Does body growth impair immune function in a large herbivore?

According to the principle of allocation, trade-offs are inevitable when resources allocated to one biological function are no longer available for other functions. Growth, and to a lesser extent, immunity are energetically costly functions that may compete with allocation to reproductive success and survival. However, whether high allocation to growth impairs immune system development during the growing period or immune system performance during adulthood is currently unknown in wild mammals. Using three roe deer (Capreolus capreolus) populations experiencing contrasting environmental conditions, we tested for potential costs of growth on immune phenotype over both the short-term (during growth), and the long-term (during adulthood) over the course of an individuals' life. We investigated potential costs on a set of 12 immune traits that reflect both innate and adaptive responses, and compared them between sexes and populations. Although fast growth tended to be associated with low levels of some humoral traits (globulins) during the growing period and some cellular immune traits (i.e. eosinophil and neutrophil counts) during adulthood, evidence for a trade-off between growth and other immune components was limited. Unexpectedly, no detectable growth costs on immunity were found in females from the population experiencing the least favourable environment. We discuss our findings in the light of the complex interplay between resource allocation strategies among reproduction, maintenance and immunity, in relation to local environmental conditions experienced by roe deer.

Between-population differences in the genetic and maternal components of body mass in roe deer.

BACKGROUND: Understanding the genetic and environmental mechanisms governing variation in morphology or phenology in wild populations is currently an important challenge. While there is a general consensus that selection is stronger under stressful conditions, it remains unclear whether the evolutionary potential of traits should increase or decrease with increasingly stressful conditions. Here, we investigate how contrasting environmental conditions during growth may affect the maternal and genetic components of body mass in roe deer, the most abundant and widespread wild ungulate in Western Europe. Body mass is a key life history trait that strongly influences both survival and reproductive performance in large herbivores. We used pedigrees and animal models to determine the variance components of juvenile and adult winter body mass in two populations experiencing contrasting early-life conditions. RESULTS: Our analyses showed that roe deer at Chizé, where habitat was poor and unpredictable, exhibited very low genetic variance in juvenile body mass. Instead, variance in mass was mainly driven by among-cohort differences in early-life conditions and maternal environment. In contrast, roe deer at Bogesund, where resource availability during the critical period of fawn rearing was higher, displayed a substantial level of genetic variance in body mass. We discuss the potential role of past demography and viability selection on fawn body mass on the erosion of genetic variance in the poor habitat. CONCLUSIONS: Our study highlights the importance of accounting for both spatial (i.e. between-population variation) and temporal (i.e. cohort variation) heterogeneity in environmental conditions, especially in early life, to understand the potential for adaptive responses of wild populations to selection.

L-arginine supplemented nondiluted blood cardioplegia: a clinical trial.

AIM: L-arginine was shown to improve protection of the myocardium during coronary artery bypass graft (CABG) surgery. The objective of the present study was to determine the concentration of L-arginine to obtain the most effective protection of the myocardium during CABG surgery. METHODS: Seventy-five patients undergoing CABG surgery were randomized in 3 groups. The first group (N.=25) was administered a placebo injection in the blood cardioplegic solution, the second group (N.=25) received an injection of 4 mmol/L of L-arginine and a third group (N.=25) an injection of 6 mmol/L of L-arginine in the blood cardioplegic solution. Blood samples from the ascending aorta and the coronary sinus catheter were collected before, immediately after and at 20 minutes after aortic cross-clamping. Total plasmatic nitrite and nitrate ratio and lactate release from the myocardium in the collected blood samples were measured. RESULTS: Seventy-five patients averaging 62+/-7 years of age and undergoing 3.1+/-1 coronary bypass grafts during 41+/-17 minutes of aortic cross clamping time were recruited. Values of total plasmatic nitrite and nitrate ratio remains non-significant before and after aortic clamping and also between groups (P=0.9812 and 0.3573 respectively). Myocardial lactate release was statistically different before and after cross clamping (P=0.0002) and also between the 3 groups (P=0.0311). CONCLUSION: Nondiluted blood cardioplegic solution supplemented with 4 mmol/L of L-arginine was associated with a significant decrease of myocardial lactate release after aortic cross-clamping and reperfusion during CABG surgery.

