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Biomedical subjects

Daniel Loisance

Publications and source records attributed to Daniel Loisance.

At least 19 recordsLinked to original sources

Coronary vasomotor response to phenylephrine in heart transplant patients.

BACKGROUND: Coronary vasomotor responses to sympathetic stimulation vary with endothelial-layer integrity or presence of atherosclerosis. Our study objective was to assess the effects of phenylephrine-induced alpha-adrenergic stimulation on coronary vasomotion in heart transplant recipients with and without graft atherosclerosis. METHODS: Intracoronary phenylephrine (alpha(1)-selective agonist) was injected in 6 control subjects, 9 recipients with angiographically normal coronary arteries and 8 recipients with mild or moderate atherosclerosis. Coronary flow velocity was measured using a Doppler guide-wire. The diameters of 3 epicardial segments of the left coronary artery and coronary blood flow and resistance were assessed at baseline, after infusion of increasing acetylcholine doses (10(-7) and 10(-6) mol/liter) and after phenylephrine (150- to 200-microg bolus). Systemic and coronary hemodynamic parameters were measured immediately after acetylcholine and 1, 3, 5, 7, 10 and 15 minutes after phenylephrine. RESULTS: Phenylephrine induced similar significant increases in rate pressure product in the 3 groups. Acetylcholine induced epicardial vasodilation in controls and vasoconstriction in transplant recipients. Phenylephrine induced epicardial vasodilation in controls and in angiographically normal recipients; subsequent vasoconstriction occurred in this last group. In the recipients with angiographic abnormalities, sustained vasoconstriction occurred. At peak phenylephrine effect, coronary blood flow (CBF) increased significantly (p < 0.001 vs baseline) in all 3 groups. Coronary resistance decreased in the 3 groups but the decrease was smaller in the recipients with angiographic abnormalities (p < 0.05 vs controls). CONCLUSIONS: In heart transplant patients, graft atherosclerosis unmasks the direct coronary vasoconstricting effects of pharmacologic alpha-adrenergic stimulation.

Acetylcholine↗

Successful combined heart and kidney transplantation in a patient with sickle-cell anemia.

Little is known about the management of dual-organ transplantation for sickle-cell disease (SCD)-related complications. In this case study, we report the successful outcome of combined heart and kidney transplantation in a patient with SCD. The recipient was a 33-year-old man with homozygous SCD, who developed end-stage heart and renal failure requiring combined heart and kidney transplantation. The patient was managed with pre-operative blood transfusion and moderate hypothermic cardiopulmonary bypass, with limited peri-operative complications. During the first 6 months there was one episode of acute heart rejection without concomitant renal rejection. Eighteen months after surgery, the patient is at home without vaso-occlusive crises or septic complications. Heart and renal allograft function is preserved, without coronary artery vasculopathy, but with asymptomatic moderate transplant renal artery stenosis. SCD is managed by periodic transfusion. This case study demonstrates that combined heart and kidney transplantation is feasible in patients with SCD. Careful attention to peri- and post-operative management is required.

Adult↗

Coronary vasomotor response to the selective B1-kinin-receptor agonist Des-Arg9-bradykinin in humans.

OBJECTIVES: The aim of the present study was to assess the effects of selective B1-receptor stimulation with des-Arg9-bradykinin on coronary vasomotion in transplanted and non-transplanted patients. BACKGROUND: Bradykinin B1-receptors have been identified on endothelial and smooth muscle cells in human coronary arteries in vitro; however, their physiologic role in the coronary circulation is unknown. METHODS: Twelve heart transplant patients were compared with 10 control subjects at 3.2 +/- 2.2 months after surgery. Coronary flow velocity was measured using guide-wire Doppler. The diameter of 3 epicardial segments of the left coronary artery and coronary blood flow were assessed at baseline, immediately after infusions of increasing doses of des-arginine(Arg9)-bradykinin at estimated coronary blood concentrations of 5.4 x 10(-9), 5.4 x 10(-8), 5.4 x 10(-7) and 1.6 x 10(-6) mol/liter, and of acetylcholine at 10(-8), 10(-7) and 10(-6) mol/liter). RESULTS: Des-Arg9-bradykinin induced a similar decrease in all measured epicardial diameters in both groups and no change in coronary blood flow. Vasoconstriction was significant only at the 2 highest concentrations: -6 +/- 9% (p < 0.01) and -7 +/- 11% (p < 0.01) in control subjects, and -8 +/- 8% (p < 0.001) and -9 +/- 11% (p < 0.001) in heart transplant patients. Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in transplant patients. The presence of allograft rejection did not modify the responses to des-Arg9-bradykinin with regard to both conductance and resistance vessels. CONCLUSIONS: Kinin B1-receptors exist and can be stimulated in humans. The vasoconstrictive action on epicardial coronary arteries of des-Arg(9)-bradykinin in humans argues for a predominant action of B1-receptor stimulation at the level of smooth muscle cells.

