Renal hemodynamics and ammoniagenesis. Characteristics of the antiluminal site for glutamine extraction.

Renal production of ammonia by the left kidney was studied in 31 acidotic dogs (NH(4)Cl) after acute constriction of the renal artery. Renal ammoniagenesis fell in direct proportion with the reduction in glomerular filtration rate and renal plasma flow. The renal extraction of glutamine by the experimental kidney fell in direct proportion with the reduction in renal hemodynamics. Extracted glutamine remained greater than filtered glutamine indicating that both the luminal and antiluminal transport sites were operative. The relationship between renal extraction of glutamine and ammoniagenesis observed during control was maintained after renal artery constriction (1.7 mumol NH(3) produced for each mumol of glutamine extracted). Systemic venous or renal intra-arterial infusion of glutamine during arterial constriction increased renal production of ammonia to or above control values. These observations indicate that the mechanisms responsible for glutamine extraction and ammonia production were operating normally despite reduced hemodynamics. When measured immediately after arterial clamping, the renal venous pNH(3) was found to rise significantly decreasing progressively thereafter towards control values. The extracted fraction of total glutamine delivered to the kidney (31%) did not change after acute reduction of the glutamine load. Thus, the antiluminal extraction site was incapable of lowering renal venous plasma glutamine concentration below 0.33 muM/ml. In a second series of experiments, the properties of the antiluminal site of transport for glutamine were studied after complete occlusion of the left ureter in acidotic and nonacidotic animals. Under these circumstances, it was demonstrated that the antiluminal site is capable of extracting sufficient glutamine to maintain total ammonia production at 60% or more of control. In acidotic animals, changes in cellular pNH(3) appeared to play a key role on the antiluminal extraction of glutamine since the significant rise in renal blood flow often observed after ureteral occlusion prevented the rise in pNH(3) noted when blood flow remained constant. Thus, when renal blood flow rose glutamine extraction and ammonia production were maintained at control values. In these acidotic animals, glutamine infusion failed to influence ammonia production until luminal transport was restored by release of ureteral clamp and resumption of glomerular filtration. The latter observation establishes that reabsorbed glutamine is utilized at least in part for ammonia production.

Consequences of the salvage of purine compounds on the proliferation of rat T-lymphocytes with normal or inhibited purine de novo synthesis.

We studied the ability of purine compounds to restore the proliferation of concanavalin-A-stimulated rat T-lymphocytes under conditions of purine de novo synthesis inhibition and, on the other hand, the inhibition by purine nucleosides of the response of these cells to a mitogenic stimulation under conditions of normal purine de novo synthesis. The use of 50 microM azaserine, a potent inhibitor of purine de novo synthesis, allowed us to define the physiologically active salvage pathways of purine bases, ribo- and deoxyribonucleosides in concanavalin-A-stimulated rat T-lymphocytes. Except for guanylic compounds, all purines completely restored cell proliferation at a concentration of 50 microM. Guanine, guanosine and 2'-deoxyguanosine at concentrations up to 500 microM did not allow us to restore more than 50% of the cell proliferation. In conditions of normal purine de novo synthesis, the addition of 1000 microM adenine, adenosine, 2'-deoxyadenosine or 100 microM 2'-deoxyguanosine inhibited rat T-lymphocyte proliferation. The differences between the degree of inhibition of cell proliferation could be explained only in part by the differences between the capacities of salvage of these compounds. Furthermore, the fact that 2'-deoxyguanosine toxicity was dependent and 2'-deoxyadenosine toxicity independent on the activation state of the cells provided more evidence that the biochemical mechanisms of inhibition of cell proliferation should be different for these two nucleosides.

Metabolism of pyrimidine bases and nucleosides by pyrimidine-nucleoside phosphorylases in cultured human lymphoid cells.

