Structural evidence for ammonia tunneling across the (beta alpha)(8) barrel of the imidazole glycerol phosphate synthase bienzyme complex.

Since reactive ammonia is not available under physiological conditions, glutamine is used as a source for the incorporation of nitrogen in a number of metabolic pathway intermediates. The heterodimeric ImGP synthase that links histidine and purine biosynthesis belongs to the family of glutamine amidotransferases in which the glutaminase activity is coupled with a subsequent synthase activity specific for each member of the enzyme family. Its X-ray structure from the hyperthermophile Thermotoga maritima shows that the glutaminase subunit is associated with the N-terminal face of the (beta alpha)(8) barrel cyclase subunit. The complex reveals a putative tunnel for the transfer of ammonia over a distance of 25 A. Although ammonia tunneling has been reported for glutamine amidotransferases, the ImGP synthase has evolved a novel mechanism, which extends the known functional properties of the versatile (beta alpha)(8) barrel fold.

Influence of prosthesis size and left ventricular mass on left ventricular diastolic reserve in patients with aortic valve prostheses.

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the influence of valve size and left ventricular (LV) mass on long-term LV diastolic reserve in patients subjected to aortic valve replacement for stenosis. METHODS: Seventy-four patients (33 women, 41 men; mean age 64 years) after aortic valve replacement with 40 pericardial bioprostheses and 34 bileaflet mechanical prostheses were studied. All valves were of nominal size 19, 21 or 23 mm. The patients were studied by Doppler echocardiography, at rest and during peak effort, between 12 and 47 months after valve replacement. RESULTS: All patients achieved significantly increased heart rate, blood pressure and cardiac output in response to effort. Effort also significantly modified transvalvular pressure drops and valve areas. The mean diastolic reserve was 29.3 ml, and mean stroke volume reserve 23.2 ml; in neither case were there any significant differences between valve types, or among valve sizes. CONCLUSION: At about one year after surgery, the diastolic reserve of patients subjected to aortic valve replacement on account of stenosis was considerable, and independent of valve size. Despite the persistence of LV hypertrophy after valve replacement, LV diastolic function during effort was similar to that of the normal heart.

The influence of the design on the medium to long-term hemodynamic behavior of 19 mm pericardial aortic valve prostheses.

BACKGROUND AND AIMS OF THE STUDY: The hemodynamics of five designs of 19 mm pericardial aortic valve bioprosthesis were examined by Doppler echocardiography in 48 resting patients at medium or long term follow up. METHODS: The salient differences among the five designs are that valve leaflets are mounted inside the support frame in one (the Carpentier-Edwards valve, evaluated in five patients) and outside the frame in the other four (the Ionescu-Shiley (14 patients), Mitroflow (six patients), Bioflo (eight patients) and Labcor-Santiago (15 patients)); and that two models have either total (Bioflo) or partial (Labcor-Santiago) protective pericardial sheaths on the stent, while the other three do not. The hemodynamic parameters determined included transvalvular pressure drop, valve area, left ventricular outflow tract diameter, subvalvular/valvular velocity ratio and subvalvular/valvular velocity-time integral ratio. RESULTS: There were no significant differences among the various valves as regards left ventricular outflow tract diameter, subvalvular/valvular velocity ratio or subvalvular/valvular velocity-time integral ratio. Negative correlation between left ventricular outflow tract diameter and subvalvular velocity (r = -0.63, p < 0.001) confirmed the need to correct for prevalvular velocities when using the Bernoulli equation to calculate the pressure drop across small pericardial aortic valve bioprostheses. The Bioflo design caused significantly greater pressure drops (peak 49.6 +/- 11.3 mmHg, mean 28.1 +/- 6.1 mmHg) and provided smaller areas (0.80 +/- 0.16 cm2) than the Ionescu-Shiley (26.7 +/- 6.6 and 15.2 +/- 4.1 mmHg, 1.17 +/- 0.17 cm2) and Labcor-Santiago (24.8 +/- 5.9 and 15.1 +/- 3.7 mmHg, 1.24 +/- 0.12 cm2) valves. CONCLUSIONS: Of the currently available 19 mm bovine pericardium heart valve bioprostheses, the Mitroflow and Labcor-Santiago valves, in both of which the leaflets are mounted outside the stent, have better hemodynamics in the aortic position than the Carpentier-Edwards valve, which has internal leaflet mounting. Sheathing the stent totally in pericardium, as in the withdrawn Bioflo valve, gives rise to relatively poor hemodynamics.

Influence of the size of aortic valve prostheses on hemodynamics and change in left ventricular mass: implications for the surgical management of aortic stenosis.

