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Biomedical subjects

M Jahangiri

Publications and source records attributed to M Jahangiri.

At least 19 recordsLinked to original sources

Autoimmune mechanisms of atherosclerosis.

Accumulating evidence supports an autoimmune mechanism as one of the prime pathogenic processes involved in the development of atherosclerosis. So far, three proteins, including heat shock proteins (HSPs), oxidized low-density lipoprotein (oxLDL), and beta2 glycoprotein1 (beta2GP1) have been recognized as autoantigens. It has been demonstrated that risk factors for atherosclerosis, such as hypercholesterolemia, hypertension, infections, and oxidative stress, evoke increased expression of HSPs in cells of atherosclerotic lesions. Autoantibody levels against HSPs are significantly increased in patients with atherosclerosis and T lymphocytes specifically responding to these autoantigens have been demonstrated within atherosclerotic plaques. Subcutaneous immunization of animals with HSP65 induced atheroma formation in the arterial wall. Furthermore, circulating immunoglobulin (Ig) G and IgM oxidized low-density lipoprotein (oxLDL) antibodies are present in the plasma of animals and humans and form immune complexes with oxLDL in atherosclerotic lesions. These antibodies closely correlate with the progression and regression of atherosclerosis in murine models. Interestingly, recent reports demonstrated that pneumococcal vaccination to LDL receptor-deficient mice results in elevation of anti-oxLDL IgM Ab EO6, which is inversely correlated with the development of atherosclerosis. Finally, it has been observed that autoantigen beta2GP1 localizes in the atheroma and that autoantibodies to beta2GP1 are correlated with the incidence of atherosclerosis in patients. Hence, these autoimmune reactions to HSPs, oxLDL and beta2GP1 can contribute to the initiation and progression of atherosclerosis.

Animals↗

Role of antiheat shock protein 60 autoantibodies in atherosclerosis.

Immuno-inflammatory processes are implicated, as one of the prime pathogenic processes involved, in the development and progression of early atherosclerosis. High levels of circulating antiheat shock protein 60 (HSP60) autoantibodies have been associated with increasing severity of atherosclerosis in patients. We have recently presented evidence, extending this statistical association to that of causality, by showing that anti-HSP60 antibodies purified from sera of patients with documented atherosclerosis when injected into tail vein of apoE deficient mice resulted in accelerated atherosclerosis in them. High degree of sequence homology between microbial and mammalian HSP60, due to evolutionary conservation, carries a risk of misdirected autoimmunity against HSPs expressed on the stressed cells of vascular endothelium. HSPs and anti-HSP antibodies have been shown to elicit production of pro-inflammatory cytokines. These autoimmune reactions to HSPs expressed in the vascular tissue can contribute to both initiation and perpetuation of atherosclerosis.

Animals↗

Hydatid disease of the heart.

A 27-year-old physical education teacher, from a rural sheep farming area of South Africa, was referred following an isolated episode of collapse. Transthoracic echocardiography and MRI showed a cystic lesion under the septal leaflet of the tricuspid valve attached to the right ventricular wall. A provisional diagnosis of hydatid cyst was made. Hydatid serology was negative and there was no evidence of hydatidosis elsewhere. Preoperatively, the patient was treated with praziquantel and albendazole. Surgery was performed using cardiopulmonary bypass. Cyst was excised without any spillage. The patient was weaned off bypass without any support and made an uneventful recovery. Cytology and microbiology of the specimen confirmed hydatid pathology. This case describes excision of a right ventricular hydatid with techniques used to avoid spillage. It also describes an up-to-date antihelminthic therapy used in the management of hydatid cysts.

Adult↗

Long-term results of relief of subaortic stenosis in univentricular atrioventricular connection with discordant ventriculoarterial connections.

