Cyclic GMP regulation of the L-type Ca(2+) channel current in human atrial myocytes.

1. The regulation of the L-type Ca(2+) current (I(Ca)) by intracellular cGMP was investigated in human atrial myocytes using the whole-cell patch-clamp technique. 2. Intracellular application of 0.5 microM cGMP produced a strong stimulation of basal I(Ca) (+64 +/- 5 %, n = 60), whereas a 10-fold higher cGMP concentration induced a 2-fold smaller increase (+36 +/- 8 %, n = 35). 3. The biphasic response of I(Ca) to cGMP was not mimicked by the cGMP-dependent protein kinase (PKG) activator 8-bromoguanosine 3',5' cyclic monophosphate (8-bromo-cGMP, 0.5 or 5 microM), and was not affected by the PKG inhibitor KT 5823 (100 nM). 4. In contrast, cGMP stimulation of I(Ca) was abolished by intracellular perfusion with PKI (10 microM), a selective inhibitor of the cAMP-dependent protein kinase (PKA). 5. Selective inhibition of the cGMP-inhibited phosphodiesterase (PDE3) by extracellular cilostamide (100 nM) strongly enhanced basal I(Ca) in control conditions (+78 +/- 13 %, n = 7) but had only a marginal effect in the presence of intracellular cGMP (+22 +/- 7 % in addition to 0.5 microM cGMP, n = 11; +20 +/- 22 % in addition to 5 microM cGMP, n = 7). 6. Application of erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA, 30 microM), a selective inhibitor of the cGMP-stimulated phosphodiesterase (PDE2), fully reversed the secondary inhibitory effect of 5 microM cGMP on I(Ca) (+99 +/- 16 % stimulation, n = 7). 7. Altogether, these data indicate that intracellular cGMP regulates basal I(Ca) in human atrial myocytes in a similar manner to NO donors. The effect of cGMP involves modulation of the cAMP level and PKA activity via opposite actions of the nucleotide on PDE2 and PDE3.

New arylpiperazine derivatives as antagonists of the human cloned 5-HT(4) receptor isoforms.

New derivatives of arylpiperazine 9 were designed from ML 10302, a potent 5-HT(4) receptor agonist in the gastrointestinal system. Compounds were synthesized by condensation of a number of available arylpiperazines or heteroarylpiperazines with 2-bromoethyl 4-amino-5-chloro-2-methoxybenzoate. They were evaluated in binding assays on the recently cloned human 5-HT(4(e)) isoform stably expressed in C6 glial cells with [(3)H]GR 113808 as the radioligand. The affinity values (K(i)) depended upon the substituent on the aromatic ring. A chlorine atom produced a marked drop in activity (K(i) > 100 nM), while a m-methoxy group gave a compound with nanomolar affinity (K(i) = 3 nM). The most potent compounds were the heterocyclic derivatives with pyrimidine, pyrazine, pyridazine, or pyridine moieties (compounds 9r, 9t, 9u, 9x, respectively). K(i) values for 9a and 9r were determined for the 5-HT(4(a)), 5-HT(4(b)), 5-HT(4(c)), and 5-HT(4(d)) receptor isoforms transiently expressed in COS cells. The results indicated that the compounds were not selective. They produced an inhibition of the 5-HT-stimulated cyclic AMP synthesis in the C6 glial cells stably expressing the 5-HT(4(e)) receptor and shifted the 5-HT concentration-effect curve on adenylyl cyclase activity with pK(D) values of 7.44 and 8.47, respectively. In isolated human atrial myocytes, 9r antagonized the stimulatory effect of 5-HT on the L-type calcium current (I(Ca)) with a K(D) value of 0.7 nM.

Isolation of the serotoninergic 5-HT4(e) receptor from human heart and comparative analysis of its pharmacological profile in C6-glial and CHO cell lines.

RT - PCR technique was used to clone the human 5-HT(4(e)) receptor (h5-HT(4(e))) from heart atrium. We showed that this h5-HT(4(e)) receptor splice variant is restricted to brain and heart atrium. Recombinant h5-HT(4(e)) receptor was stably expressed in CHO and C6-glial cell lines at 347 and 88 fmol mg(-1) protein, respectively. Expression of h5-HT(4(e)) receptors at the cell membrane was confirmed by immunoblotting. The receptor binding profile, determined by competition with [(3)H]-GR113808 of a number of 5-HT(4) ligands, was consistent with that previously reported for other 5-HT(4) receptor isoforms. Surprisingly, we found that the rank order of potencies (EC(50)) of 5-HT(4) agonists obtained from adenylyl cyclase functional assays was inversely correlated to their rank order of affinities (K(i)) obtained from binding assays. Furthermore, EC(50) values for 5-HT, renzapride and cisapride were 2 fold lower in C6-glial cells than in CHO cells. ML10302 and renzapride behaved like partial agonists on the h5-HT(4(e)) receptor. These results are in agreement with the reported low efficacy of the these two compounds on L-type Ca(2+) currents and myocyte contractility in human atrium. A constitutive activity of the h5-HT(4(e)) receptor was observed in CHO cells in the absence of any 5-HT(4) ligand and two 5-HT(4) antagonists, GR113808 and ML10375, behaved as inverse agonists. These data show that the h5-HT(4(e)) receptor has a pharmacological profile which is close to the native h5-HT(4) receptor in human atrium with a functional potency which is dependent on the cellular context in which the receptor is expressed.

