Increased myocardial cAMP in patients with transplant coronary vasculopathy.
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Adult↗
Biomedical subjects
A Haverich
Publications and source records attributed to A Haverich.
Thoracic organ transplantation in the paediatric age group. The Hannover experience.
Growing experience in terms of immunosuppression, recipient and donor selection as well as organ preservation has established thoracic organ transplantation as a therapeutic option for many children with end-stage cardiopulmonary diseases. While dilated cardiomyopathy and isolated myocardial failure represent the main indications for cardiac transplantation, replacement of the lungs or heart and lungs is necessitated in cystic fibrosis, primary and secondary pulmonary hypertension as well as some types of complex congenital heart defects involving the pulmonary arteries. We have performed a total of 20 heart, 4 heart-lung, 2 single lung and 1 double lung transplantation in the paediatric group up to 17 years of age. While with respect to the limited experience worldwide, early mortality after lung and heart-lung transplantation is still high (50%), long-term results in isolated cardiac transplantation using triple drug immunosuppression are excellent (79% survival after 6 years) without major impairment of renal function, arterial blood pressure, growth development and physical rehabilitation as well as social reintegration. Freedom from graft atherosclerosis of the allografted heart is documented over a 5 year follow up, while no data are available on the incidence of obliterative bronchiolitis after lung transplantation in the paediatric group. Despite only limited evidence of long-term dysfunction, diagnosis and prevention of chronic rejection should be given utmost attention to allow for a normal life span in this younger age group.
Adolescent↗
Nifedipine and diltiazem reduce pulmonary edema formation during postischemic reperfusion of the rabbit lung.
A protective effect of calcium antagonists in pulmonary preservation for transplantation has been observed recently. This report focuses on the potential use of diltiazem and nifedipine in the early phase of reperfusion after normothermic pulmonary ischemia. Rabbits weighing 4-5 kg were tracheotomized and ventilated with 50% oxygen. In a control group (group I, n = 7), the hilus of the right lung was clamped for 210 min without ischemia of the left lung. Lung ischemia was created in a second group (n = 7) by clamping the left hilum for 2 h. Subsequently, reperfusion of the left lung was maintained for 210 min, while the right hilus was kept occluded. In group III (n = 6) and group IV (n = 8) the conditions were the same as in group II, but either diltiazem (62.5 micrograms/kg i.v., group III) or nifedipine (3 micrograms/kg i.v., group IV) was administered during the first 20 min of reperfusion. After 210 min of reperfusion, the pulmonary vascular resistance was elevated in group II (mean: 5120 dyn.sec.cm-5), group III (5518 dyn.sec.cm-5), and group IV (4324 dyn.sec.cm-5) compared with group I (3390; n.s.). Arterial oxygenation showed no significant differences among group I (mean: 257 mmHg), group II (261 mmHg), group III (208 mmHg), and group IV (247 mmHg). Pulmonary ischemia resulted in an increased extravascular lung water content in group II as compared to group I (73 and 64 g/g wet weight; P less than 0.0125 vs group I). No such increase was seen in groups III and IV (53 and 54 g/g wet weight respectively; P less than 0.001 vs group II).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Changes in cardiac beta 1- and beta 2-adrenoceptor densities after human cardiac transplantation: relation to transplant coronary vasculopathy and pretransplantation disease.
In 100 patients 12 to 60 months after cardiac transplantation, the influence of transplant coronary vasculopathy and of the pretransplantation disease (end-stage heart failure caused by coronary artery disease or dilated cardiomyopathy) on the beta-adrenergic receptor (AR) numbers and beta 1/beta 2-AR ratio of right ventricular biopsies was determined. Patients with coronary vasculopathy (CVP) after cardiac transplantation had lower absolute numbers of beta 1-AR compared with patients without CVP. Since patients with CVP had increased left ventricular (LV) end-diastolic pressure and LV muscle mass, it is suggested that decreased beta 1-AR may be the result of an altered hemodynamic situation of the transplanted heart after development of CVP. Patients with dilated cardiomyopathy (DCM) before cardiac transplantation showed a decrease in total beta-AR and of the beta 1/beta 2-AR ratio as a result of an increase in beta 2-AR and a decrease in beta 1-AR numbers. The decreased beta 1/beta 2-AR ratio in patients with previous DCM may indicate that the beta-AR system of the transplanted heart might be influenced (at least in part) by pathophysiologic factors that are characteristic of the pretransplantation disease ultimately leading to cardiac transplantation and persisting after cardiac transplantation.
