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1.
J Thorac Cardiovasc Surg ; 119(3): 596-600, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10694622

ABSTRACT

OBJECTIVE: The Thoratec ventricular assist device (Thoratec Laboratories, Pleasanton, Calif) is widely accepted for univentricular and biventricular support in patients with various indications. The aim of this study is to describe our experience with implantation of the Thoratec ventricular assist device in more than 100 patients. METHODS: From March 1992 to June 1998, 114 patients (98 men and 16 women; mean age, 47.9 years) received the Thoratec ventricular assist device for a mean duration of 44.9 days. The patients were divided into 3 groups. Group 1 included 84 patients in whom the system was applied as a bridge-to-transplant procedure. Group 2 included 17 patients with postcardiotomy cardiogenic shock, and group 3 included 13 patients with cardiogenic shock of other causes. RESULTS: Sixty-eight percent of patients in group 1 survived to transplantation with a posttransplant survival of 88%. The only independent risk factor affecting survival was age more than 60 years. Survivals in groups 2 and 3 were 47% and 31%, respectively. Main complications in all groups were bleeding, multiple organ failure, liver failure, sepsis, and neurologic disorders. CONCLUSIONS: The Thoratec ventricular assist device has proved to be a reliable device for bridge to transplantation and postcardiotomy support. Further studies are required on patient selection and on patient and device management to reduce the incidence of complications in these patient populations.


Subject(s)
Heart-Assist Devices , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Prosthesis Design , Survival Rate
2.
Transplantation ; 66(9): 1163-7, 1998 Nov 15.
Article in English | MEDLINE | ID: mdl-9825812

ABSTRACT

BACKGROUND: The current shortage of donor organs, combined with an increasing demand for cardiac allografts, means that extended donor criteria are becoming more and more accepted. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion; few data are currently available in the medical literature. We describe our experience with 19 orthotopic heart transplant recipients of organs from donors after acute intoxication with different agents. METHODS: Between March 1989 and December 1997, 883 orthotopic heart transplantations were performed at our transplant unit. Within this group, we accepted donor hearts after ethanol intoxication (n=1), benzodiazepine (n=1), alkylphosphate (E 605) in combination with beta-blocker intoxication (n=1), carbon monoxide poisoning (n=5), digitalis (n=1), digitalis/glibenclamide (n=1), chlormethiazole (n=1), propoxyphene (n=1), alkylphosphate (E 605) (n=1), insulin (n=2), neprobamate/ thiocyacide/flurazepam (n=1), paracetamol (n=1), carbamazepine (n=1), and cyanide (n=1) intoxication. At the time of organ explantation, hemodynamic data were available from all patients. RESULTS: Early mortality in this group was 11%; cumulative survival after 5 years was 74%. CONCLUSIONS: Based on our limited experience, cardiac allografts from donors exposed to different kinds of poisons can be transplanted in selected cases. If the donor organ is not hemodynamically compromised, showing regular filling pressures on low or mild inotropic support just before explantation, and if there are no electrocardiographic changes in combination with elevation of the transaminases, cardiac allograft transplantation seems to be a safe and life-saving procedure.


Subject(s)
Heart Transplantation/physiology , Heart Transplantation/statistics & numerical data , Hemodynamics , Poisoning/blood , Tissue Donors , Follow-Up Studies , Humans , Survival Rate , Tissue and Organ Procurement , Transplantation, Homologous
3.
Cardiovasc Res ; 37(1): 46-57, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9539857

