J Thorac Cardiovasc Surg 2001;121:592-4

Hatem. Tyrosine kinase and protein kinase C regulate L-type Ca 2 1 current cooperatively in human atrial myocytes. Am. J. Physiol. Heart Circ. Physiol. 278: H670– H676, 2000.—The effects of tyrosine protein kinases (TK) on the L-type Ca 2 1 current ( I Ca ) were examined in whole cell patch-clamped human atrial myocytes. The TK inhibitors genistein (50 µM), lavendustin A (50 µM), and tyrphostin 23 (50 µM) stimulated I Ca by 132 6 18% ( P , 0.001), 116 6 18% ( P , 0.05), and 60 6 6% ( P , 0.001), respectively. After I Ca stimulation by genistein, external application of isoproterenol (1 µM) caused an additional increase in I Ca . Dialyzing the cells with a protein kinase A inhibitor suppressed the effect of isoproterenol on I Ca but not that of genistein. Inhibition of protein kinase C (PKC) by pretreatment of cells with 100 nM staurosporine or 100 nM calphostin C prevented the effects of genistein on I Ca . The PKC activator phorbol 12-myristate 13-acetate (PMA), after an initial stimulation (75 6 17%, P , 0.05), decreased I Ca ( 2 36 6 5%, P , 0.001). Once the inhibitory effect of PMA on I Ca had stabilized, genistein strongly stimulated the current (323 6 25%, P , 0.05). Pretreating myocytes with genistein reduced the inhibitory effect of PMA on I Ca . We conclude that, in human atrial myocytes, TK inhibit I Ca via a mechanism that involves PKC. human cells; whole cell patch calcium

The effects of tyrosine protein kinases (TK) on the L-type Ca(2+) current (I(Ca)) were examined in whole cell patch-clamped human atrial myocytes. The TK inhibitors genistein (50 microM), lavendustin A (50 microM), and tyrphostin 23 (50 microM) stimulated I(Ca) by 132 +/- 18% (P < 0.001), 116 +/- 18% (P < 0.05), and 60 +/- 6% (P < 0.001), respectively. After I(Ca) stimulation by genistein, external application of isoproterenol (1 microM) caused an additional increase in I(Ca). Dialyzing the cells with a protein kinase A inhibitor suppressed the effect of isoproterenol on I(Ca) but not that of genistein. Inhibition of protein kinase C (PKC) by pretreatment of cells with 100 nM staurosporine or 100 nM calphostin C prevented the effects of genistein on I(Ca). The PKC activator phorbol 12-myristate 13-acetate (PMA), after an initial stimulation (75 +/- 17%, P < 0.05), decreased I(Ca) (-36 +/- 5%, P < 0.001). Once the inhibitory effect of PMA on I(Ca) had stabilized, genistein strongly stimulated the current (323 +/- 25%, P < 0.05). Pretreating myocytes with genistein reduced the inhibitory effect of PMA on I(Ca). We conclude that, in human atrial myocytes, TK inhibit I(Ca) via a mechanism that involves PKC.

Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) have important functions in regulating cardiac excitability and contractility. In the present study, we examined whether CaMKII regulated the transient outward K(+) current (I(to)) in whole-cell patch-clamped human atrial myocytes. We found that a specific CaMKII inhibitor, KN-93 (20 micromol/L), but not its inactive analog, KN-92, accelerated the inactivation of I(to) (tau(fast): 66.9+/-4.4 versus 43.0+/-4.4 ms, n=35; P<0.0001) and inhibited its maintained component (at +60 mV, 4.9+/-0.4 versus 2.8+/-0.4 pA/pF, n = 35; P<0. 0001), leading to an increase in the extent of its inactivation. Similar effects were observed by dialyzing cells with a peptide corresponding to CaMKII residues 281 to 309 or with autocamtide-2-related inhibitory peptide and by external application of the calmodulin inhibitor calmidazolium, which also suppressed the effects of KN-93. Furthermore, the phosphatase inhibitor okadaic acid (500 nmol/L) slowed I(to) inactivation, increased I(sus), and inhibited the effects of KN-93. Changes in [Ca(2+)](i) by dialyzing cells with approximately 30 nmol/L Ca(2+) or by using the fast Ca(2+) buffer BAPTA had opposite effects on I(to). In BAPTA-loaded myocytes, I(to) was less sensitive to KN-93. In myocytes from patients in chronic atrial fibrillation, characterized by a prominent I(sus), KN-93 still increased the extent of inactivation of I(to). Western blot analysis of atrial samples showed that delta-CaMKII expression was enhanced during chronic atrial fibrillation. In conclusion, CaMKII control the extent of inactivation of I(to) in human atrial myocytes, a process that could contribute to I(to) alterations observed during chronic atrial fibrillation.