The anabolism of pyrimidine ribo- and deoxyribonucleosides from uracil and thymine was investigated in phytohemagglutinin-stimulated human peripheral blood lymphocytes and in a Burkitt's lymphoma-derived cell line (Raji). We studied the ability of these cells to synthesize pyrimidine nucleosides by ribo- and deoxyribosyl transfer between pyrimidine bases or nucleosides and the purine nucleosides inosine and deoxyinosine as donors of ribose 1-phosphate and deoxyribose 1-phosphate, respectively: these reactions involve the activities of purine-nucleoside phosphorylase, and of the two pyrimidine-nucleoside phosphorylases (uridine phosphorylase and thymidine phosphorylase). The ability of the cells to synthesize uridine was estimated from their ability to grow on uridine precursors in the presence of an inhibitor of pyrimidine de novo synthesis (pyrazofurin). Their ability to synthesize thymidine and deoxyuridine was estimated from the inhibition of the incorporation of radiolabelled thymidine in cells cultured in the presence of unlabelled precursors. In addition to these studies on intact cells, we determined the activities of purine- and pyrimidine-nucleoside phosphorylases in cell extracts. Our results show that Raji cells efficiently metabolize preformed uridine, deoxyuridine and thymidine, are unable to salvage pyrimidine bases, and possess a low uridine phosphorylase activity and markedly decreased (about 1% of peripheral blood lymphocytes) thymidine phosphorylase activity. Lymphocytes have higher pyrimidine-nucleoside phosphorylases activities, they can synthesize deoxyuridine and thymidine from bases, but at high an non-physiological concentrations of precursors. Neither type of cell is able to salvage uracil into uridine. These results suggest that pyrimidine-nucleoside phosphorylases have a catabolic, rather than an anabolic, role in human lymphoid cells. The facts that, compared to peripheral blood lymphocytes, lymphoblasts possess decreased pyrimidine-nucleoside phosphorylases activities, and, on the other hand, more efficiently salvage pyrimidine nucleosides, are consistent with a greater need of these rapidly proliferating cells for pyrimidine nucleotides.

Midterm echocardiographic follow-up after Ross operation.

BACKGROUND: The pulmonary autograft (Ross) operation is an attractive treatment for aortic valve disease, but hemodynamic follow-up is not well defined. METHODS AND RESULTS: One hundred thirty-two consecutive patients (62% male, mean age 40+/-11 years) were followed up to 5 years after the Ross operation. Echocardiography was performed early (within 30 days), 3 to 6 months, and yearly after surgery. The valve effective orifice area (EOA) and mean transvalvular gradient of both aortic and pulmonary valves were measured, and transvalvular regurgitation was assessed by using color Doppler echocardiography. EOA was indexed for body surface area. The hemodynamic performance was excellent for both the aortic and pulmonary valves early after surgery (gradient, 3+/-4 and 3+/-4 mm Hg, respectively). It remained stable thereafter for the aortic valve, whereas there was a significant deterioration of the EOA (-0. 74+/-0.82 cm(2)) and gradient (+6+/-8 mm Hg) for the pulmonary valve, which occurred mostly during the first 6 months after surgery. This hemodynamic deterioration resulted in suboptimal (defined as an EOA index <0.85 cm(2)/m(2)) hemodynamics in 19.3% of the patients, to the extent that 3 (2%) of the 132 patients eventually had to be subjected to further surgery for severe pulmonary valve stenosis. CONCLUSIONS: The pulmonary autograft provides continued excellent hemodynamics in the aortic position, whereas moderately high gradients can be found across the pulmonary homograft in some patients. Further studies are necessary to identify the factors responsible for the deterioration of the hemodynamic performance of the homograft in the pulmonary position and to determine its impact on right ventricular function and clinical status.

Hemodynamic and physical performance during maximal exercise in patients with an aortic bioprosthetic valve: comparison of stentless versus stented bioprostheses.

