Review: role of cerebral vessels in ischaemic injury of the brain.

This review discusses the pathological changes in the heart and vessels underlying brain ischaemic injury, with a major focus on atherosclerotic disease of the brain induced by lesions of the extracranial cervical and major intracranial arteries and small-vessel disease of the brain. The carotid bifurcation is the primary site for atherosclerotic changes, for which extensive clinical trials and pathological analyses on carotid endarterectomy specimens have been performed. Plaque rupture and erosion give rise to thrombus formation, which leads to brain ischaemic injury. These changes have much in common with atherosclerotic lesions of the subepicardial coronary arteries. Emboli of various types of particles are characteristics of brain ischaemic injury. Thrombi rich in fibrin and red blood cells (red thrombi) that develop in the cardiac chambers are common sources of cerebral emboli. Small-vessel disease of the brain induces fibrinoid necrosis, microaneurysm, fibrohyalinosis, lipohyalinosis and microatheroma, changes commonly associated with hypertension. The acute hypertensive small-vessel changes organize to create segmental arterial disorganization and deep small infarcts when they escape from rupture. Some specific vascular diseases responsible for brain ischaemic injury are briefly reviewed also.

Hyperlipidemia in mast cell-deficient W/WV mice.

Approximately 70% of the W/WV mice lacking mast cells due to a genetic defect showed hypertriglyceridemia combined with hypercholesterolemia. Increases of various magnitudes in chylomicrons, very-low-density lipoprotein, and intermediate-density lipoprotein were observed in the plasma of W/WV mice compared to those in the plasma of congenic normal mice. The increase in these lipoproteins was seen even in normolipidemic W/WV mice. Activities of both lipoprotein lipase and hepatic triacylglycerol lipase in the plasma after heparin injection were markedly lower in the W/WV mice than in the congenic normal mice, although activities of both lipoprotein lipase in the heart and adipose tissue and hepatic triacylglycerol lipase in the liver were not decreased. These results suggest that the W/WV mice have genetic defects in one or more of the following: secretion of both lipases from their synthesising cells, transport to the endothelium, and anchoring to the endothelial surface. Heparin deficiency in these mice may be responsible for the impairment and, thereby, may partially contribute to the hyperlipidemia.

Development of microporous covered stents: geometrical design of the luminal surface.

To reduce in-stent restenosis rates we have developed newly designed covered stents, in which a stent strut is buried into a microporous elastomeric cover film to provide a physical barrier against tissue ingrowth and a pharmacological reservoir for drug-eluting. The covered stents were prepared by dip-coating balloon expandable stents mounted on a stainless steel rod in a segmented polyurethane (SPU) solution, and were subsequently subjected to laser-processed microporing (pore diameter, 100 microm; interpore distance, 200 microm). The covered stents, which possessed flat luminal surfaces and micropores that were homogeneously arranged on the whole surface of the covering film, were deployed into the bilateral common carotid arteries of normal New Zealand white rabbits. Angiography after one month of implantation showed all stents were patent with little thrombus formation. The mean thickness of the formed neointimal layers was 292 +/- 177 microm (n=8), which was close to the size in non-covered bare stent (231 +/- 58 microm, n=7), but markedly decreased (about 2/3) from that in the previously developed wrapping-type covered stents (415 +/- 173 microm, P<0.01, n=8).

Cause of residual hypertension after adrenalectomy in patients with primary aldosteronism.

The cause of residual hypertension after adrenalectomy for primary aldosteronism (PA) is unknown. The purpose of this study is to investigate the characteristic pathological kidney features associated with PA. Between 1977 and 1999 at our hospital, 26 patients with PA caused by a unilateral adrenal cortical adenoma (Conn's syndrome) underwent unilateral adrenalectomy with concurrent open-wedge renal biopsy. Patients were categorized into two groups: (1) those with normotension with diastolic blood pressure less than 90 mm Hg who were not administered antihypertensive drugs, and (2) those with residual hypertension with diastolic blood pressure of 90 mm Hg or greater who were administered medication for 6 months after surgery. Thirteen patients were cured of hypertension postoperatively, and 12 patients were administered antihypertensive medications. Glomerulosclerosis, renal arteriolosclerosis, and preoperative left ventricular mass (LVM) index were worse in the group with residual hypertension than in that with normotension (17.8% +/- 7.8% versus 9.6% +/- 3.8%; P = 0.01; 2.5 +/- 0.5 versus 1.6 +/- 0.4, Bader's grade; P = 0.005; and 165 +/- 31 versus 139 +/- 24 g/m(2); P = 0.02, respectively). Severity of tubulointerstitial injury, preoperative duration of hypertension, preoperative severity of proteinuria, plasma aldosterone level, and serum potassium concentration were not significantly different between the two groups. In conclusion, severity of glomerulosclerosis and arteriolosclerosis and LVM are related to blood pressure after adrenalectomy in patients with PA.

