Injected matrix stimulates myogenesis and regeneration of mouse skeletal muscle after ischaemic injury.

Biomaterial-guided regeneration represents a novel approach for the treatment of myopathies. Revascularisation and the intramuscular extracellular matrix are important factors in stimulating myogenesis and regenerating muscle damaged by ischaemia. In this study, we used an injectable collagen matrix, enhanced with sialyl LewisX (sLeX), to guide skeletal muscle differentiation and regeneration. The elastic properties of collagen and sLeX-collagen matrices were similar to those of skeletal muscle, and culture of pluripotent mESCs on the matrices promoted their differentiation into myocyte-like cells expressing Pax3, MHC3, myogenin and Myf5. The regenerative properties of matrices were evaluated in ischaemic mouse hind-limbs. Treatment with the sLeX-matrix augmented the production of myogenic-mediated factors insulin-like growth factor (IGF)-1, and IGF binding protein-2 and -5 after 3 days. This was followed by muscle regeneration, including a greater number of regenerating myofibres and increased transcription of Six1, M-cadherin, myogenin and Myf5 after 10 days. Simultaneously, the sLeX-matrix promoted increased mobilisation and engraftment of bone marrow-derived progenitor cells, the development of larger arterioles and the restoration of tissue perfusion. Both matrix treatments tended to reduce maximal forces of ischaemic solei muscles, but sLeX-matrix lessened this loss of force and also prevented muscle fatigue. Only sLeX-matrix treatment improved mobility of mice on a treadmill. Together, these results suggest a novel approach for regenerative myogenesis, whereby treatment only with a matrix, which possesses an inherent ability to guide myogenic differentiation of pluripotent stem cells, can enhance the endogenous vascular and myogenic regeneration of skeletal muscle, thus holding promise for future clinical use.

Assessment of cyclosporine pharmacokinetic parameters to facilitate conversion from C0 to C2 monitoring in heart transplant recipients.

BACKGROUND: Cyclosporine (CsA) 2-hour postdose (C2) monitoring is recommended to assess CsA exposure and predict clinical outcomes among heart transplant recipients. We correlated pharmacokinetic parameters and clinical outcomes in stable long-term heart transplant recipients monitored with C0 to develop an algorithm to convert patients from C0 to C2 monitoring. METHODS: Paired CsA C0-C2 measurements and serum creatinine levels were obtained from 35 heart transplant recipients more than 2 years posttransplantation (mean 8.8+/-4.7 years). RESULTS: The mean CsA dose and C0, C2, and C0/C2 ratio were 85+/-23 mg/12 hours, 123+/-41 ng/mL, 572+/-274 ng/mL and 4.8+/-2.1, respectively. C0 correlated weakly with C2 (r=.42, P=.011). The CsA dose correlated better with C2 (r=.58; P<.001) than with C0 (r=.37; P=.026). A good correlation was noted between C2 and the C2/C0 ratio (r=.73; P<.001), but none between C0 and the C2/C0 ratio. A borderline significant inverse correlation was noted between C0 and the worst endomyocardial biopsy score (r=-.34; P=.045), whereas none was noted with C2. Serum creatinine level did not correlate with either C2 or C0. Among patients with C0 within our target of 100 to 150 ug/L, six had C2 above 300 to 600 ug/L as suggested by the literature. CONCLUSIONS: In long-term heart transplant recipients, we could not identify a single pharmacokinetic parameter that could be used to develop an algorithm to convert from C0 to C2 monitoring; however, C2 may be better than C0 for identifying patients at risk of overexposure to CsA.

Severe lower limbs lymphedema following breast carcinoma treatment revealing radiation-induced constrictive pericarditis--a case report.