ABSTRACT

BACKGROUND: For reasons of simplicity, studies on isolated human myocardium have been conducted using exclusively isometric contractions, although positive inotropic interventions may differently influence force development, extent of shortening and myocardial work performance. We investigated human left ventricular failing and non-failing preparations comparing isometric versus isotonic, i.e., shortening contractions. RESULTS: (1) When muscle length is increased from 90% to 100% lMAX, peak developed force increases by 36% and 43% (p < 0.05) in non-failing and failing human left ventricular myocardium, respectively. Maximum performed work increases similarly in non-failing but decreases in failing myocardium. It can be shown that this discrepancy is due to significantly higher resting tension and does not present an insufficient intrinsic shortening capacity in failing myocardium. (2) When stimulation rate is increased from 0.5 to 2.0 Hz, isometric force increases significantly by 59% in non-failing and decreases by 27% in failing myocardium, whereas maximum performed work increases by 98% and decreases by 46%, respectively. (3) Pharmacological positive inotropic interventions by 7.2 mM calcium (n = 9), 3 x 10(-8) M isoproterenol (n = 7), 3 x 10(-8) M ouabain (n = 5), and 10(-5) M EMD 57033 (n = 3) equally increased force development and extent of shortening: When the fractional effect on shortening (y) was correlated to the fractional effect on force (x), the following linear regression equation was obtained: y = 0.91x + 0.26 (r = 0.86; p < 0.001). CONCLUSIONS: The data presented are of clinical and pharmacological importance: (1) The Frank-Starling mechanism is demonstrated to be existent in the failing human myocardium regarding both isometric force developed and maximum work performed. (2) Both force-frequency relations and--to a greater extent--work-frequency relations are reversed in failing human myocardium. (3) Independent of the pharmacological mode of action, positive inotropic compounds increase developed isometric force to the same extent as isotonic shortening and therefore potentiate maximum performed work.


Subject(s)
Cardiomyopathy, Dilated/physiopathology , Myocardial Contraction/drug effects , Ventricular Function, Left/physiology , Adolescent , Adult , Aged , Calcium/pharmacology , Cardiomyopathy, Dilated/pathology , Cardiotonic Agents/pharmacology , Heart Rate/drug effects , Humans , Isoproterenol/pharmacology , Middle Aged , Ouabain/pharmacology , Quinolines/pharmacology , Regression Analysis , Stimulation, Chemical , Thiadiazines/pharmacology
4.
Cardiovasc Res ; 40(3): 580-90, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10070500

ABSTRACT

CONDENSED ABSTRACT: We analyzed actomyosin cross-bridge kinetics in human atrial and ventricular muscle strip preparations by using sinusoidal length changes from 0.1 to 60 Hz. The minimum stiffness frequency was higher in atrial than in ventricular human myocardium and lower in failing than in non-failing left ventricular human myocardium. beta-Adrenergic stimulation increased the minimum stiffness frequency by 18 +/- 3% (p < 0.05). Cross-bridge kinetics are temperature-dependent, with a Q10 of at least 2.7. BACKGROUND: Dynamic stiffness measurements have revealed acute and chronic alterations of actomyosin cross-bridge kinetics in cardiac muscles of a variety of different animal species. We studied dynamic stiffness in right atrial and left ventricular preparations of non-failing and failing human hearts and tested the influence of the temperature and beta-adrenergic stimulation on cross-bridge kinetics. METHODS AND RESULTS: Muscle strips were prepared from right atria and left ventricles from human non-failing and failing hearts. After withdrawal of calcium, steady contracture tension was induced by the addition of 1.5 mM barium chloride. Sinusoidal length oscillations of 1% muscle length were applied, with a frequency spectrum of between 0.1 and 60 Hz. Dynamic stiffness was calculated from the length change and the corresponding force response amplitude. The specific minimum stiffness frequency, which indicates the interaction between cross-bridge recruitment and cross-bridge cycling dynamics, was analyzed for each condition: (1) The minimum stiffness frequency was 0.78 +/- 0.04 Hz in left ventricular myocardium and 2.80 +/- 0.31 Hz in right atrial myocardium (p < 0.01) at 27 degrees C. (2) The minimum stiffness frequency was 41% higher in non-failing compared to failing left ventricular human myocardium. (3) Over a wide range of experimental temperatures, the minimum stiffness frequency changed, with a Q10 of at least 2.7. (4) beta-Adrenergic stimulation significantly (p < 0.05) increased the minimum stiffness to 18 +/- 3% higher frequencies and significantly (p < 0.05) lowered contracture tension by 7 +/- 1%. CONCLUSIONS: The contractility of human heart muscle is not only regulated by excitation-contraction coupling but also by modulation of intrinsic properties of the actomyosin system. Acute and chronic alterations of cross-bridge kinetics have been demonstrated, which play a significant role in the physiology and pathophysiology of the human heart.


