Gene polymorphisms in APOE, NOS3, and LIPC genes may be risk factors for cardiac adverse events after primary CABG

<p>Abstract</p> <p>Introduction</p> <p>Coronary artery disease progression after primary coronary artery bypass grafting may, beside classical atherosclerosis risk factors, be depending on genetic predisposition.</p> <p>Methods</p> <p>We investigated 192 CABG patients (18% female, age: 60.9 ± 7.4 years). Clinically cardiac adverse events were defined as need for reoperation (n = 88; 46%), reintervention (n = 58; 30%), or angina (n = 89; 46%). Mean follow-up time measured 10.1 ± 5.1 years. Gene polymorphisms (<b><it>ApoE, NOS3, LIPC, CETP, SERPINE-1, Prothrombin</it></b>) were investigated separately and combined (gene risk profile).</p> <p>Results</p> <p>Among classical risk factors, arterial hypertension and hypercholesterinemia significantly influenced CAD progression. Single <b><it>ApoE, NOS3 </it></b>and <b><it>LIPC </it></b>polymorphisms provided limited information. Patients missing the most common <b><it>ApoE </it></b>ε3 allele (5,2%), showed recurrent symptoms (p = 0,077) and had more frequently reintervention (p = 0,001). <b><it>NOS3 </it></b>a allele was associated with a significant increase for reintervention (p = 0,041) and recurrent symptoms (p = 0,042).</p> <p>Homozygous <b><it>LIPC </it></b>patients had a higher reoperation rate (p = 0.049).</p> <p>A gene risk profile enabled us to discriminate between faster and slower occurrence of cardiac adverse events (p = 0.0012).</p> <p>Conclusion</p> <p>Single <b><it>APOE, LIPC </it></b>and <b><it>NOS3 </it></b>polymorphisms permitted limited prognosis of cardiac adverse events in patients after CABG. Risk profile, in contrast, allowed for risk stratification.</p

Forty-one years of surgical experience with congenital supravalvular aortic stenosis

AbstractObjective: Several techniques for symmetric reconstruction of the aortic root in congenital supravalvular aortic stenosis have been developed, but it remains unclear whether these prove superior to patch enlargement of the noncoronary sinus alone. We reviewed our experience with surgical treatment of supravalvular aortic stenosis and investigated the impact of the surgical technique on long-term results. Methods and results: Seventy-five patients underwent operations to treat congenital supravalvular aortic stenosis at our institution between 1957 and 1998. Surgical procedures included patch enlargement of the noncoronary sinus only (n = 34), inverted bifurcated patch plasty (n = 35), and 3-sinus reconstruction of the aortic root (n = 6). There were 7 early deaths. Among those who survived the operation, 100% were alive at 5 years, 96% were alive at 10 years, and 77% were alive at 20 years. According to time-related analysis diffuse stenosis of the ascending aorta proved a risk factor for both survival and reoperation (P < .01 for each). Patients with multiple-sinus reconstructions of the aortic root accounted for only 2 of the 14 reoperations and none of the late deaths (both P < .001). Residual gradients were lower after multiple-sinus reconstruction of the aortic root (median 10 mm Hg vs 20 mm Hg for patch enlargement of the noncoronary sinus only, P = .008), as was the prevalence of moderate aortic regurgitation at follow-up (3% vs 22%, P = .05). Conclusions: Results of operations for supravalvular aortic stenosis improved greatly after the introduction of more symmetric reconstructions of the aortic root. Multiple-sinus reconstructions (inverted bifurcated patch plasty and 3-sinus reconstruction) resulted in superior hemodynamics and were associated with reductions in both mortality rate and need for reoperation. (J Thorac Cardiovasc Surg 1999;118:874-85

A novel sialyl lewis x analog attenuates cerebral injury after deep hypothermic circulatory arrest