OBJECTIVES: The objective of this study was to compare stentless bioprostheses with stented bioprostheses with regard to their hemodynamic behavior during exercise. BACKGROUND: Stentless aortic bioprostheses have better hemodynamic performances at rest than stented bioprostheses, but very few comparisons were performed during exercise. METHODS: Thirty-eight patients with normally functioning stentless (n = 19) or stented (n = 19) bioprostheses were submitted to a maximal ramp upright bicycle exercise test. Valve effective orifice area and mean transvalvular pressure gradient at rest and during peak exercise were successfully measured using Doppler echocardiography in 30 of the 38 patients. RESULTS: At peak exercise, the mean gradient increased significantly less in stentless than in stented bioprostheses (+5 +/- 3 vs. +12 +/- 8 mm Hg; p = 0.002) despite similar increases in mean flow rates (+137 +/- 58 vs. +125 +/- 65 ml/s; p = 0.58); valve area also increased but with no significant difference between groups. Despite this hemodynamic difference, exercise capacity was not significantly different, but left ventricular (LV) mass and function were closer to normal in stentless bioprostheses. Overall, there was a strong inverse relation between the mean gradient during peak exercise and the indexed valve area at rest (r = 0.90). CONCLUSIONS: Hemodynamics during exercise are better in stentless than stented bioprostheses due to the larger resting indexed valve area of stentless bioprostheses. This is associated with beneficial effects with regard to LV mass and function. The relation found between the resting indexed valve area and the gradient during exercise can be used to project the hemodynamic behavior of these bioprostheses at the time of operation. It should thus be useful to select the optimal prosthesis given the patient's body surface area and level of physical activity.

Which biologic valve should we select for the 45- to 65-year-old age group requiring aortic valve replacement?

OBJECTIVE: The diversity of biologic valves available to replace the aortic valve renders selection difficult for the 45- to 65-year-old patient. To evaluate and compare the results of biologic valves in the 45- to 65-year-old patient, we reviewed our experience (1991-2004). METHODS: Three hundred thirty-two patients between 45 and 65 years old with isolated aortic valve disease had a biologic valve implanted: Freestyle valve in 140 patients, a homograft in 54 patients, a stented Mosaic or Perimount valve (stented xenograft) in 62 patients, and a Ross procedure in 76 patients. RESULTS: Perioperative mortality was comparable for all groups (Freestyle, 2.1%; homograft, 3.7%; stented xenograft, 3.2%; Ross procedure, 1.3%; P = .8). Echocardiographically determined valve performance at discharge was significantly enhanced in the Ross procedure and homograft groups (indexed effective orifice area: Freestyle, 0.9 +/- 0.3 cm 2 /m 2 ; homograft, 1.3 +/- 0.3 cm 2 /m 2 ; stented xenograft, 0.8 +/- 0.2 cm 2 /m 2 ; Ross procedure, 1.4 +/- 0.4; P < .0001; mean gradient: Freestyle, 12.0 +/- 6.6 mm Hg; homograft, 7.4 +/- 4.0 mm Hg; stented xenograft, 15.4 +/- 5.4 mm Hg; Ross procedure, 4.6 +/- 3.2 mm Hg; P < .0001). For all yearly follow-up, freedom from New York Heart Association class III or IV was comparable and greater than 95% for all groups. At 7 years, cardiac survival (homograft, 96.3% +/- 3.7%; Ross procedure, 90.6% +/- 6.3%; stented xenograft, 86.0% +/- 10.3%; Freestyle, 89.2% +/- 10.8%; P = .7) and freedom from reoperation (Ross procedure, 98.5% +/- 1.4%; homograft, 90.6% +/- 5.7%; Freestyle, 88.0% +/- 4.9%; stented xenograft, 90.0% +/- 8.0%; P = .4) were comparable. Freedoms from significant bleeding events, valve-related neurologic events, or endocarditis were comparable and greater than 95% for all groups. CONCLUSION: Type of aortic biologic valve for the 45- to 65-year-old patient does not affect midterm survival or valve-related morbidity. Thus the choice of biologic valve for the 45- to 65-year-old patient should be dictated by patient-surgeon preference, ease of implantation, and reoperation until longer comparative studies are available.

Uridine as the only alternative to pyrimidine de novo synthesis in rat T lymphocytes.

Concanavalin A-induced proliferation of rat T-lymphocytes is completely inhibited by 10(-5) M pyrazofurin, a potent inhibitor of pyrimidine de novo synthesis, as judged by cell viability and [3H]thymidine incorporation. Proliferation is completely restored by 5 X 10(-5) M uridine. Cytidine, deoxycytidine, deoxyuridine and thymidine 10 X 10(-5) M each, fail to re-establish proliferation but produce an isotropic dilution of [3H]thymidine uptake in DNA. Bases (cytosine, uracil and thymine) neither restore proliferation nor induce isotopic dilution. The unexpected inability of cytidine to reverse de novo pyrimidine synthesis inhibition suggests a lack of cytidine deaminase activity in rat T-lymphocytes. This is confirmed by a direct sensitive radioisotopic assay (less than 0.001 nmol X min-1 X 10(-6) cells).

Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients.

OBJECTIVE: To compare the acute and chronic effects of nifedipine retard (NPA), nifedipine gastrointestinal therapeutic system (NGITS) and amlodipine at trough and peak plasma concentrations of drug on blood pressure and heart rate, and on plasma norepinephrine and epinephrine levels in patients with mild-to-moderate hypertension (diastolic blood pressure 95-115 mmHg). DESIGN AND METHODS: After 3-4 weeks' placebo treatment, patients of both sexes were randomly allocated to be administered 10 or 20 mg NPA twice a day, 30 or 60 mg NGITS once a day, and 5 or 10 mg amlodipine once a day for 6 weeks. Initially, for the first 2 weeks, the lowest dose of each drug was used, but higher doses were administered after 2 weeks if sitting diastolic blood pressure was > 90 mmHg. Patients were evaluated after administration of the first dose and after 6 weeks' therapy in a hospital setting. Blood samples were taken for high-performance liquid chromatography measurement of catecholamine and drug levels at various intervals for a period covering trough to peak drug level ranges. RESULTS: Administration of all three drugs reduced clinic blood pressure to the same level after 6 weeks' therapy, but heart rate was increased slightly only with amlodipine (P < 0.05). Administration of NPA reduced blood pressure more abruptly whereas administrations of NGITS and amlodipine induced smoother falls after acute and chronic treatments: a significant increase in heart rate was observed with amlodipine after chronic treatment. Both acute and chronic treatments with NPA (n = 19) increased norepinephrine levels (P < 0.01) transiently (2-4 h). In contrast, administration of NGITS (n = 22) did not increase norepinephrine levels and even induced a slight but significant decrease in norepinephrine levels 5-6 h after chronic treatments. Although administration of amlodipine (n = 22) did not increase norepinephrine levels transiently either after acute or after chronic administration, it did induce a sustained rise in basal norepinephrine levels by more than 50% after chronic therapy (P < 0.01). Plasma epinephrine levels were not increased by any of the treatments and even a slight decrease was observed 4 h after administration of a dose following chronic treatments with NGITS and amlodipine (P < 0.05). CONCLUSIONS: The transient increase in norepinephrine levels observed with NPA and the sustained increases in norepinephrine levels observed after chronic treatment with amlodipine suggest that sympathetic activation occurs with those two drugs. The lack of increase in norepinephrine levels after administration of NGITS suggests that this formulation does not activate the sympathetic system. The lowering of epinephrine levels after administrations of NGITS and amlodipine suggests that inhibition of release of epinephrine by the adrenal medulla occurs with longer-acting dihydropyridine formulations.

Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients.

OBJECTIVE: To compare the acute and chronic effects of nifedipine retard (NPA), nifedipine gastrointestinal therapeutic system (NGITS) and amlodipine at trough and peak plasma concentrations of drug on blood pressure and heart rate, and on plasma norepinephrine and epinephrine levels in patients with mild-to-moderate hypertension (diastolic blood pressure 95-115 mmHg). DESIGN AND METHODS: After 3-4 weeks' placebo treatment, patients of both sexes were randomly allocated to be administered 10 or 20 mg NPA twice a day, 30 or 60 mg NGITS once a day, and 5 or 10 mg amlodipine once a day for 6 weeks. Initially, for the first 2 weeks, the lowest dose of each drug was used, but higher doses were administered after 2 weeks if sitting diastolic blood pressure was > 90 mmHg. Patients were evaluated after administration of the first dose and after 6 weeks' therapy in a hospital setting. Blood samples were taken for high-performance liquid chromatography measurement of catecholamine and drug levels at various intervals for a period covering trough to peak drug level ranges. RESULTS: Administration of all three drugs reduced clinic blood pressure to the same level after 6 weeks' therapy, but heart rate was increased slightly only with amlodipine (P < 0.05). Administration of NPA reduced blood pressure more abruptly whereas administrations of NGITS and amlodipine induced smoother falls after acute and chronic treatments: a significant increase in heart rate was observed with amlodipine after chronic treatment. Both acute and chronic treatments with NPA (n = 19) increased norepinephrine levels (P < 0.01) transiently (2-4 h). In contrast, administration of NGITS (n = 22) did not increase norepinephrine levels and even induced a slight but significant decrease in norepinephrine levels 5-6 h after chronic treatments. Although administration of amlodipine (n = 22) did not increase norepinephrine levels transiently either after acute or after chronic administration, it did induce a sustained rise in basal norepinephrine levels by more than 50% after chronic therapy (P < 0.01). Plasma epinephrine levels were not increased by any of the treatments and even a slight decrease was observed 4 h after administration of a dose following chronic treatments with NGITS and amlodipine (P < 0.05). CONCLUSIONS: The transient increase in norepinephrine levels observed with NPA and the sustained increases in norepinephrine levels observed after chronic treatment with amlodipine suggest that sympathetic activation occurs with those two drugs. The lack of increase in norepinephrine levels after administration of NGITS suggests that this formulation does not activate the sympathetic system. The lowering of epinephrine levels after administrations of NGITS and amlodipine suggests that inhibition of release of epinephrine by the adrenal medulla occurs with longer-acting dihydropyridine formulations.

