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1.
Br J Surg ; 99(10): 1331-44, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22961510

ABSTRACT

BACKGROUND: Acute aortic dissection type A (AADA) is a life-threatening vascular emergency. Clinical presentation ranges from pain related to the acute event, collapse due to aortic rupture or pericardial tamponade, or manifestations of organ or limb ischaemia. The purpose of this review was to clarify important clinical issues of AADA management, with a focus on diagnostic and therapeutic challenges. METHODS: Based on a MEDLINE search the latest literature on this topic was reviewed. Results from the German Registry for Acute Aortic Dissection Type A (GERAADA) are also described. RESULTS: Currently, the perioperative mortality rate of AADA is below 20 per cent, the rate of definitive postoperative neurological impairment approaches 12 per cent and the long-term prognosis after surviving the acute phase of the disease is good. Many pathology- and therapy-associated factors influence the outcome of AADA, including prompt diagnosis with computed tomography and better cerebral protection strategies during aortic arch reconstruction. Endovascular technologies are emerging that may lead to less invasive treatment options. CONCLUSION: AADA is an emergency that can present with a wide variety of clinical scenarios. Advances in the surgical management of this complex disease are improving outcomes.


Subject(s)
Aortic Aneurysm/surgery , Aortic Dissection/surgery , Acute Disease , Aortic Dissection/diagnosis , Aortic Aneurysm/diagnosis , Aortic Rupture/prevention & control , Brain Ischemia/prevention & control , Extracorporeal Circulation/methods , Humans , Hypothermia, Induced/methods , Perioperative Care/methods , Prognosis
2.
J Card Surg ; 23(2): 126-32, 2008.
Article in English | MEDLINE | ID: mdl-18304126

ABSTRACT

BACKGROUND: Magnetic Resonance Imaging (MRI) and transthoracic echocardiography have been shown to be noninvasive highly sensitive diagnostic tools to identify changes in LV mass and volume. We therefore investigated the effects of mitral valve repair (MVR) on LV function parameters including ejection fraction (EF; %), indices of LV mass (LVMI; g/m2) and volume (LVEDVI, LVESVI; mL/m2) as detected by MRI and echocardiography. METHODS: Eight consecutive patients (mean age 53.3 +/- 10.0 years) with severe mitral regurgitation (MR; grade III-IV), normal LV function and sinus rhythm were included in this prospective study. Cine MRI and transthoracic M-mode echocardiography were performed pre-operatively, as well as 6 months post-op, to identify changes in EF and in LV mass and volume. Data are given as mean +/- standard deviation. RESULTS: Post-op MR was grade 0-I in all patients. Early mortality and late mortality was 0%. EF by either method did not change significantly within the follow-up period. A significant improvement of indices of LV mass and volume was detected by Cine MRI and echocardiography within 6 months following surgery (LVMIMRI: pre-op: 76.3 +/- 20.1 vs. post-op: 66.5 +/- 14.3, p < 0.05; LVMIEcho: pre-op: 184.2 +/- 38.1 vs. post-op: 136.5 +/- 28.4, p < 0.05. LVEDVIMRI: pre-op: 119.3 +/- 26.0 vs. post-op: 75.4 +/- 13.1, p < 0.05; LVEDVIEcho: pre-op: 97.4 +/- 28.8 vs. post-op: 69.2 +/- 13.1, p < 0.05. LVESVIMRI: pre-op: 44.6 +/- 12.0 vs. post-op: 32.5 +/- 9.5, p < 0.05; LVESVIEcho: pre-op: 29.3 +/- 8.3 vs. post-op: 21.8 +/- 4.6, p < 0.05). CONCLUSIONS: MRI and echocardiography show a significant reduction of LV volume and mass 6 months after MVR. The data show that for routine follow-up transthoracic M-mode echocardiography provides reliable information for the identification of LV mass and volume regression in patients after MVR.