Acetylcholine↗

Vascular-wall remodeling of 3 human bypass vessels: organ culture and smooth muscle cell properties.

OBJECTIVES: Late graft occlusions after coronary artery bypass grafting have been ascribed to neointimal hyperplasia. Given the pivotal role of smooth muscle cells in the pathogenesis of neointimal hyperplasia and the phenotypic heterogeneity of smooth muscle cells across vessels, we hypothesized that differences in long-term graft patency are at least partly related to differences in smooth muscle cell properties. The aim of the present study was to compare the vascular-wall remodeling of human internal thoracic artery, radial artery, and saphenous vein bypass conduits. METHODS: We evaluated the intimal thickening of the human graft segments in organ cultures (histopathology, morphometric, and immunofluorescence analyses) and assessed the properties of cultured smooth muscle cells isolated from these vessels in terms of cell proliferation (tritiated thymidine incorporation), migration (modified Boyden chamber), and collagen synthesis (tritiated proline incorporation). RESULTS: The total vessel-wall growth index and the intimal growth index were significantly higher for saphenous vein rings than for radial artery and internal thoracic artery rings. Immunofluorescence analyses showed predominant involvement of smooth muscle cells in neointimal growth induced by organ culture of saphenous vein rings. Cell proliferation was significantly higher in saphenous vein smooth muscle cells than in radial artery smooth muscle cells and significantly higher in radial artery smooth muscle cells than in internal thoracic artery smooth muscle cells. Migration of smooth muscle cells from saphenous vein grafts was significantly greater than from internal thoracic artery or radial artery grafts. Collagen synthesis was similar in smooth muscle cells from internal thoracic artery, radial artery, and saphenous vein grafts. CONCLUSIONS: Ex vivo vascular-wall remodeling and smooth muscle cell intrinsic growth and migratory properties are dissimilar between arterial and venous grafts and might shed light on reported angiographic patency rates of these grafts.

Aged↗

Aortic root replacement after previous surgical intervention on the aortic valve, aortic root, or ascending aorta.

BACKGROUND: Aortic root replacement after a previous operation on the aortic valve, aortic root, or ascending aorta remains a major challenge. METHODS: Records of 56 consecutive patients (44 men; mean age, 56.4 +/- 13.6 years) undergoing reoperative aortic root replacement between June 1994 and June 2005 were reviewed retrospectively. RESULTS: Reoperation was performed 9.4 +/- 6.7 years after the last cardiac operation. Indications for reoperation were true aneurysm (n = 14 [25%]), false aneurysm (n = 10 [18%]), dissection or redissection (n = 9 [16%]), structural or nonstructural valve dysfunction (n = 10 [18%]), prosthetic valve-graft infection (n = 12 [21%]), and miscellaneous (n = 1 [2%]). Procedures performed were aortic root replacement (n = 47 [84%]), aortic root replacement plus mitral valve procedure (n = 5 [9%]), and aortic root replacement plus arch replacement (n = 4 [7%]). In 14 (25%) patients coronary artery bypass grafting had to be performed unexpectedly during the same procedure or immediately after the procedure to re-establish coronary perfusion. Hospital mortality reached 17.9% (n = 10). Multivariate logistic regression analysis revealed the need for unplanned perioperative coronary artery bypass grafting as the sole independent risk factor for hospital death (P = .005). Actuarial survival was 83.8% +/- 4.9% at 1 month, 73.0% +/- 6.3% at 1 year, and 65.7% +/- 9.0% at 5 years after the operation. One patient had recurrence of endocarditis 6.7 months after the operation and required repeated homograft aortic root replacement. CONCLUSION: Reoperative aortic root replacement remains associated with a high postoperative mortality. The need to perform unplanned coronary artery bypass grafting during reoperative aortic root replacement is a major risk factor for hospital death. The optimal technique for coronary reconstruction in this setting remains to be debated.

Adult↗

Blood neutrophil bactericidal activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus during cardiac surgery.