Luminescence properties of ZnGa2O4:Cr3+,Bi3+ nanophosphors for thermometry applications.

Chromium(iii) and bismuth(iii) co-doped ZnGa2O4 nanoparticles are synthesized by a hydrothermal method assisted by microwave heating. The obtained nanoparticles, with a diameter smaller than 10 nm, present good luminescence emission in the deep red range centered at 695 nm after coating with a silica layer and calcination at 1000 °C during 2 h. Persistent luminescence and photoluminescence properties are investigated at several temperatures. Bandwidth and luminescence intensity ratio of persistent emission do not present enough change with temperature to obtain a competitive nanothermometer with high sensitivity. Nevertheless, persistent luminescence decay curves present a significant shape change since the trap levels involved in the deexcitation mechanism are unfilled with increase of temperature. Even if the sensitivity reaches 1.7% °C-1 at 190 °C, the repeatability is not optimal. Furthermore, photoluminescent lifetime in the millisecond range extracted from the photoluminescence decay profiles drastically decreases with temperature increase. This variation is attributed to the thermal equilibrium between two thermally coupled chromium(iii) levels (2E and 4T2) that have very different deexcitation lifetimes. For ZnGa2O4:Cr3+ 0.5%,Bi3+ 0.5%, the temperature sensitivity reaches 1.93% °C-1 at 200 °C. Therefore, this kind of nanoparticle is a very promising thermal sensor for temperature determination at the nanoscale.

Immunosenescence patterns differ between populations but not between sexes in a long-lived mammal.

In animals, physiological mechanisms underlying reproductive and actuarial senescence remain poorly understood. Immunosenescence, the decline in the ability to display an efficient immune response with increasing age, is likely to influence both reproductive and actuarial senescence through increased risk of disease. Evidence for such a link has been reported from laboratory animal models but has been poorly investigated in the wild, where variation in resource acquisitions usually drives life-history trade-offs. We investigated immunosenescence patterns over 7 years in both sexes of two contrasting roe deer populations (Capreolus capreolus). We first measured twelve immune markers to obtain a thorough identification of innate and adaptive components of immunity and assessed, from the same individuals, the age-dependent variation observed in parasitic infections. Although the level of innate traits was maintained at old age, the functional innate immune traits declined with increasing age in one of two populations. In both populations, the production of inflammatory markers increased with advancing age. Finally, the adaptive response declined in late adulthood. The increasing parasite burden with age we reported suggests the effective existence of immunosenescence. Age-specific patterns differed between populations but not between sexes, which indicate that habitat quality could shape age-dependent immune phenotype in the wild.

[Pulmonary artery rupture with Swan-Ganz catheter during cardiac surgery: management and decision-making]. / Rupture de l'artère pulmonaire par cathéter de Swan-Ganz au cours de la chirurgie cardiaque: conduite à tenir et stratégie.

Pulmonary artery catheterization is almost uniformly used nowadays in cardiac surgery. Although rare, rupture of the pulmonary artery following catheterization is highly lethal. This review examines ways of avoiding its occurrence and means of improving outcomes in case of rupture.

Influence of diabetes and bilateral internal thoracic artery grafts on long-term outcome for multivessel coronary artery bypass grafting.