Adult↗
University of Wisconsin versus modified Euro-Collins solution for lung preservation.
In a canine model, the quality of lung preservation was assessed using pulmonary artery flush after prostacyclin administration with either modified Euro-Collins solution or University of Wisconsin solution. Twelve combined heterotopic heart and orthotopic left lung allotransplantations were performed after 6 hours of cold ischemia. Myocardial preservation was achieved using St. Thomas Hospital solution. Donor organs were anastomosed parallel to the recipient's heart and right lung, and the superior vena cava inflow was directed into the transplanted heart-left lung block after ligation of the recipient's superior vena cava proximal to the caval anastomosis. Postoperatively, cardiorespiratory function was evaluated separately for donor and recipient organs at an inspired oxygen fraction of 0.4 for a maximum of 12 hours. Significantly improved oxygenation and lower pulmonary vascular resistance index of the donor lung was observed in the University of Wisconsin + prostacyclin group, whereas pulmonary artery pressures showed no significant differences in between both groups. It is concluded that superior results in lung preservation can be achieved with pulmonary artery flush perfusion using University of Wisconsin solution and prostacyclin when compared with Euro-Collins solution and prostacyclin.
Adenosine↗
Predictive criteria for the need of extracorporeal circulation in single-lung transplantation.
Use of extracorporeal circulation is mandatory in heart-lung and en bloc double-lung transplantation. However, no criteria exist to predict the necessity of its application during single-lung transplantation for parenchymal lung diseases. We therefore reviewed our experience in 23 patients undergoing single-lung transplantation for idiopathic pulmonary fibrosis. All patients were evaluated by preoperative right heart catheterization. For intraoperative monitoring, a pulmonary artery thermodilution catheter was placed in the contralateral lung to repeatedly assess pulmonary artery pressure, cardiac output, and pulmonary vascular resistance. Extracorporeal circulation was necessary during graft implantation in 4 patients, whereas 19 patients underwent operation without it. Preoperative demographic patient data, time of ischemia, and hemodynamic values obtained preoperatively and before the clamping of the pulmonary artery showed no significant differences between groups. In contrast, after the clamping of the pulmonary artery, a significant drop in cardiac index of about 1.5 L.min-1.m-2 (p less than 0.01) and a concomitant rise in pulmonary vascular resistance (p less than 0.01) was observed in the group requiring extracorporeal circulation, whereas these variables showed no significant changes in the other 19 patients. Pulmonary artery pressure rose significantly in both groups (p less than 0.05), without significant differences between them. It is concluded that intraoperative assessment of cardiac index and pulmonary vascular resistance is essential for estimation of cardiac performance during single-lung transplantation. A decrease in cardiac index of more than 1.5 L.min-1.m-2 after the clamping of the pulmonary artery rather than the degree of pulmonary hypertension is indicative of the need of extracorporeal circulation.
Adult↗
Systemic recombinant tissue plasminogen activator lysis for left atrial thrombus formation after single-lung retransplantation.
This report describes a recipient of single-lung transplantation surviving extraordinary complications: (1) early graft failure mandating retransplantation; (2) left atrial thrombus formation, which resolved by recombinant tissue plasminogen activator lysis; (3) and development of a "locked-in-syndrome." Possible underlying mechanisms are discussed.
Extracorporeal Membrane Oxygenation↗
Decrease in beta 1- and increase in beta 2-adrenoceptors in long-term follow-up after orthotopic cardiac transplantation.
Total beta 1- and beta 2- subtype distribution were examined in right ventricular biopsies taken from 100 patients 1-60 months after orthotopic cardiac transplantation and from eight prospective transplant donor hearts serving as controls. The patients were classified into eight groups depending on the time after transplantation that the biopsies were taken: 1-3 (n = 15), 4-7 (n = 15), 8-11 (n = 6), 12 (n = 15), 24 (n = 15), 36 (n = 12), 48 (n = 12) and 60 months (n = 10). The non-selective beta-adrenoceptor antagonist (-)-[125I]-iodocyanopindolol (ICYP) was used as a radioligand to assess total beta-adrenoceptor density. The beta 1- and beta 2-subtype distribution was determined with a beta 1-adrenoceptor saturating concentration of the selective beta 1-adrenoceptor antagonist CGP 20712A (300 nmol/l). In transplant donor hearts the total beta-adrenoceptor density was found to be 70.8 +/- 7.1 fmol/mg protein including a beta 1:beta 2-adrenoceptor ratio of about 80:20%. Until 36 months after cardiac transplantation the total number of beta-adrenoceptors showed no significant change. A slight but insignificant decrease was observed after 48 (16.2%) and 60 (21.2%) months. In contrast, from 12 to 60 months after cardiac transplantation the beta 1:beta 2-adrenoceptor ratio was shifted significantly (66:33% to 61:39%) as compared with transplant donor hearts which was due to an increase in beta 2- and a decrease in beta 1-adrenoceptor number. Thus, the surgically denervated, transplanted human heart exhibits a beta 2-adrenoceptor up-regulation during long-term follow-up. It is suggested that this up-regulation of the beta 2-adrenoceptor subtype could be owing to an increased importance of circulating catecholamines in modulating positive chronotropic and inotropic effects.