Whether methicillin-resistant Staphylococcus aureus (MRSA) constitutes per se an independent risk factor for morbidity and mortality after surgery as compared with methicillin-sensitive Staphylococcus aureus (MSSA) remains a subject of debate. The aim of this study was to assess whether innate defenses against MRSA and MSSA strains are similarly impaired after cardiac surgery. Both intracellular (isolated neutrophil functions) and extracellular (plasma) defenses of 12 patients undergoing scheduled cardiac surgery were evaluated preoperatively (day 0) and postoperatively (day 3) against two MSSA strains with a low level of catalase secretion and two MRSA strains with a high level of catalase secretion, inasmuch as SA killing by neutrophils relies on oxygen-dependent mechanisms. After surgery, an increase in plasma concentration of IL-10, an anti-inflammatory cytokine able to inhibit reactive oxygen species secretion and bactericidal activity of neutrophils, was evidenced. Despite the fact that univariate analysis suggested a specific impairment of neutrophil functions against MRSA strains, two-way repeated-measures ANOVA failed to demonstrate that the effect of S. aureus phenotype was significant. On the other hand, an increase in type-II secretory phospholipase A2 activity, a circulating enzyme involved in SA lysis, was evidenced and was associated with an enhancement of extracellular defenses (bactericidal activity of plasma) against MRSA. Overall, cardiac surgery and S. aureus phenotype had a significant effect on plasma bactericidal activity. Cardiac surgery was characterized by enhanced antibacterial defenses of plasma, whereas neutrophil killing properties were reduced. The overall effect of S. aureus phenotype on neutrophil functions did not seem significant.

Aged↗

Clinical and hemodynamic performance of the 19-mm medtronic mosaic bioprosthesis.

BACKGROUND AND AIM OF THE STUDY: The Medtronic Mosaic valve (MMV) is a latest generation supra-annular stented porcine valve, which combines a low-profile stent, leaflet fixation at zero pressure in a predilated aortic root, and amino-oleic acid anti-mineralization treatment for improved hemodynamics and durability. A study was conducted to evaluate the clinical and hemodynamic performances of the MMV in patients with a small aortic root (19 mm aortic annulus). METHODS: Between 1998 and 2004, 81 consecutive patients (69 females, 12 males; mean age 78.0 +/- 5.5 years) underwent aortic valve replacement using the 19-mm MMV. Concomitant coronary artery bypass grafting was performed in 28 patients (29.2%), and mitral valve surgery in one patient (1.2%). RESULTS: The 30-day mortality rate was 9.9% (eight deaths). Postoperative actuarial survival estimates were 90.1 +/- 3.3%, 78.5 +/- 4.6% and 69.1 +/- 5.5% at one month, one year and two years, respectively. After a mean follow up of 2.7 +/- 1.9 years, no cases of structural dysfunction, non-structural dysfunction or valve thrombosis were noted. Four ischemic cerebral complications (2.0% per patient-year (pt-yr)), five bleeding complications (2.0%/pt-yr) and two prosthetic valve infections (1.0%/pt-yr) were observed. No reoperation on a MMV was performed. Postoperatively, the mean systolic gradient was 23.4 +/- 7.0 mmHg, and the effective orifice area (EOA) 1.06 +/- 0.33 cm2. Valve prosthesis-patient mismatch (VP-PM) was moderate (indexed EOA > 0.65 cm2/m2 and < or = 0.85 cm2/m2) in 40 patients (49.4%), and severe (indexed EOA < or = 0.65 cm2/m2) in 41 (50.6%). CONCLUSION: Although providing acceptable clinical results, implantation of the 19-mm MMV resulted in a high incidence of postoperative VP-PM. Hence, this valve should be reserved for patients in whom the projected indexed EOA calculated preoperatively is deemed acceptable, given the patient's clinical condition.

Aged↗

[Innovative techniques in coronary bypass surgery].

Coronary artery surgery is now being challenged by percutaneous techniques of coronary revascularization, coronary dilatation and arterial stenting. Improvements are being made in three directions, namely selection of optimal conduits, with the aim of improving long-term graft patency; minimizing complications of cardiopulmonary circulation (or avoiding it altogether), and improving access to coronary vessels. The ultimate goal is robotic keyhole surgery of the beating heart. This paper offers a critical analysis of these developments.

Blood Vessel Prosthesis↗

Mechanical circulatory support systems-future opportunities.