Subject(s)
Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/pathology , Magnetic Resonance Imaging , Mitral Valve/surgery , Adult , Aged , Diastole , Disease Progression , Echocardiography/instrumentation , Female , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Humans , Hypertrophy, Left Ventricular/physiopathology , Male , Middle Aged , Mitral Valve/pathology , Postoperative Period , Prospective Studies , Stroke Volume , Systole , Time Factors , Treatment Outcome
4.
Int J Med Robot ; 1(3): 74-9, 2005 Sep.
Article in English | MEDLINE | ID: mdl-17518393

ABSTRACT

The introduction of telemanipulator systems into cardiac surgery enabled the heart surgeon to perform minimally invasive procedures with high precision and stereoscopic view. For further improvement and especially for inclusion of autonomous action sequences, implementation of force-feedback is necessary. The aim of our study was to provide a robotic scenario giving the surgeon an impression very similar to open procedures (high immersion) and to enable autonomous surgical knot tying with delicate suture material. In this experimental set-up the feasibility of autonomous surgical knot tying is demonstrated for the first time using stereoscopic view and force feedback.


Subject(s)
Cardiac Surgical Procedures/methods , Minimally Invasive Surgical Procedures/methods , Robotics , Cardiac Surgical Procedures/instrumentation , Depth Perception , Feasibility Studies , Feedback , Humans , Minimally Invasive Surgical Procedures/instrumentation , Robotics/instrumentation , Surgical Equipment , Surgical Instruments , Suture Techniques , Touch
5.
Br J Anaesth ; 92(6): 808-13, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15096443

ABSTRACT

BACKGROUND: Mid-line thoracotomy is a standard approach for cardiac surgery. However, little is known how this surgical approach affects the interaction between the circulation and mechanical ventilation. We studied how mid-line thoracotomy affects cardiac filling volumes and cardiovascular haemodynamics, particularly variations in stroke volume and pulse pressure caused by mechanical ventilation. METHODS: We studied 19 patients during elective coronary artery bypass surgery. Before and after mid-line thoracotomy, we measured arterial pressure, cardiac index (CI) and global end-diastolic volume index (GEDVI) by thermodilution, left ventricular end-diastolic area index (LVEDAI) by transoesophageal echocardiography and the variations in left ventricular stroke volume and pulse pressure during ventilation by arterial pulse contour analysis. RESULTS: After thoracotomy, CI increased from 2.3 (0.4) to 2.9 (0.6) litre min(-1) m(-2), GEDVI increased from 605 (110) to 640 (94) litre min(-1) m(-2), and LVEDAI increased from 9.2 (3.7) to 11.2 (4.1) cm(2) m(-2). All these changes were significant. In contrast, stroke volume variation (SVV) decreased from 10 (3) to 6 (2)% and pulse pressure variation (PPV) decreased from 11 (3) to 5 (3)%. Before thoracotomy, SVV and PPV significantly correlated with GEDVI (both P<0.01). When the chest was open, similar significant correlations of SVV (P<0.001) and PPV (P<0.01) were found with GEDVI. CONCLUSION: Thoracotomy increases cardiac filling and preload. Further, thoracotomy reduces the effect of mechanical ventilation on left ventricular stroke volume. However, also under open chest conditions, SVV and PPV are preload-dependent.


Subject(s)
Cardiac Output , Coronary Artery Bypass , Respiration, Artificial , Thoracotomy/methods , Adult , Aged , Echocardiography, Transesophageal , Female , Hemodynamics , Humans , Intraoperative Period , Male , Middle Aged , Monitoring, Intraoperative/methods , Stroke Volume , Thermodilution
7.
Eur J Cardiothorac Surg ; 24(4): 475-80; discussion 480, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14500062