OBJECTIVE: Diabetes mellitus is a major independent risk factor for morbidity and mortality after coronary artery bypass grafting (CABG). The aim of this study was to assess the effect of bilateral (B) internal thoracic artery grafting (ITA) in diabetic patients with multivessel CABG. METHODS: Between 1985 and 1995, 4382 patients underwent primary isolated multivessel CABG with ITA grafting and concomitant saphenous vein grafting (SVG). Outcome of diabetic and nondiabetic patients undergoing single (S) ITA+SVG (n=419 and 2079) and BITA+SVG (n=214 and 1594) grafting was obtained at a mean follow-up of 11+/-3 years. RESULTS: Diabetic patients were older, included more women, and had more obesity, hypertension and peripheral vascular disease than nondiabetic patients. Deep sternal wound infection rate was 1.9% for diabetic patients vs 1.2% for nondiabetic patients (P=0.2) and 30-day mortality was 1.7 vs 1.8% (P=0.9). Cox regression analysis with interaction term and propensity scoring showed that BITA grafting decreased the risk of death (Hazard Ratio=0.72 [0.57-0.91, 95%CI]) and coronary reoperation (HR=0.38 [0.19-0.77]) in both diabetic and nondiabetic patients, with no significant interaction noted. BITA grafting decreased the risk of myocardial infarction at long-term follow-up in nondiabetic patients (HR=0.72 [0.60-0.86]) but not in diabetic patients. Ten-year freedom rate from myocardial infarction in diabetic patients was 80 and 76% for SITA and BITA grafting patients, respectively. However, survival following myocardial infarction was better for patients who underwent BITA grafting, in both diabetic and nondiabetic subgroups. CONCLUSIONS: BITA+SVG grafting in diabetic patients improves survival and decrease coronary reoperation compared with SITA+SVG at long-term follow-up. Survival following myocardial infarction is improved with BITA grafting.

An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract.

A toxicity/toxicokinetic swine-adapted infant formula feeding study was conducted in Domestic Yorkshire Crossbred Swine from lactation day 3 for 28 consecutive days during the preweaning period at carrageenan concentrations of 0, 300, 1000 and 2250 ppm under GLP guidelines. This study extends the observations in newborn baboons (McGill et al., 1977) to piglets and evaluates additional parameters: organ weights, clinical chemistry, special gastrointestinal tract stains (toluidine blue, Periodic Acid-Schiff), plasma levels of carrageenan; and evaluation of potential immune system effects. Using validated methods, immunophenotyping of blood cell types (lymphocytes, monocytes, B cells, helper T cells, cytotoxic T cells, mature T cells), sandwich immunoassays for blood cytokine evaluations (IL-6, IL-8, IL1ß, TNF-α), and immunohistochemical staining of the gut for IL-8 and TNF-α were conducted. No treatment-related adverse effects at any carrageenan concentration were found on any parameter. Glucosuria in a few animals was not considered treatment-related. The high dose in this study, equivalent to ~430 mg/kg/day, provides an adequate margin of exposure for human infants, as affirmed by JECFA and supports the safe use of carrageenan for infants ages 0-12 weeks and older and infants with special medical needs.

Extensive calcification of the mitral valve anulus: pathology and surgical management.

Extensive calcification of the mitral valve anulus is a pathologic entity frequently associated with degenerative valvular disease. The calcification process remains localized to the anulus in 77% of the cases. It may extend, however, to the underlying myocardium. Whenever an operation is necessary for an associated valve insufficiency, the question arises whether it is preferable to repair or to replace the valve and how to manage the calcification. In the first part of this paper the pathology of this disease is studied, and in the discussion a mechanism is proposed to explain the development of the process of calcification. In the second part, a new operation is described, which comprises the temporary detachment of the leaflets, en bloc resection of the calcium deposit, annular reconstruction, and valve repair. For patients in whom the calcification extends to the myocardium a "sliding atrioplasty" of the left atrium is described, which allows the area of exposed muscular fibers to be covered. Between 1986 and 1994, among 68 patients with extensive calcification of the anulus and severe mitral valve insufficiency, 67 benefited from these repair techniques. Ages ranged from 18 to 82 years (mean 62 years). Thirty-two patients had a billowing mitral valve (Barlow), 27 a fibroelastic deficiency, and two Marfan's disease. The calcification involved more than one third of the anulus in 88% of the patients, the posterior anulus in 10.5%, and the whole anulus in 1.5%. The calcification process extended to the myocardial wall in 12% of the patients and to the papillary muscles in 4.5%. In the group of 67 valve repairs, there were two hospital deaths (2.9%), no instances of anulus dehiscence, and no early reoperations. The follow-up period extended from 4 months to 8 years (mean 3 years 8 months). There were two late deaths, 2 and 17 months after the operations, for an actuarial survival of 93% at 7 years. Late reoperation (6 to 62 months) was necessary in four patients (6.4%) for residual mitral valve incompetence (n=2), hemolysis (n=1), or endocarditis (n=1). In one of these patients a new repair was possible, whereas the three other patients required a valve replacement. All patients but one survived the reoperation. Actuarial freedom from reoperation was 87% at 7 years. All 60 patients with valve repair were reviewed for this study by clinical examination and echocardiography. All but one were in functional class I or II. There was no incompetence or trivial residual mitral valve incompetence in 55 patients and moderate incompetence in five. Two thromboembolic events have been recorded for a linearized rate of 1%/pt-yr. This study shows that complete anulus decalcification and valve repair can be done safely in patients with mitral valve insufficiency and extensive calcification of the anulus, even when the calcification process deeply involves the myocardium. It also demonstrates that an initially good result remained stable up to 7 years.

