Patrick Nataf

Endothelin-1 in primary pulmonary hypertension and the Eisenmenger syndrome

Abstract Primary pulmonary hypertension (PPH) is an uncommon condition, the etiology and pathogenesis of which are unknown. PPH is histologically characterized by endothelial injury and the proliferation of pulmonary arterial smooth muscle cells. A role for vasoconstriction in the pathophysiology of PPH is supported by the possibility of spontaneous reversal at early stages and by the greater than expected incidence of Raynauds phenomenon in patients with PPH.1 The mechanism of the initiation of vasoconstriction, and the perpetuation or progression of the obstruction are unclear. Endothelin-1 (ETL1), a newly isolated peptide from vascular endothelial cells,2 has potent vasoconstricting activity and induces vascular smooth muscle cell proliferation.3,4 These observations suggest that ETL1 may have an important role in the increased vascular tone or medial hypertrophy, or both, of small arteries observed in PPH. In this study, we measured venous plasma ETL1 concentrations in patients with PPH, and compared them with those found in patients with pulmonary hypertension secondary to congenital heart defects and in normal subjects.

Plasma levels of thrombomodulin in pulmonary hypertension

BACKGROUNDnLong-standing pulmonary hypertension (PH) leads to structural alterations of the pulmonary vasculature and its endothelium, and occlusion of small vessels by microthrombi. In patients with PH, the search for factors inducing or worsening endothelium damage and in situ thrombi is still ongoing. Thrombomodulin (TM), an endothelial cell membrane protein, is a receptor for thrombin and a major anticoagulant proteoglycan.nnnPURPOSEnTo analyze plasma TM levels in patients with different forms of severe PH.nnnPATIENTSnWe prospectively studied 32 consecutive patients with PH referred for heart, lung, or heart-lung transplantation: 11 patients with primary PH (group 1), 11 patients with secondary precapillary PH (Eisenmengers syndrome, group 2) and 10 patients with secondary postcapillary PH due to congestive heart failure (group 3). Thirty-eight healthy subjects were also studied as a control group.nnnMETHODSnPlasma concentrations of TM were measured by an immunoenzymatic technique that uses two anti-TM monoclonal antibodies that have a strong avidity and react with different epitopes of the molecule.nnnRESULTSnThrombomodulin plasma levels decreased in all patients with precapillary PH, and this decrease was highly significant compared with controls (26 +/- 2 versus 44 +/- 2 ng/mL, P = 0.0001). In primary PH, the TM decrease was only significant in males whereas in the Eisenmengers syndrome TM values were the lowest of all the patients studied, with mean values twice as low as controls (22 +/- 2 versus 44 +/- 2 ng/mL, P = 0.0001). In contrast, in postcapillary PH, studied only in males, TM levels were increased (85 +/- 17 versus 54 +/- 3 ng/mL, P = 0.02). Patients with precapillary PH had more severe disease than patients with postcapillary PH, with higher pulmonary artery pressure and pulmonary vascular resistance (P < 0.001). There was no correlation between TM plasma levels and all hemodynamic variables.nnnCONCLUSIONnWe found low levels of plasma TM in patients with precapillary PH but not in postcapillary PH compared with healthy controls. This may be related to the severity of PH and may contribute to the initiation or worsening of in situ thromboses frequently found in pulmonary hypertension. Further studies should analyze whether other markers of endothelial cell damage are correlated with plasma TM levels in patients with precapillary pulmonary hypertension.

Nonpenetrating clips for coronary anastomosis

BACKGROUNDnA nonsuture clip technique (nonpenetrating titanium clips applied to everted tissue edges at high compressive forces) was used to perform coronary anastomoses in a clinical setting.nnnMETHODSnClipped coronary anastomoses were performed in 10 patients. The anastomoses incorporated the left internal mammary artery to the left anterior descending artery (n = 1) and the saphenous vein to the right coronary artery (n = 5), the posterior descending artery (n = 2), the diagonal artery (n = 2), and one vein-to-vein proximal anastomosis (n = 1).nnnRESULTSnThe mean duration for completion of the anastomoses was 15 minutes (range, 7 to 20 minutes). This time was reduced from 20 minutes at the beginning of the clinical experience to 7 minutes for the last 3 patients. No technical complication was related to clip application and all patients had uneventful outcomes. Three anastomoses studied by coronary angiography were patent without stenosis.nnnCONCLUSIONnThe clipped anastomotic technique has a rapid learning curve, the same safety as suture methods, and the potential for facilitating endoscopic vascular reconstructions.