ABSTRACT

OBJECTIVE: Radiofrequency or the use of microwave energy in combination with atrial size reduction during open heart surgery have been reported to be effective in up to 75% in the treatment of permanent atrial fibrillation. However, no data from prospective randomized trials using microwave energy are available. METHODS: Forty-three patients with permanent atrial fibrillation undergoing open-heart surgery were randomly stratified into treatment group receiving microwave ablation and atrial size reduction (n=24) or control group (n=19). Patients in either group were treated with amiodarone or sotalol for 3 months if sinus rhythm or any atrioventricular rhythm was successfully restored. Follow-up time points were at 3, 6 and 12 month after surgery. RESULTS: In the treatment group 22 out of 24 patients (91,7%) were successfully converted to sinus rhythm by using intraoperative microwave ablation therapy whereas only six out of 19 (31.5%) patients converted to sinus rhythm directly after surgery. At 12-month follow-up there were still a significantly higher percentage of patients in the treatment group free from atrial fibrillation when compared to control (80 vs. 33.3%, P=0.036). CONCLUSION: The preliminary data from this first prospectively randomized trial indicate that microwave ablation combined with atrial size reduction is a safe and highly efficient treatment in permanent atrial fibrillation.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation/methods , Microwaves/therapeutic use , Aged , Aged, 80 and over , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Chemotherapy, Adjuvant , Chronic Disease , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Care/methods , Prospective Studies , Treatment Outcome
8.
MMW Fortschr Med ; 145(51-52): 26-8, 2003 Dec 18.
Article in German | MEDLINE | ID: mdl-14974324

ABSTRACT

In terms of long-term survival and quality of life, excellent results with aortic valve replacement (AVR) can also be achieved in patients older than 70 years of age. An indication for this procedure is given in symptomatic patients with significant aortic valve stenosis, patients with severe acute aortic insufficiency (AI), those with signs of cardiac insufficiency but still normal left ventricular function, and asymptomatic AI patients with an ejection fraction of less than 50% and/or an end-diastolic LV diameter (EDD) of more than 75 mm or an end-systolic diameter (ESD) of more than 55 mm. Many patients with a heart defect in need of surgical treatment also have CAD as well, in which case a bypass should be performed at the same time. For AVR, both mechanical and biological prostheses are available, the latter being regarded as the method of choice in patients aged over 70. The mechanical variant requires life-long anticoagulation therapy with phenprocoumon.


Subject(s)
Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/surgery , Aortic Valve , Bioprosthesis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Age Factors , Aged , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Contraindications , Humans , Phenprocoumon/administration & dosage , Phenprocoumon/therapeutic use , Postoperative Care , Reoperation , Stroke Volume , Ventricular Function, Left
9.
Vasc Surg ; 35(2): 149-55, 2001.
Article in English | MEDLINE | ID: mdl-11668385

ABSTRACT

Despite successful surgical revascularization of ischemic limbs, a local and systemic reperfusion injury may occur after normal blood reperfusion. Recent experimental and clinical application of controlled limb reperfusion in Europe has demonstrated superior results, with lower morbidity and mortality. This new surgical technique includes modification of the reperfusate (calcium, pH, substrates, osmolarity, free radical scavenger) and the circumstances of initial reperfusion (time, temperature, pressure). This report describes the first application of controlled limb reperfusion after reperfusion injury. A 16-year-old boy underwent femoral access cardiopulmonary bypass for repeat cardiac repair with an ischemic time of 245 minutes. Postoperatively, severe ischemia/reperfusion syndrome developed with muscle contracture, immobility, and anesthesia of the right leg with a second ischemic time of about 6 hours. The systemic creatine phosphokinase level was 88,000 U/L; myoglobin was 27,000 ng/mL. He underwent controlled limb reperfusion by withdrawing blood from the aorta and mixing it with a crystalloid solution (calcium-reduced, hyperosmolar, hyperglycemic, alkalotic, glutamate- and aspartate-enriched, and containing a free radical scavenger) under controlled conditions (blood:crystalloid solution 6:1, for 30 minutes, reperfusion pressure < 50 mm Hg, and normothermia) before establishing normal blood reperfusion. Metabolic data from the central and femoral vein demonstrated a significant reduction of all previous elevated enzyme levels, avoidance of hyperkalemia, normalization of acidosis, and avoidance of systemic reperfusion injury with no multiorgan failure. Limb salvage was accomplished and functional recovery almost complete. To the authors' knowledge, this is the first application of controlled limb reperfusion reported in North America. With this surgical technique we were able to prevent metabolic local and systemic reperfusion changes after prolonged ischemia and also reduced previous reperfusion changes. This report confirms former experimental data, and further clinical studies are warranted.