In patients treated for breast carcinoma, unilateral lymphedema of the upper limb is usual. However, to the authors' knowledge, lower limb lymphedema has never been reported as a complication of breast carcinoma therapy. They report here the first case of a radiation-induced constrictive pericarditis revealed by severe lower limbs lymphedema. A 60-year-old woman was treated for left breast carcinoma with quadrantectomy, axillary lymphadenectomy, and combined radio chemotherapy (60 grays). Three and a half years later she suffered from a diffuse and increasing lower limbs lymphedema, which became huge and disabling. Radiation-induced constrictive pericarditis was evidenced by right cardiac cavities catheterization. A dramatic improvement was rapidly obtained after pericardectomy. Histopathologic analysis of the pericardium did not reveal neoplastic cells. Radiation-induced constrictive pericarditis is usually responsible for lower limbs edema, but lymphedema is exceptional. This case highlights the need to search for a constrictive pericarditis also in the case of lower limbs lymphedema, particularly in a patient treated with mediastinal radiotherapy or combined radio chemotherapy.

[Adult apico-aortic shunts. A case followed for 6 years]. / Dérivation apico-aortique chez l'adulte. A propos d'un cas suivi durant 6 ans.

An apico-aortic shunt enables a reduction in the aortic transvalvular pressure gradient. It is recommended for patients with symptomatic severe stenosis when anatomical constraints contra-indicate valvular replacement. The authors report the case of a patient who underwent this uncommon procedure, which was indicated due to previous coronary bypass surgery using both mammary arteries, plus massive calcification of the ascending aorta. Angio-haemodynamic investigation and MRI performed three years and five years respectively following the procedure confirmed its efficiency. An analysis of the few reported series confirms the value of this special procedure.

Comparison of clinical and echocardiographic characteristics of Streptococcus bovis endocarditis with that caused by other pathogens.

The aim of our study was to compare the clinical, echographic, and prognostic features of Streptococcus bovis (S. bovis) endocarditis with those caused by other streptococci and pathogens in a large sample of patients with definite endocarditis by Duke criteria, using transesophageal echocardiography. Two hundred six patients (149 men, mean age 57 +/- 15 years) with a diagnosis of infective endocarditis formed the study population. All patients underwent multiplane transesophageal echocardiography and blood cultures. Cerebral, thoracoabdominal computed tomographic scan was performed in almost all patients (95%). All patients with S. bovis endocarditis underwent colonoscopy. Incidence of S. bovis endocarditis in our sample was 19%. Patients with S. bovis endocarditis were older than other groups. Multiple valve involvement, native valves, and large vegetations (>10 mm) were more frequent in patients with S. bovis. There was a significantly higher occurrence of embolism in the S. bovis group. Splenic embolism and multiple embolisms were significantly more frequent in patients with S. bovis. Gastrointestinal lesions, anemia, and spondylitis were observed more frequently with S. bovis endocarditis. In addition to the requirement for gastrointestinal examination for S. bovis endocarditis, our study underlines the need for systematic screening for vertebral and splenic localizations, and suggests the use of early surgery to prevent the high risk of embolism in these patients.

Rescue revascularization for acute coronary occlusion late after radiotherapy.

Because radiation-induced coronary artery stenoses are frequently severe and located proximally, some patients are admitted in emergency. This report describes the case of a 47-year-old woman with radiation-induced stenosis of the left main coronary artery who presented with cardiac arrest during angiography. The patient was successfully treated using circulatory assistance and percutaneous transluminal coronary angioplasty as a bridge to coronary artery bypass grafting.

Cora valveless pulsatile rotary pump: new design and control.

For decades, research for developing a totally implantable artificial ventricle has been carried on. For 4 to 5 years, two devices have been investigated clinically. For many years, we have studied a rotary (but not centrifugal) pump that furnishes pulsatile flow without a valve and does not need external venting or a compliance chamber. It is a hypocycloidal pump based on the principle of the Maillard-Wankel rotary compressor. Currently made of titanium, it is activated by an electrical brushless direct-current motor. The motor-pump unit is totally sealed and implantable, without noise or vibration. This pump was implanted as a left ventricular assist device in calves. The midterm experiments showed good hemodynamic function. The hemolysis was low, but serious problems were encountered: blood components collecting on the gear mechanism inside the rotor jammed the pump. We therefore redesigned the pump to seal the gear mechanism. We used a double system to seal the open end of the rotor cavity with components polished to superfine optical quality. In addition, we developed a control system based on the study of the predicted shape of the motor current. The new design is now underway. We hope to start chronic experiments again in a few months. If the problem of sealing the bearing could be solved, the Cora ventricle could be used as permanent totally implantable left ventricular assist device.

