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Biomedical subjects

D Loisance

Publications and source records attributed to D Loisance.

At least 73 records · Page 4Linked to original sources

Bridge to transplantation with the wearable Novacor left ventricular assist system: operative technique.

Although the outcome of patients transplanted after univentricular cardiac support is similar to that of conventional patients, death on the device remains a substantial problem. The wearable Novacor left ventricular assist system (LVAS) may offer advantages over console-based systems by improving rehabilitation before transplantation. For these advantages to be realised, however, a smooth perioperative course is necessary. We describe our operative technique, based on minimising blood loss and preserving right ventricular function, and the results in the first three patients to have the wearable Novacor LVAS implanted in this institution.

Cardiac Surgical Procedures↗

Early impairment of acetylcholine-induced endothelium-dependent coronary vasodilation is not predictive of secondary graft atherosclerosis.

STUDY OBJECTIVE: To test the hypothesis that the magnitude of early constriction of coronary arteries to acetylcholine might be a useful predictor of secondary graft atherosclerosis. DESIGN: The responses of epicardial coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8)M to 10(-5)M) were compared in 7 control subjects and in 18 patients who had undergone transplants within 2 months after surgery. MEASUREMENTS AND RESULTS: Vessel dimensions (percent basal diameter) were measured by quantitative angiography. Follow-up at 1 year showed angiographically normal coronary arteries in 12 patients (group 1) and coronary atherosclerosis in 6 patients (group 2). In control subjects, acetylcholine induced a dose-dependent dilation from 10(-8)M to 10(-6)M. No significant variation was observed at 10(-5)M. In patients with transplants early after surgery, diameters did not vary significantly from base at 10(-8)M in either group and constricted significantly at higher concentrations. Vasodilator responses to intracoronary isosorbide dinitrate were similar in both groups with transplants early after surgery, and at 1 year in group 1, but significantly lower than in control subjects. CONCLUSIONS: In patients who had undergone transplants, acetylcholine-induced endothelium-dependent coronary artery dilation is similarly impaired early after surgery (within 2 months) in patients with and without coronary atherosclerosis at 1-year follow-up. Thus, response to acetylcholine is not a predictor of secondary atherosclerosis in patients with heart transplants.

Acetylcholine↗

[What are the criteria of priority for the patient to be accepted on the waiting list for cardiac transplantation?].

The limited resources (in grafts, human and financial resources) incited the authors to carry out a prospective assessment of the value of assessing adrenergic function (scintigraphy with meta- iodo- benzyl guanidine, MIBG) for the procedure of inscription on the waiting list of patients with cardiac failure awaiting cardiac transplantation. The study was undertaken from October 1988 to October 1992. Seventy-eight candidates for transplantation were included in the study. Forty-six patients with a MIBG cardiothoracic ratio less than 120% were placed on the waiting list. In July 1993, 35 had undergone transplantation after a 5 months delay. Four patients are still awaiting transplantation and 7 died whilst on the waiting list. Thirty two with a MIBG cardiothoracic ratio greater than 120% were treated medically: in 14 cases (43%) this decision was reviewed after 17 +/- 12 months. The clinical course was stable in the other 18 patients with a follow-up of 46 +/- 18 months (range: 12-72 months). In all, the results of this study show that a procedure of selection for inscription on the waiting list of patients with cardiac failure judged to be good candidates for transplantation based on the value of the MIBG cardiothoracic ratio allows deferrement of inscription of patients at least risk without changing the chances of survival in the whole population group within a 2 year period.

3-Iodobenzylguanidine↗

[Cardiovascular biomaterials].

Hemocompatible biomaterials, i.e. materials to be used in a biological environment, are of various origins (biological, synthetic). The great variety of physical and chemical characteristics has allowed design of various prosthesis and artificial organs. Use of biomaterials and artificial organs has made possible the development of substitutive therapies, a growing component of medical care. None of the biomaterials presently used is ideal. Everyone of them is responsible for a local and general reaction: foreign body reaction, coagulation, whole body inflammatory response. For years, these reactions have been poorly understood and development was of a very empirical nature. Progress in cellular and molecular biology permits today a better understanding of the mechanisms involved in these reactions. Use of biomaterials is facing to day a difficult problem; liability concerns threaten further developments and leads to market withdrawal of major basic materials.

Biocompatible Materials↗

Canine myocardial beta-adrenergic, muscarinic receptor densities after denervation: a PET study.