Subject(s)
Muscle, Skeletal/injuries , Reperfusion Injury , Adolescent , Extremities/surgery , Humans , Male , Muscle, Skeletal/surgery , Reperfusion , Reperfusion Injury/surgery
10.
Circulation ; 104(12 Suppl 1): I336-43, 2001 Sep 18.
Article in English | MEDLINE | ID: mdl-11568079

ABSTRACT

BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed and is functionally active in the presence of transplant arteriosclerosis. However, the early involvement of iNOS in alterations of microvascular endothelial function in the absence of preexisting lesions remains unclear; this information would be of prognostic value. We studied the course of iNOS mRNA expression, transcardiac nitric oxide production, and their potential association with microvascular coronary endothelial dysfunction in human cardiac allografts. METHODS AND RESULTS: A total of 42 patients were studied at 1, 6, and 12 months after heart transplantation. Microvascular coronary flow velocity reserve (CFVR) was tested in an endothelium-dependent (acetylcholine) and -independent manner (adenosine) using a Doppler flow wire. Endomyocardial iNOS expression was determined by reverse transcription polymerase chain reaction. iNOS protein and nitrotyrosine levels were detected by immunohistochemistry. Transcardiac plasma nitrite/nitrate (NOx) levels were measured by the Griess reaction. CFVR was impaired in 26.1% of patients (n=11) at 1 month and in 31% of patients (n=13) at 12 months after heart transplantation. Patients who developed impaired CFVR in the first year showed a significant increase in iNOS gene expression. Patients with impairment of CFVR 1 month after heart transplantation had higher levels of iNOS mRNA than patients with a normal CFVR. Patients with an initial impairment of CFVR who did not improve over time presented with significantly higher iNOS mRNA levels. iNOS protein and nitrotyrosine were expressed in the endomyocardial vessels of patients with impaired CFVR. Transcardiac NOx release was higher in patients with impaired CFVR. CONCLUSIONS: In human cardiac allografts, microvascular endothelial dysfunction is associated with an enhanced endomyocardial iNOS mRNA expression and higher transcardiac NOx production and is accompanied by the expression of nitrotyrosine protein, suggesting peroxynitrite plays a role in the disease process. The data from the present study suggest an important role for the iNOS/nitric oxide pathway in the regulation of microvascular function in the absence of preexisting atherosclerotic lesions.


Subject(s)
Coronary Vessels/metabolism , Endothelium, Vascular/metabolism , Heart Transplantation , Myocardium/metabolism , Nitric Oxide Synthase/biosynthesis , Tyrosine/analogs & derivatives , Acetylcholine/pharmacology , Adolescent , Adult , Aged , Biopsy , Demography , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Microcirculation/drug effects , Microcirculation/metabolism , Middle Aged , Myocardium/pathology , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Predictive Value of Tests , Prospective Studies , RNA, Messenger/biosynthesis , Tyrosine/metabolism , Vasomotor System/drug effects
11.
Thorac Cardiovasc Surg ; 49(3): 144-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11432471

ABSTRACT

BACKGROUND: The present study compared redo coronary artery bypass grafting (Re-OPCAB) techniques with conventional redo coronary artery bypass grafting (Re-CABG) with particular focus on myocardial damage and clinical outcome parameters. METHODS: Redo OPCAB (Re-OPCAB) was performed on 20 consecutive patients (15 males, mean age 63.2 +/- 9.3 years) using either the anterolateral approach for minimally invasive direct coronary artery bypass (n = 4) or the Octopus technique with regular sternotomy (n = 16). The Re-CABG group consisted of 20 consecutive patients (18 males, mean age 67.1 +/- 6.6 years). Groups did not differ in the number of atherosclerotic risk factors, or left ventricular, renal or liver function. RESULTS: Duration of surgery, number of bypass grafts and amount of transfused red blood cells did not differ significantly between both groups. Requirement of epinephrine (mg/h) within the first 24 h was lower in the Re-OPCAB group (Re-OPCAB: 0.14 +/- 0.22 vs. CABG: 0.88 +/- 0.97; p<0.01). In addition, CKMB levels at 24 h after operation were lower in the Re-OPCAB group (Re-OPCAB: 10.0 +/- 10.1 vs. Re-CABG: 38.7 +/- 28.1 U/l, p<0.001). There were no acute myocardial infarctions or deaths in the perioperative period. In the CABG group, there was a longer time period to extubation (hours) (Re-OPCAB: 9.8 +/- 3.9 vs. Re-CABG: 28.7 +/- 25.5; p<0.001), and the length of ICU stay was significantly prolonged (OPCAB: 1.3 +/- 0.5 versus Re-CABG: 4.4 +/- 8.7; p<0.001). The graft patency rate at follow-up was 95% in the Re-OPCAB group. CONCLUSION: Re-OPCAB results in decreased cardiac specific enzyme release, reduced requirement of inotropes and comparable clinical outcome in the early postoperative period. It is an appropriate alternative to conventional Re-CABG in selected patients awaiting reoperation for myocardial revascularization. Larger prospective and randomized trials are required to select the appropriate patient who benefits most from one or the other treatment regime.


