Biomedical subjects
Publications and source records attributed to H Sadeghi.
The semicontinuous suture technique as an alternative method in valve replacement is described. This specific technique is applicable for both adults and children requiring valvular prosthetic operations. This method combines advantages of the continuous and interrupted suture techniques.
BACKGROUND: Cyanotic congenital hearts have an increased susceptibility to ischemia and subsequent reperfusion. The role of platelet-activating factor antagonism and mechanical neutrophil depletion with leukocyte-depleting filters for control of ischemia-reperfusion injury was assessed in corrective surgical procedures for cyanotic heart disease. METHODS: A swine model of cyanotic heart disease was evaluated with three study groups: a control group; a group given a platelet-activating factor antagonist (PAFA group); and a group with leukocyte-depleting filtration (LDF group). The cyanotic model was created with a left atrial appendage-pulmonary artery fistula with peripheral banding through a left anterior thoracotomy in weanling swine. The experimental procedure was performed 5 to 7 weeks later when body weight was greater than 20 kg and oxygen saturation was 85% or less. The corrective procedure was performed through a median sternotomy on cardiopulmonary bypass with repair of the shunt. Myocardial protection was accomplished with hypothermic blood-crystalloid (4:1) cardioplegia; the period of ischemic arrest was 90 minutes. In the PAFA group, the platelet-activating factor antagonist CV-6209 was delivered intravenously 15 to 20 minutes before aortic cross-clamping. In the LDF group, Pall leukocyte-depleting filters were used in the CPB arterial line. Hemodynamic data were taken before operation and 10 and 30 minutes after CPB with impedance ventriculography. RESULTS: There were four deaths in the control group within 30 minutes after CPB; all animals in the treated groups survived longer than 60 minutes (p < 0.05). The ventricular assessment of end-systolic elastance revealed superior performance in the LDF group 30 minutes after CPB compared with the control group (p < 0.05) (controls, 4.0+/-9; PAFA group, 6.5+/-3.7; and LDF group, 12.0+/-4.6). CONCLUSIONS: Both leukocyte-depleting filters and platelet-activating factor antagonism provided myocardial protection, and the filters afforded superior postoperative myocardial contractility.
Tamponade from free wall rupture of the cardiac chambers following blunt thoracic trauma is relatively frequent. Diagnosis requires a high index of suspicion and is rapidly confirmed by echocardiography. Emergent surgery is always mandatory despite apparent stable vital signs. We report a successful repair of a lacerated right atrium without cardiopulmonary bypass (CPB), saved in extremis after undue in-hospital delay.
BACKGROUND: Blood loss after cardiac surgery is a continuing concern of caregivers and patients. The acute inflammatory reaction initiated by the extracorporeal circuitry, necessary to perform the procedure, stimulates the coagulation cascade, and the resultant hyperfibrinolysis is considered to be a major contributing factor of blood loss. The necessity to reduce transfused blood products after cardiac surgery is important, as it reduces the potential transmission of serious viral infections, improves operative outcomes, and provides containment of costs. The purpose of this study was to compare the effect of synthetic antifibrinolytic tranexamic acid with naturally occurring antifibrinolytic aprotinin on blood loss and to study requirements for transfusion of blood products after repeat cardiac valve surgery. METHODS AND RESULTS: Two randomized trials had been previously conducted, each comparing the respective treatment groups, aprotonin (AP group) and transexamic acid (TA group), with a control group [placebo (P)] in double-blind fashion with the same inclusion and exclusion criteria. The number of patients in the four designated groups are as follows: TA, 22; TA-P, 19; AP, 24; and AP-P, 36. The dosage of aprotinin (high-dose) encompassed a 280-mg loading dose infused after induction of anesthesia, 280 mg in the CPB prime solution, and 70 mg/h for a period of 6 hours. The tranexamic acid dose was 10 mg infused in 500 mL of normal saline. The blood loss was measured intraoperatively and postoperatively. The transfusion of homologous blood products was conducted in a standardized fashion. Both the TA and AP groups lost less blood intraoperatively, in total, less than either of the placebo groups, and less blood postoperatively than the TA-P group (P<.05). The postoperative blood loss (median) was 538 mL for the TA group, 455 mL for the AP group, and for the respective placebo groups, 1170 mL and 595 mL. The total blood loss was 1340 mL for the TA group, 1383 mL for the AP group, and 3250 mL and 2450 mL, respectively for the placebo groups. The total blood product use revealed no differences between the two placebo groups (P=NS) nor between the two treatment groups (P=NS). CONCLUSIONS: Tranexamic acid and aprotinin are both effective in reducing intraoperative and postoperative blood loss and the need for blood product transfusion for patients undergoing reoperative cardiac valvular surgery.