Changing flow pattern of the internal thoracic artery undergoing coronary bypass grafting: continuous-wave Doppler assessment.

Surgeons have limited ability to evaluate intraoperatively the patency of internal thoracic artery graft as a bypass for coronary artery revascularization. We used continuous-wave Doppler ultrasonography to study the velocity of the internal thoracic artery before harvesting and after grafting (scanning probe, 8 MHz). Systolic and diastolic frequency shift (in kilohertz) and systolic frequency/diastolic frequency index were analyzed. Twenty four internal thoracic artery grafts in 15 patients were studied. Fourteen internal thoracic artery grafts were anastomosed to the left anterior descending artery, one to a diagonal artery, and nine to the circumflex artery. The mean systolic frequency before harvesting was 1.19 +/- 0.40 KHz and no significant differences were found between the right and the left internal thoracic artery (right, 1.17 +/- 0.37; left, 1.19 +/- 0.42 KHz). There was a 40% drop in systolic frequency related to the harvesting. Mean systolic frequency decreased after grafting (1.19 +/- 0.40 versus 0.87 +/- 0.32 KHz; p < 0.01) whereas mean diastolic frequency doubled (0.32 +/- 0.12 versus 0.83 +/- 0.4 KHz; p < 0.001) and mean diastolic frequency/systolic frequency index increased from 28% +/- 11% to 101% +/- 39% (p < 0.001), indicating an increased myocardial vascularization during diastole. No significant difference was found between grafted arteries (left anterior descending versus circumflex). All patients had an uneventful postoperative course and no perioperative myocardial infarction was reported. Doppler flow quantification of internal thoracic artery bypasses may give the surgeon an opportunity to evaluate intraoperatively the physiologic features and patency of the internal thoracic artery before and after coronary artery bypasses.

In elective coronary artery bypass grafting, preoperative troponin T level predicts the risk of myocardial infarction.

OBJECTIVE: Several combinations of risk factors for death or cardiac events after coronary artery bypass grafting have been described. We studied the prognostic value of the preoperative serum levels of cardiac troponin T. METHODS: We studied 468 patients who underwent elective coronary artery bypass grafting. Preoperative and postoperative levels of cardiac troponin T and creatine kinase MB, electrocardiograms, clinical data, and events were recorded prospectively. No acute ischemic changes were present on the electrocardiogram before the operations, and preoperative creatine kinase MB serum levels were within normal limits in all patients. RESULTS: Ninety-seven (97/468, 21%) patients had serum levels of troponin T greater than 0.02 microg/L within 24 hours before coronary artery bypass grafting. Hospital mortality was similar in this group and in the patients with preoperative levels less than 0.02 microg/L (1% in each group). Nine patients (9/97, 9%) with elevated levels of troponin T before the operation had a perioperative myocardial infarction compared with 12 patients (12/371, 3%) among the group with lower troponin T levels (p = 0.015, RR = 2.9). Congestive heart failure occurred in 10 (10/97, 10%) and 8 (8/371,2%) patients, respectively (p = 0.0009, RR = 4.8). Intensive care unit (p = 0.002) and postoperative hospital length of stay (p = 0.09) were all longer in patients with the elevated preoperative troponin T level. In a logistic regression analysis, troponin T level before the operation was the variable most strongly correlated with postoperative myocardial infarction (p = 0.003). CONCLUSION: Preoperative troponin T stratification before coronary artery bypass grafting identifies a subgroup of patients with increased risk of postoperative cardiac complications.