Subject(s)
Coronary Artery Bypass , Coronary Disease/surgery , Myocardial Revascularization , Aged , Angiography , Coronary Disease/diagnostic imaging , Coronary Disease/mortality , Creatine Kinase/metabolism , Creatine Kinase, MB Form , Female , Follow-Up Studies , Humans , Isoenzymes/metabolism , Length of Stay , Male , Middle Aged , Reoperation , Time Factors , Treatment Outcome , Vascular Patency/physiology
12.
Eur J Cardiothorac Surg ; 19(6): 840-7, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11404140

ABSTRACT

OBJECTIVE: Coronary endothelial dysfunction may precede morphological changes in both the epicardial conduit and microvascular resistance vessels in heart transplant recipients. Since the development of transplant atherosclerosis is the major limiting factor for long-term survival, the identification of early mediators of vasomotor dysfunction may be of therapeutic interest. We therefore investigated the potential relationship between the expression of nitric oxide synthases (NOS) and coronary endothelial function in human cardiac transplant recipients over time. METHODS: Forty-two human cardiac transplant recipients were studied at 1 and 12 months after heart transplantation (HTx). The microvascular coronary flow velocity reserve (CFVR) was tested for endothelium-dependent (acetylcholine) and -independent (adenosine) stimuli by intravascular Doppler flow-wire. Epicardial diameter changes were evaluated by quantitative coronary angiography. Endomyocardial inducible (iNOS) and endothelial constitutive nitric oxide synthase were determined by RT-PCR. Nitric oxide production (nitrite and nitrate (NOx)) and TNF-alpha were measured in plasma samples from the aorta and coronary sinus. RESULTS: CFVR was impaired in 26.1% (n=11) of patients at 1 month and in 31% (n=13) 12 months after HTx. iNOS-mRNA levels were significantly higher in patients with impaired endothelium-dependent CFVR. In addition, only in these patients were TNF-alpha levels higher and these correlated with plasma NOx levels at 1 and 12 months post-HTx (1 month: r=0.81, P=0.001; 12 months: r=0.62, P=0.04). CONCLUSIONS: Coronary microcirculatory dysfunction in response to acetylcholine is present in nearly 30% of patients during the first year following transplantation. These patients present with higher iNOS-mRNA expression and TNF-alpha plasma levels. Selective modulation of the TNF-alpha/iNOS-pathway may be of therapeutic value to improve coronary endothelial dysfunction in cardiac transplant recipients.


Subject(s)
Coronary Vessels/physiology , Heart Transplantation , Nitric Oxide Synthase/biosynthesis , Vasomotor System/physiology , Adult , Blood Flow Velocity/physiology , Coronary Angiography , Endothelium, Vascular/physiology , Female , Humans , Male , Microcirculation/physiology , Nitrates/blood , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Nitrites/blood , Polymerase Chain Reaction , Postoperative Period , Tumor Necrosis Factor-alpha/analysis
16.
MMW Fortschr Med ; 143(10): 34-6, 2001 Mar 08.
Article in German | MEDLINE | ID: mdl-11268737

ABSTRACT

The leading minimally invasive procedures employed in coronary surgery are minimally invasive direct coronary arterial bypass surgery (MIDCAB) and the Octopus system. These interventions are performed on the beating heart and require no extracorporeal circulation (ECC), thus avoiding the side effects, such as pulmonary or neurological complications, associated with ECC. In surgery on the mitral or aortic valve, the procedures are carried out via small incisions in the non-beating heart, and endovascular bypass systems (e.g. Port-Access) are sometimes needed for EEC. The advantages of small incisions are a reduction in the risk of infection, shorter hospital stay and, in particular, improved cosmesis. A disadvantage is the longer operating time. Only careful patients selection guarantees successful surgery.