The prognosis of patients with end-stage cardiac disease has dramatically changed with transplantation. The incidence of complications remains relatively high and needs a very careful follow-up to have good long term results.
The V2 vasopressin receptor undergoes ligand-induced sequestration and desensitization (Birnbaumer, M., Antaramian, A., Themmen, A. P. N., and Gilbert, S. (1992) J. Biol. Chem. 267, 11783-11788). The V2 receptor expressed in transfected cells labeled with [32P] orthophosphate was phosphorylated following the addition of 100 nM arginine vasopressin (AVP). Phosphorylation was complete 5 min after addition of AVP, and was not stimulated by increased levels of Ca2+ or cAMP. The half-maximal dose of AVP that stimulated phosphorylation was 2.4 +/- 0.4 nM, similar to the receptor KD of 4. 5 +/- 0.4 nM. The role of phosphorylation on receptor desensitization was investigated by studying two vasopressin receptors 14 and 27 amino acids shorter than the wild type receptor. The missing segments were not needed for normal ligand binding or coupling to Gs, but the last 14 amino acids were required for phosphorylation. The truncated receptors exposed to 100 nM AVP were sequestered and desensitized. The R137H V2R mutant receptor that binds vasopressin with wild type-like affinity and does not couple to Gs (Rosenthal, W., Antaramian, A., Gilbert, S., and Birnbaumer, M. (1993) J. Biol. Chem. 268, 13030-13033) was phosphorylated and subjected to ligand-induced sequestration. These results established that phosphorylation is not essential for sequestration and desensitization of the V2 vasopressin receptor. Furthermore, they revealed that the conformation acquired after ligand occupancy is necessary for receptor phosphorylation and sequestration, while coupling to Gs is not.
PURPOSE: The objective of this study was to assess the effect of tranexamic acid (TA), a synthetic antifibrinolytic, on blood loss and the need for transfusion of blood products following repeat cardiac valve surgery. METHODS: After ethics committee approval, 41 patients scheduled for reoperative valve replacement were enrolled in this randomized, double blind, placebo controlled study. Patients were randomized to receive TA (10 g in 500 ml NSaline) or placebo (NSaline) as an iv bolus over 30 min, after anaesthesia induction and prior to skin incision. Intraoperative blood loss was assessed by estimating blood volume on drapes, weighing surgical sponges, and measuring suction bottle returns. Postoperative blood loss was measured from mediastinal chest tube drainage following surgery. Blood products were transfused according to a standardized protocol. RESULTS: Patient demographics were similar for age, sex, cardiopulmonary bypass pump time, cross clamp time, surgical time, preoperative haemoglobin, coagulation profile, and the number of valves replaced during surgery. Tranexamic acid administration reduced intraoperative blood loss [median (range)] from 1656 (575-6270) to 720 ml (355-5616) (P < 0.01) and postoperative blood loss from 1170 (180-4025) to 538 ml (135-1465) (Intent to Treat n = 41, P < 0.01). The total red blood cells transfused (median, range) was reduced from 1500 (0-9300) ml to 480 (0-2850) ml (P < 0.01) in the TA group. In hospital complications and mortality rates were not reduced in the TA group. CONCLUSION: Tranexamic acid reduced blood loss and the need for blood product transfusion and appears to be an effective treatment for patients undergoing reoperative cardiac valvular surgery.