BACKGROUND: We set out to examine the long-term results of relief of subaortic stenosis by enlargement of ventricular septal defect in patients with univentricular atrioventricular connection to a dominant left ventricle and discordant ventriculoarterial connections. METHODS: Twenty-four patients underwent enlargement of ventricular septal defect between 1985 and 1998 at a median age of 3.2 years (range, 3 weeks to 14 years). Ten patients were younger than 1 year of age. Eighteen had undergone previous banding of the pulmonary trunk, 9 of whom also required repair of coarctation of the aorta. The median subaortic gradient before enlargement was 46 mm Hg. Twenty-three patients had a patch to enlarge the rudimentary right ventricle. RESULTS: Five patients (21%) died in the early postoperative period. The overall survival at 1 and 3 years was 73%, and at 5 and 10 years was 68% and 60%, respectively. Complete heart block requiring insertion of a pacemaker occurred in 2 patients (8%). A Fontan operation was performed in 10 patients, 5 underwent a bidirectional Glenn procedure, and 2 required cardiac transplantation. Follow-up was complete in all survivors at a median time of 6.7 years (range, 8 months to 13 years). From the earlier part of the series, 3 patients experienced aortic insufficiency and 2 had recurrent obstruction. Factors adversely affecting survival were age younger than 1 year at operation and presence of obstruction within the aortic arch. CONCLUSIONS: Our experience shows that, in patients with univentricular atrioventricular connection to a dominant left ventricle and subaortic stenosis, enlargement of the ventricular septal defect provides satisfactory relief of obstruction except in those younger than 1 year of age, and those who have associated obstruction in the aortic arch.

Anastomosis, Surgical↗

A case for anatomic correction in atrioventricular discordance? Effects of surgery on tricuspid valve function.

OBJECTIVE: To assess tricuspid valve function in atrioventricular discordance after palliative procedures (pulmonary artery banding and Blalock-Taussig shunt) and corrective procedures (anatomic and physiologic repair). METHODS: Tricuspid valve dysfunction was assessed by transthoracic echocardiography and graded as no regurgitation (0), mild (1), moderate (2), and severe (3) before and after palliative and corrective procedures performed in 97 patients with atrioventricular discordance between 1988 and 1999. Thirty-two percent had an isolated ventricular septal defect, 43% had a ventricular septal defect and pulmonary stenosis, and 16% had pulmonary stenosis. Twenty-six patients underwent pulmonary artery banding and 28 had a Blalock-Taussig shunt. Seventy patients underwent physiologic and 19 underwent anatomic repair. Six patients underwent one-ventricle repair. RESULTS: After pulmonary artery banding, the tricuspid regurgitation score decreased from 1.7 +/- 0.8 to 0.9 +/- 0.6 (P <.001). In patients who underwent a Blalock-Taussig shunt, the tricuspid regurgitation score increased from 0.7 +/- 0.5 preoperatively to 1.4 +/- 0.6 postoperatively (P <.001). After physiologic repair, there was no significant change in the tricuspid regurgitation score; however, 7 patients required additional repair or replacement. The regurgitation score was significantly reduced from 1.5 +/- 0.8 to 0.4 +/- 0.5 (P <.001) after anatomic repair. The operative mortality in patients who underwent physiologic repair was 7% as compared with 0% in the anatomic repair group (P =.59). The median follow-up was 3.2 years. CONCLUSIONS: Right ventricular volume loading (shunt) worsens tricuspid regurgitation, whereas volume reduction (banding) or left-to-right septal shift (anatomic repair) has beneficial effects. We have not observed a significant change in the tricuspid regurgitation score after physiologic repair. Anatomic repair can be performed in selected patients with atrioventricular discordance and provides superior functional results.

Abnormalities, Multiple↗

Repair of the truncal valve and associated interrupted arch in neonates with truncus arteriosus.