Subject(s)
Actomyosin/physiology , Cardiomyopathy, Dilated/physiopathology , Heart/physiopathology , Adrenergic beta-Agonists/pharmacology , Barium Compounds/pharmacology , Body Temperature , Chlorides/pharmacology , Elasticity/drug effects , Heart/drug effects , Heart Atria , Heart Ventricles , Humans , In Vitro Techniques , Isoproterenol/pharmacology , Stimulation, Chemical
5.
Z Kardiol ; 87(11): 900-5, 1998 Nov.
Article in German | MEDLINE | ID: mdl-9885184

ABSTRACT

Papillary fibroelastomas are rare benign tumors of the heart. We report about two cases in which these tumors do not--as characteristically--arise from a heart valve but originate from the free wall of the left ventricle. In the case of a 74-year-old woman with signs of a cerebral ischemia in the vascular system of the A. cerebri posterior, the tumor was resected transaortically. At a 67-year-old patient with symptoms of instable angina pectoris and increasing dyspnoea echocardiography or coronary angiography showed an aortic stenosis III degrees, a coronary artery disease as well as a tumor within the region of the apex of the left ventricle. Beside a fourfold aortocoronary venous bypass and an aortic valve replacement tumor excision via left ventriculotomy was carried out. In the diagnostics of intracardiac tumors transthoracic and transesophageal echocardiography provide the methods of choice to visualize quickly and noninvasively the extent, mobility, and origin of the tumor. Considering the systemic thromboembolic potential with the high risk of cerebrovascular respectively neurological symptoms total surgical tumor excision is clearly indicated.


Subject(s)
Fibroma/diagnosis , Heart Neoplasms/diagnosis , Heart Valve Diseases/diagnosis , Aged , Brain Ischemia/diagnosis , Brain Ischemia/pathology , Diagnosis, Differential , Electrocardiography , Female , Fibroma/pathology , Heart Neoplasms/pathology , Heart Valve Diseases/pathology , Humans , Male
6.
Eur J Cardiothorac Surg ; 11 Suppl: S1-4, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9271173

ABSTRACT

Advanced coronary artery disease (CAD) and ischemic cardiomyopathy with elevated pulmonary artery pressures are criteria of a severe illness. In selected cases surgical revascularization has proved beneficial in terms of survival, reduction of morbidity and lowering the frequency of angina pectoris [6] in numerous studies over the past 25 years. But most of the earlier publications concentrated on patients with angina pectoris (AP) as a dominant symptom. Patients without AP but with predominant signs of congestive heart failure were largely excluded. This has changed recently [1-3,7,8,10,12,16,18] with the advent of the concept of hibernating myocardium. This term is defined as the presence of persistent myocardial and left ventricular dysfunction at rest due to reduced regional coronary blood flow that can be partially or completely restored to normal by myocardial revascularization [5,19]. Salvage of viable myocardium by successful revascularization improves left ventricular dysfunction. Diagnosis of hibernating myocardium is crucial because it does not leave the patient with chronic heart failure a candidate only for cardiac transplantation. Instead, these patients' left ventricular dysfunction is potentially reversible following revascularization by coronary bypass surgery. Furthermore we face a critical shortage of donor organs and extending waiting lists for possible transplant candidates. Following the start of the heart transplantation (HTX) program at our institution more than 690 operations were performed until September 1995. We screened more than 1600 patients for their eligibility as cardiac transplant recipients or for other forms of treatment. In this group of patients it has always been our policy to revascularize rather than transplant whenever possible.


Subject(s)
Heart Transplantation , Myocardial Ischemia/surgery , Myocardial Revascularization , Adult , Aged , Female , Hemodynamics , Humans , Male , Middle Aged , Myocardial Ischemia/mortality , Myocardial Ischemia/physiopathology , Patient Selection , Postoperative Complications , Ventricular Dysfunction, Left/surgery
7.
Eur J Cardiothorac Surg ; 11 Suppl: S51-3, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9271182