Hemodynamic performance during maximum exercise in adult patients with the ross operation and comparison with normal controls and patients with aortic bioprostheses.

This study examines the resting and exercise hemodynamic performance of the pulmonary autografts in the aortic position as well as of the homografts used for right ventricular outflow reconstruction in patients undergoing the Ross operation. Previous studies have reported excellent resting hemodynamics in patients who underwent aortic valve replacement with a pulmonary autograft. However, there are very few studies of their hemodynamic performance during exercise. Twenty adult subjects who underwent the Ross operation and 12 normal control subjects were submitted to maximum romp bicycle exercise. The valve effective orifice areas and transvalvular gradients of both aortic (autograft) and pulmonary (homograft) valves were measured at rest and at peak of maximum exercise using Doppler echocardiography. Valve areas were indexed for body surface area. The hemodynamics of the aortic valve were very similar in Ross subjects and in control subjects at rest and during exercise. However, the indexed valve area of the pulmonary valve at rest was significantly (p < 0.001) lower in the Ross subjects (1.10 +/- 0.46 cm2/ m2) than in the control subjects (1.95 +/- 0.41 cm2/m2), resulting in higher (p = 0.004) mean gradients at rest (Ross: 9 +/- 7 mm Hg vs control: 2 +/- 1 mm Hg) and at peak exercise (Ross: 21 +/- 14 mm Hg vs control: 7 +/- 2 mm Hg). The pulmonary autograft provided excellent hemodynamics in the aortic position either at rest or during maximum exercise, whereas moderately high gradients were found during exercise across the homograft implanted in the pulmonary valve position. Future improvement of the Ross procedure should be oriented toward the search of new methods to prevent the deterioration of the homografts.

Hypertension with renal arterial stenosis: humoral, hemodynamic and histopathologic factors.

In 46 hypertensive patients with unilateral renal arterial stenosis, peripheral and renal venous plasma renin activity, juxtaglomerular cell count and granularity and systolic pressure gradient across the stenosis were determined. After corrective surgery and a mean postoperative observation period of 4.3 years, 18 patients were completely relieved of hypertension (good responders), 14 had a substantial reduction in arterial pressure (fair responders) and 14 remained hypertensive (poor responders). Analysis of plasma renin activity in both renal veins indicated that a ratio (stenotic/nonstenotic side) greater than 2.0 correctly predicted a favorable surgical result in all cases. Peripheral plasma renin activity was greater than normal in 65 percent of good responders, in 50 percent of fair responders and in one nonresponder. The prognostic accuracy of a pressure gradient greater than 40 mm Hg was 78 percent; no patient with a gradient of less than 40 mm Hg benefited from surgery. An increased juxtaglomerular cell count on the affected side predicted a successful operative result in 88 percent, as did increased granularity in 85 percent of cases. Renal venous renin ratio correlated positively (r =0.738, P less than 0.001) with the pressure gradient across the stenosis. The renal venous plasma renin activity of the affected side also correlated positively (r = 0.771, P less than 0.001) with the absolute count of granular cells in the juxtaglomerular apparatus. Plasma renin activity in both renal veins is the most reliable predictor of operative outcome. The addition of juxtaglomerular cell count or pressure gradient across the stenosis increases prognostic accuracy only slightly. The close mutual correlations between renal venous renin ratio, pressure gradient and juxtaglomerular cell count support the experimental evidence of a causal relation between the hemodynamic effects of the arterial lesion and the humoral and histologic changes observed in hypertension with renal arterial stenosis.

