Vasorelaxation induced by new third-generation dihydropyridine calcium antagonist azelnidipine in human internal mammary artery.

BACKGROUND: Graft spasm remains challenging in coronary artery bypass graft (CABG) surgery. Calcium antagonists are commonly used in patients with coronary artery disease. We investigated the inhibitory effect of the new third-generation dihydropyridine calcium antagonist azelnidipine on the vasoconstriction in human internal mammary artery (IMA) from patients undergoing CABG. METHODS: Isolated IMA rings (n = 68, taken from 28 patients) were studied in myograph in two ways: the relaxing effect of azelnidipine on vasoconstrictor-induced precontraction by potassium chloride (KCl) and U46619; and the depressing effect of azelnidipine at plasma concentrations on the contraction. RESULTS: Azelnidipine caused full relaxation in KCl-contracted (96.5% ± 0.7%) and in U46619-contracted (96.5% ± 1.4%) IMA rings (n = 8), with 28.8-fold higher potency to KCl than to U46619 (EC50 -7.49 ± 0.21 versus -6.03 ± 0.11 log M, p < 0.01). Pretreatment of IMA with plasma concentrations of azelnidipine (-6.1 log M) significantly depressed subsequent contraction to KCl (from 25.8 ± 2.2 mN to 16.0 ± 1.5 mN, p < 0.01) and U46619 (from 30.6 ± 4.0 mN to 16.5 ± 2.2 mN, p < 0.05). CONCLUSIONS: We conclude that in human IMA, azelnidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Thus, use of azelnidipine in CABG patients is favored for treating and preventing graft spasm.

Alteration of plasma trace elements in patients undergoing open heart surgery.

Trace elements may contribute to myocardial dysfunction and susceptibility of the phospholipid cell membrane to free-radical damage and oxidative changes. We studied the concentration of trace elements copper, zinc, and magnesium in cardiac surgery. Fifty-four consecutive patients for elective coronary artery bypass grafting (n = 30) and valve replacement (n = 24) were studied. Blood samples were collected every 30 min (T1-T5) during cardiopulmonary bypass and postoperatively (T6-T9). Plasma concentrations of copper, zinc, and magnesium were measured with flame atomic absorption spectrophotometry. The concentrations of copper, zinc, and magnesium were significantly different during and after cardiopulmonary bypass (p < 0.01). The zinc concentration at T7 and T8 (p < 0.01) and the copper concentration at T1, T9 (p < 0.05) were significantly different between two groups. However, the magnesium concentration had no significant differences between the two groups (p > 0.05). In patients undergoing valve replacement or coronary artery bypass grafting, the concentrations of copper and zinc decreased significantly during cardiopulmonary bypass. Our study suggests that the current cardiopulmonary bypass protocol is adequate in the maintenance of c magnesium. However, the low copper and zinc concentrations found in the present study may suggest that in the future, supplementation particularly of copper and zinc may become a necessary procedure in cardiac surgery with cardiopulmonary bypass.

Role of TRPC3 channel in human internal mammary artery.

BACKGROUND AND AIMS: Intracellular calcium regulation in endothelial cells depends on transient receptor potential channels (TRPs). Canonical TRPs (TRPCs) are now recognized as the most important Ca(2+)-permeable cation channels in vascular endothelium and TRPC3 channel is reported to play a role in vasodilation in animal vessels. However, little is known about the role of TRPCs in human arteries. We therefore tested the hypothesis that TRPCs play a role in human arteries. METHODS: Cumulative concentration-relaxation curves to acetylcholine (-11 to -4.5 log M) were established in the human internal mammary artery (IMA) rings (n = 42) taken from 28 patients undergoing coronary artery bypass grafting in precontraction induced by U46619 (-8 log M) in the absence or presence of SKF96365 (10 µmol/L) or Pyr3 (3 µmol/L). Protein expressions of TRPC3 were determined by Western blot and immunohistochemistry staining. RESULTS: The maximal relaxation induced by acetylcholine was significantly attenuated by the nonspecific cation channels inhibitor, SKF96365 (48.2 ± 3.7 vs. 66.0 ± 0.9% in control, p <0.01) or the selective TRPC3 blocker, Pyr3 (58.4 ± 2.3% vs. 67.7 ± 1.1% in control, p <0.01). Protein expression of TRPC3 was detected in human IMA. CONCLUSIONS: TRPC3 exists and plays a role in the acetylcholine-induced endothelium-dependent relaxation in the human IMA. This study suggests that TRPC3 may be a potential new target in endothelial protection in patients with endothelial dysfunction such as in patients with coronary artery disease in order to improve the long-term patency of the grafting vessels.

A novel variation of PLAGL1 in Chinese patients with isolated ventricular septal defect.

AIMS: Ventricular septal defect (VSD) is the most common congenital heart disease (CHD). A number of genetic studies have linked the gene of PLAGL1 to the etiology of CHD. The present study aimed to identify potential pathogenic mutations for PLAGL1 and to provide insights into the etiology of isolated VSD. METHODS: Case-control mutational analysis was performed in 300 patients with isolated VSD and 300 healthy controls. Two protein-coding extons of PLAGL1 and their partial flanking intron sequences were amplified by polymerase chain reaction and sequenced on an ABI3730 Automated Sequencer. CLC workbench software was used to compare the conservatism of PLAGL1 protein with other multiple species. RESULTS: Neither missense nor frame-shift mutations were detected in two protein-coding extons of PLAGL1. But a novel synonymous variation (c.486A>G, p. E162E) was detected in protein-coding exon-2. The glutamic that translated with the mutational codon is conservative when compared with other species. CONCLUSIONS: We detected a synonymous variation in the protein-coding exon-2 of PLAGL1 in isolated VSD patients. It is possible that the etiology of isolated VSD might not be directly linked with this mutation, but might be associated with other patterns of gene expression regulation in PLAGL1, such as in the methylation-dependent manner.