ABSTRACT

From March 1993 to August 1995, 33 patients received implantable VAD systems at our center. Nineteen patients received the wearable Novacor LVAS and 14 patients the TCI HeartMate device. Both systems enable the patients to be mobilized very quickly and some of them even do not require critical care after a few days. In our series 17 patients (eight Novacor, nine TCI) could be transferred to the normal floor. The wearable electrically driven Novacor system opens the opportunity of sending patients out of hospital. Since July 1994 we have referred five patients to a rehabilitation center, and six patients were sent home, three of them for more than 70 days. A number of factors are necessary to prepare the patient for being discharged. One of the most important things is to guarantee ambulatory patient care and to find an easy way for effective home monitoring. Our experience has shown that discharging these patients means giving them a maximum in quality of life and decreasing the costs by more than 50% in comparison to a stay in hospital for the whole time. Our results are encouraging to improve this strategy in the future.


Subject(s)
Ambulatory Care , Heart-Assist Devices , Adolescent , Adult , Aged , Aged, 80 and over , Child , Electricity , Female , Forecasting , Health Personnel/education , Heart Transplantation , Humans , Male , Middle Aged , Patient Discharge , Quality of Life
8.
Article in German | MEDLINE | ID: mdl-9498097

ABSTRACT

We report on a 21-year old patient who nearly drowned in cold water under inexplicable circumstances. About 1/2 hour later he was found with cardiac arrest. Immediate cardiopulmonary resuscitation remained unsuccessfully but was continued. After transportation to the nearest hospital a core temperature of 26.1 degrees C was recorded. A team of our hospital arrived 2 1/2 hours after start of cardiopulmonary resuscitation. After introducing a femo-femoral bypass the patient was rapidly rewarmed and oxygenated using a portable extracorporeal circulation and membrane oxygenation. Defibrillation succeeded at a core temperature of 34.4 degrees C. A severe ARDS developed the same day which was successfully treated by membrane oxygenation. 41 days later the patient left the hospital fully recovered.


Subject(s)
Extracorporeal Circulation , Extracorporeal Membrane Oxygenation , Near Drowning/therapy , Resuscitation/methods , Adult , Body Temperature , Electric Countershock , Humans , Hypothermia , Male , Near Drowning/complications , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Resuscitation/instrumentation
9.
Circulation ; 94(4): 683-9, 1996 Aug 15.
Article in English | MEDLINE | ID: mdl-8772688

ABSTRACT

BACKGROUND: The Frank-Starling mechanism is one of the most important physiological principles for regulation of contractile performance. We therefore studied the question of whether this mechanism may be absent or attenuated in end-stage failing human left ventricular myocardium. METHODS AND RESULTS: Different methodological approaches were used to analyze the effects of this mechanism on the organ, tissue, and sarcomere levels: (1) In excised human whole left ventricles (2 donor hearts, 5 failing hearts), diastolic and systolic pressure-volume relationships were obtained. (2) In isolated muscle strip preparations from the left ventricular wall of donor hearts (n = 14) and failing hearts from patients with idiopathic dilated cardiomyopathy (n = 21) and ischemic cardiomyopathy (n = 11), peak developed force was measured at different muscle lengths of the preparation. (3) Skinned fiber preparations were obtained from failing right and left ventricles (n = 12). In all three studies, we clearly observed the existence of the Frank-Starling mechanism: (1) In isolated failing human left ventricles, peak developed isometric pressure is increased when the preload is elevated. (2) Peak developed tension is increased by approximately 50% to 70% (P < .01) in left ventricular preparations of failing and nonfailing ventricles when the muscles are stretched from 90% to 100% optimum length. (3) An increase in sarcomere length leads to a sensitization of contractile proteins of ventricular skinned fiber preparations from failing human hearts. At 1.9-microns sarcomere length, the EC50 value was 5.56 +/- 0.06, and at 2.3 microns it was 5.70 +/- 0.05 (P < .01; n = 7). CONCLUSIONS: The Frank-Starling mechanism is maintained in end-stage failing human hearts, whereas significant alterations of diastolic myocardial distensibility are evident in chronic heart failure.