Subject(s)
Coronary Artery Bypass , Heart Valve Prosthesis Implantation , Minimally Invasive Surgical Procedures , Cardiopulmonary Bypass/instrumentation , Coronary Artery Bypass/instrumentation , Heart Valve Prosthesis Implantation/instrumentation , Humans , Minimally Invasive Surgical Procedures/instrumentation , Robotics/instrumentation , Surgical Instruments
18.
Shock ; 16 Suppl 1: 55-9, 2001.
Article in English | MEDLINE | ID: mdl-11770035

ABSTRACT

Cardiopulmonary bypass (CPB) and operative trauma are associated with increased expression of proinflammatory mediators. We determined the relative contribution of CPB on activation of cytokines and adhesion molecules in patients undergoing coronary revascularization by comparing them with patients receiving off-pump coronary artery bypass grafting (OPCAB). Twenty-six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13), or were treated conventionally using extracorporeal circulation, blood cardioplegia, and hypothermic arrest (29 degrees C-31 degrees C; n = 13). Systemic levels of TNF-alpha and the soluble adhesion molecules P-selectin and intracellular adhesion molecule 1 (ICAM-1) were assayed. Immunohistochemistry was used to account for cardiac-specific expression of adhesion molecules in interventricular endomyocardial sections. Both systemic and endomyocardial expression of adhesion molecules were lower in the OPCAB group. Coronary revascularization with CPB resulted in a significant higher expression of TNF-alpha, which was associated with P-selectin and ICAM-1 expression. This was accompanied with higher catecholamine requirement in the CPB group in the early postoperative period. Despite comparable surgical trauma, the OPCAB procedure without the use of CPB and cardioplegic arrest significantly reduces systemic and cardiac adhesion molecule expression and catecholamine requirement. Since the clinical course in the early postoperative period was comparable, larger trials are required to select the appropriate patient who benefits most from one or the other treatment regime.


Subject(s)
Cell Adhesion Molecules/metabolism , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/methods , Adult , Aged , Female , Humans , Immunohistochemistry , Inflammation Mediators/metabolism , Intercellular Adhesion Molecule-1/metabolism , Male , Middle Aged , Myocardial Revascularization/adverse effects , Myocardial Revascularization/methods , Myocardium/immunology , P-Selectin/metabolism , Postoperative Complications/etiology , Postoperative Complications/immunology , Postoperative Complications/prevention & control , Solubility , Treatment Outcome , Tumor Necrosis Factor-alpha/metabolism
19.
J Cardiovasc Pharmacol ; 36(6): 776-84, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11117379