Fifty years of intensive experimental and clinical research have not permitted to reach the stage of the ideal artificial heart available on the shelf, the one the patient will forget. Nevertheless, in the same time frame, major advances have been observed in the technology and the clinical experience of various systems of mechanical circulatory support (MCS), for the treatment of the most severe forms of cardiac failure. These systems are now used routinely in patients awaiting transplantation who cannot receive a suitable donor heart, and in patients with reversible myocardial Lesions, who may recover an adequate native cardiac function. Eventually, in few selected cases, MCS systems will be the last major therapy and allow a prolonged survival with a reasonable quality of Life. This experience could be the ground for an important development of cardiac surgery in the domain of chronic cardiac failure.

Heart Failure↗

Usefulness of routine epicardial pacing wire culture for early prediction of poststernotomy mediastinitis.

Poststernotomy mediastinitis (PSM) is one of the most serious complications of cardiac surgery, and its associated morbidity and mortality demand early recognition for emergency therapy. In this study, we investigated the usefulness of epicardial pacing wire (EPW) cultures for the prediction of PSM. Among 2,200 patients who underwent a cardiac surgical procedure at our hospital between 1 January 1999 and 31 December 2001, 82 (3.7%) had PSM; Staphylococcus aureus was the organism (45.1%) most frequently isolated at the time of surgical debridement. EPWs from 1,607 (73.0%) patients, 73 (4.5%) of whom developed PSM, were cultured. EPW cultures from 466 (29.0%) were positive, most often (74.9%) for coagulase-negative Staphylococci. EPW cultures were truly positive in 26 cases, truly negative in 1,106 cases, falsely positive in 428 cases, and falsely negative in 47 cases (with sterile cultures in 35 cases and a culture positive for an organism different from that isolated at the time of debridement in 12 cases). EPW culture had a positive predictive value of only 5.7% and a high negative predictive value (95.9%) for the diagnosis of PSM, with an accuracy of 70.4%. However, the likelihood ratio of positive (1.27) and negative (0.89) tests indicated only small changes in pretest-to-posttest probability. Therefore, a strategy of routine culture of EPWs to predict PSM seems questionable.

Adolescent↗

Cardiac assist devices: present status and future opportunities.

Over the last 20 years, continuous progress has been made in the technology and clinical applications of mechanical circulatory support systems for the treatment of the most severe forms of cardiac failure. In a few pioneering centers, their efficacy has been demonstrated in selected groups of patients. This experience enables assessment of the state-of-the-art devices and prediction of likely future developments.

Equipment Design↗

The risk of reoperative heart valve procedures in Octogenarian patients.

BACKGROUND AND AIM OF THE STUDY: The authors' experience is reported of cardiac reoperations for valvular heart disease in octogenarian patients. METHODS: The records of 22 consecutive patients (10 men, 12 women) aged > or =80 years (mean age 82.4+/-2.3 years) who underwent cardiac reoperation for aortic and/or mitral valvular heart disease at the authors' institution between 1991 and 2001 were retrospectively reviewed. RESULTS: Indications for reoperation were structural dysfunction of a previously implanted bioprosthetic valve in 11 patients (50%), new valvular heart disease in six (27%), progression of rheumatic valvular heart disease in four (18%), and prosthetic valve infective endocarditis in one patient (5%). Fourteen patients (64%) underwent isolated aortic valve replacement (AVR), two (9%) had AVR plus coronary artery bypass grafting (CABG), one patient (5%) had aortic root replacement plus CABG, three patients (14%) had isolated mitral valve replacement (MVR), one patient (5%) had MVR plus ascending aorta replacement, and one (5%) had AVR plus MVR. Postoperative complications occurred in 18 patients (82%). The hospital mortality rate was 32%. Actuarial survival estimates at one year, and at three and five years were 62.6%, 56.3% and 40.2%, respectively. CONCLUSION: Cardiac reoperations for valvular heart disease in octogenarians carry a high postoperative morbidity and mortality. These findings must be taken into account in the management of associated mild or moderate valvular heart disease, and in the choice of heart valve prosthesis at the initial operation in younger patients.

Aged↗

Evaluation of a new invasive continuous cardiac output monitoring system: the truCCOMS system.