Between 1979 and 1984, 321 patients received 354 St. Jude Medical prostheses (194 aortic, 94 mitral, 1 tricuspid, and 32 multiple valve replacements). Follow-up was 96% complete (2967 patient-years; mean 9.5 years per patient). Actuarial event-free rates at 10 years and linearized rates (in parentheses) of late complications were as follows: embolism, 85.0% +/- 2.3% (2.3% per patient-year); anticoagulant-related hemorrhage, 74.8% +/- 2.7% (3.3% per patient-year); cerebrovascular accident, 81.8% +/- 2.5% (2.6% per patient-year); prosthesis thrombosis, 98.5% +/- 0.7% (0.1% per patient-year); endocarditis, 97.2% +/- 1.1% (0.4% per patient-year); prosthesis dysfunction, 97.1% +/- 1.0% (0.4% per patient-year); hemolytic anemia, 98.5% +/- 0.7% (0.1% per patient-year); reoperation, 97.4% +/- 1.0% (0.4% per patient-year); overall mortality, 63.3% +/- 2.7% (4.2% per patient-year); and valve-related death (including sudden death), 84.7% +/- 2.2% (1.4% per patient-year). Independent preoperative risk factors were as follows: (1) for embolism, cardiac failure as indication for operation and history of prior systemic embolism; (2) for cerebrovascular accidents, the same two factors and age; (3) for endocarditis, diabetes, chronic alcoholism, and aortic valve replacement; (4) for overall mortality, age, ejection fraction (or cardiac index or cardiothoracic index), chronic alcoholism, and history of systemic embolism; and (5) for valve-related death, chronic alcoholism, degenerative cause of valve disease, and prosthetic diameter 23 mm or smaller. Ninety percent of survivors were in New York Heart Association functional class I or II at the end of follow-up. In conclusion, this study confirms the excellent durability of the St. Jude Medical valve and the remarkable functional benefit for the majority of the patients. However, prosthesis-related complications are still common, particularly for small-diameter prostheses. Outcome is strongly related to the patient's preoperative cardiac condition and to the adequacy of anticoagulation control.
Biochemical properties of mutant type 2 vasopressin receptors (V2Rs) causing a partial phenotype of nephrogenic diabetes insipidus were investigated in transiently transfected HEK 293 cells. Cell surface expression of the V2R was not altered by substituting Asp85 in the second transmembrane region by Asn as determined by saturation binding assays. Although the affinity of the mutant V2R for arginine vasopressin (AVP) was reduced only 6-fold, the response of adenylyl cyclase activity to AVP revealed a 50-fold right shift in EC50 and a decreased maximum response for the mutant V2R. These data indicated that replacement of Asp85 by Asn affected coupling of the receptor to Gs, a conclusion substantiated by a 20-fold decrease in the calculated coupling efficiency of this receptor. The Gly201Asp mutation in the second extracellular loop, also found associated with an NDI partial phenotype, decreased cell surface expression of the V2R with minor reduction in ligand-binding affinity and coupling efficiency to Gs. A pronounced difference was observed for this mutant V2R between the stimulation of adenylyl cyclase activity promoted by AVP and the V2 vasopressin receptor agonist deamino[Cys1,D-Arg8]-vasopressin, suggesting an involvement of Gly201 in the selectivity of the receptor for different ligands. These data demonstrated that while decreased ligand-binding affinity and decreased coupling to Gs are responsible for the attenuation of response to ligand in the Asp85Asn mutant V2R, cell surface expression of the V2R is the major factor reducing cellular responses to ligand for the Gly201Asp mutant V2R.
During the last 2 years, our laboratory has worked on the elucidation of the molecular basis of capacitative calcium entry (CCE) into cells. Specifically, we tested the hypothesis that CCE channels are formed of subunits encoded in genes related to the Drosophila trp gene. The first step in this pursuit was to search for mammalian trp genes. We found not one but six mammalian genes and cloned several of their cDNAs, some in their full length. As assayed in mammalian cells, overexpression of some mammalian Trps increases CCE, while expression of partial trp cDNAs in antisense orientation can interfere with endogenous CCE. These findings provided a firm connection between CCE and mammalian Trps. This article reviews the known forms of CCE and highlights unanswered questions in our understanding of intracellular Ca2+ homeostasis and the physiological roles of CCE.
Combined heart and renal transplantation from the same donor is an uncommon procedure. We describe the case of a patient with prior kidney transplantation whose renal graft had to be removed a few years later because of chronic rejection. The patient then developed severe hypertensive and ischemic left ventricular dysfunction. Combined heart and kidney transplantation was performed several years after the first renal transplantation. This observation is the first description of a combined heart and kidney transplantation after removal of a former renal graft whose failure was due to chronic rejection. Great care was taken to avoid identical MHC antigens (HLA-A; -B; -DR) between the two donors, to prevent recurrent rejection of the grafted organs. After 18 months, no rejection was detected in either organ. This case report confirms the feasibility of this complex procedure, provided care is taken to avoid identical HLA groups between the two donors so as to reduce immunological complications.