UNLABELLED: Discussion of aortic valve replacement has primarily concerned the choice between tissue and mechanical prostheses. Less emphasis has been placed on prosthesis size. Despite technical advances increasing prosthesis orifice area, small valves implanted in the unenlarged aortic root may not be significantly less obstructive than the stenotic native valves they replace. METHODS: In this work we studied 52 patients (31 women, 21 men; mean age 59.2 years) in whom valve prostheses sized 19, 21, 23, or 25 mm (30 bioprostheses and 22 tilting disc valves) had been implanted to replace stenotic aortic valves. Most patients with 19 or 21 mm prostheses were women. Doppler and conventional echocardiographic studies were performed in the 10 days preceding the operation and between 10 and 40 months (mean 18 months) after the operation. The patients receiving larger valve sizes had significantly larger body surface areas than those receiving smaller valve sizes (mainly women). RESULTS: No significant differences were observed between preoperative and postoperative diameters or left ventricular systolic function parameters, but left ventricular mass and mass index decreased in all four groups (albeit nonsignificantly in the 19 mm group, and with less statistical significance in the 21 mm group than in the 23 and 25 mm groups). Postoperative peak and mean transvalvular pressure drops were significantly greater in the 19 mm group than in the other groups, and the 21 mm group had significantly greater transvalvular pressure drops than the 25 mm group. Postoperative effective valve area was significantly smaller in the 19 mm group than in the 21 mm group, and significantly smaller in the 21 mm group than in the 23 and 25 mm groups. CONCLUSION: We conclude that despite undeniable recent improvements in the design of artificial heart valves, 19 mm aortic prostheses continue to create significant obstruction of the left ventricular outflow tract and, possibly as a consequence of this, fail to bring about significant reduction in left ventricular hypertrophy.

Hemodynamics of various designs of 19 mm pericardial aortic valve bioprosthesis.

The hemodynamics of five designs of 19 mm pericardial aortic valve bioprostheses were examined in 47 resting patients by Doppler echocardiography. The salient differences among the five designs are that valve leaflets are mounted inside the support frame in one (the Carpentier-Edwards valve, evaluated in 4 patients) and outside the frame in the other four (the Ionescu-Shiley (16 patients), Mitroflow (4), Bioflo (8) and Labcor-Santiago (15)); and that two models have either total (Bioflo) or partial (Labcor-Santiago) protective pericardial sheaths on the stent, while the other three do not. The hemodynamic parameters determined included transvalvular pressure drop, valve area, left ventricular outflow tract diameter, subvalvular/valvular velocity ratio and subvalvular/valvular velocity-time integral ratio. There were no significant differences among the various valves as regards left ventricular outflow tract diameter, subvalvular/valvular velocity ratio or subvalvular/valvular velocity-time integral ratio. Negative correlation between left ventricular outflow tract diameter and subvalvular velocity (r = -0.66, P < 0.001) confirmed the need to correct for prevalvular velocities when using the Bernouilli equation to calculate the pressure drop across small pericardial aortic valve bioprostheses. The Bioflo design caused significantly greater pressure drops (peak 38.3 +/- 8.3 mmHg, mean 24.6 +/- 4.8 mmHg) and smaller areas (0.82 +/- 0.17 cm2) than the Ionescu-Shiley (20.3 +/- 5.6 and 11.7 +/- 3.8 mmHg, 1.19 +/- 5.3 and 10.1 +/- 3.1 mmHg, 1.27 +/- 0.12 cm2) valves.

[Regression of left ventricular mass in arterial hypertension. Efficacy of 3 different treatment protocols]. / Regresión de la masa ventricular izquierda en la hipertensión arterial. Eficacia de tres diferentes pautas de tratamiento.

BACKGROUND: To evaluate the antihypertensive efficacy, at rest and under exercise, in patients treated with three different antihypertensive drugs and the modifications induced on the left ventricular mass. METHODS: Fifty hypertensive males, mean age 51 years, 15 received 50 mg/day of chlorthalidone, 20 atenolol (100 mg/day) and 15 enalapril (20-40 mg/day). Baseline pressure control and echocardiogram, and 3, 6 and 9 months after starting therapy were performed. Thickness of the interventricular septum and posterior left ventricular wall in mm, left ventricular mass index in g/m2 were determined. RESULTS: The baseline septum in the diuretic group was 15 +/- 3 mm and 14 +/- 3 mm at 9 months, in the atenolol group was 16 +/- 3 mm and 12 +/- 2 mm (p less than 0.001), and in the enalapril group 15 +/- 2 mm and 12 +/- 3 mm (p less than 0.01). The posterior wall was 14 +/- 3 mm and 13 +/- 2 mm in the diuretic group, in the atenolol group 15 +/- 2 mm and 12 +/- 2 mm (p less than 0.001) and in the enalapril group 15 +/- 2 mm and 12 +/- 3 mm (p less than 0.01). The left ventricular mass index was in he diuretic group 153 +/- 45 g/m2 and 146 +/- 36 g/m2, in the atenolol group 167 +/- 34 g/m2 and 128 +/- 24 g/m2 (p less than 0.001) and in the enalapril group 156 +/- 36 g/m2 and 131 +/- 26 g/m2 (p less than 0.05). CONCLUSIONS: The antihypertensive efficacy at rest was similar with the three drugs, being under exercise superior atenolol and enalapril. Only atenolol and enalapril induced regression of left ventricular mass.