The aim of the study was to compare the supra-annular and intra-annular implantation techniques by evaluating the differences in early haemodynamic outcome (gradients, effective orifice area, regurgitation). Since August 1991, 200 stentless Bravo model 300 valves have been implanted. Patients were divided into three groups of consecutive cases: group 1 (n = 50) represents exclusively intra-annular implantation; group 2 (n = 50) is a transitional period: and group 3 (n = 100) comprises only patients with supra-annular implantation. Significant differences were found (P<0.001) in low postoperative gradients (mean < or = 10 mmHg): 24% in group 1, 42% in group 2, and 95% in group 3. Comparing groups 1 and 3, gradients were lower and effective orifice area was augmented in all valve sizes in group 3. Trivial central regurgitation was present in groups 1-3 (6%, 12% and 0% respectively). Peripheral regurgitation was trivial in 6%, 8% and 0% and mild to moderate in 4%, 2% and 0% (P<0.001).

Relapsing polychondritis is a rare inflammatory multiorgan disorder affecting cartillaginous structures and other connective tissues. More than 600 cases have been reported to date in the literature. Serious cardiovascular complications appear in about 25% of patients with relapsing polychondritis, the most frequent being aortic or mitral regurgitation (11.1%) and aortic aneurysms (6.1%). We report the first Bentall-type operation in a patient with relapsing polychondritis and review the literature to point out the factors that influenced morbidity and mortality of patients requiring aortic valve replacement to determine the ideal surgical procedure for patients with relapsing polychondritis. A 39-year-old man with relapsing polychondritis (RP) for 4 years and requiring permanent corticoid and immunosuppressive therapy for severe bilateral scleritis was admitted to our institution for recent shortness of breath. Severe aortic regurgitation associated with moderate aneurysmal dilatation of the ascending aorta (46 mm in diameter) were diagnosed, and the patient was referred to our department for surgical correction. He underwent operation on February 24, 1995. The surgical procedure consisted of a Bentall-type operation with a No. 25 mechanical valvular prosthesis, with the coronary arteries being reimplanted with the use of the button technique. The postoperative course was uneventful, and the patient was discharged home on day 30. Histologic examination of the aortic root showed acute panaortitis lesions: the intima was thickened, and the media showed extensive loss and fragmentation of elastic fibers. There were also perivascular mononuclear cell infiltrates in the outer media and in the adventitia. The aortic valve was thickened and contained inflammatory mononuclear cell infiltrates. Eighteen months after the operation, the patient was without symptoms with a regimen of prednisone 25 mg/day and a permanent immnunosuppressive therapy. Doppler echocardiography showed a well-functioning aortic prosthesis, no paraprosthetic leak, no false aneurysm, and a remaining thoracic aorta of normal caliber. Although the first aortic valve replacement in a patient with RP was reported in 1967, the ideal surgical procedure for such patients still remains to be determined. An extensive review of the literature reported by us in 1995 disclosed only 21 cases of aortic valve replacement, associated with mitral valve replacement in six and supracoronary graft replacement of the ascending aorta in three.1Lang-Lazdunski L Hvass U Paillole C Pansard Y Langlois J Cardiac valve replacement in relapsing polychondritis. A review.J Heart Valve Dis. 1995; 4: 227-235PubMed Google Scholar All patients had aortic insufficiency related to aortic root enlargement (77.7%) or exclusive valve involvement (22.3%) or both mechanisms. All patients with aortic root involvement exhibited macroscopic or microscopic signs of aortitis. Six patients had an aneurysm of the ascending aorta within a mean 2.2-year postoperative delay. Three patients underwent reoperation for aortic prosthesis dehiscence with an operative mortality of 66.6%; the three others died. In these patients, there is no doubt that corticosteroid therapy contributed to aortic tissue fragilization that resulted in suture leakage and prosthesis dehiscence. Also, two additional patients probably died of a ruptured ascending aorta within a 2-year postoperative delay (sudden death, no autopsy obtained).1Lang-Lazdunski L Hvass U Paillole C Pansard Y Langlois J Cardiac valve replacement in relapsing polychondritis. A review.J Heart Valve Dis. 1995; 4: 227-235PubMed Google Scholar Consequently, we recommend a prophylactic Bentall-type operation in all patients with RP requiring aortic valve replacement. This procedure carries a minimal risk of morbidity/mortality and has proven to be safe and efficient in other diseases with aortic involvement, such as Marfan syndrome.2Gott VL Pyeritz RE Cameron DE Greene PS McKusik VA Composite graft repair of Marfan aneurysym of the ascending aorta. Results in 100 patients.Ann Thorac Surg. 1991; 52: 38-45Abstract Full Text PDF PubMed Scopus (104) Google Scholar, 3Cohn L Rizzo RJ Adams DH et al.Reduced mortality and morbidity for ascending aortic aneurysm resection regardless of cause.Ann Thorac Surg. 1996; 62: 463-468Abstract Full Text PDF PubMed Scopus (13) Google Scholar, 4Lewis CTP Cooley DA Murphy MC Talledo O Vega D Surgical repair of aortic root aneurysms in 280 patients.Ann Thorac Surg. 1992; 53: 38-46Abstract Full Text PDF PubMed Scopus (104) Google Scholar, 5Kouchoukos NT Wareing TH Murphy SF Perrillo JB Sixteen-year experience with aortic root replacement. Results in 172 operations.Ann Surg. 1991; 214: 308-320Crossref PubMed Scopus (365) Google Scholar Furthermore, we believe that the coronary button reimplantation technique associated with the exclusion technique for the aortic anastomoses is the most reliable method for prevention of bleeding and late false aneurysm formation at suture lines because all diseased aortic tissue is eliminated.5Kouchoukos NT Wareing TH Murphy SF Perrillo JB Sixteen-year experience with aortic root replacement. Results in 172 operations.Ann Surg. 1991; 214: 308-320Crossref PubMed Scopus (365) Google Scholar This option may prevent precoce or late anastomosis dehiscence and thus avoid further high-risk reoperations in fragile immunosuppressed patients.

