Heparins increase endothelial nitric oxide bioavailability by liberating vessel-immobilized myeloperoxidase.

BACKGROUND: Neutrophils and monocytes are centrally linked to vascular inflammatory disease, and leukocyte-derived myeloperoxidase (MPO) has emerged as an important mechanistic participant in impaired vasomotor function. MPO binds to and transcytoses endothelial cells in a glycosaminoglycan-dependent manner, and MPO binding to the vessel wall is a prerequisite for MPO-dependent oxidation of endothelium-derived nitric oxide (NO) and impairment of endothelial function in animal models. In the present study, we investigated whether heparin mobilizes MPO from vascular compartments in humans and defined whether this translates into increased vascular NO bioavailability and function. METHODS AND RESULTS: Plasma MPO levels before and after heparin administration were assessed by ELISA in 109 patients undergoing coronary angiography. Whereas baseline plasma MPO levels did not differ between patients with or without angiographically detectable coronary artery disease (CAD), the increase in MPO plasma content on bolus heparin administration was higher in patients with CAD (P=0.01). Heparin treatment also improved endothelial NO bioavailability, as evidenced by flow-mediated dilation (P<0.01) and by acetylcholine-induced changes in forearm blood flow (P<0.01). The extent of heparin-induced MPO release was correlated with improvement in endothelial function (r=0.69, P<0.01). Moreover, and consistent with this tenet, ex vivo heparin treatment of extracellular matrix proteins, cultured endothelial cells, and saphenous vein graft specimens from CAD patients decreased MPO burden. CONCLUSIONS: Mobilization of vessel-associated MPO may represent an important mechanism by which heparins exert antiinflammatory effects and increase vascular NO bioavailability. These data add to the growing body of evidence for a causal role of MPO in compromised vascular NO signaling in humans.

Survival and incidence of acute rejection in heart transplant recipients undergoing successful withdrawal from steroid therapy.

BACKGROUND: Steroid-free immunosuppression is feasible in selected patients after heart transplantation. Survival and incidence of acute rejection are important parameters to evaluate when weighing risks and benefits of steroid withdrawal. METHODS: One hundred thirty-seven patients were retrospectively reviewed who underwent heart transplant at Emory University between January 1988 and April 1994 and survived >1 year. Standard immunosuppression (cyclosporine, azathioprine and prednisone) without induction therapy was used. Weaning from steroids was attempted in all patients. Scheduled endomyocardial biopsy was used for long-term surveillance screening. RESULTS: Seventy-two patients (52.5%) underwent successful prednisone withdrawal (Group P0) at an average of 13 months after heart transplant, whereas 65 patients (47.5%) did not achieve steroid-free immunosuppression (Group P1). Group P0 had a mean of 1.3 treated rejection episodes (ISHLT Grade > or = 1b) during the first post-transplant year and Group P1 a mean of 2.3 (p <0.0001). In Group P0, 40 patients (55.6%) suffered a subsequent acute rejection with an ISHLT Grade > or = 1b, resulting in treatment. Of these, 15% were ISHLT Grade 1b, 47.5% Grade 2, 35% Grade 3a and 2.5% Grade 3b. The estimated risk of suffering from acute rejection of at least Grade 1b after achieving steroid-free immunosuppression was 50% at 21 months. Estimated survival at 5 years after heart transplant was 92.9% in Group P0 and 72.3% in Group P1 (p <0.01). Cox proportional hazard modeling revealed black recipient race as effect modifier of group status with decreased survival time in both groups. CONCLUSION: Steroid-free immunosuppression in white heart transplant recipients is associated with improved survival. A low acute rejection score during the first year predicts successful steroid withdrawal. Black recipient race appears to be negatively associated with survival and deserves further detailed study. Long-term surveillance screening using endomyocardial biopsy is recommended.

Incorporating robotics into an open-heart program.

The above described clinical series show that after a careful and thorough training program and stepwise introduction of surgical telemanipulation systems, application of telemanipulations is safe and shows acceptable results. Still, OR times are longer than for conventional procedures, and the operation is demanding, and expensive. The main shortcoming is that the procedure is only suitable for a highly selected patient population. However, despite all the clinical experience gathered in various centers, this technique is still evolving and in its beginning. There are some very promising developments that will improve the benefit of telemanipulators. For the first time, the separation of the surgeon from the surgical field facilitates training of surgeons on simulators. This might lead to a higher standard of surgical performance. Progress in sensor technology will make tactile-force feedback available, and new 3 D-visualization systems are designed to provide a better depth perception and higher resolution of the endoscopic image. Virtual stabilizing systems will enable robotic systems to operate on a virtual arrested heart without the need for CPB or mechanical stabilizers. These and other research topics summarized under the term augmented reality will enhance the natural senses and abilities of the surgeon. More and more, automatization will find its way into the OR. Preoperatively collected data about the patient's anatomy will be used to create safety margins, the robotic system will allow for the surgeon's movements, and instruments will be able to find their way to the surgical site without remote control. Because a stepwise approach has led to the clinical results that we and others have now achieved, it is the basis for further step-by-step development of the application of telemanipulation systems in coronary artery bypass grafting, and possibly other endoscopic procedures in cardiac surgery.

First successful use of the new ab5000 portable circulatory support console as bridge to recovery in a case of dilated cardiomyopathy.

INTRODUCTION: Growing clinical experience and improved technology have led to more widespread use of ventricular assist devices in patients with end-stage heart failure. METHODS: We report the case of a patient with preexisting cardiomyopathy who arrived at our center in cardiogenic shock and received a biventricular assist device. RESULTS: The new compact Abiomed Portable Circulatory Support Console facilitated mobilization of the patient which was particularly advantageous in the face of transient hemiparesis. After recovery from cardiogenic shock, device removal was performed following a bridge-to-recovery concept. He was discharged in a state of full cardiac recompensation and is back to everyday life with stable cardiac function up to 24 months after the incident. CONCLUSIONS: This is the first report describing successful clinical use of the AB5000 assist device in combination with the portable console. Furthermore, it underlines the potential of temporary circulatory support to induce permanent myocardial recovery even in cases of preexisting cardiomyopathy.