ABSTRACT

Immunosuppression may have an important impact on early graft coronary endothelial injury. We investigated functional and morphologic coronary alterations, myocardial expression, and cardiac release of possible mediators of allograft vasculopathy within 6 months after cardiac transplantation with respect to different immunosuppressive regimens. Epicardial and microvascular endothelium-dependent and endothelium-independent vasomotor function and epicardial intimal thickening were measured in 8 transplant recipients treated with cyclosporin A (CyA), azathioprine, and prednisone (group 1), 9 transplant recipients treated with tacrolimus (TKL), azathioprine, and prednisone (group 2), and 14 patients treated with TKL, mycophenolate mofetil (MMF), and prednisone (group 3). The gene expressions of inducible and endothelial nitric oxide synthase (iNOS and eNOS), endothelin-1, prostacyclinsynthase, and thromboxansynthase were analyzed in endomyocardial biopsy specimens using semiquantitative reverse transcription polymerase chain reaction. Transcardiac cytokine release, endothelin-1, and nitrate-release were determined from plasma samples. Epicardial endothelial dysfunction (vasoconstriction to acetylcholine > 10%) and microvascular smooth muscle cell dysfunction (flow velocity increase to adenosine and nifedipine < 2.0) were enhanced in heart transplant recipients immunosuppressed with TKL, azathioprine, and prednisone. The prevalence of epicardial dysfunction was 78% in group 2 versus 44% and 46% in group 1 and 3 (p < 0.05), respectively. The prevalence of microvascular dysfunction was 56% in group 2 versus 13% and 7% in group 1 and 3 (p < 0.02), respectively. Coronary vasomotor dysfunction was associated with increased myocardial iNOS expression (p < 0.05), decreased eNOS expression (p < 0.05), and enhanced cardiac immunoreactive interleukin-6 (p < 0.01). Coronary intimal thickening was not different between the groups. The combination of TKL and MMF appears to be superior to TKL and azathioprine (and comparable to CyA and azathioprine) concerning preservation of early coronary vasomotor function, eNOS expression, iNOS suppression as well as cardiac interleukin-6 release. This may have an important impact on subsequent development of transplant coronary atherosclerosis.


Subject(s)
Coronary Disease/physiopathology , Heart Transplantation/physiology , Immunosuppressive Agents/adverse effects , Adult , Cardiac Catheterization , Cytokines/metabolism , Cytokines/pharmacology , DNA Primers , DNA, Complementary/biosynthesis , DNA, Complementary/genetics , Endothelin-1/metabolism , Endothelium, Vascular/physiology , Female , Gene Expression Regulation/drug effects , Humans , Male , Muscle, Smooth, Vascular/physiopathology , Nitrates/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Radioimmunoassay , Reverse Transcriptase Polymerase Chain Reaction , Ultrasonography, Doppler
20.
Transpl Int ; 13 Suppl 1: S203-11, 2000.
Article in English | MEDLINE | ID: mdl-11111997

ABSTRACT

Optimal preservation of the myocardium remains a major concern in clinical and experimental heart transplantation. The present study compared the efficacy of University of Wisconsin (UW) and Celsior preservation solution with respect to myocardial performance, epicardial and microvascular endothelial vasomotor function and myocardial expression of endothelin and nitric oxide synthases in humans. Forty-one cardiac transplant recipients received either UW (n = 20) or Celsior (n = 21) preserved hearts. Catecholamine and vasodilator requirements were assessed within the first 5 postoperative days. Left ventricular performance and endothelial function was assessed 1 month after transplantation. Endothelin and nitric oxide synthase gene expression were detected in myocardial biopsy samples. Celsior preserved hearts required significantly more catecholamines and vasodilators within the first 5 postoperative days. Myocardial performance and endothelial function were comparable 1 month after transplantation. Total ischemic time correlated with impaired endothelial function in the Celsior but not in the UW group. Endothelin and inducible nitric oxide synthase gene expression were significantly higher in the Celsior group. The results of the study show that both solutions provide myocardial protection with regard to left ventricular performance and endothelial function 1 month after cardiac transplantation. The necessity for higher vasodilator and catecholamine therapy in Celsior preserved hearts suggests post-ischemic myocardial stunning within the first 5 postoperative days. The positive correlation between impaired endothelial function and total ischemic time in the Celsior group requires longitudinal investigation in particular with regard to the development of allograft vasculopathy.


Subject(s)
Heart Transplantation/physiology , Heart , Hemodynamics , Organ Preservation Solutions , Adenosine , Adult , Allopurinol , Blood Pressure , Catecholamines/therapeutic use , Disaccharides , Electrolytes , Endothelins/blood , Endothelins/genetics , Endothelium, Vascular/physiology , Female , Glutamates , Glutathione , Histidine , Humans , Insulin , Male , Mannitol , Middle Aged , Myocardial Contraction , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Organ Preservation/methods , Polymerase Chain Reaction , Prospective Studies , Raffinose , Regression Analysis , Tissue Donors/statistics & numerical data , Vasodilator Agents/therapeutic use
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