A case of overlap syndrome of systemic sclerosis and dermatomyositis with right ventricular dysplasia.

We report a 39-year-old woman with overlap syndrome of systemic sclerosis and dermatomyositis who died of congestive heart failure. The pathologic findings of the heart included contraction band necrosis and myocardial fibrosis. Unique was the finding of remarkable replacement of the right ventricle with fatty tissue.

Congenital nemaline myopathy with dilated cardiomyopathy: an autopsy study.

A 3-year-old boy with congenital nemaline myopathy had generalized muscle weakness and hypotonia since birth. He developed cardiac symptoms at 2 years of age and died from congestive heart failure. At autopsy, the heart was markedly dilated, involving both ventricles. Rod bodies were recognized not only in skeletal muscles but in cardiac muscles on light and electron microscopy. Desmin and alpha-actinin, which constitute Z-line protein, were shown to localize in the rod structures in both skeletal and myocardial cells by immunohistochemistry. Seven cases of nemaline myopathy with cardiomyopathy have been reported in the literature. All of these patients were over 20 years of age, and the condition appeared mostly in the adult onset and the asymptomatic forms. This is the first infantile case of congenital nemaline myopathy which showed dilated cardiomyopathy with a fatal outcome.

Nodular regenerative hyperplasia of the liver associated with primary pulmonary hypertension.

Nodular regenerative hyperplasia (NRH), a rare hyperplastic condition of the liver, is reported in two patients with primary pulmonary hypertension (PPH). The first patient was a 26-year-old man who died of PPH and showed multiple NRH without cirrhosis of the liver. The second patient was a 25-year-old man who had a PPH with pulmonary arterial thrombi and NRH of the liver. NRH has been described in association with immune disease, hematopoietic disorder, and diabetes mellitus, so that NRH with PPH is considered to be very rare. Histologic findings of the lungs show typically plexogenic pulmonary arteriopathy in both cases, and the livers of these patients are composed of multiple nodules that are histologically represented by slightly larger hepatocytes arranged in a cobblestone-like fashion, and are ultramicroscopically characterized by massive proliferation of mitochondria. The pathogenetic association of nodular regenerative hyperplasia with primary pulmonary hypertension will be discussed.

Single lung transplantation in rats with fatal pulmonary hypertension.

Effects of single lung transplantation on fatal pulmonary hypertension were evaluated in rats receiving a lethal dose of monocrotaline. Inbred rats treated with monocrotaline (80 mg/kg) received a left lung isograft at 4 weeks (n = 9) and at 6 weeks (n = 6), when moderate and severe pulmonary hypertension, respectively, had developed. Medicated (n = 12) and nonmedicated rats (n = 12) served as control animals. Each rat was tested weekly with treadmill for exercise tolerance and oxygen consumption during a 10-week period after medication and after they were killed. Medicated control rats lost exercise tolerance and highest oxygen consumption per unit time consistently to the range of resting value (or 45% of nonmedicated control rats), and all died from severe pulmonary vascular occlusive disease with right ventricular hypertrophy before 10 weeks (right ventricular/left ventricular weight ratio of 1.16). All rats receiving a left lung isograft at 4 weeks survived and regained highest oxygen consumption per unit time (87% of nonmedicated control rats), with the lung transplant receiving 65% (nonmedicated control rats, 39%) of cardiac output and milder right ventricular hypertrophy (right ventricular/left ventricular weight ratio of 0.46). Except for one, all rats that received a left lung isograft at 6 weeks tolerated single lung transplantation, but they died soon after reperfusion because of pulmonary edema in the graft that received 58% of cardiac output with right ventricular/left ventricular weight ratio of 0.79. Results of single lung transplantation in rats were dependent on severity of pulmonary hypertension. In rats with moderate pulmonary hypertension, single lung transplantation was successful in reversing exercise intolerance and right ventricular hypertrophy. Single lung transplantation was unsuccessful when pulmonary hypertension was severe in the rat model because increased flow toward the lung transplant resulted in graft pulmonary edema.

Right-to-left interatrial shunt in rats with progressive pulmonary hypertension.