UNLABELLED: In an effort to better understand cardiac neurotransmission, PET was serially used in dogs to assess changes in ventricular muscarinic (MR) and beta-adrenergic receptor (beta-AR) densities following chemical or surgical denervation. METHODS: Beta-adrenergic and MR receptor concentrations were studied in beagle dogs nine days after chemical sympathectomy (using the neurotoxin 6-hydroxydopamine) or 3-7 wk and 23-28 wk after surgical intrapericardial denervation. RESULTS: In control dogs (n = 13), global beta-AR and MR concentrations were 32 +/- 4 and 62.2 +/- 10.4 pmole/ml tissue, respectively. Nine days after 6-hydroxytk; 1opamine (n = 8), hemodynamic tests and MIBG scintigraphy demonstrated the destruction of cardiac sympathetic innervation. Beta-adrenergic density increased by 190% (p < 0.001) while MR density remained unchanged. Three to 7 wk after surgery (n = 5), hemodynamic tests and MIBG scintigraphy demonstrated both parasympathetic and sympathetic denervations. Beta-adrenergic density was increased by 219% while MR concentration remained unchanged. Twenty-three to 28 wk after surgery, atrial innervation was restored (hemodynamic tests) while ventricular sympathetic innervation was not (MIBG scintigraphy). Beta-adrenergic density remained high. CONCLUSION: The present study demonstrates the ability of PET to serially assess myocardial receptor concentrations. The absence of change in MR density and the prolonged up-regulation of beta-AR following heart denervation are the main findings of the present study.

3-Iodobenzylguanidine↗

[Cardiac transplantation; results after 5 years].

After cardiac transplantation, long-term results were assessed in a group of 46 patients who survived more than 5 years after surgery. They were the survivors (50%) of a group of 92 patients who underwent transplantation before January 1990. On January 1995, mean follow-up was 82 +/- 14 months. Quality of life was estimated satisfactory (mean score 8.4 +/- 2); 60% of the patients were active; 89% were class NYHA I or II. Nevertheless, several problems have been identified: rise in body weight for all, over 10 kg in 31%; hypertension, renal failure, considered to be severe (serum creatinine > 250 micrograms/l) in 26%, diabetes in 13%, osteoarthropathy in 33%, cancer in 6%, and, above all, chronic alteration of the coronary arterial bed in 53% of the patients. These problems reflect the immunological conflict and complications of immuno-suppression.

Adolescent↗

Clinical use of metaiodobenzylguanidine imaging in cardiology.

Cardiac function is predominantly regulated by autonomic innervation. Many heart diseases involve alterations of cardiac adrenergic neurotransmission. In patients with cardiomyopathies, numerous therapeutic agents act directly or indirectly on cardiac adrenergic disorders. Metaiodobenzylguanidine (MIBG) imaging can provide in vivo information on one of the main components of adrenergic nerve function, i.e. the norepinephrine reuptake and storage system. Diminished MIBG uptake has been reported in patients with congestive heart failure, indicating an impaired norepinephrine reuptake and storage system. In patients with dilated cardiomyopathy (either idiopathic or ischemic), this alteration has been linked to the severity of the disease, evaluated on the basis of clinical or hemodynamic parameters. Moreover, MIBG imaging has been reported in such patients to be a potent prognostic marker in comparison with other recognized indices. After myocardial infarction, the decrease in MIBG uptake was transient in some patients and was suggested to be a viability indicator. Diminished MIBG uptake in ischemic patients was linked to the occurrence of ventricular arrhythmias. In patients with primary hypertrophic cardiomyopathy, decreased cardiac MIBG uptake has also been related to the clinical indices of severity. In patients suffering from various arrhythmias such as idiopathic ventricular arrhythmias, arrhythmogenic right ventricular cardiomyopathy or a long-QT syndrome, MIBG imaging has evidenced regional abnormalities of adrenergic nerve function and has provided new insights into the pathophysiological mechanisms of such disorders. Finally, MIBG scintigraphy may permit the evaluation of anthracyclin cardiotoxicity. Thus, MIBG imaging appears to be a promising tool for the cardiologist.

3-Iodobenzylguanidine↗

Additive haemodynamic effects of piroximone and prostacyclin in severe chronic heart failure.