[Multiple pulmonary coronary fistulae. Apropos of a case]. / Fistules coronaro-artérielles pulmonaires multiples. A propos d'un cas.

Coronary-pulmonary fistula is a rare congenital anomaly. It is usually detected fortuitously in adulthood during a coronary angiography carried out to assess signs of myocardial ischemia. Multiple coronary fistulae are still more rare. Coronary angiography evaluates the lesions and indicates the most appropriate treatment. The congenital lesions are frequently combined with atheromatous lesions. The case described is that of a double fistula in a 61-year old man which was revealed by angina; the stenoses and occlusions which accompanied the fistulae lead to a discussion of their atheromatous nature and the nature of the pathological link between them: is this fortuitous or are they a progressive complication? Treatment involves both exclusion of the fistulae and coronary revascularization.

[Primary leiomyosarcoma of the pulmonary artery. Apropos of a case. Review of the literature]. / Léiomyosarcome primitif de l'artère pulmonaire. A propos d'un cas: revue de la littérature.

A 59-year-old woman hospitalised because of dyspnea and a heart murmur in a context of pyrexia was found to have evidence of obstruction of the pulmonary arterial system, clearly defined by ultrasonography, catheterisation and angiography and Imatron scan. The particular feature of this fifth reported case of pulmonary artery leiomyosarcoma is its documentation by transesophageal ultrasonography and tumor biopsy during catheterisation. Surgery with partial excision of the tumor was followed by survival for 6 months, bearing in mind the absence of chemo- or radiosensitivity of this type of tumor. Cases from the literature are reviewed.

[Retrograde dissection of the common trunk of the left coronary vessel during angioplasty of left anterior descending coronary artery. Apropos of 2 cases]. / Dissection rétrograde du tronc commun coronaire gauche pendant une angioplastie coronaire de l'artère interventriculaire antérieure. A propos de 2 cas.

Acute dissection of the left main coronary artery during coronary angiography or angioplasty is a rare but well known complication; it is attributed to a mechanical trauma caused by the tip of the catheter guide wire. The authors present two cases of dissection at the site of coronary angioplasty with a retrograde extension to the left main stem requiring emergency coronary surgery.

[Coronary artery bypass with bovine internal mammary artery graft]. / Pontages coronaires par artère mammaire interne de boeuf.

Ten of 1,025 patients undergoing coronary bypass surgery received one or two bovine internal mammary artery grafts. Surgery consisted in quadruple coronary bypass in 1 case, triple coronary bypass in 3 cases and double coronary bypass in 6 cases using 4 autologous saphenous vein grafts, 6 autologous internal mammary artery grafts and 13 bovine internal mammary artery grafts. It was necessary to use bovine internal mammary artery grafts because of total bilateral venous stripping in 5 patients, diffuse, bilateral varicose veins in 4 patients and because of the insufficient length of the vein in 1 patient. Short and medium-term (12 months) angiographic studies of the bovine grafts showed 5 occluded grafts, 2 proximal graft stenoses, and 1 patient graft up to the time of his death of extracardiac causes, with a maximum follow-up of 13 months. One of these 10 patients died in the early postoperative period of extracardiac causes with a patent bovine coronary graft. Another patient died in the 5th postoperative month during reoperation motivated by occlusion of the two implanted bovine coronary grafts. The other 8 patients are alive and stable from the coronary view point. Bovine internal mammary artery grafts may be used to manage an acute episode of coronary insufficiency by providing the time for the collateral circulation to develop but it does not provide a complete and durable method of revascularisation. Their use should therefore be reserved for exceptional cases.

[Non-ruptured calcified aneurysm of the Valsalva's sinus with angina pectoris and aortic insufficiency. Surgical treatment]. / Anévrysme calcifié non rompu du sinus de Valsalva avec angor et insuffisance aortique. Cure chirurgicale.

We report a case of aneurysm of the straight frontal, and not coronary, aortic sinus, non ruptured and calcified, responsible for a refractory angina pectoris and a massive aortic failure in a 71 year old woman. The surgical treatment consisted in the exclusion of the aneurysm of the aortic sinus by a tubular prosthesis in which only two thirds of the circumference have been used, associated with the replacement of an aortic valve by a bioprosthesis, without associated coronary by-pass.

[Coronary artery bypass using bovine internal mammary artery]. / Pontages coronaires par artère mammaire interne de boeuf.