A right-to-left interatrial shunt may prolong survival in patients with pulmonary hypertension presumably because of decompression of the right side of the heart. To test this hypothesis, 74 rats with monocrotaline-induced pulmonary hypertension were followed up weekly with cardiopulmonary exercise testing with a metabolic treadmill system for exercise tolerance, heart rate, oxygen uptake, carbon dioxide production, and survival until subsequent or induced death 8 weeks after monocrotaline treatment. In rats with an interatrial shunt, oxygen uptake and carbon dioxide production were higher and survival was better (n = 22, 27%) than those in rats without a shunt (n = 52, 0%; p < 0.05). For the prospective assessment of the effects of a reversed shunt, 24 other rats underwent a left superior vena cava-to-left atrial appendage anastomosis as a functional interatrial shunt (atrial septal defect group) 4 weeks after monocrotaline treatment when severe pulmonary hypertension had developed and were compared with an additional 25 rats receiving a sham operation. Both groups had exercise capacity depressed to the resting levels by 2 weeks after operation. Although transcutaneous oxygen levels decreased in response to exercise in the atrial septal defect group, uptake and carbon dioxide production stayed higher than those in the sham operation group with significantly better survival 4 weeks after operation (atrial septal defect 30% versus sham operation, 0%; p < 0.05), at which time a reversed shunt was determined with systemic embolization of intravenously infused microspheres. A right-to-left interatrial shunt, anatomic or functional, preserved basal metabolism and prolonged survival in rats with progressive pulmonary hypertension.

A morphologic study of Carpentier-Edwards pericardial xenografts in the mitral position exhibiting primary tissue failure in adults in comparison with Ionescu-Shiley pericardial xenografts.

OBJECTIVE: We sought to investigate the durability and mechanism of the Carpentier-Edwards pericardial xenograft in the mitral position in comparison with that of the Ionescu-Shiley pericardial xenograft. METHODS: A total of 284 patients who received the Ionescu-Shiley pericardial xenograft in the mitral position between 1980 and 1984 and 84 patients who received the Carpentier-Edwards pericardial xenograft in the mitral position between 1984 and 1999 were included in the study. The freedom from reoperation rates for both graft types were determined. For morphologic study, the pathologic findings of 23 valves of 123 explanted Ionescu-Shiley pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both were determined and compared with those of 20 explanted Carpentier-Edwards pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both. Each pathologic finding was graded and assigned a score. Both types were matched for age at reoperation (50-75 years) and duration of valve function (8-11 years). RESULTS: Freedom from reoperation caused by structural valve deterioration, nonstructural valve deterioration, or both was significantly better for Carpentier-Edwards pericardial xenografts than for Ionescu-Shiley pericardial xenografts at 8 years after the operation (Carpentier-Edwards pericardial xenografts: 91.3% vs Ionescu-Shiley pericardial xenografts: 71.9%, P =.0061), but it was similar for both types at 12 years (Carpentier-Edwards pericardial xenografts: 43.6% vs Ionescu-Shiley pericardial xenografts: 43.6%, P =.2865). No severe leaflet tears were seen among Carpentier-Edwards pericardial xenografts. The mean area percentage of tissue overgrowth was 15.3% in Carpentier-Edwards pericardial xenografts and 3.4% in Ionescu-Shiley pericardial xenografts (P =.0001). The mean calcification area percentage was 13.6% in Carpentier-Edwards pericardial xenografts and 31.5% in Ionescu-Shiley pericardial xenografts (P =.0001). CONCLUSIONS: Tissue overgrowth on the atrial surface, ventricular surface, or both was the cause of structural valve deterioration, nonstructural valve deterioration, or both of Carpentier-Edwards pericardial xenografts in adults. This was different from Ionescu-Shiley pericardial xenograft failure, which resulted from severe calcification and leaflet tears. Organized thrombi on cusps, in addition to valve design, may have contributed to such tissue overgrowth on Carpentier-Edwards pericardial xenografts.

Monocrotaline-induced pulmonary vascular disease after contralateral lung transplantation in the rat.