Incidence and predictors of ARDS after cardiac surgery.

BACKGROUND: Severe pulmonary injury with the development of ARDS is a potential complication of cardiac surgery and cardiopulmonary bypass (CPB). STUDY OBJECTIVES: This retrospective, case-control study was designed to determine the incidence and mortality of ARDS after cardiac surgery and CPB, as well as to identify preoperative and perioperative predisposing factors of this complication. METHODS: Of 3,278 patients who underwent cardiac surgery and CPB between January 1995 and December 1998, 13 patients developed ARDS during the postoperative period. Each patient was matched with four or five control subjects who had the same type of surgery on the same day but did not develop postoperative respiratory complications. RESULTS: The incidence of ARDS was 0.4%, with an ARDS mortality of 15%. In the ARDS group, 38% had previous cardiac surgery, as compared to 3.5% in the control group (p < 0.002). During the postoperative period, ARDS patients received more blood products (4 +/- 5 vs 2 +/- 3; p < 0.01) and developed shock more frequently (31% vs 5%; p < 0.02) than patients in the control group. Multivariate regression analysis identified previous cardiac surgery, shock, and the number of transfused blood products as significant independent predictors for ARDS, with odds ratios of 31.5 (p = 0.015), 10.8 (p = 0.03), and 1.6 (p = 0.03), respectively. CONCLUSIONS: ARDS following cardiac surgery and CPB was a rare complication that carried a 15% mortality rate. Previous cardiac surgery, shock, and number of blood products received are important predicting factors for this complication.

Mosaic valve international clinical trial: early performance results.

BACKGROUND: A new third generation porcine bioprosthesis was developed in an attempt to improve on hemodynamic performance and durability of current prostheses. METHODS: One thousand, two hundred, sixty patients underwent aortic valve replacement and 366 patients underwent mitral valve replacement between February 1994 and September 2000. The cumulative follow-up was 3,696.3 patient-years for aortic valve replacement and 880.1 patient-years for mitral valve replacement. Follow-up was complete for 95.5% of aortic valve replacement patients and 97.5% of mitral valve replacement patients. RESULTS: For aortic valve replacement, freedom from valve-related adverse events at 1 year was 96.5%+/-0.5% for antithromboembolic-related hemorrhage and 100% for structural valve deterioration. Freedom from valve-related adverse events at 5 years was 93.8%+/-2.6% for antithromboembolic-related hemorrhage and 99.3%+/-0.9% for structural valve deterioration. For mitral valve replacement, freedom from valve-related adverse events at 1 year was 96.0%+/-1.1% for antithromboembolic-related hemorrhage and 100% for structural valve deterioration. Freedom from valve-related adverse events at 4 years was 92.1%+/-3.7% for antithromboembolic-related hemorrhage and 100% for structural valve deterioration. CONCLUSIONS: These results support the claim that the Mosaic bioprosthetic valve is efficacious and safe, but continued follow-up is mandatory to determine mid- and long-term performance.

Lobectomy in the treatment of the scimitar syndrome.

The scimitar syndrome is a congenital anomaly that consists mainly of total or partial anomalous venous drainage of the right lung to the inferior vena cava. We report the case of an 8-year-old girl diagnosed at birth as having a scimitar syndrome and who presented with recurrent right lower lung infections. She underwent resection of the lower half of her right lung without diversion of the anomalous venous drainage of the upper portion of the lung. She improved rapidly postoperatively and the shunt fraction diminished.

Patient-prosthesis mismatch can be predicted at the time of operation.