The authors report their experience with a simple and efficient technique for repair of left ventricular free wall rupture complicating myocardial infarction. The technique consists, with the aid of cardiopulmonary bypass, in suturing a plaque of the patients own pericardium (6 to 8 cm in diameter) to the more normal tissue encircling the pathologic myocardium, and by injecting five ml of human fibrin glue as a cement under the pericardium to reinforce the remair and prevent leaking throughout the suture line. With a 10 year follow-up, we are able to be confident with the long term results. The five patients, at the time of operation were aged 46 to 74 years. The post-operative results and the annual echocardiographic controls have proved the technique to be sound without recurrences and without late complications such as pseudo aneurysms at the site of the repair.

Mitral valve repair was performed in six patients by transferring the posterior tricuspid leaflet with its sub-valvular apparatus onto the mitral valve. This new technique considers the tricuspid valve as the patients own tissue bank where the posterior leaflet and eventually the adjacent part of the anterior leaflet is used as a ''donor'' valve, based on the knowledge that the right atrio-ventricular valve can be efficiently repaired with a very low risk of significant dysfunction. The mitral repair consists of incorporating the tricuspid autograft by securing the tricuspid papillary muscle to the mitral papillary muscle and by suturing the leaflet tissue where required. A mitral annuloplasty ring reinforces the repair. The tricuspid valve is subsequently repaired by annular plication and leaflet suture. A tricuspid ring is necessary to maintain efficient remodeling. The six patients ages ranged from 20 to 70 years. A etiology, was rheumatic in the first case and degenerative in the following. In three cases, sterilised endocarditis was responsible for ruptured chordae and leaflet destruction. The mitral insufficiency was located in a commissural area in 4 cases, and was due to a widespread posterior prolapse in 2. Post-operative control transesophageal echocardiography confirmed the excellent results of the repair and proved that, in selected cases, the tricuspid leaflet inserted onto the mitral apparatus is very efficient in correcting mitral insufficiency, without causing significant tricuspid impairement. With a 3 to 7 month follow-up, the results are stable.

