Efficacy of MCI-186, a free-radical scavenger and antioxidant, for resuscitation of nonbeating donor hearts

ObjectiveOxygen-derived free radicals are responsible in part for reperfusion injury in globally ischemic myocardium. In this study, the efficacy for resuscitation of nonbeating donor hearts of MCI-186, a free-radical scavenger and antioxidant, was investigated in a pig transplantation model.MethodsCardiac arrest was induced by asphyxiation. After 30 minutes of global ischemia, the hearts were excised and immediately reperfused from the aortic root with normoxemic blood cardioplegia (Po2 100 mm Hg) for 20 minutes, followed by perfusion with hyperoxemic blood (Po2 300 mm Hg). MCI-186 (3 mg/kg) was administered into the aortic root for the first 30 minutes of reperfusion in the treated group (n = 6), and untreated hearts were used as a control group (n = 6). Transplantation was performed with the heart beating.ResultsPosttransplantation recovery of cardiac output, end-systolic pressure–volume ratio, and first derivative of pressure of the left ventricle in the treated group were significantly better than those in the control group. The coronary sinus–aortic root difference in malondialdehyde levels remained low throughout reperfusion in the treated group but abruptly increased after initiation of oxygenated blood perfusion in the control group. The MCI-186–treated hearts showed low degree of edema and well-preserved ultrastructure with normal-appearing organelles, whereas the untreated hearts had marked swelling of mitochondria and scant glycogen granules.ConclusionMCI-186 exerts a cardioprotective action at least partly by inhibition of lipid peroxidation. Antioxidant therapy at the initial reperfusion is essential to successful resuscitation of nonbeating hearts by continuous myocardial perfusion

Malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart: a case report

A rare case is presented of a 61-year-old man with a malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart. The primary tumor originated in the right thigh in 1982. Since then, the patient has had repeated local recurrences in spite of repeated surgical treatment and adjuvant chemotherapy. He has developed previous metastases of the lung and heart. The patient died of cardiac involvement

EXTENT OF SINOATRIAL AND ATRIOVENTRICULAR NODAL DEPOSITS IN CARDIAC AMYLOIDOSIS : A CORRELATIVE INVESTIGATION

Objectives. We morphometrically determined the relative area of amyloid deposition (%D) in sinoatrial and atrioventricular nodes in cardiac amyloidosis. Materials and Methods. We divided 13 hearts with amyloidosis and arrhythmia (arrhythmia group) and 4 hearts with amyloidosis and no arrhytimia (controls) into subgroups. The arrhythmia group included 3 patients with sick sinus syndrome (SSS), 3 with atrioventricular (AV) block, 9 with bundle branch block, 7 with atrial fibrillation, and 4 with ventricular arrhytlnnias. Among all 17 cases, 14 represented primary (AL) amyloidosis and 3 represented secondary (AA) amyloidosis. We selected five microscopic fields for each case and node for quantitative analysis with an image analyzer to determine %D. Results. The %D in both nodes was similar between control and arrhythmia groups. Only in the AV block subgroup was the %D in the sinoatrial node significantly greater than controls (p<0.05), although %D in the SSS subgroup showed some tendency to be greater than in controls. In the atrioventricular node, %D in the AV block subgroup tended to be greater than in controls. The %D was similar between the two nodes for groups with ALλ, ALκ, and AA amyloid, while %D tended to be greater in the AL group than in the AA group. Conclusion. Although a close relationship was not decisively demonstrated between arrhytimias and extent of amyloid deposition in sinoatrial or atrioventricular nodes, SSS might be caused by amyloid deposition in the sinoatrial node and AV block might be caused by amyloid deposition in the atrioventricular node

Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia

Background The aortic valve dysfunction of patients with homozygous familial hypercholesterolemia (FH) suggests that hypercholesterolemia affects not only coronary arteries, but also the aortic valve. We studied the aortic root of patients with homozygous FH and those of heterozygous FH to characterize the premature atherosclerotic lesions, using histopathological specimens. Methods and results The aortic roots of 10 homozygous FH patients, aged 9 to 58 years, were studied by cardiac catheterization with several angiographies. The aortic root of 39 heterozygous FH patients under age 60 were also examined for aortic and mitral valvular functions by color Doppler echocardiography, and 30 normocholesterolemic patients with coronary artery disease were examined as controls. In addition, in 22 FH and 20 control subjects, the internal diameter of the aortic annulus and the aortic ridge in cardiac cycles were measured. Of the 10 FH homozygotes, 8 patients had aortic regurgitation demonstrated by aortography; three of them showed significant transvalvular pressure gradients. Stenotic changes of coronary ostia were observed in 8 of the 10 homozygotes with moderate coronary atherosclerosis. Of the 39 FH heterozygotes, ten patients had aortic regurgitation shown by Doppler echocardiography, as did only one of the 30 control subjects (P<0.05). The average diameter and distensibility of the ascending aorta were significantly reduced in the heterozygotes compared to the control subjects. The surgically resected cusp specimens of aortic valves obtained from one homozygous and one heterozygous patient showed significant thickening of the cusp with foam cell infiltration. Conclusions Premature atherosclerosis in FH had a characteristic distribution, affecting the aortic root dominantly. The involvement of the aortic valve indicating “hypercholesterolemic valvulopathy” was a peculiar feature of FH, especially its homozygous form, but was reminiscent of ubiquitous processes due to hypercholesterolemia

