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.

Gender differences in the long-term outcomes after valve replacement surgery.

OBJECTIVE: To compare the long-term outcomes in women and men after valve replacement surgery. DESIGN: Observational study. SETTING: Postoperative aortic valve replacement (AVR) or mitral valve replacement (MVR). PATIENTS: 3118 patients (1261 women, 1857 men) who underwent AVR or MVR between 1976 and 2006 (2255 AVR, 863 MVR), with mean follow-up of 5.6 (4.5) years. MAIN OUTCOME MEASURES: The independent effect of gender on the risk of long-term complications (reoperation, stroke and death) after valve replacement surgery using multivariate actuarial methods. RESULTS: After implantation of an aortic valve bioprosthesis, women had a significantly lower rate of reoperation compared to men (comorbidity-adjusted hazard ratio (HR) 0.4; 95% confidence intervals (CI) 0.2 to 0.9). In contrast, if an aortic mechanical prosthesis had been implanted, women were more at risk for late stroke compared to men (HR 1.7; CI 1.1 to 2.7). After adjustment for age and co-morbidities, women had significantly better long-term survival compared to men after bioprosthetic AVR (HR 0.5; CI 0.3 to 0.6), but there was no survival difference between genders after mechanical AVR. Trends existed towards better survival for women after bioprosthetic MVR (HR 0.6; CI 0.4 to 1.0) and mechanical MVR (HR 0.8; CI 0.5 to 1.1). CONCLUSION: The long-term outcomes after valve replacement surgery differ between women and men. Although women have more late strokes after valve replacement, they undergo fewer reoperations and have better overall long-term survival compared to men.

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.

Dynamic aortomyoplasty: clinical experience and thoracoscopic surgery feasibility study.

BACKGROUND: Surgical procedures using the latissimus dorsi (LD) muscle to assist chronic heart failure inflict major trauma on severely sick patients. A less invasive approach may prove beneficial. The aim of this article is to review our clinical and experimental approaches of dynamic aortomyoplasty (AMP) and emphasize the necessity to reorient surgical technique towards new directions and a less invasive thoracoscopic approach. MATERIALS AND METHODS: A clinical pilot study on dynamic descending AMP started in June 1995 and included four patients. Two of them could benefit from LD counterpulsation, surviving 6 months and 18 months. Following this clinical experience, we investigated, on an animal model, minimally invasive thoracoscopic surgery for this procedure. Twelve goats underwent endoscopic LD harvest and video-assisted aortic wrap, and were studied after surgical recovery from an anatomical and functional standpoint. RESULTS: Clinical AMP using open techniques provided extraaortic counterpulsation in NYHA Class IV patients contraindicated for other surgical therapies. However, surgical technique and strategy needed improvements for optimal cardiac assistance and better patient outcome. Minimally invasive thoracoscopic surgery was feasible and reproducible in goats, achieving improved anatomy and physiology as compared to the open technique in humans. When appropriate the wrapping technique and stimulation protocol were used, an optimal counterpulsation was demonstrated. We concluded that thoracoscopic AMP may provide a minimally invasive approach to cardiac assistance and thus, a new surgical option for patients presenting with chronic heart failure.

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.

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.