Intraatrial insertion of a mitral prosthesis in a destroyed or calcified mitral annulus.

Infectious lesions and extreme calcification of the mitral valve annulus can make classic anatomic implantation of a prosthesis impossible. Confronted with these circumstances, we have developed a technique of intraatrial insertion of a mitral prosthesis. The prosthesis has been modified by enlarging the circumference of the sewing ring with a Dacron collar. The collar can be sutured to the left atrial wall above the mitral annulus. From 1981 to 1989, this technique has been employed in 36 patients: 15 had acute valve endocarditis with destruction of the mitral annulus and 21 had extensive annular calcification. In all cases, circumferential or partial intraatrial insertion permitted a secure implantation of the prosthesis. One operative death was related to the technique. It was an intractable bleeding caused by tearing of the very thin and fragile wall of the left atrium in a kidney transplant patient. Four patients were reoperated on for periprosthetic leak, in 3 of whom healing and cleaning of the mitral annulus permitted annular implantation of a prosthetic valve. There was no ventricular wall rupture. Our results suggest that the technique can be performed in high operative risk patients when mitral valve replacement is impossible by conventional techniques.

Minimally Invasive Coronary Surgery with Thoracoscopic Internal Mammary Artery Dissection: Surgical Technique

Abstract Background: We describe our technique of revascularization of the left anterior descending artery (LAD), using the left internal mammary artery (LIMA) without cardio‐ pulmonary bypass (CPB), by means of a 4‐cm left thoracotomy and video‐thoracoscopic harvesting of the LIMA. Methods: The patient is placed in a semioblique position. The LIMA is harvested under thoracoscopic guidance. Trocars are introduced via three thoracic incisions of less than 15 mm at the level of the fourth and seventh intercostal spaces. Perforating arterial branches are cauterized or clipped. This approach allows complete dissection of the LIMA from the subclavian artery to the fifth intercostal space. A 4‐cm left anterior thoracotomy is then made along the fourth or the fifth intercostal space. Rib excision is not necessary for LAD exposure. Coronary artery control is obtained with looping sutures (4/0 prolene) placed proximally and distally to the site of the anastomosis. Anastomosis is then performed with 8/0 prolene on the beating heart, under direct vision, without CPB. Results: Between September 1995 and May 1996, this procedure was performed on 20 consecutive patients under age 80. There were no operative complications. The mean duration of hospitalization was six days. Conclusions: This new procedure enlarges the field of minimally invasive coronary artery bypass grafting techniques.

Clinical Experience with a Total Artificial Heart as a Bridge for Transplantation: The Pitie Experience

Since April 1986, 82 patients have received a pneumatic total artificial heart, 62 a JARVIK‐7, and 20 a Cardiowest. The duration of support ranged from less than 1 day to 603 days (mean duration: 27 ± 82). The indications were for acute shock (38 cases) or for chronic deterioration on the transplant waiting list (44 cases). The etiology was mainly due to idiopathic and ischemic cardiomyopathy. With the help of our scoring system, we divided our patients in three groups: Chronic Implantation, represented by two females staying on device for 6 and 19 months, respectively; a High‐Risk group of 29 patients characterized by high‐risk indications; graft failure, rejection, postcardiotomy patient, postpartum cardiomyopathy, and valvular and congenital reoperation. In addition, the dilated and ischemic cardiomyopathy patients with a score over 6 were included in this group; and an Elective Indication group (51 patients) represented all of the dilated and ischemic cardiomyopathy patients with a score under 6. Due to the shortage of donors, our criteria for transplantation are very strict. Transplants should be made only in cases of hemodynamic stability, on an extubated patient with normal renal and liver functions, without coagulation problems or infection. With such criteria, in the high‐risk group, only four patients could be transplanted and of these two are still alive. In contrast, in the elective group, 31 were transplanted (61%), and 71% of these patients were discharged. The rate is improved in the most recent cases, with 90% of the Cardiowest patients being survivors.