Single versus bilateral internal thoracic artery grafts with concomitant saphenous vein grafts for multivessel coronary artery bypass grafting: effects on mortality and event-free survival.

BACKGROUND: The issue of superiority of single internal thoracic artery grafting versus bilateral internal thoracic artery grafting remains unresolved. The aim of this study was to compare the long-term outcome of single and bilateral internal thoracic artery grafting with concomitant saphenous vein grafting for multivessel coronary artery bypass grafting. METHODS: Between March 1985 and April 1995, 6650 patients underwent primary isolated coronary artery bypass grafting with internal thoracic artery grafts, including 4382 patients with multivessel bypass grafting requiring at least 3 grafts. Outcomes of patients undergoing single internal thoracic artery plus saphenous vein grafting (n = 2547) and bilateral internal thoracic artery plus saphenous vein grafting (n = 1835) were obtained at a mean follow-up of 11 +/- 3 years. RESULTS: Patients with bilateral internal thoracic artery grafting were younger, were mostly male, and had less diabetes, hypertension, unstable angina, and recent myocardial infarction than patients undergoing single internal thoracic artery grafting. Thirty-day mortality was 2.3% for the group undergoing single internal thoracic artery grafting versus 1.2% for those undergoing bilateral internal thoracic artery grafting (P =.007). Survival probability at 10 years was 88% for the single-graft group compared with 93% for the bilateral-graft group (P <.001). Multivariate analysis with propensity scoring showed that bilateral internal thoracic artery grafting decreased the risk of death (hazard ratio, 0.74; 95% confidence interval, 0.60-0.90), myocardial infarction (hazard ratio, 0.79; 95% confidence interval, 0.67-0.93), and coronary reoperation (hazard ratio, 0.41; 95% confidence interval, 0.21-0.80) throughout the follow-up period. Other significant predictors of death were diabetes, prior myocardial infarction, need for intra-aortic balloon pump, chronic heart failure, and peripheral vascular disease. CONCLUSION: Patients undergoing bilateral internal thoracic plus saphenous vein grafting appear to have a significantly better long-term clinical outcome than patients undergoing single internal thoracic artery plus saphenous vein grafting for multivessel coronary artery bypass grafting.

Reinfusion of mediastinal blood after heart surgery.

BACKGROUND: Several authors studying autotransfusion of shed mediastinal blood in patients undergoing heart operations have published conflicting results regarding reduction of the need for homologous blood transfusion. The effect on coagulation parameters is also unclear. METHODS: In a prospective randomized study, 198 patients who underwent coronary artery bypass grafting or a valvular operation were divided into 2 groups: a group with autotransfusion of shed mediastinal blood after an operation and a control group. Continuous reinfusion of mediastinal blood was done until no drainage was present or for a period of 12 hours after the operation. The amount of blood lost and autotransfused, the number of homologous blood products transfused, and the coagulation parameters were monitored. RESULTS: The number of patients requiring homologous blood transfusion was significantly different between the 2 groups (54/98 [55%] in autotransfused patients vs 73/100 [73%] in the control group, P =.01). The number of re-explorations for excessive bleeding was similar in the 2 groups (7/98 [7.1%] vs 8/100 [8%]), but the amount of blood collected postoperatively was higher in the autotransfused patients compared with control patients (1200 +/- 201 mL vs 758 +/- 152 mL, P =.0007). Coagulation parameters analyzed and complication rates were similar in the 2 groups after the operations. CONCLUSION: Autotransfusion of shed mediastinal blood reduces the need for homologous blood transfusion in patients undergoing various cardiac operations. The cause of increased shed blood in patients undergoing autotransfusion remains unclear.

Pulmonary metabolism of endothelin 1 during on-pump and beating heart coronary artery bypass operations.