To test a hypothesis that reduction in pulmonary perfusion pressure and flow affect underlying vascular disease, pulmonary pathology was studied in monocrotaline-treated rats undergoing single lung transplantation. Inbred rats were treated with 40 mg/kg (group T1, n = 6) and 80 mg/kg of monocrotaline (group T2, n = 9), received a left lung isograft 2 and 4 weeks after medication, and were killed 4 and 6 weeks after single lung transplantation, respectively. For each group, rats receiving the same amount of monocrotaline (M1, M2) or vehicle (N1, N2) served as controls. Monocrotaline-treated rats developed pulmonary vascular disease and right heart failure, resulting in severe exercise intolerance in M1 or death in M2 unless single lung transplantation had been carried out. At death, pulmonary blood flow was directed toward the left lung isograft, and the retained right lung received a significantly reduced fraction of cardiac output. Right to left ventricular weight ratio was significantly reduced in both groups as compared to the respective control rats, suggesting reduced perfusion pressure. Although thickness of media in small pulmonary arteries (media/radius) was normal (34% +/- 4%) in the lung isografts, it was significantly increased in the contralateral lung (group T1, 45% +/- 5%; group T2, 48% +/- 3%), which was not significantly different from that of monocrotaline-treated control rats, respectively (group M1, 47% +/- 7%; group M2, 49% +/- 6%). Although single lung transplantation reduced perfusion pressure and flow toward the monocrotaline-treated native lung, it failed to affect vascular morphology significantly.

Afferent reinnervation after lung transplantation in the rat.

Denervation at lung transplantation results in loss of cough reflex and attenuated local defense mechanisms, accounting for increased incidence and severity of infection after lung transplantation. We studied the presence or absence of spontaneous afferent reinnervation in rats at various intervals after orthotopic left pulmonary isografting (n = 52). Normal rats (n = 21) and rats undergoing left hilar stripping (n = 14) served as control subjects. Afferent reinnervation was tested physiologically by reflex bradycardia in response to intravenous infusion of capsaicin (30 microg/kg), an extract of paprika stimulating pulmonary C-fibers. Injection of capsaicin was repeated before and after right pulmonary artery occlusion to divert all pulmonary blood flow to the left lung or isograft. Whereas rats early after surgical denervation lost the reflex after right pulmonary artery occlusion, rats examined 8 months or longer after surgery showed potent reflex bradycardia in response to capsaicin, as did the control rats. Immunohistochemical staining for sensory neuron-specific substances, such as calcitonin gene-related peptide and substance P, were identified only in the right native lung and left pulmonary isografts 2 months or longer after transplantation. Fluorogold was found only in the ipsilateral nodose ganglion after left lung intrapleural injection of the neuron-specific tracer in rats 8 months or longer after denervation. These experiments provide physiological, morphologic, and neurologic evidence suggesting that afferent lung innervation, abolished early after transplantation, is spontaneously reestablished and functioning in the ipsilateral vagus nerve by 8 months after pulmonary isografting in the rat.

Tricuspid valve replacement with bioprostheses: long-term results and causes of valve dysfunction.

BACKGROUND: Although the clinical performance of bioprostheses after valve replacement in the aortic and mitral position has been reported, little is known of the performance of tricuspid bioprostheses. The mechanism of bioprosthetic valve dysfunction after tricuspid valve replacement (TVR) is not clear. METHODS: We reviewed 98 cases of TVR with bioprostheses. To clarify the causes of valve dysfunction, pathologic examination of the explanted valve at the reoperation was performed. RESULTS: Actuarial survival at 18 years was 68.7% +/- 5.8%. There were 12 redo TVRs. In six of the 12 cases, isolated redo TVR was performed. In the other cases, concomitant cardiac procedures were performed. The causes of prosthetic valve dysfunction were pannus formation on the cusps of the right ventricle side (four cases), native valve attachment (two cases), pannus formation + native valve attachment (two cases), sclerotic change (one case), pannus formation + sclerotic change (one case), and native valve attachment + valve infection (one case). Freedom from reoperation, structural valve deterioration, and nonstructural dysfunction at 18 years was 62.7% +/- 10.7%, 96.0% +/- 2.9%, and 76.7% +/- 8.3%, respectively. CONCLUSIONS: In our 18 years of experience, although the survival after TVR with bioprostheses is acceptable, the reoperation free rate is not satisfactory. Pannus formation on the cusps of the ventricular side seems to be a serious problem that causes bioprosthetic dysfunction in the tricuspid position.

Thrombus formation by the application of thrombin to the outer surface of mouse mesenteric vein: comparison with the application of ADP.

Mesenteries of mice under anesthesia were stretched over an inverted microscope. A micropipette filled with solution containing various concentrations of ADP or thrombin was brought into contact with the outside of a mesenteric vein by micromanipulation, and then poured over the outer surface of the vein. Morphological characteristics of the thrombi and the time needed for thrombus formation were examined. Application of either thrombin or ADP to the adventitia of mesenteric veins caused thrombus formation. Although thrombi by application of ADP seemed to be anchored by direct adhesion of platelets to the exposed subendothelium, thrombi by application of thrombin seemed to be anchored by deposited fibrin.