BACKGROUND: Patient-prosthesis mismatch is a frequent cause of high postoperative gradients in normally functioning prostheses. The objective of this study was to determine whether mismatch can be predicted at the time of operation. METHODS: Indices used to predict mismatch were valve size, indexed internal geometric area, and projected indexed effective orifice area (EOA) calculated at the time of operation, and results were compared with indexed EOA and mean gradients measured by Doppler echocardiography after operation in 396 patients. RESULTS: The sensitivity and specificity of these indices to detect mismatch, defined as a postoperative indexed EOA of 0.85 cm2/m2 or less, were respectively: 35% and 84% for valve size, 46% and 85% for indexed internal geometric area, and 73% and 80% for projected indexed EOA. Projected indexed EOA also correlated best with resting (r = 0.67) and exercise (r = 0.77) postoperative gradients. CONCLUSIONS: The projected indexed EOA calculated at the time of operation accurately predicts mismatch as well as resting and exercise postoperative gradients, whereas valve size and indexed internal geometric area cannot be used for this purpose.

Aortic valve replacement with pulmonary autograft in children and adults.

Aortic valve replacement with a conventional prosthesis is still flawed with complications, especially in children and young adults. Complex aortic root enlargement (Konno) is often needed because of small aortic diameter. The poor compliance with anticoagulation by teenagers and the risks associated with this made us look at alternative techniques. From November 1990 to June 1994, 70 patients were considered for pulmonary autografts in our institution; 64 underwent the procedure with one death and one failure to implant. Short-term results are excellent, with minimal gradient in 90% and minimal regurgitation in 96% of the patients. The long-term follow-up, hopefully, will confirm the superiority of this procedure over more conventional replacement.

Medtronic intact porcine bioprosthesis: 10 years' experience.

BACKGROUND: The Medtronic Intact porcine bioprosthesis experience was evaluated over a period of 10 years to determine the influence of structural valve deterioration by valve position in various age groupings. METHODS: From 1986 to 1996 inclusive, at three centers, 1,272 patients had the prosthesis implanted in 1,296 procedures. The mean age of the population was 67 years (range, 9 to 91 years). There were 836 aortic valve replacements (AVR) (64.5%), 333 mitral valve replacements (MVR) (25.7%), and 110 multiple valve replacements (MR) (8.5%). RESULTS: The early mortality was 7.3% (94 of 1,296 procedures). The early mortality with concomitant procedures (primarily coronary artery bypass grafting) was 9.8% (52 of 528) and without, 5.5% (42 of 768). The late mortality was 4.25%/patient-year. The linearized rate of major thromboembolism was 0.86%/patient-year. The rate of reoperation was 1.19%/patient-year and valve-related mortality, 1.06%/patient-year. There were 36 cases of structural valve deterioration for aortic valve replacement (16), mitral valve replacement (15), tricuspid valve replacement (2), and multiple valve replacement (3). The freedom from structural valve deterioration for aortic valve replacement was in patients 21 to 40 years, 62.5%+/-25.8% at 7 years; 41 to 50 years, 75.0%+/-15.3% at 7 years; 51 to 60 years, 91.0%+/-4.5% at 8 years; 61 to 70 years, 98.7%+/-0.7% at 10 years; and older than 70 years, 98.3%+/-1.0% at 10 years (p < 0.05). The freedom from structural valve deterioration for mitral valve replacement was for patients 41 to 50 years, 91.7%+/-8.0% at 7 years; 51 to 60 years, 85.9%+/-9.9% at 8 years; 61 to 70 years, 86.3%+/-6.8% at 8 years; and older than 70 years, 93.9%+/-4.8% at 8 years (not significant). CONCLUSIONS: The Medtronic Intact porcine bioprosthesis has acceptable freedom from structural valve deterioration in both the aortic and mitral positions approaching 10 years of evaluation.

Hemodynamic features of the freestyle aortic bioprosthesis compared with stented bioprosthesis.