Adult↗
Prolonged myocardial protection with St. Thomas' Hospital solution and University of Wisconsin solution. The importance of preservation techniques.
The effectiveness of University of Wisconsin solution (UWS) and oxygenated St. Thomas' Hospital solution (STS) for prolonged myocardial protection was evaluated in isolated working rat hearts preserved for 12 h at 4 degrees C using three different preservation techniques: induction of cardiac arrest and subsequent hypothermic storage with STS (group 1, n = 9) or UWS (group 4, n = 9), intermittent coronary flush (every 90 min) with STS (group 2, n = 9) or UWS (group 5, n = 9), or continuous coronary perfusion with STS (group 2, n = 7) or UWS (group 6, n = 7) before 60 min of reperfusion. In the UWS preserved hearts, recovery of aortic flow was greater when the simple storage technique was employed compared to intermittent or continuous coronary perfusion (groups 5 and 6). In the STS preserved hearts, aortic flow recovery was superior when the intermittent perfusion technique was applied. The same pattern was observed with regard to recovery of left ventricular pressure. Lactate dehydrogenase release during reperfusion was significantly less pronounced in group 4 (UWS, single flush, simple storage) as compared to group 1 (STS, single flush and simple storage), whereas best preservation of myocardial high energy phosphates was observed when hearts were preserved with multiple dose cardioplegia using STS. Simple hypothermic storage with UWS affords the best functional recovery after prolonged myocardial ischemia in all groups. Repetitive or continuous application of this solution is detrimental, possibly due to potassium overloading. In STS treated groups, multiple dose application of oxygenated STS enhances functional and metabolic recovery compared to its single dose application.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine↗
Decreased incidence of bronchial complications following lung transplantation.
Despite omental wrap and avoidance of prophylactic administration of corticosteroids in the early postoperative phase, ischemic bronchial complications still represent an important source of early morbidity and mortality following lung transplantation. In a retrospective analysis, the effect of pharmacological enhancement of pulmonary collateral flow on bronchial healing was investigated. Thirty-nine consecutive unilateral or bilateral transplant procedures (Tx) were analyzed. Immunosuppression consisted of rabbit antithymocyte globulin (RATG), cyclosporine A, and azathioprine. In group 1 (10 Tx, 12 anastomoses) routine immunosuppression was employed and the anastomoses wrapped with an omental or pericardial pedicle. In group 2 (29 Tx, 41 anastomoses) PGI2 (4 ng/kg per min x 48 h), heparin (200 U/kg per day), and prednisolone (0.5 mg/kg per day) were added to the therapeutic regimen. The 2 groups were comparable with respect to age and sex of the patients, primary diagnosis, type of transplant, intraoperative use of extracorporeal circulation, graft ischemia, duration of mechanical ventilation, and mortality. Bronchoscopic evidence of a significant bronchial ischemia (extending more than 1 cartilaginous ring beyond the anastomosis) was seen in 8 of 12 anastomoses in group 1 vs 14 of 53 anastomoses in group 2 (P = NS). In group 1, significant bronchial stenosis required implantation of an endobronchial silicone stent in 6 of 12 anastomoses, whereas in group 2, no significant bronchial stenosis occurred (P less than 0.01). No negative effects possibly related to the prophylactic administration of corticosteroids could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Artificial intravascular oxygenation (IVOX). Application to the treatment of postoperative respiratory failure].