This study was undertaken to assess the haemodynamic effects of the combined infusion of prostacyclin and piroximone, a phosphodiesterase inhibitor, in 18 patients with severe congestive heart failure. Right heart catheterization was performed with a Swan-Ganz thermodilution catheter and arterial blood pressure was monitored using a radial line. After baseline haemodynamic measurements, prostacyclin was administered in all patients at the incremental infusion rate of 2, 4, 6 and 8 and 10 ng.kg-1.min-1 during 15 min each. After recovery of baseline haemodynamics, patients were randomly assigned to the piroximone infusion rate of 5 or 10 micrograms.kg-1.min-1 or placebo. After 24 h piroximone or placebo infusion, the same prostacyclin protocol was applied. Prostacyclin infusion added to piroximone resulted in a significant improvement in haemodynamics, as compared to the group receiving prostacyclin added to placebo. As compared to the curve observed with the placebo infusion, 10 ng.kg-1.min-1 prostacyclin infusion resulted in a further increase in cardiac index, by 41 and 38% (P < 0.01) at the piroximone-infusion rates of 5 and 10 micrograms.kg-1.min-1, respectively, whereas systemic vascular resistance decreased by 25 and 21%, respectively (P < 0.01). Additionally, a further decrease in pulmonary capillary wedge pressure by 13 and 11% (P < 0.05) and in pulmonary vascular resistance by 21 and 19% (P < 0.05) was observed at the piroximone-infusion rates of 5 and 10 micrograms.kg-1.min-1, respectively. Consequently, stroke work index increased significantly, as compared to the group receiving prostacyclin added to placebo. This haemodynamic improvement occurred without significant changes in heart rate and mean arterial pressure. Thus, this study shows that in patients with severe congestive heart failure, short-term infusion of prostacyclin is safe and has additive haemodynamic effects on phosphodiesterase inhibitors.

Adult↗

Experimental assessment of right ventricular function in normal pigs with a left ventricular assist device.

Right ventricular (RV) failure during the use of a left ventricular assist device (LVAD) is the leading cause of death in circulatory support patients. Previous work, both experimentally and clinically, has shown the difficulties in predicting the behavior of the right ventricle at the start of LVAD. An experimental study has been designed to evaluate RV functional changes during LVAD and its relation to preload changes. The model used adult mongrel pigs (n = 10). Right ventricular functional parameters were measured with a thermodilution RV ejection fraction catheter. The left ventricle was supported by a Nippon Zeon blood pump. Two groups were studied, the first one was the LVAD-off group (n = 5) and the other was the LVAD-on group (n = 5) which was supported by LVAD at maximum flow. Change of cardiac output, mean pulmonary artery pressure (PAP), RV stroke work, and RV ejection fraction in both groups were not significantly different. However, the relationship between right ventricular end-diastolic pressure (RV-EDP) and right ventricular stroke volume (RVSV) was significantly changed at a high level of RV-EDP. When RV-EDP was over 6.5 mm Hg in the LVAD-off group, RVSV decreased to 52.3 +/- 11.5 ml while in the LVAD-on group, RVSV increased to 97.2 +/- 22.0 ml. The change in PAP in the LVAD-on group was lower than in the LVAD-off group. We conclude that, at the volume overload state, LVAD can reduce the afterload of the right ventricle and maintain Frank-Starling's effect, thus having a beneficial effect on right ventricular performance.

Animals↗

Human vascular endothelial cells on expanded PTFE precoated with an engineered protein adhesion factor.

To elucidate the role of the molecular structure of adhesive proteins in an endothelialization of synthetic vascular prosthesis in vitro, a recombinant fibronectin-like engineered adhesion factor (FP) constructed from the specific Arg-Gly-Asp cell adhesion repeats was assayed as adhesive substrate to culture human saphenous vein endothelial cells on ePTFE. ePTFE samples (1 cm2) inserted into cell culture chambers were coated by incubation with increasing amounts of FP (up to 100 micrograms/cm2) prior to cell seeding. At 24 hours after low density cell seeding and 20 micrograms/ml/cm2 FP concentration, the number of adhered cells reached a plateau and the adhered cells did not proliferate up to 6 days of culture. At 24 hours after high density seeding (10(5) cells/cm2), the number of adhered cells was significantly higher on ePTFE with preadsorbed FP than on fibronectin coated PTFE. About 55% of the initially adhered cells survived up to 7 days on FP, whereas cell debris and free nuclei were predominant on fibronectin coated PTFE. In the investigated model the engineered RGD polymer potentialized a short-term adhesion of vascular endothelial cells to PTFE, nevertheless it did not ensure proliferation and long-term survival of these cells.