The authors report their experience with a simple and efficient technique for repair of left ventricular free wall rupture complicating myocardial infarction. The technique consists, with the aid of cardiopulmonary bypass, in suturing a plaque of the patients own pericardium (6 to 8 cm in diametre) to the more normal tissue encircling the pathologic myocardium, and by injecting five mi of human fibrin glue as a cement under the pericardium to reinforce the remair and prevent leaking throught the suture line. With a 10 year follow-up, we are able to be confident with the long term results. The five patients, at the time of operation were aged 46 to 74 years. The post-operative results and the annual echocardiographic controls have proved the technique to be sound without recurrences and without late complications such as pseudo aneurisms at the site of the repair.

The authors report a rare case which is interesting from three points of view; tricuspid valve endocarditis in a child complicating a fistula between the right coronary artery and right ventricle with negative blood cultures but a positive serology for Coxiella burnetii. This mutilating tricuspid endocarditis was complicated by multiple pulmonary embolism of the right lung. After two months of antibiotic therapy the coronaro-cardiac fistula was closed and the tricuspid valve replaced with a mitral homograft. All cases of blood culture negative endocarditis require serological investigation to detect intracellular organisms which are difficult to diagnose and justify specific prolonged antibiotic therapy. Control serological tests are essential in the long-term because of the risk of chronic infection, especially in cases with prosthetic intracardiac material. Treatment, based mainly on tetracyclines, should be continued for at least two years.

The authors report a rare case which is interesting from three points of view: tricuspid valve endocarditis in a child complicating a fistula between the right coronary artery and right ventricle with negative blood cultures but a positive serology for Coxiella burnetii. This mutilating tricuspid endocarditis was complicated by multiple pulmonary embolism of the right lung. After two months of antibiotic therapy the coronaro-cardiac fistula was closed and the tricuspid valve replaced with a mitral homograft. All cases of blood culture negative endocarditis require serological investigation to detect intracellular organisms which are difficult to diagnose and justify specific prolonged antibiotic therapy. Control serological tests are essential in the long-term because of the risk of chronic infection, especially in cases with prosthetic intracardiac material. Treatment, based mainly on tetracyclines, should be continued for at least two years.

Mitral valve repair was performed in six patients by transferring the posterior tricuspid leaflet with its sub-valvular apparatus onto the mitral valve. This new technique considers the tricuspid valve as the patients own tissue bank where the posterior leaflet and eventually the adjacent part of the anterior leaflet is used as a "donor" valve, based on the knowledge that the right atrio-ventricular valve can be efficiently repaired with a very low risk of significant dysfunction. The mitral repair consists of incorporating the tricuspid autograft by securing the tricuspid papillary muscle to the mitral papillary muscle and by suturing the leaflet tissue where required. A mitral annuloplasty ring reinforces the repair. The tricuspid valve is subsequently repaired by annular plication and leaflet suture. A tricuspid ring is necessary to maintain efficient remodeling. The six patients ages ranged from 20 to 70 years. A etiology, was rheumatic in the first case and degenerative in the following. In three cases, sterilised endocarditis was responsible for ruptured chordae and leaflet destruction. The mitral insufficiency was located in a commissural area in 4 cases, and was due to a widespread posterior prolapse in 2. Post-operative control transesophageal echocardiography confirmed the excellent results of the repair and proved that, in selected cases, the tricuspid leaflet inserted onto the mitral apparatus is very efficient in correcting mitral insufficiency, without causing significant tricuspid impairment. With a 3 to 7 month follow-up, the results are stable.

Background Transferring the posterior leaflet of the patient's own tricuspid Valve with its subvalvular apparatus to the mitral valve is a new technique that allows a conservative approach to mitral-valve repair. The technique is based on the knowledge that the tricuspid valve can be remodelled from tricuspid to bicuspid, with a very low risk of significant dysfunction.Methods We describe six patients (age range 20-70 years) with mitral insufficiency in whom we have used the technique.Findings All patients survived the operation and were in sinus rhythm. Transoesophageal echocardiography before discharge showed trivial or no regurgitation at the site of mitral repair. Before operation, all patients were in New York Heart Association class Ill-IV; at follow-up after 6-13 months all patients were in class I-IIInterpretation Compared with using segments of mitral homografts in similar situations, the intraoperative availability of the tricuspid's viable natural chordae and valvular leaflet means that there are no immunological disadvantages to the procedure. With this new operation, the patient is his own tissue bank.