Very recently, the concept of artificial intracorporeal oxygenation of blood for patients suffering from respiratory failure has been introduced into clinical practice through development of a totally implantable intravascular oxygenator (IVOX). We report on the use of such a device in a patient who developed severe respiratory insufficiency secondary to prolonged hypovolaemic shock and pneumonia following successful repair of a ruptured abdominal aortic aneurysm in September, 1990. Postoperatively, severe hypoxaemia occurred (AaDO2 548-602 torr) despite extensive mechanical ventilatory support. There was no obvious chance to overcome this situation by conventional therapeutic measures and the decision was made to institute IVOX therapy. Hypoxaemia was resolved immediately and both FiO2 and tidal volume could be reduced within hours. The patient's respiratory condition continued to improve over the next days leading to termination of IVOX therapy after 71 hours. However, the necessity of long-term ventilatory support secondary to recurrent pneumonia and sepsis, multiple abdominal reoperations for ischemic colitis and retroperitoneal abscess prolonged his recovery. He was discharged from the hospital after four months and is alive and well now 14 months after his operation. He is the first long-term survivor after IVOX therapy in Europe. IVOX may be successfully used in selected patients while the indications and it's potential role in the therapy of severe respiratory failure still need to be defined.
Humans↗
Prevention of graft infection by bonding of gentamycin to Dacron prostheses.
To increase the efficacy of perioperative antibiotic prophylaxis in vascular surgery an experimental study including topical application of the gentamicin derivative EMD 46/217 and fibrin sealant as antibiotic carrier to Dacron prostheses was initiated. In vitro treatment of Dacron with gentamicin and fibrin was followed by constant antibiotic release for 3 weeks. In a subsequent animal study Dacron grafts were implanted in the aorta of 10 pigs after direct contamination with Staphylococcus aureus solution. One graft was pretreated with the antibiotic/fibrin compound, a second with the antibiotic alone. Grafts 3 (no pretreatment) and 4 (fibrin alone) served as controls. After 1 week the grafts and their corresponding implantation sites were excised for measurement of antibiotic content and for culture. The antibiotic content of grafts with the antibiotic/fibrin compound was 25.0 +/- 7.2 micrograms/gm wet weight, whereas Dacron pretreated with the antibiotic alone contained no measurable drug amounts except for one specimen (0.5 microgram/gm) (antibiotic/fibrin vs antibiotic, p less than .0005). The corresponding implantation sites to antibiotic/fibrin grafts contained 1.07 +/- 0.54 microgram/gm antibiotic, whereas in only 2/10 implantation sites of antibiotic grafts low antibiotic levels were found (0.05 and 0.2 microgram/gm) (antibiotic/fibrin vs antibiotic, p less than 0.005). All control grafts and 9/10 antibiotic grafts were infected. By contrast, only five were contaminated, and 5 of 10 remained sterile after culture (antibiotic/fibrin vs antibiotic, p less than 0.05). This finding correlates with the antibiotic content in the Dacron. It is concluded that pretreatment of prosthetic Dacron grafts with the antibiotic/fibrin compound results in binding of sufficient amounts of antibiotic for at least 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Enoximone, a post-operative inodilator in patients following mitral valve operation: a prospective and controlled study.
Inotropic support is often required for post-operative management of patients following mitral valve operation. The use of positive inotropes is limited by tolerance development and increase in myocardial oxygen demand. We have compared i.v. enoximone (E) (group E, n = 13), a recently developed phosphodiesterase (PDE) inhibitor, to the conventional i.v. therapeutics dopamine (D) and glyceroltrinitrate (G) in patients following mitral valve operation. The two groups were comparable in terms of physical and pre-operative haemodynamic data. Haemodynamic measurements including cardiac index (CI) determinations were recorded for the first 18 h post surgery in both groups. Group E received a bolus of 1 mg.kg-1 E followed by 4-20 micrograms.kg-1.min-1 (mean = 5 +/- 2 micrograms.kg-1.min-1) for 14 h according to therapeutic requirements, while group D received dopamine (4-10 micrograms.kg-1.min-1, mean = 3.8 +/- 1.9 micrograms.kg-1.min-1) and glyceroltrinitrate (0.5-5 micrograms.kg-1.min-1; mean = 4 +/- 2 micrograms.kg-1.min-1). Adrenaline was added if the MAP was below 60 mmHg or the CI was below 2.5 in both groups (range 50-500 ng.kg-1.min-1; mean E = 0.7 +/- 2 ng.kg-1.min-1; mean D = 2 +/- 2.8 ng.kg-1.min-1). Bolus injection of E resulted in a rise in CI from 2.6 to 3.21.min-1.m-2 (P less than 0.05) within 30 min, followed by a further rise to a maximum of 3.51.min-1.m-2 6 h post bolus. Termination of the E drip resulted in a drop of CI to baseline values (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Beta-adrenergic receptor number in surgically denervated, transplanted human hearts.