Blood Vessel Prosthesis↗

Acetylcholine-induced constriction of angiographically normal coronary arteries is not time dependent in transplant recipients. Effects of stepwise infusion at 1, 6, 12 and more than 24 months after transplantation.

OBJECTIVES: The aim of this study was to evaluate whether acetylcholine may be a useful tool for detection of early angiographically undetectable coronary atherosclerosis in heart transplant recipients. BACKGROUND: Coronary artery disease is the main determinant of long-term prognosis in transplant recipients. Acetylcholine-induced constriction of angiographically normal coronary arteries in heart transplant recipients could be due to early atherosclerosis, and acetylcholine has been proposed for early detection of coronary artery disease. METHODS: The responses of large coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) mol/liter) were compared in five control subjects and in four groups of transplant recipients 1, 6, 12 and > 24 months postoperatively (group 1, n = 6; group 2, n = 7; group 3, n = 6; group 4, n = 6, respectively). All patients had normal coronary arteriographic findings. Vessel dimensions were measured in four segments in each patient. RESULTS: In control subjects, acetylcholine increased diameters significantly at 10(-8), 10(-7) and 10(-6) mol/liter (all p < 0.001 vs. basal value). No significant variation was observed at 10(-5) mol/liter. Intracoronary isosorbide dinitrate increased diameters of all segments (p < 0.001). In transplant recipients, vessel diameters did not vary significantly from baseline at 10(-8) and 10(-7) mol/liter concentrations in groups 1 and 3 and at 10(-8) mol/liter in group 4. Vessels constricted significantly in all the other cases. Comparisons of each group with control subjects showed that responses were significantly different for all concentrations but 10(-8) mol/liter in groups 3 and 4. Intracoronary isosorbide dinitrate elicited coronary vasodilation similar to that of control subjects in all groups of transplant recipients. CONCLUSIONS: This study indicates that the acetylcholine response is persistently abnormal in transplant recipients compared with that in normal control subjects and that this abnormality may not be related simply to the presence of atherosclerosis. Thus, acetylcholine may not be a useful tool for early detection of coronary atherosclerosis in heart transplant recipients.

Acetylcholine↗

Effects of plasma lipid levels on blood distribution and pharmacokinetics of cyclosporin A.

The present study attempted to characterize the distribution of cyclosporin A (CsA) among the lipoprotein fractions, very-low-, intermediate-, low-, and high-density (VLDL, IDL, LDL, and HDL, respectively) in the plasma of patients awaiting heart transplantation and the influence of plasma lipid constituents on the pharmacokinetics of CsA. Major fractions of a therapeutic concentration of CsA were found in HDL and in LDL. In addition, plasma lipid concentrations (total cholesterol, triglycerides, phospholipids, VLDL-cholesterol--TC, TG, PL, VLDLc, respectively) are positively correlated with the CsA distribution within the LDL fraction, and negatively correlated with the CsA distribution within the HDL fraction. Thus, the percentage of CsA in each type of lipoproteins was shown to vary with the lipid levels among individuals. A significant negative correlation was found between apparent distribution volume at steady state (Vss) in plasma and TC, PL, and LDLc and between the area under the curve measured in blood (AUCB) for whole blood and PL.

Adult↗

A new device for endothelial cell seeding of a small-caliber vascular prosthesis.

A device permitting homogeneous endothelial cell seeding of a small-caliber arterial prosthesis has been developed. The prosthesis is maintained firmly attached to a rotative scaffolding device. This device is activated by an electrical motor at constant and adjustable speed. The whole system is maintained at 37 degrees C in a cell culture incubator. The 4 mm internal diameter polytetrafluoroethylene (PTFE) prosthesis was coated with biological glue and seeded with human saphenous vein endothelial cells obtained by mechanical detachment. Cell seeding density was 2.10(4) cells/cm2 (Group A, n = 6) or 10(5) cells/cm2 (Group B, n = 6). Rotation speed was 8 revolutions per hour (rph) during 90 min. Analysis of the homogeneity of cell seeding was permitted by cell counts on five different segments of the prosthesis. Each longitudinal segment was analyzed at three different subsegments of the circumference. The average adhesion was 43 +/- 4% in Group A and 38% +/- in Group B of seeded cells. No difference could be observed between the different segments and subsegments. In the two groups, cells were spread, and in Group B, a complete endothelial cell layer was obtained on the graft surface. This study permits validation of the device to allow homogeneous cell seeding in an arterial prosthesis.

Blood Vessel Prosthesis↗