Late results of double-valve replacement with biologic or mechanical prostheses.

BACKGROUND: We previously showed that the risk of reoperation for structural degeneration of bioprostheses was higher in cases involving patients older than 65 years (p = 0.003) and double-valve replacement (p = 0.02). The purpose of this study was to compare late outcome of mitral-aortic valve replacement using bioprostheses or mechanical valves. METHODS: The bioprosthesis group included all mainland France residents (n = 48) between 55 and 65 years old operated on between 1980 and 1995 for mitral-aortic valve replacement using bioprostheses. The mechanical valve group was obtained by matching each of these patients with a patient operated on using mechanical valves at approximately the same time during the study. RESULTS: In the bioprosthesis group, 10-year survival was 45%+/-8% versus 62%+/-7% in the mechanical valve group (not significant). The linearized reoperation rate was 6.8 per patient-year versus 1.1 per patient-year (p = 0.001), and the linearized reoperative mortality rate was 1.8 per patient-year and 0.7 per patient-year (not significant), respectively. CONCLUSIONS: The reoperative mortality risk after mitral-aortic valve replacement using two bioprostheses does not significantly decrease overall survival after age 65 years.

Multiple valve replacement increases the risk of reoperation for structural degeneration of bioprostheses.

BACKGROUND AND AIM OF THE STUDY: The study aim was to analyze the results of reoperations for structural degeneration of bioprostheses, and to define a high-risk population for reoperative procedures. METHODS: A series of 524 consecutive patients who had undergone a first reoperative replacement for a failed bioprosthesis between 1978 and 1998 was reviewed retrospectively. The reoperative procedure comprised 363 single valve replacements, and 161 multiple valve replacements. During the original procedure, 648 bioprostheses had been implanted in the mitral (n = 403), aortic (n = 220) and tricuspid (n = 25) positions. RESULTS: The mean interval between the original procedure and reoperation was 8.8 +/- 3.3 years. Tissue valve failure was revealed by recurrence of cardiac insufficiency in 70% of cases. The overall early mortality rate was 8%, but early mortality rates for elective single mitral and aortic reoperative valve replacements were only 3.9% and 4%, respectively. Early mortality following reoperation for single and multiple valve replacement was 6.0% and 12.4% respectively (p = 0.02). Other significant multivariable predictors for early mortality were old age (p = 0.003), NYHA functional class (p = 0.007), presence of ascites (p = 0.02) and reoperation performed before 1988 (p = 0.013). CONCLUSIONS: The risk of reoperation for structural degeneration of bioprostheses is acceptable for elective single reoperative valve replacement as opposed to multiple reoperative valve replacement. This may limit the use of bioprostheses during the original procedure when multiple valve replacement is required.

Late complications after prosthetic replacement of the ascending aorta: what did we learn from routine magnetic resonance imaging follow-up?

