 41 % in group 1, 100% in group 2, 80% in group 3 and 100% in group 4. Left ventricular (LV) end-diastolic pressure, enddiastolic volume and ejection fraction were abnormal in 32% of the patients in group 1, a frequency less than that in other groups (83% in group 2, 78%. in group 3 and 100% in group 4). Fifty percent had mitral regurgitation and 73% had left ventricular wall motion abnormalities. No patient in groups 1 or 2 has died, but 8 of 14 patients in groups 3 and 4 have died. These observations indicate that coronary obstruction owing to Kawasaki disease can cause depressed LV function, mitral regurgitation and LV wall motion abnormalities in children. Clinical and hemodynamic features of right coronary obstruction (isolated) are relatively benign compared with those of left coronary obstruction (isolated or combined with right obstruction).

Etiology and prevention of coronary obstructive lesions in infancy and childhood.

It is now well established that coronary atherosclerosis should be considered as a problem from infancy or even from embryonal life. Its development, although genetically determined to some extent, is influenced by many factors, some of which may be beneficially modified. Such primary prevention should start in early childhood, and in some aspects, even during pregnancy. Nonatherosclerotic coronary obstruction may also be present in infancy and childhood, usually with severe consequences.

The pathophysiologic basis of acute coronary insufficiency. Observations favoring the hypothesis of intermittent reversible coronary obstruction

Clinical, coronary angiographic, and myocardial metabolic data were analyzed to test alternative hypotheses for the pathophysiologic basis of acute coronary insufficiency. The initial incidence of coronary collaterals was not low in relation to coexisting coronary obstructive disease; the early subsequent coronary occlusion rate was high; and in asymptomatic intervals during the acute illness, myocardial hypoxia was infrequent and coronary reserve substantial. These observations support the hypothesis that the acute coronary insufficiency syndrome is caused by reversible coronary ischemic episodes rather than by a new permanent atherosclerotic lesion.

The effect of severity of coronary artery obstructive disease and the coronary collateral circulation on local histopathologic and electrographic observations in man

The relationship between both angiographically defined proximal coronary obstructions of varying severity and coronary collaterals and the subserved left ventricular myocardium in living man is incompletely understood. Therefore, their electrophysiologic and histopathologic characteristics were evaluated in 48 patients at the time of open heart surgery. Of 28 areas supplied by ≥90 per cent obstructed arteries, the histopathology in 12, based on local biopsy specimens, was normal; in the remaining 16 there was significant muscle loss. In contrast, of five areas with < 90 per cent obstructions, four were normal (p < 0.05). Epicardial electrograms recorded from 55 areas with ≥90 per cent obstruction showed R waves in 42 and Q waves in 13. Of 24 areas with < 90 per cent obstruction, there were R waves in 21 and Q waves in only three. When areas supplied by collaterals were compared to those without angiographically demonstrable collaterals, the frequency of both histopathologic abnormalities and epicardial Q waves was similar. In addition, the effect of collateral blood flow to vessels with similar degrees of obstruction was compared. Of seven areas with ≥ 90 per cent obstructions and collateral supply, the histopathology was normal in two, and there was muscle loss in five. Of 21 areas with >90 per cent obstructions without collaterals, 10 were normal whereas 11 showed muscle loss. Similarly, in 16 areas with collaterals, epicardial electrograms showed R waves in 11 and Q waves in five; whereas of 39 without collaterals, there were R waves in 31 and Q waves in eight. Thus, ≥ 90 per cent coronary obstructive lesions are associated with both more muscle loss and epicardial Q waves than lesser obstructions. No beneficial effect of collaterals was demonstrable.

Diagnosis, medical and surgical management of coronary insufficiency.

Coronary artery injections of radio-opaque material into the vessels of autopsy hearts first disclosed that angina pectoris in most cases is due to extensive narrowing and occlusion of these vessels by atherosclerotic disease. These studies also showed that the development of coronary collateral anastomoses could compensate to a great extent for obstructions in the coronary arteries. The electrocardiographic hallmark of myocardial hypoxia, ST segment depression, has provided a valuable diagnostic method that identifies the presence of coronary insufficiency when it accompanies either spontaneous or induced anginal pain. The two-step test is a useful diagnostic method, and treadmill testing with electrocardiogram (EKG) monitoring provides a quantitative measure of the severity of angina as well as evidence of adaptation in the coronary circulation. Coronary arteriography discloses the extent of coronary obstructive disease, its accessibility for surgical correction, and the extent of compensatory collateral development. Surgical attempts at direct relief of coronary obstruction have been disappointing, but some brilliant successes point out the need for further study of this field. Control of serum lipid levels by diet and drugs offers hope of reducing the risk of coronary disease. A carefully graded walking exercise program may lead to improvement of clinical angina and treadmill performance in selected patients; this may provide a method for medical revascularization of the heart.