AbstractBackground: The initial step in the inflammatory process, which can be initiated by cardiopulmonary bypass and by ischemia/reperfusion, is mediated by interactions between selectins on endothelial cells and on neutrophils. We studied the effects of selectin blockade using a novel Sialyl Lewis X analog (CY-1503) on recovery after deep hypothermic circulatory arrest in a piglet model. Methods: Twelve Yorkshire piglets were subjected to cardiopulmonary bypass, 30 minutes of cooling, 100 minutes of circulatory arrest at 15°C, and 40 minutes of rewarming. Five animals received a bolus of 60 mg/kg of CY-1503 and an infusion (3 mg/kg per hour) for 24 hours from reperfusion (group O), and 7 randomly selected control piglets received saline solution (group C). Body weight and total body water content were evaluated 3 hours and 24 hours after reperfusion by a bio-impedance technique. Neurologic recovery of animals was evaluated daily by neurologic deficit score (0 = normal, 500 = brain death) and overall performance categories (1 = normal, 5 = brain death). The brain was fixed in situ on the fourth postoperative day and examined by histologic score (0 = normal, 5+ = necrosis) in a blinded fashion. Results: Two of 7 animals in group C died. The neurologic deficit score was significantly lower in group O than in group C (postoperative day 1, P < .001; postoperative day 2, P = .02). The overall performance category was significantly lower in group O than in group C on postoperative day 2 (P = .01). Percentage total body water after cardiopulmonary bypass was significantly higher in group C than in group O (P = .03). Histologic score tended to be higher in group C than in group O, but this difference did not reach statistical significance (group O = 0.5 ± 0.7; group C = 1.3 ± 1.9). Conclusion: Blockade of selectin adhesion molecules by saturation with a Sialyl Lewisxanalog accelerates recovery after 100 minutes of deep hypothermic circulatory arrest in a piglet survival model. (J Thorac Cardiovasc Surg 1999; 117:1204-11

Tissue-engineered valved conduits in the pulmonary circulation

AbstractObjective: Bioprosthetic and mechanical valves and valved conduits are unable to grow, repair, or remodel. In an attempt to overcome these shortcomings, we have evaluated the feasibility of creating 3-leaflet, valved, pulmonary conduits from autologous ovine vascular cells and biodegradable polymers with tissue-engineering techniques. Methods: Endothelial cells and vascular medial cells were harvested from ovine carotid arteries. Composite scaffolds of polyglycolic acid and polyhydroxyoctanoates were formed into a conduit, and 3 leaflets (polyhydroxyoctanoates) were sewn into the conduit. These constructs were seeded with autologous medial cells on 4 consecutive days and coated once with autologous endothelial cells. Thirty-one days (±3 days) after cell harvesting, 8 seeded and 1 unseeded control constructs were implanted to replace the pulmonary valve and main pulmonary artery on cardiopulmonary bypass. No postoperative anticoagulation was given. Valve function was assessed by means of echocardiography. The constructs were explanted after 1, 2, 4, 6, 8, 12, 16, and 24 weeks and evaluated macroscopically, histologically, and biochemically. Results: Postoperative echocardiography of the seeded constructs demonstrated no thrombus formation with mild, nonprogressive, valvular regurgitation up to 24 weeks after implantation. Histologic examination showed organized and viable tissue without thrombus. Biochemical assays revealed increasing cellular and extracellular matrix contents. The unseeded construct developed thrombus formation on all 3 leaflets after 4 weeks. Conclusion: This experimental study showed that valved conduits constructed from autologous cells and biodegradable matrix can function in the pulmonary circulation. The progressive cellular and extracellular matrix formation indicates that the remodeling of the tissue-engineered structure continues for at least 6 months. (J Thorac Cardiovasc Surg 2000;119:732-40

Controlled In Meso Phase Crystallization – A Method for the Structural Investigation of Membrane Proteins

We investigated in meso crystallization of membrane proteins to develop a fast screening technology which combines features of the well established classical vapor diffusion experiment with the batch meso phase crystallization, but without premixing of protein and monoolein. It inherits the advantages of both methods, namely (i) the stabilization of membrane proteins in the meso phase, (ii) the control of hydration level and additive concentration by vapor diffusion. The new technology (iii) significantly simplifies in meso crystallization experiments and allows the use of standard liquid handling robots suitable for 96 well formats. CIMP crystallization furthermore allows (iv) direct monitoring of phase transformation and crystallization events. Bacteriorhodopsin (BR) crystals of high quality and diffraction up to 1.3 Å resolution have been obtained in this approach. CIMP and the developed consumables and protocols have been successfully applied to obtain crystals of sensory rhodopsin II (SRII) from Halobacterium salinarum for the first time