Surgical treatment of tricuspid regurgitation after mitral valve surgery: a retrospective study in China.

BACKGROUND: Functional tricuspid regurgitation (TR) occurs in patients with rheumatic mitral valve disease even after mitral valve surgery. The aim of this study was to analyze surgical results of TR after previous successful mitral valve surgery. METHODS: From September 1996 to September 2008, 45 patients with TR after previous mitral valve replacement underwent second operation for TR. In those, 43 patients (95.6%) had right heart failure symptoms (edema of lower extremities, ascites, hepatic congestion, etc.) and 40 patients (88.9%) had atrial fibrillation. Twenty-six patients (57.8%) were in New York Heart Association (NYHA) functional class III, and 19 (42.2%) in class IV. Previous operations included: 41 for mechanical mitral valve replacement (91.1%), 4 for bioprosthetic mitral valve replacement (8.9%), and 7 for tricuspid annuloplasty (15.6%). RESULTS: The tricuspid valves were repaired with Kay's (7 cases, 15.6%) or De Vega technique (4 cases, 8.9%). Tricuspid valve replacement was performed in 34 cases (75.6%). One patient (2.2%) died. Postoperative low cardiac output (LCO) occurred in 5 patients and treated successfully. Postoperative echocardiography showed obvious reduction of right atrium and ventricle. The anterioposterior diameter of the right ventricle decreased to 25.5 ± 7.1 mm from 33.7 ± 6.2 mm preoperatively (P < 0. 05). CONCLUSION: TR after mitral valve replacement in rheumatic heart disease is a serious clinical problem. If it occurs or progresses late after mitral valve surgery, tricuspid valve annuloplasty or replacement may be performed with satisfactory results. Due to the serious consequence of untreated TR, aggressive treatment of existing TR during mitral valve surgery is recommended.

Effect of amlodipine in human internal mammary artery and clinical implications.

BACKGROUND: Graft spasm remains challenging in CABG (coronary artery bypass grafting) surgery. We investigated the inhibitory effect of a dihydropyridine calcium antagonist amlodipine on the vasoconstriction mediated by potassium chloride (KCl), human urotensin-II (hU-II), and U46619 in human internal mammary artery (IMA) from patients undergoing CABG. METHODS: Isolated IMA rings (n = 78, taken from 42 patients) were studied in organ baths in two ways: the relaxing effect of amlodipine on vasoconstrictor-induced precontraction by KCl, hU-II, and U46619 and the depressing effect of amlodipine on the contraction. RESULTS: Amlodipine caused full relaxation in KCl-contracted (98.0% ± 2.1%), in hU-II-contracted (98.5% ± 2.4%), and in U46619-contracted (96.3% ± 1.3%) IMA rings (n = 8) with 15.5-fold higher potency to KCl than to hU-II (effective concentration causing 50% of maximal response [EC(50)]: -8.17 ± 0.28 vs -6.98 ± 0.01 log M, p < 0.001) and 19.5-fold that to U46619 (EC(50): -8.17 ± 0.28 vs -6.88 ± 0.08 log M, p < 0.001). Pretreatment of IMA with plasma concentrations of amlodipine (-6.6 log M) significantly depressed subsequent contraction to KCl (from 20.8 ± 2.5 mN to 7.6 ± 3.0 mN, p = 0.004) and hU-II (from 14.1 ± 4.2 mN to 3.8 ± 2.0 mN, p = 0.026), but did not significantly affect the contraction to U46619. CONCLUSIONS: We conclude that in human IMA amlodipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Thus, use of amlodipine in CABG patients is favored in treating and preventing graft spasm.

The current strategy of repair of tetralogy of Fallot in children and adults.

OBJECTIVES: The strategies of repair of tetralogy of Fallot change with the age of patients. In children older than 4 years and adults, the optimal strategy may be to use different method of reconstruction of the right ventricular outflow tract from those followed in younger children, so as to avoid, or reduce, the pulmonary insufficiency that is increasingly known to compromise right ventricular function. METHODS: From April, 2001, through May, 2008, we undertook complete repair in 312 patients, 180 male and 132 female, with a mean age of 11.3 years +/-0.4 years, and a range from 4 to 48 years, with typical clinical and morphological features of tetralogy of Fallot, including 42 patients with the ventriculo-arterial connection of double outlet right ventricle. The operation was performed under moderate hypothermia using blood cardioplegia. The ventricular septal defect was closed with a Dacron patch. When it was considered necessary to resect the musculature within the right ventricular outflow tract, or perform pulmonary valvotomy, we sought to preserve the function of the pulmonary valve by protecting as far as possible the native leaflets, or creating a folded monocusp of autologous pericardium. RESULTS: The repair was achieved completely through right atrium in 192, through the right ventricular outflow tract in 83, and through the right atrium, the outflow tract, and the pulmonary trunk in 36 patients. A transjunctional patch was inserted in 169 patients, non-valved in all but 9. There were no differences regarding the periods of aortic cross-clamping or cardiopulmonary bypass. Of the patients, 5 died (1.6%), with no influence noted for the transjunctional patch. Of those having a non-valved patch inserted, three-tenths had pulmonary regurgitation of various degree, while those having a valved patch had minimal pulmonary insufficiency and good right ventricular function postoperatively, this being maintained after follow-up of 8 to 24-months. CONCLUSIONS: Based on our experience, we suggest that the current strategy of repair of tetralogy of Fallot in older children and adults should be based on minimizing the insertion of transjunctional patches, this being indicated only in those with very small ventriculo-pulmonary junctions. If such a patch is necessary, then steps should be taken to preserve the function of the pulmonary valve.