Transplant atherosclerotic coronary disease remains the leading cause of death in heart transplant recipients. We report the first case of coronary stent implantation in a heart graft for epicardial focal stenosis. Due to the lower rate of restenosis after stenting in the native coronary artery, we suggest that coronary stenting be considered an acceptable, first intention therapeutic option instead of angioplasty alone whenever possible.
Prevention of recurrent stroke in adults with patent foramen ovale represents a therapeutic challenge. Antiplatelet or anticoagulant treatment is widely introduced, but its exact indication is not known. In this pilot study, eight men and three women with previous ischemic cerebral events underwent direct surgical closure of the patent foramen ovale. Mean age was 39.4 (from 30 to 58) years. No coexisting cause of stroke was found after extensive investigations, including blood and coagulation tests, echocardiography, 24-hour three-lead electrocardiographic monitoring, extracranial and transcranial Doppler ultrasonography, and cerebral angiography. Criteria for operation also included at least two of the following: atrial septal aneurysm, multiple cerebral infarcts, a history of multiple cerebral events, and Valsalva strain before stroke. Before operation, one patient had two shunts (1 patent foramen ovale, 1 intrapulmonary shunt). No intraoperative or postoperative complications occurred, but a few hours after operation transient arrhythmias developed in two patients without atrial fibrillation, hemodynamic instability, or embolism. During a median follow-up of 12.2 months, no patient had recurrent stroke. All patients prospectively underwent brain magnetic resonance imaging and contrast echocardiography with simultaneous transcranial Doppler ultrasonography. A residual right-to-left interatrial shunt, smaller than the preoperative one, was observed in only one patient, whereas no lesion was seen on magnetic resonance imaging. Our study suggests that surgical closure of patent foramen ovale in patients with presumed paradoxic embolism is safe, with no recurrent stroke in the first year of follow-up. Further studies are needed to evaluate the long-term prognosis of patients with versus without operation and to define the role of operation as an alternative to prolonged antithrombotic treatment.
BACKGROUND: The risk of stroke and the long-term prognosis of recurrent strokes in young patients with patent foramen ovale (PFO) are not well known. For this reason, the treatment of these patients remains empirical. An alternative treatment to prolonged antithrombotic therapy may be surgical closure of the PFO. METHODS: Thirty patients (20 men and 10 women) with stroke and PFO were prospectively selected among 138 patients with stroke and PFO for a study of surgical closure of PFO at our center. Eligible patients were < 60 years old, had negative results of a systematic search for another cause of stroke (first criterion), and met two of the four following criteria: (1) recurrent clinical cerebrovascular events or multiple ischemic lesions on brain MR, (2) PFO associated with an atrial septal aneurysm, (3) > 50 microbubbles counted in the left atrium on contrast transesophageal echocardiography (TEE), and (4) Valsalva maneuver or cough preceding the stroke. Patients selected in this manner for surgery were considered to be a subgroup with a higher risk of stroke recurrence. RESULTS: All patients had a direct suture of PFO while under cardiopulmonary bypass without recorded early or delayed significant complication. All patients underwent a new brain MRI and TEE simultaneous with transcranial Doppler ultrasonography after contrast injection at 8 +/- 3 months after surgery. After a mean follow-up of 2 years without antithrombotic treatment, no recurrent cerebrovascular event (stroke or transient ischemic attack [TIA]) and no new lesion on MRI had developed. Postoperative contrast TEE and transcranial Doppler ultrasonography showed that two patients had residual interatrial right-to-left shunting, although much smaller than before surgery, associated with single versus double continuous suture. CONCLUSIONS: Our study of 30 selected stroke patients with surgical suture of PFO showed a stroke recurrence rate of 0% and no significant complication. Residual right-to-left shunting may be avoided by double continuous suture of the PFO. In the absence of controlled studies to guide individual therapeutic decisions, our findings show that PFO closure can be done safely and may be considered to avoid recurrence in selected patients with long life expectancy and presumed paradoxic embolism.