Among 760 patients who underwent coronary artery bypass graft (CABG) 8 received one or two bovine internal mammary artery grafts. The surgical procedures were 4, 3 and 3 CABG respectively in 1, 3 and 4 cases with greater saphenous veins in 4 cases, internal mammary artery in 4 cases and bovine internal mammary artery in 11 cases. The 3 mm bioflow grafts were used to revascularize the left coronary artery in 6 cases (to the left anterior descending, circumflex artery) and the right coronary artery in 5 cases. The indications for the use of bovine mammary artery grafts were lack of suitable autologous vessels because of bilateral saphenous vein stripping in 4 cases, bilateral varicose veins in 3 cases and inadequate length of vein in 1 case. Post-operative angiographic studies of these bovine mammary grafts with a maximum follow-up of 11 months showed 5 occluded grafts, 2 grafts with proximal stenosis, one graft which remained patent until the patient died and 3 grafts still under evaluation. Bovine internal mammary artery grafts provide a solution for the acute stage of coronary disease, but do not achieve total and durable revascularization. Their use must remain exceptional.

[Intracoronary fracture of a guidewire tip in percutaneous coronary angioplasty]. / Rupture intracoronaire de l'extrémité d'un guide d'angioplastie coronaire percutanée.

The authors report a case of intracoronary rupture of the tip of a guidewire used for angioplasty. They discuss its mechanism and management. The hazards involved in re-using coronary dilatation material are underlined.

Late results after left-sided cardiac valve replacement in children.

Selection of types of cardiac valve substitutes for children remains controversial. Between 1976 and 1984, 166 children, 15 years of age or younger, underwent aortic (N = 53) or mitral valve replacement (N = 90) or both (N = 23). Biological prostheses were used in 84 patients and mechanical prostheses in 71; both a mitral bioprosthesis and an aortic mechanical valve were used in 11 patients. The overall early mortality was 9%. Mean follow-up intervals were 4.1 years for the bioprosthesis group, 3.3 years for the mechanical valve group, and 3.5 years for the group receiving both. The 7 year survival rates (+/- standard error) were 63% +/- 6% in the bioprosthesis group and 70% +/- 7% in the mechanical valve group (p = NS). After aortic valve replacement the 7 year survival rates were 66% +/- 14% (bioprosthesis group) and 77% +/- 9% (mechanical valve group) (p = NS); after mitral valve replacement the rates were 65% +/- 7% (bioprosthesis group) and 54% +/- 17% (mechanical valve group) (p = NS). The incidence of thromboembolic events was 0.6% +/- 0.4% per patient-year in the bioprosthesis group (none after aortic valve replacement, 0.8% +/- 0.6% per patient-year after mitral valve replacement) and 1.4% +/- 0.8% per patient-year in the mechanical valve group (0.7% +/- 0.7% per patient-year after aortic valve replacement, 4.0% +/- 2.8% per patient-year after mitral valve replacement) (p = NS). The linearized rates of reoperation were 10.4% +/- 1.8% per patient-year (bioprosthesis group) and 2.3% +/- 1.0% per patient-year (mechanical valve group) (p less than 0.001). The 7 year probability rates of freedom from all valve-related complications were 43% +/- 6% in the bioprosthesis group and 86% +/- 4% in the mechanical valve group (p less than 0.001). In the aortic position, a mechanical adult-sized prosthesis can always be implanted, and satisfactory long-term results can be anticipated. In the systemic atrioventricular position, the results are less than satisfactory with either type of prosthesis; every effort should be made to preserve the natural valve of the child.

[Long-term course of septal rupture operated on during the acute phase of a myocardial infarct]. / Evolution à long terme des ruptures septales opérées à la phase aiguë d'un infarctus du myocarde.

Between 1970 and 1979, 28 patients (18 men and 10 women, aged 46 to 76 years, average 62 years) with acute myocardial infarction complicated by septal rupture survived surgery performed during the acute phase. In the same period 62 patients were admitted to the Cardiology Department and were operated early for septal rupture complicating myocardial infarction. The site of infarction was the anterior wall in 22 cases and the posterior wall in 6 cases; septal rupture occurred on average after 4.2 days (range 1 to 10 days); 15 patients including 13 with cardiogenic shock underwent intraaortic balloon pumping for an average of 3:7 (range 1 to 11 days) before surgery; the operation performed after an average interval of 11 days consisted in direct suture of the defect in 3 cases and a patch repair in the other 25 cases, associated in all cases with infarctectomy and LAD coronary bypass grafting in 1 case. The immediate postoperative course was simple; three patients with residual shunts were not reoperated. Five to 14 years later, in 1984, 4 patients had been lost to follow-up; 4 patients had died, 2 of cardiac causes (LVF after 1 year and an arrhythmia after 4 years). Of the 20 survivors, 2 were successfully reoperated (1 coronary bypass after 10 years and 1 false aneurysm after 5 years). Only one patient had recurrent myocardial infarction. The quality and longevity of long-term survival encourage early surgery. The factors affecting long-term survival are discussed: correction of associated valvular defects, resifual shunts, conservation of left ventricular function and evaluation of the coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute thrombosis of a St. Jude Medical aortic prosthesis in a pregnant woman.

A 24-year-old, 4-months pregnant woman developed an acute thrombosis of a St. Jude Medical aortic valve prosthesis. Upon admission, she was in cardiogenic shock. A thrombectomy was achieved in emergency under cardiopulmonary bypass. The patient survived but not the fetus. Diagnosis, surgical procedure, anticoagulation drugs and valve prostheses in pregnant women are discussed.