OBJECTIVE: Truncal valve regurgitation and interrupted aortic arch have frequently been identified as risk factors in the repair of truncus arteriosus. We wished to examine these factors in the current era including the impact of truncal valve repair. METHODS: Between January 1992 and August 1998, 50 patients underwent surgical repair of truncus arteriosus. Their ages ranged from 2 days to 6 months (median, 2 weeks). Nine patients had associated interrupted aortic arch. Of the 14 patients (28%) in whom truncal valve regurgitation was diagnosed preoperatively, 5 had mild regurgitation, 5 had moderate regurgitation, and 4 had severe regurgitation. Five underwent truncal valve repair and 1 underwent homograft replacement of the truncal valve with coronary reimplantation. RESULTS: The actuarial survival was 96% at 30 days, 1 year, and 3 years. There were no deaths in patients with associated interrupted aortic arch. The 2 deaths in the series occurred in patients with truncal valve regurgitation, neither of whom underwent repair. Postoperative transthoracic echocardiography in patients who underwent valve repair showed minimal residual valvular regurgitation. None of the patients has required reoperation because of truncal valve problems or aortic arch stenosis at a median follow-up of 23 months (range, 1-60 months). Conduit replacement has been done in 17 patients (34%) after a mean duration of 2 years. The freedom from reoperation for those who had an aortic homograft was 4 years and for those who had a pulmonary homograft was 3 years. CONCLUSION: Despite the magnitude of the operation, excellent results can be achieved in complex forms of truncus arteriosus. In the current era interrupted aortic arch is no longer a risk factor for repair of truncus. Aggressive application of truncal valvuloplasty methods should neutralize the traditional risk factor of truncal valve regurgitation.

Abnormalities, Multiple↗

Surgical management of complex and tunnel-like subaortic stenosis.

BACKGROUND: Relief of primary or secondary subaortic stenosis (SAS) remains a surgical challenge. Heart block, aortic valve regurgitation and recurrent obstruction have been persistent problems. METHODS: Forty six patients who underwent surgery for complex and tunnel-like SAS between January 1990 and November 1998 were reviewed. In 45 of the 46 patients SAS developed following repair of a primary congenital heart defect and only one patient presented with de novo tunnel-like SAS. Fifteen of the 45 patients had undergone repair of double-outlet right ventricle (DORV) and the remaining 30 had undergone repair of a variety of defects. The median age at the time of surgery was 5 years. The modified Konno procedure was performed in 15 patients, Konno procedure in three, Ross-Konno procedure in two and resection of the conal septum in 12 patients. Five patients with DORV underwent replacement of the intraventricular baffle and two patients underwent an aortic valve-preserving procedure in conjunction with mitral valve replacement. RESULTS: There were no deaths. None of the patients had an exacerbation of aortic regurgitation and none developed complete heart block. The median follow-up was 3 years (range 1 month-8.5 years). Two patients developed recurrent SAS defined as a gradient of 40 mmHg or greater diagnosed by transthoracic echocardiography. Freedom from SAS at 1, 3 and 5 years was 100, 94 and 86%, respectively. CONCLUSIONS: We favor the modified Konno procedure and conal resection to the Konno or the Ross procedure, since insertion of a prosthetic valve or homograft is avoided and aortic valve function is preserved. Excellent relief of tunnel-like SAS can be achieved without damage to the conduction tissue.

Aortic Stenosis, Subvalvular↗

Subclavian flap angioplasty: does the arch look after itself?

OBJECTIVES: We sought to assess the early and long-term results of subclavian flap angioplasty in neonates and infants, with particular attention to growth of the hypoplastic arch. METHODS: A retrospective analysis of 185 consecutive patients who underwent subclavian flap angioplasty between 1974 and 1998 was carried out. The patients included 125 neonates and 60 infants, with a median age of 18 days. Sixty-six (36%) patients had an additional ventricular septal defect, 41 (22%) patients had aortic arch hypoplasia diagnosed preoperatively, 141 (76%) had an associated patent ductus arteriosus, and 41 (22%) had additional complex heart disease. Follow-up was with transthoracic Doppler echocardiography in all patients. RESULTS: The early mortality was 3%. Recoarctation, defined as a Doppler gradient of 25 mm Hg or more, occurred in 11 (6%) patients at a median follow-up of 6.2 years (6.2 +/- 4.6 years). This included 4 of the 41 patients in whom arch hypoplasia was diagnosed preoperatively. There were no complications with the left arm. By multivariate analysis, risk factors for death were determined to be residual arch hypoplasia and low birth weight. The only risk factor for recoarctation was persistent arch hypoplasia after surgical treatment. However, angiographic imaging of the aorta showed that recoarctation was not due to a hypoplastic transverse arch, and it was probably at the site of ductal tissue. Survival at 5 and 10 years was 98% and 96%, respectively. Freedom from reoperation for recoarctation at 2 years was 95%, and at 5, 10, and 15 years, it was 92%. CONCLUSIONS: Subclavian flap repair remains an effective technique for repair of aortic coarctation with excellent results and low mortality. In the majority of patients, arch hypoplasia regresses after this procedure.