BACKGROUND: Coronary artery bypass operations are associated with increased circulating levels of the powerful vasoconstrictor endothelin 1. The pulmonary circulation is an important site for both production and clearance of endothelin 1. Lung endothelial injury resulting from cardiopulmonary bypass could modify pulmonary endothelin 1 metabolism through an increase in production, a reduction in removal, or a combination of both. METHODS: Pulmonary endothelin 1 kinetics were quantified by using the indicator-dilution technique in patients undergoing coronary artery bypass grafting with (n = 11) or without cardiopulmonary bypass (ie, beating heart; n = 10). Mixed venous endothelin 1 levels were also measured in samples from the pulmonary artery, and systemic levels were obtained from the radial artery. RESULTS: Pulmonary artery endothelin 1 levels were similar before and after cardiopulmonary bypass, with means of 1.59 +/- 0.37 pg/mL and 1.33 +/- 0.15 pg/mL (P =.45), respectively. Systemic endothelin 1 levels, however, increased after bypass from 1.64 +/- 0.22 pg/mL to 2.07 +/- 0.16 pg/mL (P =.01). In the beating heart group, endothelin 1 levels before and after the operation were similar in the pulmonary artery (1.25 +/- 0.27 pg/mL and 1.45 +/- 0.31 pg/mL, respectively; P =.38), as well as in the radial artery (1.70 +/- 0.26 pg/mL and 1.73 +/- 0.35 pg/mL, respectively; P =.92). The capacity to clear endothelin 1 from the pulmonary circulation, as computed from the permeability-surface area product for endothelin 1, was not affected by cardiopulmonary bypass before and after the operation (25.19 +/- 2.67 mL/s and 23.12 +/- 4.39 mL/s, respectively; P =.49). It was similar and also unaffected in the beating heart group. CONCLUSION: Coronary artery bypass grafting with cardiopulmonary bypass is associated with an increase in systemic endothelin 1 levels. The mechanism involved is not related to a decreased pulmonary clearance of endothelin 1 from the systemic circulation but rather to an increased endothelin 1 release by the lungs.

Quantitative angiographic assessment of coronary anastomoses performed without cardiopulmonary bypass.

BACKGROUND: The quality of the anastomosis performed during coronary artery bypass grafting without cardiopulmonary bypass is a current concern, and myocardial wall restraining devices have been designed to optimize results. A quantitative angiographic analysis was performed to assess coronary anastomoses performed on beating hearts. METHODS: We studied 34 patients who underwent coronary artery bypass grafting without cardiopulmonary bypass between February 1996 and April 1997. The left internal thoracic artery was anastomosed to the left anterior descending coronary artery in all patients. Coronary angiograms were performed 4 +/- 2 days after the operation. The diameter of the anastomoses was quantified by computer-assisted analysis of grafts and native coronary arteries at the toe and heel of the anastomosis. RESULTS: Five of the patients who underwent coronary artery bypass without a stabilizer (n = 20) had stenoses of the internal thoracic artery grafted to the left anterior descending coronary artery of more than 50% at the level of the anastomosis proper, 3 had stenoses at the heel of the coronary anastomosis, and 5 had stenoses at the toe. One of the patients in whom a stabilizer was used (n = 14) had a stenosis of more than 50% at the anastomosis, and 1 had stenosis at the heel. Eight patients in whom the anastomoses were performed without stabilization (8/20, 40%) had stenoses of more than 50%, whereas there was only 1 stenosis of more than 50% of coronary luminal diameter among the patients in whom the operation was performed with a stabilizer (P =.02). CONCLUSION: The quantitative angiographic evaluation suggests that left internal thoracic artery graft to left anterior descending coronary artery anastomoses have a lesser degree of intraluminal stenosis when performed with the use of a myocardial wall stabilizer.

Structural valve deterioration in mitral replacement surgery: comparison of Carpentier-Edwards supra-annular porcine and perimount pericardial bioprostheses.