Extension of Hemorrhage After Reperfusion of Occluded Coronary Artery: Contrast Echocardiographic Assessment in Dogs

AbstractObjectives. The aim of this study was to elucidate the progression of intramural hemorrhage complicated by reperfusion with the use of myocardial contrast echocardiography.Background. Although hemorrhagic infarction is known to occur in ischemia followed by reperfusion, its onset and sequence have not been well characterized.Methods. In 20 anesthetized dogs, 3-h occlusion of the left circumflex coronary artery was followed by reperfusion. The area at risk during coronary occlusion was ∼25%. Myocardial contrast echocardiogram was examined, and the time-intensity curves for both ischemic and nonischemic areas were obtained at baseline, at 3 min after reperfusion and then at 15-min intervals until 90 min after reperfusion. The wall thickness of both areas was also measured.Results. Gross hemorrhage in the reperfused areas was observed in five dogs (Group H) but not in seven dogs (Group NH). All wall segments were opacified at 3 min after reperfusion in both groups. However, the contrast defect spread significantly with time after reperfusion in Group H but not in Group NH (18.7 ± 3.4% and 3.3 ± 1.8%, respectively, at 90 min after reperfusion p < 0.005). The wall of the risk area at 90 min after reperfusion had thickened to 1.3 times baseline thickness in Group H but was unchanged in Group NH. The other eight dogs were excluded from study because of fatal arrhythmias or the existence of collateral circulation during coronary occlusion.Conclusions. Both progression of the contrast defect area on myocardial contrast echocardiography and a gradual thickening of the wall with reperfusion are characteristic of hemorrhagic infarction

High prevalence of atrial fibrosis in patients with dilated cardiomyopathy

Objectives.We examined the extent of fibrotic changes in the left atrium of cardiomyopathic human hearts and investigated the relation of mechanical overload caused by left ventricular dysfunction to fibrosis of the left atrium.Background.Left atrial dysfunction in dilated cardiomyopathy may contribute to progression of heart failure. In contrast to fibrosis of the left ventricle, atrial fibrosis has not been extensively studied in cardiomyopathic hearts.Methods.The extent of fibrosis in the left atrium and left ventricle was determined by an automatic image analyzer in 38 autopsied hearts obtained from 9 patients who died of noncardiac illness (control group), 16 patients with dilated cardiomyopathy, 6 patients with hypertrophic cardiomyopathy with features mimicking dilated cardiomyopathy and 7 patients with a previous myocardial infarction. Transverse sections were obtained at the upper margins of the foramen ovale and left auricle in the left atrium and the median level of the left ventricle.Results.There were no significant differences in extent of left atrial dilation, left ventricular dysfunction or duration of illness among the three groups with cardiac disease. Percent area of left atrial fibrosis (mean ± SD) was significantly greater in the specimens from patients with dilated cardiomyopathy (13.1 ± 6.1%, p < 0.01) and hypertrophic cardiomyopathy mimicking dilated cardiomyopathy (26.5 ± 9.5%, p < 0.01) than in those from patients with an old myocardial infarction (3.8 ± 1.1%). Percent area of left ventricular fibrosis in hearts from patients with dilated cardiomyopathy (12.9 ± 8.6%) was significantly smaller than that in hearts from patients with hypertrophic cardiomyopathy mimicking dilated cardiomyopathy (35.8 ± 11.9%, p < 0.01) and a previous myocardial infarction (38.4 ± 8.0%, p < 0.01). Percent area of atrial fibrosis was significantly correlated with left ventricular ejection fraction in the group with a previous myocardial infarction but not in the other groups.Conclusions.There was a high degree of fibrotic change in the left atrium in the groups with dilated cardiomyopathy and hypertrophic cardiomyopathy mimicking dilated cardiomyopathy. Our findings suggest that atrial fibrosis in these patients may not have been related to mechanical overload of the left atrium but to some other, still unknown mechanisms