Subject(s)
Cardiomyopathy, Dilated/physiopathology , Heart Failure/physiopathology , Heart/physiopathology , Myocardial Contraction , Sarcomeres/physiology , Analysis of Variance , Cardiomyopathy, Dilated/surgery , Diastole , Heart/physiology , Heart Transplantation , Heart Ventricles , Humans , In Vitro Techniques , Models, Cardiovascular , Muscle Fibers, Skeletal/physiology , Reference Values , Stroke Volume , Systole
10.
Artif Organs ; 20(8): 959-63, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8853815

ABSTRACT

Advances in medical technology have made it possible to use emergency femoro-femoral bypass (FFB) for transport of hemodynamically unstable patients. In this study, we report on our experience of transport of patients with refractory heart failure by a special mobile mechanical circulatory support team (MMCST) using an intraaortic balloon pump (IABP) or FFB. A total of 22 patients (14 men, 8 women) were supported by the MMCST and transported to our clinic for further diagnostic or therapeutic procedures. The diagnoses in 12 patients was acute myocardial infarction, in 7 patients, dilatative cardiomyopathy (DCM), and in 3 patients, acute fulminant myocarditis. In 15 cases, FFB was implanted (5 in combination with IABP), and in 5 cases, IABP only was implanted. Two patients received maximal dosages of catecholamines. After arrival at our clinic, 11 patients received implants of a more sophisticated support system. From the myocardial infarction group, 3 patients received coronary artery bypass grafting, 1 patient received percutaneous transluminal coronary angioplasty, and 1 patient received heart transplantation as final therapy. In the myocarditis and DCM groups, 7 patients underwent heart transplantation. Finally, 11 patients (50%) survived, and 11 patients died of multiorgan failure or septicemia.


Subject(s)
Heart Failure/physiopathology , Hemodynamics/physiology , Life Support Systems/standards , Transportation of Patients/standards , Adult , Ambulances/standards , Cardiomyopathy, Dilated/mortality , Cardiomyopathy, Dilated/therapy , Cardiopulmonary Bypass , Female , Heart Failure/mortality , Humans , Intensive Care Units , Intra-Aortic Balloon Pumping , Male , Middle Aged , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Myocarditis/mortality , Myocarditis/therapy
11.
Artif Organs ; 20(8): 964-70, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8853816

ABSTRACT

Although the natural history of acute myocarditis leads to complete recovery in the majority of patients, rapid and irreversible cardiac decompensation resulting in death is known to occur. One possible therapy to improve the poor prognosis of this patient group may be the implantation of circulatory support systems that allow myocardial recovery or bridging to heart transplantation. Therapeutic protocols have been suggested, but clinical experiences in this area are few. In this paper we report on our clinical experiences in cardiogenic shock after acute fulminant myocarditis using different types of circulatory support systems. Three different systems were used: a biomedicus centrifugal pump as a ventricular assist device (VAD) or femoro-femoral bypass (FFB) including oxygenator; Abiomed BVS 5000, and Thoratec ventricular assist device. Hemodynamic criteria for implantation of support systems were cardiac index < 2.0 L/min/m2. SVR = 1000 dyne-s-cm-5, central venous pressure (CVP) or left atrial pressure (LAP) > 20 mm Hg, and urine output < 20 ml/h despite maximal pharmacological therapy. Age total of 5 patients (mean age 29 years, range 15-55 years) in cardiogenic shock after acute fulminant myocarditis were included. Two patients initially were supported for stabilization and transportation from an outside hospital by FFB. Both patients died after a support time of 24 h because of multiorgan failure or neurological disorders after longer periods of resuscitation in the referral hospital. The third patient (55 years) received the Biomedicus pump as CVAD. Myocardial function recovered after a support time of 120 h, and the patient could be weaned. Unfortunately, 2 days after weaning, he developed malignant arrhythmias and died. The 2 remaining patients (15 years and 27 years) with diagnosis of acute fulminant virus myocarditis were supported by biventricular assist device (1 x Thoratec/111 days, 1 x Abiomed/7 days). During the entire time of support, there were no signs of myocardial recovery. The patients were accepted for the heart transplantation (HTX) program. In both cases, HTXs were performed without any complication. The postoperative course was uneventful. The results of mechanical circulatory support in patients with acute fulminant myocarditis are encouraging and justify the resources.