Calcific degeneration of bioprosthetic aortic valves in patients receiving steroid therapy.

BACKGROUND AND AIMS OF THE STUDY: Calcification of glutaraldehyde-preserved bioprosthetic valves is a frequent long-term complication of valve replacement, although the mechanism responsible for such degeneration is not clearly understood. In the current study, we investigated the calcific degeneration of bioprosthetic aortic valves in patients who had been given steroid treatment for aortitis in order to evaluate the immune response to glutaraldehyde-preserved bioprostheses. METHODS: Ten patients who had undergone aortic valve replacement with bioprosthetic valves were studied. Their mean age was 48.4 years (range: 27 to 64 years). Aortitis was due to Takayasu disease in eight patients and to Behcet aortitis in two. The bioprosthetic valves used included bovine pericardial xenografts (n = 8) and porcine aortic valves (n = 2). The mean daily dosage of prednisone was 10.1 mg (range: 2.5 to 60 mg); mean duration of therapy was 8.0 years. The mean patient follow up, using echocardiography, was 11.5 years (range: 8.5 to 16 years). The total follow up period was 115 patient-years. RESULTS: During follow up, three reoperations were required because of valve detachment, aortic insufficiency due to perforation of the aortic cusp, and aortic insufficiency with coronary orifice stenosis, respectively. No reoperations were required for stenotic degeneration of the bioprosthetic valves. Seven bioprosthetic valves were still functioning between 8.5 and 16 years after implantation. Calcific degeneration in two of three bovine pericardial valves that required replacing was surprisingly minimal; separation of collagen fibers in the valves by infiltration with plasma proteins was also minimal. CONCLUSIONS: These results suggest that the calcific degeneration of bioprosthetic valves may be decreased by concomitant steroid therapy for aortitis, though further research will be required to confirm this effect and to determine the mechanism(s) involved.

Long-term pathological changes of expanded polytetrafluoroethylene (ePTFE) suture in the human heart.

Expanded PTFE (ePTFE) sutures have been used widely as a mitral chordal substitute. We present a structural analysis of ePTFE sutures implanted as artificial chordae for 7.5 years and 8.6 years in patients with mitral regurgitation. No calcification was found either macroscopically or microscopically, and the ePTFE suture retained its normal flexibility. The suture was totally encapsulated with host tissues composed of dense fibrous tissue covered with endothelial cells.

Right lung transplantation followed by left pneumonectomy in the rat.

OBJECTIVE: To develop a rodent lung transplant model which depends on graft function for survival, total microsutureless lung transplantation was carried out and followed by contralateral native pneumonectomy in the rat. METHODS: Total non-microsuture right lung transplantation was undertaken using a cuff technique with anastomotic areas twice as big as those for the left lung transplantation. Inbred rats received either right (n = 10) or left lung isograft (n = 10) with non-microsuture techniques and underwent contralateral native pneumonectomy 2 weeks later to test the function of the grafted lung. RESULTS: While none of the left lung recipients could be disconnected from the respirator after right pneumonectomy, eight of ten right lung recipients tolerated left pneumonectomy, increased body weight and regained exercise capacity (oxygen uptake 49 +/- 4 ml/kg per min) comparable to that of control rats undergoing right hilar stripping and left pneumonectomy. CONCLUSIONS: The results suggest that the grafted right lung, but not the left lung, allows survival, growth and exercise of the recipient. Right lung transplantation followed by native left pneumonectomy may serve as a physiologic model of lung transplantation in the rat.

Giant cell arteritis involving the cerebral artery.

We describe a 59-year-old Japanese man with rare complications of giant cell arteritis. He presented with aortic insufficiency due to dilatation of the aortic root. Nine years after the occurrence of aortic insufficiency, he suffered from a cerebral infarction due to occlusion of the left middle and anterior cerebral arteries, showing giant cell arteritis.

Giant cell pneumonia caused by varicella zoster virus in a neonate.

A premature male neonate, born at the 25th gestational week, developed pneumonia six days after delivery and died. Postmortem examination of the lungs revealed giant cell pneumonia with intranuclear inclusion bodies; varicella zoster infection was confirmed by immunoperoxidase stain using monoclonal antibody to varicella zoster virus and electron microscopic examination. In previously reported necropsy cases of numerous giant-cell formation in the lung is not mentioned. Therefore, the unusual features prompting this report include the absence of skin lesions in this mother and infant and the presence of giant cell pneumonia, not previously reported in varicella zoster infection.