OBJECTIVE: To compare measurements of cardiac output using a new pulmonary artery catheter with those obtained using two "gold standard" methods: the periaortic transit time ultrasonic flow probe and the conventional pulmonary artery thermodilution. DESIGN: Prospective clinical trial. SETTING: Cardiac surgery operating room and surgical ICU in a university hospital. MATERIAL AND METHODS: In the operating room, a new pulmonary artery catheter (truCCOMS system) was inserted in eight patients. A periaortic flow probe was inserted in four of them. Measurements of cardiac output obtained with the truCCOMS catheter and with the flow probe were compared at different phases of the surgical procedure. In the intensive care unit, the cardiac output displayed by the truCCOMS monitor was compared with the value obtained after bolus injection performed subsequently. RESULTS: In the operating room (70 measurements), the coefficient of correlation between cardiac output measured by the flow probe and the truCCOMS system was r2 = 0.79, the bias was +0.11 l/min with a precision of 0.47 l/min, and limits of agreement -0.83 to +1.05 l/min. In the intensive care unit (108 measurements), the coefficient of correlation between cardiac output measured by thermodilution and the truCCOMS system was r2 = 0.56, the bias was -0.07 l/min, the precision was 0.66 l/min, and the limits of agreement were -1.39 to +1.25 l/min. CONCLUSION: The truCCOMS system is a reliable method of continuous cardiac output measurement in cardiac surgery patients.

Aorta↗

Paracrine secretion of transforming growth factor-beta1 in aneurysm healing and stabilization with endovascular smooth muscle cell therapy.

BACKGROUND: Identification of molecular factors involved in artery wall stabilization after extracellular matrix injury elicited by inflammation and proteolysis has a major role in the development of new therapies for atherosclerosis. A study from our group demonstrated that endovascular seeding of vascular smooth muscle cells (VSMCs) promotes healing and stabilizes experimental aneurysms by downregulating matrix metalloproteinase and upregulating tissue inhibitor of metalloproteinase and collagen gene expression. We analyzed expression of transforming growth factor-beta (TGF-beta) and its receptors in experimental aneurysms treated with endovascular VSMC therapy. METHODS AND RESULTS: Aneurysms were generated in Fischer 344 rats by 14-day orthotopic implantation of a segment of guinea pig abdominal aorta (xenograft). During an endovascular repeat operation, syngeneic VSMCs were seeded in the aneurysm, always resulting in aneurysm diameter stabilization after 8 weeks, whereas diameter of control aneurysms infused with culture medium further increased. Seven days after repeat operation the intima or thrombus was separated from the aneurysmal wall in the two groups. Reverse transcriptase polymerase chain reaction with the domestic gene 18s as a standard demonstrated that aneurysm stabilization was associated with a statistically significant increase in TGF-beta(1), but not TGF-beta(2) or TGF-beta(3), messenger RNA levels in the intima. Enzyme-linked immunosorbent assay demonstrated increased TGF-beta(1) protein in the aneurysmal wall. mRNA levels of the two serine and threonine kinase TGF-beta receptors remained unchanged. CONCLUSIONS: Healing and stabilization of aneurysms with endovascular cell therapy is associated with a specific pattern of gene expression, resulting in paracrine secretion of TGF-beta(1). Our study provides insight into the molecular mechanisms of arterial aneurysm healing and stabilization.

Animals↗

beta2-Adrenergic signaling in human heart: shift from the cyclic AMP to the arachidonic acid pathway.

We have recently established that enhancement of intracellular calcium cycling and contraction in response to beta2-adrenergic receptor (beta2-AR) stimulation exclusively relies on the activation of the cytosolic phospholipase A2 (cPLA2) and arachidonic acid production, via a pertussis toxin-sensitive G protein (possibly Gi), in embryonic chick cardiomyocytes. We aimed to investigate the relevance of the beta2-AR/Gi/cPLA2 pathway in the human myocardium. In left ventricular biopsies obtained from explanted hearts, beta2-AR stimulation exerted either an inhibition of cPLA2 that was insensitive to pertussis toxin (PTX) treatment, or an activation of cPLA2, sensitive to PTX treatment. In right atrial appendages from patients who were undergoing open heart surgery, we demonstrated that beta2-AR-induced activation of cPLA2 was favored in situations of altered beta1-AR and/or beta2-AR/adenylyl cyclase (AC) stimulations. Alterations were characterized by an increase in EC50value of norepinephrine and a decrease in the maximal AC activation in response to zinterol, respectively. Quantitative reverse transcription-polymerase chain reaction analyses highlighted a positive correlation between the expression of AC5 and AC6 mRNAs in human cardiac atria, which suggested that functional alterations in AC responses were unlikely to be related to changes in the AC5/AC6 mRNA ratio. In addition, the shift from the cyclic AMP to the arachidonic acid pathway was not supported at the transcriptional level by opposite regulation of AC and cPLA2mRNAs expression. This study gives the first evidence of the recruitment of cPLA2by beta2-ARs in the human heart and suggests that the Gi/cPLA2pathway could substitute for a deficient Gs/AC pathway in mediating beta2-AR responses.

Adenylyl Cyclases↗