Subject(s)
Cardiomyopathies/therapy , Cardiopulmonary Bypass , Heart Transplantation , Heart-Assist Devices , Myocarditis/therapy , Adult , Cardiomyopathies/surgery , Female , Humans , Male , Multiple Organ Failure/mortality , Myocarditis/surgery , Postoperative Complications , Shock, Cardiogenic/therapy , Transportation of Patients/standards
12.
Perfusion ; 11(2): 93-102, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8740350

ABSTRACT

Over recent years, a number of different mechanical circulatory support (MCS) products have been developed to a stage where they are no longer investigational devices. Registry data provide some information, but this is limited by the mix of historical and contemporary data and the voluntary nature of the contributions. As yet, there are no clear guidelines for patient selection, the differential application of generically different devices or for optimal patient management. Ours is a busy centre offering a comprehensive cardiovascular service. This review details our experience since 1987 and 189 patients supported with five different types of device, used in all of the common applications. Our experience has permitted the formulation of some general principles and guidelines. Data published by registries and by individual manufacturers are, as yet, not standardized. We hope that our experience will be of interest to those centres wishing to establish a mechanical assist service.


Subject(s)
Assisted Circulation , Academic Medical Centers , Clinical Trials as Topic , Female , Humans , Male , Treatment Outcome
13.
Ann Thorac Surg ; 61(1): 314-6, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8561596

ABSTRACT

BACKGROUND: In spite of modern cardiac surgical techniques, severe cardiogenic shock not responding to pharmacologic therapy and intraaortic balloon pumping develops in about 0.2% to 1.2% of patients undergoing cardiac operations. METHODS: From September 1987 to September 1994, 184 patients were supported with different mechanical circulatory support systems. Nine patients with postcardiotomy cardiogenic shock were supported with the Thoratec ventricular assist device. Four patients suffered early postcardiotomy cardiogenic shock, and 5 patients suffered late postcardiotomy cardiogenic shock. In 6 patients the Thoratec device was applied exclusively, in 2 patients both Bio-Medicus and Thoratec, and in 1 patient both ABIOMED and Thoratec devices were used. Duration of support ranged from 5 to 46 days with a mean duration of 15 days. RESULTS: Four patients (44%) survived and were discharged. Main complications and causes of death were multiple organ failure and sepsis. CONCLUSIONS: The results justify the use of Thoratec assist device in patients with severe preoperative cardiogenic shock.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Heart-Assist Devices , Shock, Cardiogenic/therapy , Adult , Aged , Coronary Artery Bypass/adverse effects , Female , Humans , Male , Middle Aged , Shock, Cardiogenic/etiology
14.
Thorac Cardiovasc Surg ; 43(6): 347-51, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8775860

ABSTRACT

From September 1987 to September 1994 61 patients between 29 and 78 years of age received mechanical circulatory support by means of the Biomedicus centrifugal pump. The patients were divided into three groups by indication: Group I included 15 patients with early postcardiotomy cardiogenic shock and 24 patients with late postcardiotomy cardiogenic shock. Group II 11 patients with therapy-resistant cardiogenic shock following acute myocardial infarction, and Group III 11 patients with cardiogenic shock of other etiologies. Duration of support was 1 to 347 hours. Survival rates were 46.7% and 33.3% in patients with early and late postcardiotomy cardiogenic shock, respectively (Group I), 27.2% in Group II, and 18.1% in Group III. Most frequent complications were bleeding (40%, 58%) and acute renal failure (26.7%, 29.2%) in Group I and multiple organ failure in Groups II and III (64% and 45.5%). Major causes of death were bleeding and multiple organ failure in Group I (37.5%) and multiple organ failure in Groups II and III (87.5% and 50%). Groups II and III (87.5% and 50%).