Angioplasty↗

Evaluation of hemostatic and coagulation factor abnormalities in patients undergoing the Fontan operation.

OBJECTIVE: Low-velocity and nonlaminar flow patterns in the Fontan circulation, as well as abnormal liver function in some patients, may partly account for the coagulation abnormalities seen. We examined (1) coagulation factor abnormalities before and after the Fontan procedure and (2) regional coagulation factor abnormalities in the Fontan circulation. METHODS: Levels of factors V, VII, VIII, X, antithrombin III, prothrombin fragment F1+2, protein C, and protein S were measured in 2 groups of patients: In 14 patients undergoing the Fontan procedure, blood was analyzed before the operation and 5 days after the operation (group 1). The median age in this group was 3.2 years. In 10 patients who had undergone the Fontan procedure, cardiac catheterization was performed and samples were taken from the femoral vein, inferior vena cava, right atrium, and pulmonary artery (group 2). The median age in this group was 6.2 years and the median follow-up from the Fontan procedure was 4.1 years. RESULTS: In group 1 a significant increase was noted postoperatively in the concentration of factor VIII (P<.001), factor X (P<.001), and prothrombin fraction F1+2 (P <.001). A significant decrease in the levels of antithrombin III (P <.001), protein C (P<.004), and protein S (P<.02) was also found. The increase in factors VIII and X persisted at 4 years' follow-up in group 2 patients. In group 2, no significant regional differences were observed between the coagulation factors measured at different sites. CONCLUSIONS: There is an increased tendency toward coagulation after the Fontan procedure. A prothrombotic state is supported by thrombin generation associated with reduced antithrombin III concentration. This increase in coagulation may contribute to the early and late risks of thromboembolism observed after the Fontan procedure. We did not find any regional differences in coagulation abnormalities in patients late after the Fontan procedure. Therefore, the mechanisms and causes of the coagulation abnormalities remain unclear.

Antithrombin III↗

Coronary artery surgery is associated with different forms of atherogenic lipoprotein modifications.

BACKGROUND: Increasing evidence shows that thrombogenicity and atherogenicity of lipoproteins are related to modifications involving oxidative, enzymatic, or physical alterations of these molecules. Findings on lipid peroxidation associated with cardiopulmonary bypass are conflicting, and the possible other forms of atherogenic lipid modification are unknown. The various forms of lipoprotein modifications including lipid peroxidation, desialylation, and leukocytic elastase activity after coronary artery bypass graft operations are examined. METHODS: In patients undergoing coronary artery bypass graft operations, plasma total lipid hydroperoxides (n = 102), plasma leukocytic elastase activity (n = 125), free radical formation (n = 30), low-density lipoprotein oxidation, and sialic acid content before operation and at 2, 24, 48, and 72 hours after cardiopulmonary bypass and 3 months after operation were measured. RESULTS: Preoperative plasma lipid peroxide concentration (2.2 micromol/L) increased after cardiopulmonary bypass (peak, 7.5 micromol/L; p<0.001) and remained significantly elevated at 3 months after surgery (4.2 micromol/L; p<0.01). There was a significant correlation between increased free radical generation and lipid peroxide levels in blood at all postoperative intervals. Low-density lipoprotein separated from plasma samples showed increased oxidation 48 hours after bypass. Sialic acid content of low-density lipoprotein was significantly reduced 48 hours after bypass. Plasma elastase activity increased significantly at all postoperative intervals. CONCLUSIONS: Coronary artery bypass graft operation is associated with generation of sustained blood levels of modified lipoproteins. These thrombogenic and atherogenic particles may play an important role in hemostatic and arteriosclerotic complications of coronary artery bypass graft operations.

Adult↗

Does the modified Blalock-Taussig shunt cause growth of the contralateral pulmonary artery?