The human V2 vasopressin receptor belongs to the superfamily of G protein-coupled receptors believed to be anchored to the plasma membrane by seven transmembrane regions. The extracellular portion of the human V2 vasopressin receptor contains one site susceptible to N-linked glycosylation. Metabolic labeling and immunoprecipitation of the receptor expressed in transfected cells were applied to examine whether the protein was indeed glycosylated. The V2 vasopressin receptor expressed transiently was glycosylated, but glycosidase treatment to test the complexity of the sugar moiety linked to asparagine revealed that the majority of the receptor protein lacked complex carbohydrates, an indication of an improperly processed protein. This immature protein displayed a tendency to form aggregates. In contrast with these data, testing of the sugar complexity of the receptor protein synthesized in stably transfected cells identified the predominant form as an appropriately processed receptor protein. Mutagenesis of asparagine 22 to glutamine produced on expression in transfected cells a nonglycosylated receptor with ligand binding affinity and coupling characteristics almost identical to those of the wild-type form. After exposure to elevated concentrations of AVP (100 nM), the nonglycosylated form desensitized to the same extent as the wild-type receptor.
Advancing The Standard (ATS) Medical (ATS Medical Inc., Minneapolis, MN) is a new mechanical bileaflet valve, composed of pyrolitic carbon. The aim of this study was to define in a blinded manner the Doppler echocardiographic characteristics of normally functioning ATS Medical prostheses with respect to their size. Forty consecutive patients (29 men, mean age 58 +/- 13 years), clinically stable, and without evidence of valve dysfunction, were studied from 1993 to 1995. Doppler echocardiography was performed at least 3 months after valve replacement with ATS Medical valves (5 n degrees 21, 8 n degrees 23, 12 n degrees 25, 10 n degrees 27, 5 n degrees 29). Maximum and mean transprosthetic pressure gradients were calculated by the simplified Bernoulli equation. Functional valve surface area was assessed by the continuity equation using the external diameter of the prostheses to calculate the subaortic surface area. The Doppler velocity index was obtained by the ratio of subaortic and transaortic velocities and the performance index was calculated dividing the effective orifice area by the actual orifice area. For the most commonly used aortic valve (25 mm), the maximum pressure gradient was 17 +/- 8 mmHg, the mean gradient 11 +/- 4 mmHg, the functional surface area 2.2 +/- 0.4 cm2, the Doppler velocity index 0.44 +/- 0.07, and the performance index 0.68 +/- 0.11. This study provides the normal range for Doppler hemodynamic characteristics of the various sizes of the ATS valve.
37 patients aged 80 or over underwent cardiac surgery during an 11-year period. Operative indications included angina, dyspnea and syncope. The majority of patients (n = 32) had a left ventricular ejection fraction greater than 0.5. There were 28 aortic valve procedures, of which seven were combined with coronary artery bypass grafts (CABG), and 2 with mitral valve repair; in addition, 7 isolated CABG procedures and one isolated mitral valve repair were performed. 36-day mortality was 5.4% (2 patients); 9 patients died at a later date (2.5 to 118 months after surgery). The most frequent postoperative complications were atrial fibrillation, pulmonary infection or atelectasis, transient delirium and atrioventricular conduction disturbances. Mean hospital stay was 14.5 days. 1- and 5-year actuarial survival rates were 83% and 57%. In a control group of patients aged 60-69 matched for preoperative characteristics, there were no in-hospital fatalities and 1- and 5-year survival were, respectively, 100% and 82%. Among complications, only conduction disturbances and transient delirium were significantly more frequent in the octogenarian group. At follow-up, the proportion of severely symptomatic octogenarians had diminished to 24% from 84%. In conclusion, cardiac surgery can be performed on octagenarians with adequate myocardial reserve, exposing them to a perioperative mortality that is in the range of younger age groups while offering an equivalent prospect for functional improvement.
Prognosis of heart transplant patients has dramatically improved in the last decade thanks to the use of cyclosporine as immunosuppressive treatment. Optimal follow-up and early recognition of complications and side effects of treatment lead to longer survival and marked improvement of these patients' quality of life. However, the incidence of complications remains high and their management calls for particular care. We review our experience of heart transplantation in Lausanne and describe in detail the results and complications such as rejection, transplant coronary artery disease, hypertension, renal failure, metabolic disorders, cancer and conduction problems. Cooperation of the medical team (cardiologist, surgeon, anesthetist, general practitioner) is essential to long term success of the transplant program.