Subject(s)
Heart-Assist Devices , Postoperative Complications/therapy , Shock, Cardiogenic/therapy , Adult , Aged , Coronary Disease/surgery , Female , Heart Diseases/surgery , Humans , Male , Middle Aged , Retrospective Studies , Shock, Cardiogenic/blood , Shock, Cardiogenic/etiology , Treatment Outcome
15.
Circulation ; 92(10): 2904-10, 1995 Nov 15.
Article in English | MEDLINE | ID: mdl-7586258

ABSTRACT

BACKGROUND: DL-Sotalol has class III antiarrhythmic activity through prolongation of the repolarization phase of the action potential as well as beta-adrenoceptor-blocking properties. Although the former effect was found to exert positive inotropic effects in animal experimental studies, the latter may be detrimental in heart failure due to negative inotropism. In contrast to DL-sotalol, D-sotalol is suggested to exert only positive inotropic effects, which were never tested in isolated human myocardium. METHODS AND RESULTS: Therefore, we investigated the effects of racemic DL-sotalol and its enantiomer D-sotalol in human right atrial muscle strip preparations and in left ventricular muscle strip preparations from nonfailing and end-stage failing human hearts. DL-sotalol and D-sotalol significantly (P < .01) increased peak developed force in atrial preparations by 14.0 +/- 3.4% and 16.7 +/- 3.8%, respectively, but had no effect in ventricular myocardium. In nonfailing ventricular myocardium, both DL-sotalol and D-sotalol shifted the dose-response curve for isoproterenol to higher concentrations (P < .01); however, DL-sotalol was 100-fold more effective than D-sotalol. In non-failing myocardium, a positive force-frequency relation was found between 30 and 120 beats per minute, but isoproterenol was much more powerful in its inotropic effects. In failing myocardium, reduction in stimulation rate from 120 to 30 beats per minute increased peak developed force more pronounced than did the application of isoproterenol. CONCLUSIONS: (1) D-Sotalol has no relevant beta-adrenoceptor-blocking activity compared with DL-sotalol. (2) Neither DL-sotalol nor D-sotalol exhibit positive inotropic effects in human left ventricular myocardium. (3) Heart rate reduction increases contractile force in end-stage failing human myocardium due to an inverse force-frequency relation and thereby counteracts the potential negative inotropic properties of beta-blockade.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Anti-Arrhythmia Agents/pharmacology , Heart/drug effects , Myocardial Contraction/drug effects , Sotalol/pharmacology , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Antagonists/chemistry , Anti-Arrhythmia Agents/chemistry , Depression, Chemical , Dose-Response Relationship, Drug , Heart Failure/pathology , Heart Failure/physiopathology , Heart Rate/drug effects , Humans , In Vitro Techniques , Isoproterenol/pharmacology , Myocardium/pathology , Propranolol/pharmacology , Sotalol/chemistry , Stereoisomerism , Stimulation, Chemical
16.
Circulation ; 92(5): 1169-78, 1995 Sep 01.
Article in English | MEDLINE | ID: mdl-7648662

ABSTRACT

BACKGROUND: The present study was performed to test the hypothesis that the altered force-frequency relation in human failing dilated cardiomyopathy may be attributed to alterations in intracellular calcium handling. METHODS AND RESULTS: The force-frequency relation was investigated in isometrically contracting ventricular muscle strip preparations from 5 nonfailing human hearts and 7 hearts with end-stage failing dilated cardiomyopathy. Intracellular calcium cycling was measured simultaneously by use of the bioluminescent photoprotein aequorin. Stimulation frequency was increased stepwise from 15 to 180 beats per minute (37 degrees C). In nonfailing myocardium, twitch tension and aequorin light emission rose with increasing rates of stimulation. Maximum average twitch tension was reached at 150 min-1 and was increased to 212 +/- 34% (P < .05) of the value at 15 min-1. Aequorin light emission was lowest at 15 min-1 and was maximally increased at 180 min-1 to 218 +/- 39% (P < .01). In the failing myocardium, average isometric tension was maximum at 60 min-1 (106 +/- 7% of the basal value at 15 min-1, P = NS) and then decreased continuously to 62 +/- 9% of the basal value at 180 min-1 (P < .002). In the failing myocardium, aequorin light emission was highest at 15 min-1. At 180 min-1, it was decreased to 71 +/- 7% of the basal value (P < .01). Including both failing and nonfailing myocardium, there was a close correlation between the frequencies at which aequorin light emission and isometric tension were maximum (r = .92; n = 19; P < .001). Action potential duration decreased similarly with increasing stimulation frequencies in nonfailing and end-stage failing myocardium. Sarcoplasmic reticulum 45Ca2+ uptake, measured in homogenates from the same hearts, was significantly reduced in failing myocardium (3.60 +/- 0.51 versus 1.94 +/- 0.18 (nmol/L).min-1.mg protein-1, P < .005). CONCLUSIONS: These data indicate that the altered force-frequency relation of the failing human myocardium results from disturbed excitation-contraction coupling with decreased calcium cycling at higher rates of stimulation.