OBJECTIVE: Advances in surgical technique have improved early survival after surgery of the ascending aorta. However, follow-up data document serious late complications, mainly evolutive peri-prosthetic false aneurysms. Magnetic resonance imaging (MRI) has proved to be highly effective for monitoring these complications. This study evaluates 10 years of experience with routine MRI for follow-up. METHODS: Since January 1988, 114 patients with replacement of the ascending aorta either for type A acute dissection (group I, 45 patients) or aneurysms (group II, 69 patients) were followed up with annual MRI. Prosthetic replacement was either limited to supra-coronary ascending aorta (45%, 51/114) or extended to the aortic root and/or the aortic arch (55%). Biological glue was always utilized. MRI focused on peri-prosthetic haematoma, analyzing signal intensity changes and volume augmentation for early detection of false aneurysms, and on persistent residual dissection with or without evolutive aortic aneurysm distant to the prosthesis. RESULTS: Peri-prosthetic hematomas were almost equally found in both groups (26 (58%) in group I and 42 (61%) in group II) and were detected within the first year. Peri-prosthetic false aneurysms developed in 15 patients (group I, seven; group II, eight) as a complication of pre-existing hematomas and were indicated for elective reoperation. Forty-three (96%) of patients in group I had persistent residual dissection. Five patients in group I and two in group II needed reoperation for evolutive aortic aneurysm. In total, 22 of 114 (19%) patients were reoperated on during follow-up (12 (27%) in group I and ten (15%) in group II). Operative mortality was 13% (3/22). Freedom from reoperation at 1 year/5 years was: group I, 93%/84%; group II, 98%/88%. CONCLUSION: Peri-prosthetic haematoma occurs equally after aneurysm or dissection repairs and is a pre-existing condition for peri-prosthetic false aneurysm; biological glue or extended repair do not prevent late complications. Long-term MRI follow-up allows successful elective reoperation for life-threatened but asymptomatic patients.

Visceral Kaposi's sarcoma associated with human herpesvirus 8 seroconversion in a heart transplant recipient.

A close association between human herpesvirus-8 (HHV-8) and Kaposi's sarcoma (KS) has been shown in transplant recipients, but donor-to-recipient transmission of HHV-8 is uncommon. Herein we report a case of a heart transplant recipient who had a fatal visceral KS in association with HHV-8 seroconversion at 18 months after transplantation with a donor having positive serology discovered after transplantation.

Circulatory assist techniques after cardiomyoplasty. Determinants for clinical outcome and later consequences.

Cardiomyoplasty, in spite of recent improvements, remains a high risk operation. The early postoperative period is sometimes very critical, even for patients selected from preoperative New York Heart Association functional class IV. During the surgical period, poor hemodynamics may be responsible for early death, as well as influence latissimus dorsi muscle long-term viability. Circulatory assist, including pharmacologic support with enoximone, intraaortic balloon counterpulsation (IABP), and ventricular assist devices (VAD), may be needed. From February, 1993 to September, 1994, 14 clinical dynamic cardiomyoplasty procedures were performed using the Medtronic (Minneapolis, MN) system at Hôpital La Timone, Marseille, France. Eight patients suffered from early and severe postoperative heart failure. Enoximone was used in three patients and IABP in five patients. Two days after cardiomyoplasty, one of the IABP patients required an implantable left VAD (Thermocardio Systems, Woburn, MA) as a bridge to cardiac transplantation. Overall hospital mortality was 7%. The authors studied the preoperative clinical data and surgical techniques to find specific risk factors that could have influenced postoperative events. Another aim of this study was to evaluate long-term benefits in these particular patients. Results showed that cardiomyoplasty patients may require complex means to overcome postoperative hemodynamic failure, but without necessarily poor long-term results. This should be an important step in improving future patient selection.

Control of a rotary pulsatile cardiac assist pump driven by an electric motor without a pressure sensor to avoid collapse of the pump inlet.

Our ventricular assist device uses a valveless volumetric pump operating on the Maillard-Wankel rotary principle. It is driven by an electric motor and provides a semi pulsatile flow. At each cycle, blood is actively aspirated into the device, and overpumping results in collapse at the pump inlet. To prevent overpumping, it is necessary to ensure that pump intake does not exceed venous return. Poor long-term reliability rules out the use of current implantable pressure sensors for this purpose. To resolve this problem, we have developed a method of control based on monitoring of the intensity of electric current consumed by the motor. The method consists of real time monitoring of current intensity at the beginning of each pump cycle. A sudden change in intensity indicates underfilling, and motor speed is reduced to prevent collapse. The current consumed by the motor also depends on the afterload, but the form of the signal remains the same when afterload changes. After demonstrating the feasibility of this technique in a simulator, we are now testing it in animals. We were able to detect and prevent collapse due to overpumping by the cardiac assist device. This system also enables us to know the maximum possible assistance and to thus adapt assistance to the user.