BACKGROUND: Bioprostheses preserved with glutaraldehyde, both porcine and pericardial, have been available as second-generation prostheses for valve replacement surgery. The performance with regard to structural valve deterioration with the Carpentier-Edwards supra-annular (CE-SAV) porcine bioprosthesis and the Carpentier-Edwards Perimount (CE-P) pericardial bioprosthesis (Baxter Healthcare Corp, Edwards Division, Santa Ana, Calif) was evaluated to determine whether there was a difference in mitral valve replacement. METHODS: The CE-SAV bioprosthesis was implanted in 1266 overall mitral valve replacements (isolated mitral, 1066; mitral in multiple, 200) and the CE-P bioprosthesis in 429 overall mitral valve replacements (isolated mitral, 328; mitral in multiple, 101). The mean age of the CE-SAV population was 64.2 +/- 12.2 years and that of the CE-P population, 60.7 +/- 11.7 years (P =.0001). For the study, structural valve deterioration was diagnosed at reoperation for explantation. RESULTS: The freedom from structural valve deterioration was evaluated to 10 years, and the freedom rates reported are at 10 years. For the overall mitral valve replacement groups, the actuarial freedom from deterioration was significant (P =.0001): CE-P > CE-SAV for 40 years or younger, 80% versus 60%; 41 to 50 years, 91% versus 61%; 51 to 60 years, 84% versus 69%; 61 to 70 years, 95% versus 75%. The older than 70-year group was 100% versus 92% (no significant difference). The actual freedom from structural valve deterioration also demonstrated the same pattern at 10 years: 40 years or younger, CE-P 82% versus CE-SAV 68%; 41 to 50 years, 92% versus 70%; 51 to 60 years, 90% versus 80%; 61 to 70 years, 97% versus 88%; and older than 70 years, 100% versus 97%. The independent risk factors of structural valve deterioration for the overall mitral valve replacement group were age and age groups and prosthesis type (CE-SAV > CE-P). The prosthesis type either in isolated replacement or in multiple replacement was not predictive of structural valve deterioration. The pathology of structural valve deterioration was different: 70% of CE-P failures were due to calcification and 57% of CE-SAV failures were due to combined calcification and leaflet tear. CONCLUSION: The actuarial and actual freedom from structural valve deterioration, diagnosed at reoperation, is greater at 10 years for CE-P than for CE-SAV bioprostheses. The mode of failure is different, and the cause remains obscure. Long-term evaluation is recommended, because the different modes of failure may alter the clinical performance by 15 and 20 years.

Ten-year follow-up of critically ill patients undergoing heart transplantation.

BACKGROUND: The long-term result following heart transplantation appears very good despite complications of coronary atherosclerosis and cancer. Critically ill patients supported with mechanical devices remain a growing and difficult group in which long-term results need to be defined. The objective of this study was to review the 10-year follow-up of critically ill patients who underwent heart transplantation after support with mechanical devices. METHODS: We retrospectively analyzed all patients who underwent heart transplantation from 1986 to 1999 at the Montreal Heart Institute. RESULTS: Twenty-two patients (22/199, 11%) underwent heart transplantation after support with intra-aortic balloon pumps (n = 17) and total artificial hearts (n = 5). One hundred seventy-seven patients (177/199, 89%) underwent heart transplantation without pre-operative mechanical assistance. Patients with pre-operative mechanical assistance were younger (41 +/- 12 vs 48 +/- 10 years old, p = 0. 002), underwent a shorter waiting time to transplantation (2 +/- 2 vs 19 +/- 27 weeks, p = 0.004), and donor hearts had longer ischemic time (166 +/- 63 vs 137 +/- 49 minutes, p = 0.002) compared with patients without pre-operative mechanical assistance. One-month, 1-, 5-, and 10-year survival averaged 86% +/- 7%, 67% +/- 10%, 67% +/- 10%, and 59% +/- 12%, respectively, in patients with pre-operative mechanical assistance compared with 95% +/- 2%, 88% +/- 2%, 81% +/- 3%, and 74% +/- 4%, respectively, in patients without assistance, a significant difference (p = 0.04) that is mainly related to higher operative mortality in the former group. Although, we found no difference between the 2 groups in the 10-year freedom rate from acute rejection, infection, cancer, and coronary atherosclerosis, sepsis was the cause of 4 early deaths among patients with pre-operative mechanical assistance. CONCLUSION: Early and long-term survival was significantly decreased in critically ill patients with pre-operative mechanical assistance compared with other patients without pre-operative assistance. Sepsis is a dominant threat among patients who underwent heart transplantation with pre-operative mechanical assistance, and the lower survival is due mainly to the increased early mortality.