Myocardial Protection by Blood Cardioplegia and Warm Reperfusion in Heart Transplantation

We describe the technique of blood cardioplegia delivery as we routinely use it in clinical heart transplantation. This technique needs a specific circuit. Perfusion of a first dose of blood cardioplegia is immediately started on the arrival of the graft in the operating room. Cardiac reperfusion of a half-dose of blood solution without potassium is performed each 20 minutes. Myocardial warm reperfusion is started at the end of the aortic suture. This technique of blood cardioplegia and warm reperfusion during heart transplantation provided an improvement in heart preservation when compared with standard crystalloid solution.

Posttransplantation cytotoxic immunoglobulin G is associated with a high rate of acute allograft dysfunctions in heart transplant recipients.

BACKGROUNDnThe significance of anti-human leukocyte antigen immunoglobin G (IgG) detected in the posttransplantation course of heart graft recipients remains unclear.nnnMETHODnSera from 121 cardiac allograft recipients transplanted between January 1992 and December 1994 were screened for the presence of lymphocytotoxic antibodies in the first year after transplantation. Dithiothreitol was used to differentiate IgG from immunoglobulin M.nnnRESULTSnNineteen patients (15%) had cytotoxic IgG develop, mainly during the first month after transplantation. The percentage of women was higher in this group (42% vs 15.7%; P <.05). Donor to recipient mismatches for sex, blood typing, cytomegalovirus serology, and human leukocyte antigen typing were comparable between IgG producers and nonproducers. The frequency of acute allograft dysfunction during the first year after transplantation was significantly higher among patients producing IgG (42% vs 5.9; P <.001). Most of these acute allograft dysfunctions were independent of cellular rejection lesions but were associated with a thickening of the posterior wall and the interventricular septum during the acute episode. Finally, all the patients but one recovered. Recurrences were not uncommon and, at 1 year after transplantation, the dose of cyclosporine used in patients producing IgG was significantly greater, as was the left ventricular thickness.nnnCONCLUSIONnPosttransplantation cytotoxic IgG is not uncommon and appears to be associated with a high rate of acute allograft dysfunction. Development of these antibodies can be caused by a previous undetected immunization, as suggested by the higher percentage of women in the producer group. Correlation with histologic lesions of humoral rejection are discussed.

Five‐Year Experience with the Medtronic Hall Prosthesis in Isolated Aortic Valve Replacement

We reviewed clinical data in 216 patients who underwent isolated aortic valve replacement with the Medtronic Hall prosthesis. Between January 1983 and December 1990, a total of 216 prosthetic valves were implanted in 180 males and 36 females. Preoperatively, 45.5% of patients were in New York Heart Association (NYHA) Class III to IV. Cumulative follow‐up was 682 years, and 3.2% of patients were lost to follow‐up. The actuarial 5‐year survival rate was 90% for the whole group. All the patients were anticoagulated with aceno‐coumarol (SintromR). There were no cases of structural dysfunction and one patient presented with valve thrombosis. The Medtronic Hall valve has a low rate of thromboembolic events without structural failure. It is an excellent device for aortic valve replacement.

Técnica de revascularização miocárdica com uso de toracoscopia

The benefits of the internal mammary artery (IMA), as a graft, particularly for the left anterior descending (LAD) coronary artery disease, have been demonstrated. Coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) is now an accepted technique of myocardial revascularization. Thoracoscopy and a minimal thoracotomy have been applied to cardiac surgery, however its use has not been well defined. In our approach, we harvested the left or the right IMA thoracoscopically. Following this the left IMA-LAD or right IMA-right coronary artery anastomoses were fashioned, by means of a left or right small anterior thoracotomy on the beating heart without CPB. A double lumen endotracheal tube was used so the lung could be collapsed. Three left or right lateral chest ports of 1.5 cm were made, and the thoracoscope was placed through the initial port, permitting inspection of the thorax. The other ports were used for IMA dissection, using endoscopic instruments (electrocautery, grasping, forceps,...), the side branches were controlled by either cautery or endoscopic clips. When it was possible, the anterior port was extended doing a small left or right anterior thoracotomy, the pericardium was exposed, the IMA was divided and exteriorized through the thoracotomy. After coronary artery control, the bypass graft was carried out on the beating heart without CPB. In certain cases, when myocardial protection was considered to be essential, this was achieved by means of an intracoronary shunt. We have operated on more than 20 patients using this technique with good results in all cases. We believe that with increasing operator experience, this minimally invasive approach will have a major impact on the management of the coronary artery disease patients, with a faster recovery, shorter hospitalization, and certainly less cost.