Innovative techniques in skeletal muscle cardiac assistance: first experimental study on minimally invasive aortomyoplasty and cardiomyoplasty.

Skeletal muscle cardiac assistance as a treatment modality for heart failure is considered a high-risk procedure subject to strict patient selection. The aim here is to develop minimally invasive techniques to improve surgical outcomes and increase clinical indications. Ten goats (45-55 kg) were studied. In six, the latissimus dorsi muscle (LDM) was harvested via an open technique on one side vs a minimally invasive technique on the other using video assistance through two 3 cm incisions. Surgical maneuvers and length of procedures were noted. Animals were recovered, observed daily for local complications, and killed after 1 week for comparative anatomic and histopathologic studies. In four other goats, minimally invasive aortomyoplasty or cardiomyoplasty was performed using video assistance (2 aortomyoplasty, 2 cardiomyoplasty). In this experimental series, there were no surgical complications. The minimally invasive LDM harvest required a mean of 81 min (range 55-116 mn) with no gross evidence of muscle damage. The technique of LDM harvesting was standardized and is reproducible. Aortic and cardiac wraping were also achieved through three ports and a left minithoracotomy of 4 cm, using the right or left LDM. A scarf technique for the descending aortomyoplasty using the left LDM, and an anterior wrapping for cardiomyoplasty using the left or right LDM was technically feasible with video assistance. This study suggests future clinical applicability.

[Repeated heart valve replacements: prognosis and results]. / Remplacements valvulaires itératifs; pronostic et résultats.

In order to determine the prognosis of reoperation for valvular replacement, we reviewed the results of a consecutive series of 124 patients operated in the department between 1974 and 1992 (163 multi redo operations). There were 69 women and 55 men, with a mean age 48 years; 77% of the patients were in functional class III or IV. Operations were performed as an emergency in 30% of cases. Endocarditis was found in 24% of cases and was an important risk factor in this content. The main indications for reoperation were periprosthetic leakage in 28.8% of cases and failure of bioprostheses in 23.7%. The valvular replacement was simple in 61%, double in 32% and triple in 7% of cases. An associated procedure was necessary in 27% of cases. Mechanical devices were implanted in 62.3% of cases. Peroperative mortality was 3% and hospital mortality, mainly from cardiac causes, was 21.7% for the second, 20% for the third and 55.6% for the fourth reoperations. Operative mortality was dependent on the number or reoperations, functional class, emergency surgery, duration of bypass and cross-clamping time. Four per cent of patients were lost to follow-up and 30 patients died secondarily. The actuarial survival rate was 52% at 5 years and 33% at 10 years, actuarial survival rate without valvular complication was 41% at 5 years and 19% at 10 years but the functional results remained good with over 90% of patients in functional class I or II at the end of follow-up.

[Right intra-atrial extension of hydatid cyst mimicking cardiac thrombosis. Apropos of a case]. / Extension intra-auriculaire droite d'un kyste hydatique simulant une thrombose cardiaque. A propos d'un cas.

The authors describe an unusual case of hydatid cyst inserted in the inferior vena cava and extending into the right atrium. The transoesoesophageal echocardiographic appearances were similar to those of a thrombus: the tumour was very mobile, echogenic, polylobular with a cord-like pedicle in the inferior vena cava. The pathological examination revealed a ruptured hydatid cyst. The mass and its insertion were not visible on CT scan or cavography. Transoesophageal echocardiography would therefore seem to be a very useful diagnostic method for tumours arising in the inferior vena cava and extending into the right atrium.

[Mitral insufficiency related to a spasm of the left anterior descending artery. A case report]. / Insuffisance mitrale due à un spasme de l'IVA. A propos d'un cas.