Cardiac valve replacement is a rare but not exceptional eventuality in patients with relapsing polychondritis. One case requiring aortic and mitral valve replacement and its follow up is described. From the review of the literature an additional twenty patients who required cardiac valve replacement are analyzed. The mean delay between the first onset of relapsing polychondritis and operation was 6.51 years and the mean age at operation was 38.8 years. There was a preponderance of male patients (73.7%). Aortic and mitral valves were replaced in 100% and 28.5% of patients, respectively. During the four first postoperative years 23.8% of them were reoperated for periprosthetic leak or aortic aneurysm, and during the same period 52.6% died of a cardiovascular cause. Immunosuppressive agents should be employed in patients with relapsing polychondritis and cardiovascular involvement because they seem to be more effective than steroids in severe forms of the disease. Therefore, we recommend close and prolonged follow up: firstly because there can be early paravalvular prosthetic leakage due to the friability of the tissue to which it has been anchored; secondly because aortic aneurysms occur frequently in relapsing polychondritis, may be multiple, may involve all parts of the aorta and result in fatal rupture even in asymptomatic patients; and thirdly because there can be a fatal outcome due to other organ involvement, like airway obstruction, acute glomerulonephritis, or systemic vasculitis. Prophylactic composite graft replacement of the ascending aorta associated with replacement of the aortic valve and re-implantation of the coronary arteries could avoid the need for reoperation in these high risk patients.

From August 1991 to June 1994, 150 patients underwent aortic valve replacement with the O'Brien-Angell stentless porcine xenograft (Brave Cardiovascular Model 300, Cryolife, Atlanta, GA). To establish trends we analyzed three consecutive groups of 50 patients. We found significant differences in low postoperative gradients (mean less than or equal to 10 mm Hg): 24% in group 1, 42% in group 2, and 96% in group 3. Comparing groups 1 and 3, gradients were significantly lower in all valve sizes. The difference is credited to better supraannular positioning of the valve, which is the key to the learning curve. Trivial central regurgitation was present in the three groups at 6%, 12%, and 0%, respectively Peripheral regurgitation was trivial in 6%, 8%, and 0%, and mild to moderate in 4%, 2% and 0%, respectively. Seventy-eight of 107 patients with an available follow-up exceeding 1 year had noninvasive controls. Two early cases with moderate perivalvular leaks evolved to moderately severe leaks. Two valves were explanted. The O'Brien-Angell stentless valve is easy to handle and correct supraannular positioning provides excellent hemodynamic results.

Independently of phenomena related to rejection, atherosclerosis of the grafted heart or high blood pressure, there exists a qualitative and quantitative degradation of response to exercise in heart transplant recipients. Maximal oxygen consumption is generally reduced to 40 to 60% of normal levels. There are several interactive mechanisms. Paradoxically, the transplanted heart is a clear demonstration of the fact that several other elements are involved in the organisms response to exercise. Indeed, ventilation, exercise load, peripheral circulation, muscle metabolism and neurohormonal response also play a role. Vasoactivity of the peripheral arteries limits distribution and extraction of oxygen during exercise. Noradrenaline, renin, atrial natriuretic factor, vasopressin and endothelin levels are normal at rest, but an overreaction occurs during exercise. The percentage of type I (oxidative) fibres is reduced in muscles. Cyclosporine has also been shown to have a toxic effect on mitochondria in muscles. The deinnervated transplanted heart is thus called upon to work in coordination with peripheral elements which have also undergone alterations. Consequently, response to exercise cannot be significantly increased above the level reached before transplantation. Usually patients are not greatly hindered in their daily activities and rarely complain of breathlessness. Nevertheless, an improvement would be appreciated. A coherent physical rehabilitation programme can increase maximal oxygen consumption by 25 to 30% in these patients, essentially via improvement in peripheral anomalies. It is more difficult to modify cardiac response.

Left ventricular free wall rupture has been treated successfully in three cases using an original technique that consists of suturing a plaque of the patient's own pericardium (6 to 8 cm in diameter) to the normal tissue encircling the pathologic myocardium, and by injecting 5 ml of human fibrin glue as a cement under the pericardium to reinforce the repair and prevent leaking through the suture line.