BACKGROUND: Although some pediatric cardiology departments have a policy of adopting primary correction of tetralogy of Fallot in all symptomatic infants, we and others still palliate neonates and infants. Effective palliation should ameliorate symptoms and allow growth of the pulmonary arteries. Although studies on the growth of the ipsilateral and contralateral pulmonary arteries after a classic Blalock-Taussig shunt have been reported, pulmonary artery growth after a modified Blalock-Taussig shunt has not been studied as thoroughly. Therefore, we examined whether there is equal growth of the contralateral pulmonary artery after a modified Blalock-Taussig shunt. METHODS: We retrospectively analyzed the records of 140 patients with symptomatic tetralogy of Fallot who had a modified Blalock-Taussig shunt between October 1985 and October 1995. The median age at the time of the Blalock-Taussig shunt was 1.6 months. All patients had corrective procedures at a median age of 1.7 years. Cineangiography was done before the corrective procedure. From the angiograms the diameter of the right and left pulmonary arteries before their first lobar branches and the diameter of the descending thoracic aorta at the level of the diaphragm were measured. For each patient the ratios of right pulmonary artery to descending thoracic aorta and left pulmonary artery to descending thoracic aorta were determined and compared using Student's t test. RESULTS: Of the 140 patients, 114 had a left-sided Blalock-Taussig shunt, 20 had a right-sided shunt, and 6 patients had bilateral shunts. The mean right pulmonary artery to descending thoracic aorta ratio was 1.10 and the mean left pulmonary artery to descending thoracic aorta ratio was 0.98. This difference was not significant. CONCLUSION: We showed equal growth of the right and left pulmonary arteries with no distortion after a modified Blalock-Taussig shunt. If palliation is considered, the modified Blalock-Taussig shunt remains our choice.

Cardiac Surgical Procedures↗

Improved results with selective management in pulmonary atresia with intact ventricular septum.

OBJECTIVE: Late outcome of neonatal pulmonary atresia with intact ventricular septum remains poor in most reported series. We have followed a selective approach toward either single ventricle repair versus complete or partial biventricular repair based on the presence of right ventricle-dependent coronary circulation and growth of the right ventricle. METHODS: A retrospective chart review was conducted of 47 patients who underwent surgery between January 1991 and September 1998. RESULTS: Sixteen (34%) patients had a right ventricle-dependent coronary circulation, with a tricuspid valve Z-score of -3.0 +/- 0.66 versus -2.0 +/- 0.95 (P =.002) for those without a right ventricle-dependent coronary circulation. A systemic-pulmonary artery shunt only was performed in all patients with a right ventricle-dependent coronary circulation, with 1 death. Fourteen of 16 patients with a right ventricle-dependent coronary circulation underwent a bidirectional Glenn shunt at a median of 9 months after their first operation, 9 of whom have had a Fontan procedure (no deaths). In the 31 (66%) patients without a right ventricle-dependent coronary circulation, 6 patients underwent only a systemic-pulmonary artery shunt, 23 had a shunt and right ventricular decompression, and 2 had only a transannular patch. In this group, 10 patients received a 2-ventricle repair, 6 a 1. 5-ventricle repair, and 8 patients had a Fontan procedure. There was 1 early death and the overall survival was 98% at 1 year, 5 years, and 7 years. CONCLUSIONS: If patients are stratified well, excellent survival can be achieved in the treatment of pulmonary atresia with intact ventricular septum. This result may be at the price of achieving a 1-ventricle as opposed to a 2-ventricle repair.

Actuarial Analysis↗

Endobronchial stenting for extrinsic compression caused by pulsatile pulmonary artery in a 4-week-old infant.

Respiratory compromise secondary to external vascular compression may complicate the course of infants and neonates undergoing repair of congeni tal heart disease. Management of such complications usually involves prolonged ventilatory support and even additional high-risk surgical procedures. In recent years, endobronchial placement of self-expanding stents became a realistic treatment option, although there is controversy as to which of the many stents available today give the best results. We report the first successful endobronchial placement of a self-expanding stent in a 4-week-old infant. This conservative treatment for extrinsic airway compression led to the rapid extubation and recovery of the patient.

Bronchial Diseases↗