BACKGROUND: The Freestyle prosthesis is a new stentless aortic bioprosthesis. Anticipated benefits are improved hemodynamics and increased longevity. METHODS: Doppler echocardiograms were performed early and at 3 to 6 months, 1 year, and 2 years after operation in 157 patients (69 men, 88 women, aged 48 to 85 years) with this prosthesis, and results were compared with hemodynamic data in patients with Intact and Mosaic stented bioprostheses. RESULTS: Distinctive features of the prosthesis compared with stented prostheses are (1) an increase in effective orifice area (+0.15+/-0.26 cm2; p < 0.05) and a decrease in mean gradient (-3.5+/-4.0 mm Hg; p < 0.001) during the first 3 to 6 months postoperatively and stabilization thereafter; (2) a markedly lower mean gradient at 1 year after operation (average, 6+/-4 mm Hg) than in stented prostheses (Intact, 22+/-8 mm Hg; Mosaic, 12+/-6 mm Hg); (3) in contrast to stented prostheses, in vivo effective orifice areas much lower (-0.91+/-0.35 cm2) than those calculated in vitro; (4) as in stented prostheses, the indexed effective orifice area (cm2/m2) is the best predictor (r = 0.77 at 1 year) of the mean gradient after operation; and (5) similar incidence of aortic regurgitation (trivial or mild, 34% versus 29% in Intact). CONCLUSIONS: The hemodynamics of the Freestyle are very satisfactory and represent a marked improvement in comparison to stented prosthesis.

Clinical and hemodynamic performance of the Freestyle aortic root bioprosthesis.

BACKGROUND: The objective of this study is to assess the clinical and hemodynamic performance of a stentless porcine bioprosthesis, the Freestyle aortic root bioprosthesis. METHODS: Consenting patients requiring isolated aortic valve or aortic root replacement received the Freestyle bioprosthesis. Clinical follow-up and echocardiographic data were obtained at discharge, 3 to 6 months, 1 year, and annually thereafter. RESULTS: Two hundred seventy-six patients received a Freestyle aortic root bioprosthesis between January 1993 and July 1997. The mean age was 67.7 years. Preoperatively, 86.3% were either New York Heart Association class III or IV. Two hundred thirty-eight patients underwent valve (subcoronary) replacement, 36 underwent aortic root replacement, and 2 underwent valve replacement using the root-inclusion technique. The early mortality was 5.4%, with 3.3% mortality for the subcoronary technique and 19.4% mortality for aortic root replacement. The mean gradient decreased significantly between discharge and the 3- to 6-month follow-up and stabilized thereafter. The effective orifice area increased significantly from discharge to 3 to 6 months' follow-up. At 3 years, 84.4% of the patients had either no or trivial regurgitation. CONCLUSIONS: The Freestyle bioprosthesis has good clinical performance and good short-term hemodynamic performance. The majority of the regurgitation identified is not clinically significant.

Medtronic Intact porcine bioprosthesis experience to twelve years.

BACKGROUND: The Medtronic Intact porcine bioprosthesis was further evaluated to determine the influence of zero-pressure glutaraldehyde fixation on structural valve deterioration (SVD). METHODS: From 1986 through 1996, at three Canadian centers, 1,272 patients had 1,296 procedures: 836 aortic valve replacement (AVR), 332 mitral valve replacement (MVR), 14 tricuspid valve replacement, 3 pulmonary valve replacement, and 111 multiple valve replacements. The mean age of the patient population was 67 years (range 9 to 91 years). The total follow-up was 8,011 patient-years (mean 6.2 years). RESULTS: The late mortality (overall) was 4.8% and 6.7% per patient-year for AVR with or without concomitant procedures, respectively; and 4.7% and 10.4% per patient-year for MVR, respectively. There were 51 cases of SVD (AVR 22 of 836; MVR 23 of 332; pulmonary valve replacement 1 of 3; and multiple valve replacement 5 of 111). The actuarial freedom from SVD at 12 years for AVR was 94.3%+/-3.3% for patients aged 61 to 70 years and 97.7%+/-1.1% for those more than 70 years; for MVR actuarial freedom from SVD at 12 years was 93.7%+/-3.9% for patients more than 70 years. The actual freedom at 12 years from SVD for AVR was 92.4%+/-3.1% for patients aged 51 to 60 years, 96.1%+/-2.1% for those 61 to 70 years, and 98.4%+/-0.7% for those older than 70 years; for MVR actual freedom from SVD at 12 years was 89.6%+/-3.2% for patients 61 to 70 years and 96.6%+/-3.4% for those more than 70 years. CONCLUSIONS: The Medtronic Intact porcine bioprosthesis, formulated with tissue preservation at zero-pressure fixation, has encouraging freedom from structural failure.