We report the case of a female patient of 76 years old admitted to our hospital for a pre-operative assessment of a symptomatic mitral regurgitation (MR) whose transthoracic echocardiography revealed only a trivial regurgitation. The occurrence during hospital stay of an acute pulmonary edema contemporary to the occurrence of a huge MR permitted to suspect the diagnosis of a paroxystic ischemic MR. Angiographic and hemodynamic evaluation revealed only a non-significant atheromateous plaque located in the distal LAD. The infusion of Methylergometrine triggered a severe spasm at the site of that plaque, associated with a huge MR visualized by TTE with restricted movements of both leaflets, responsible for an acute pulmonary edema occurring on the table of the catheterization laboratory. Recovery was quickly obtained after intravenous injection of Nitroglycerin, which removed the spasm and valvular regurgitation. The diagnosis of paroxystic ischemic mitral regurgitation was confirmed and a treatment based on high dosage of calcium-blocker was decided. After a follow-up of more than one year, the patient remains asymptomatic and the regurgitation has never occurred.

[18 and one-half years' survival after cardiac graft. Clinical course and anatomical findings]. / Survie de 18 ans et demi après greffe cardiaque. Evolution clinique et constatations anatomiques.

Operated upon in November, 1968, the last survivor of heart transplant recipients in those times has died on May 11, 1987, having survived 18 years and 6 months. The active life of this patient, however, was marred by episodes of graft rejection during the first post-operative years and by various incidents. It was mainly the complications of the immunosuppressive treatment that hampered his activities (osteoporosis) and provoked his death. Post-mortem examination confirmed that the heart was in good condition, found an active bronchial epithelioma and revealed iatrogenic lesions, namely adenomas, adenocarcinoma of the kidney and "regenerative" nodular hyperplasia of the liver with portal hypertension. Such lesions are observed in patients under long-term treatment with immunosuppressants. A "sleep apnoea" syndrome might have accounted for the formation of pulmonary hypertension lesions. The authors wish to pay their respects to this man who devoted himself to the service of other men.

[Neurological disorders disclosing auricular myxoma: 3 cases]. / Troubles neurologiques révélateurs d'un myxome auriculaire: trois cas.

We report 2 cases (n. 1 and 2) of cerebral infarction caused by a left atrial myxoma, and 1 case (n. 3). of dementia associated with a large left atrial myxoma. Cerebral emboli and neurological symptoms which can occur prior to cardiac obstructive and/or systemic signs require echocardiography. The cardiac post-operative condition was dramatically improved in cases revealed by an hemiplegia.

[Is chronic or recurrent idiopathic pericarditis an autonomous inflammatory disease?]. / La péricardite idiopathique chronique ou récidivante est-elle une maladie inflammatoire autonome?

PURPOSE: Chronic pericarditis or recurrent pericarditis is mostly considered to be idiopathic even when up-to-date medical investigations are undertaken. The absence of aetiology and the associated inflammatory process are features of a common disease for internists. As there are only a few published reports on this disease, therapeutic options are not easily envisaged. CURRENT KNOWLEDGE AND KEY POINTS: Idiopathic pericarditis and its evolution, characterized by recurrence or chronicity, has long been diagnosed and studied. Faced with a case of acute pericarditis, no clinical or biological data can preclude evolution towards a chronic or a recurrent form. The two major complications are tamponade and constriction. Classical treatment is aspirin and nonsteroidal anti-inflammatories. Steroids have a spectacular effect but steroid dependence is frequently observed. Colchicine treatment seems to be efficacious and can be used to stop steroid therapy. There are only a few published reports on the importance of immunosuppressive drugs such as azathioprine and cyclophosphamide. FUTURE PROSPECTS AND PROJECTS: Through our own experience and literature review, we propose to consider chronic and/or recurrent pericarditis as an autonomous inflammatory disease of the pericardium. Thus, large-scale studies concerning the treatment should improve the outcome of patients.