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Adult↗
Comparison of enoximone and piroximone in patients after mitral valve operation: a prospective and controlled clinical study.
Phosphodiesterase III (PDEII) inhibitors as so-called inodilators have previously proven a valuable alternative to positive inotropes in patients with cardiac insufficiency. In this study we compared patients receiving piroximone (P, n = 14, 0.5-mg/kg bolus in 30 min and then 3-6 micrograms/kg/min) with enoximone patients (E, n = 13, 1-mg/kg bolus and then 4-20 micrograms/kg/min) and with a third group (D, n = 14) receiving a combination of dopamine (4-10 micrograms/kg/min) and glyceroltrinitrate (0.5-5 micrograms/kg/min) for hemodynamic support. All three groups were comparable in terms of age, body surface area, and preoperative cardiac function [cardiac index (CI) less than or equal to 2.5 L/min/m2, LAP greater than 15 mm Hg]. Hemodynamic measurements (10) and Holter monitoring were performed until 18 h post MVR. In all groups, epinephrine was used for additional inotropic therapy if mean arterial pressure (MAP) was less than 60 mm Hg and/or CI was less than 2.5 L/min/m2. There was no early or late postoperative mortality in either group. Continuous support with epinephrine was necessary in 8 patients in group D, whereas initially 8 patients in group E and 6 patients in group P required epinephrine support. After PDE III inhibitor infusion, 2 patients in group E and 2 patients in group P remained epinephrine dependent (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
The automatic implantable cardioverter defibrillator (AICD) as a bridge to heart transplantation.
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Adult↗
Increased messenger RNA level of the inhibitory G protein alpha subunit Gi alpha-2 in human end-stage heart failure.
In human heart failure the positive inotropic and cAMP-elevating effects of both beta-adrenoceptor agonists and phosphodiesterase inhibitors are diminished. This has been explained at least in part by an increase in the inhibitory signal-transducing G protein (Gi) and unchanged stimulatory G protein (Gs). In the present study we determined the mRNA expression pattern of the alpha subunits of Gi-1, Gi-2, Gi-3, and Gs in myocardial tissue samples of patients undergoing heart transplantation. Northern blot analysis of total RNA extracted from left ventricles with 32P-labeled cDNAs demonstrated expression of Gi alpha-2, Gi alpha-3, and Gs alpha mRNA. In contrast, Gi alpha-1 mRNA was not detectable. To investigate whether the increased ratio of Gi/Gs might be due to altered gene expression, we compared mRNA levels of Gi alpha-2, Gi alpha-3, and Gs alpha in left ventricular myocardium from failing hearts with idiopathic dilated cardiomyopathy (n = 8) and ischemic cardiomyopathy (n = 6) and from nonfailing hearts from transplant donors (n = 8). Compared with nonfailing control hearts, the Gi alpha-2 mRNA was increased by 75 +/- 26% (p less than 0.05) in idiopathic dilated cardiomyopathy hearts and 90 +/- 26% (p less than 0.05) in ischemic cardiomyopathy hearts. Gi alpha-3 and Gs alpha mRNA levels were similar in the three groups. The results suggest that as in other mammalian species, Gi alpha-2 and Gi alpha-3 mRNA are the predominant Gi alpha mRNA subtypes in human ventricular myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Clinical evaluation of transtracheal Doppler for continuous cardiac output estimation.
A newly developed transtracheal Doppler (TTD) computer for cardiac output determination was studied in nine patients after open heart surgery (coronary artery bypass grafting, n = 4; mitral valve replacement, n = 5). The measurements were compared with those simultaneously obtained by thermodilation. Doppler signals were adequate in 78% of the patients studied. Limited correlation between both methods (r = 0.248; r2 = 0.0615; mean of difference, 1.714 +/- 1.67 L/min; limits of agreement, -1.6 to 5.0 L/min) was found. The large difference in cardiac output readings between TTD and thermodilation may be due to (a) false angles of the ultrasound beam in relation to the aortic wall and blood flow or (b) misplacement of the ultrasound head and underestimation of the aortic lumen. Patients must be completely sedated and paralyzed to prohibit artifacts. Routine patient care can interfere with continuous measurements. Cardiac output determinations by TTD are limited to the period during which the trachea is intubated with the special TTD tube. We conclude that the TTD system does not offer accurate cardiac output determinations and that the routine use of this device is not practical.
Aged↗