Nitric oxide inhalation in the treatment of primary graft failure following heart transplantation.

BACKGROUND: Primary graft failure from right or left ventricular insufficiency remains a serious cause of early death following heart transplantation. Inhaled nitric oxide (NO) is a potent pulmonary vasodilator that could decrease pulmonary pressure and improve right ventricular function. METHODS: Two cases of early graft failure following orthotopic heart transplantation were treated with NO inhalation. The treatment consisted of inhalation of 20 ppm of NO, introduced 4 to 6 hours following transplantation, in 2 patients supported with high doses of inotropic agents and vasopressors in addition to the intra-aortic balloon pump. RESULTS: In the first and second cases, NO inhalation resulted in a decrease in pulmonary artery pressure, in a decrease in pulmonary vascular resistance and in an increase in cardiac index. In the second patient, systemic oxygenation improved markedly 30 minutes after initiation of NO. In the 2 patients, NO inhalation, mechanical ventilation and the intra-aortic balloon pump were weaned 4 days following transplantation. CONCLUSION: Primary graft failure from donor ischemic damage, reperfusion injury or pulmonary hypertension remains a serious complication. The use of an intra-aortic balloon pump, inotropic agents and of inhaled NO appears to offer the best support for recovery of donor heart function. Primary graft failure from right or left ventricular insufficiency remains a serious cause of early mortality following heart transplantation. Ischemic damage of donor heart, reperfusion injury or pulmonary hypertension are the main causes of early graft failure. Although the cause is multifactorial, treatment of primary organ failure remains difficult with dismal results. The objective of the present study was to review the result of 2 patients with donor right heart failure following heart transplantation treated with inhaled nitric oxide (NO).

A 10-year experience with intravenous thymoglobuline in induction of immunosuppression following heart transplantation.

BACKGROUND: Intravenous thymoglobuline (125 mg a day for 3 days, Institut Mérieux, France) has been used to induce immunosuppression following heart transplantation. Cyclosporine and prednisone, with and without azathioprine or mycophenolate mofetil were used as maintenance immunosuppression. OBJECTIVE: The objective of the study was to determine the clinical effect of antibody induction of immunosuppression following heart transplantation. METHODS: A retrospective analysis of the clinical experience at the Montreal Heart Institute. From 1988 to 1998, 163 patients were administered a 3-day course of intravenous thymoglobuline immediately following heart transplantation (Group 1). From 1983 to 1987 and during an isolated period in 1994, intravenous and oral cyclosporine was used immediately following heart transplantation in 48 patients (Group 2). Routine endomyocardial biopsies were performed in all patients and only moderate and severe rejection was treated. RESULTS: One, 5- and 10-year actuarial survival rate averaged 85%+/-3, 77%+/-4 and 67%+/-5 in Group 1 compared with 88%+/-5, 81%+/-6 and 76%+/-6 in Group 2 (p = 0.5). At 1 year, the freedom rate from an episode of acute rejection averaged 43%+/-4 in Group 1 and 30%+/-7 in Group 2 (p = 0.03) and the freedom rate from an episode of infection averaged 44%+/-4 in Group 1 and 31%+/-7 in Group 2 (p = 0.2). At 1, 5 and 10 years, the freedom rate from graft coronary artery disease averaged 93%+/-2, 68%+/-5 and 50%+/-7 in Group 1 compared with 93%+/-4, 58%+/-8 and 30%+/-8 in Group 2 (p = 0.1) and the freedom rate from cancer averaged 98%+/-1, 91%+/-3 and 67%+/-8 in Group 1 compared with 100%, 95%+/-3 and 77%+/-8 in Group 2 (p = 0.2). There was no side-effect related to the systemic injection of thymoglobuline. CONCLUSION: In a cyclosporine based protocol of immunosuppression, induction with an initial 3-day course of intravenous thymoglobuline is associated with a lower rate of acute rejection. Moreover, the risk of infection and of developing cancer is not increased whereas there was a trend towards a lower incidence of coronary atherosclerosis 5 and 10 years after transplantation.