Subject(s)
Calcium/metabolism , Cardiomyopathy, Dilated/metabolism , Myocardial Contraction/physiology , Myocardium/metabolism , Action Potentials , Adult , Aequorin , Cardiomyopathy, Dilated/physiopathology , Electric Stimulation , Female , Humans , In Vitro Techniques , Male , Sarcoplasmic Reticulum/metabolism
17.
Circulation ; 92(4): 778-84, 1995 Aug 15.
Article in English | MEDLINE | ID: mdl-7641356

ABSTRACT

BACKGROUND: Previous studies provide considerable evidence that excitation-contraction coupling may be disturbed at the level of the sarcoplasmic reticulum (SR) in the failing human heart. Disturbed SR function may result from altered expression of calcium-handling proteins. METHODS AND RESULTS: Levels of SR proteins involved in calcium release (ryanodine receptor), calcium binding (calsequestrin, calreticulin), and calcium uptake (calcium ATPase, phospholamban) were measured by Western blot analysis in nonfailing human myocardium (n = 7) and in end-stage failing myocardium due to dilated cardiomyopathy (n = 14). The levels of the ryanodine receptor, calsequestrin, and calreticulin were not significantly different in nonfailing and failing human myocardium. Phospholamban protein levels (pentameric form) normalized per total protein were decreased by 18% in the failing myocardium (P < .05). However, phospholamban protein levels were not significantly different in failing and nonfailing myocardium when normalization was performed per calsequestrin. Protein levels of SR calcium ATPase, normalized per total protein or per calsequestrin, were decreased by 41% (P < .001) or 33% (P < .05), respectively, in the failing myocardium. Furthermore, SR calcium ATPase was decreased relative to ryanodine receptor by 37% (P < .05) and relative to phospholamban by 28% (P < .05). CONCLUSIONS: Levels of SR proteins involved in calcium binding and release are unchanged in failing dilated cardiomyopathy. In contrast, protein levels of calcium ATPase involved in SR calcium uptake are reduced in the failing myocardium. Moreover, SR calcium ATPase is decreased relative to its inhibitory protein, phospholamban.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Cardiomyopathy, Dilated/metabolism , Muscle Proteins/metabolism , Sarcoplasmic Reticulum/metabolism , Adenosine Triphosphatases/metabolism , Adult , Calcium Channels/metabolism , Calcium-Binding Proteins/metabolism , Calcium-Transporting ATPases/metabolism , Calmodulin-Binding Proteins/metabolism , Calreticulin , Calsequestrin/metabolism , Female , Humans , Male , Middle Aged , Ribonucleoproteins/metabolism , Ryanodine Receptor Calcium Release Channel
19.
Ann Thorac Surg ; 59(2 Suppl): S56-62; discussion S63, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7840701

ABSTRACT

From September 1987 to February 1994, we treated 147 patients ranging between 11 and 82 years old with different mechanical circulatory support systems. The applied devices were the Bio-Medicus centrifugal pump in 61 patients, the Abiomed BVS System 5000 in 49 patients, the Thoratec ventricular assist device in 42 patients, and the Novacor left ventricular assist device in 7 patients. On the basis of indication for mechanical circulatory support, the patients were divided into three groups: group 1 consisted of 72 patients with postcardiotomy cardiogenic shock; group 2, 50 patients in whom mechanical support was used as a bridge to cardiac transplantation; and group 3 (miscellaneous), 25 patients in cardiogenic shock resulting from acute myocardial infarction (n = 14), acute fulminant myocarditis (n = 3), primary graft failure (n = 2), right heart failure after heart transplantation (n = 3), and acute rejection (n = 3). Time of support ranged from 1 hour to 97 days (mean duration, 10.8 days). Seventy-five patients (51%) were discharged from the hospital. The best survival rate was achieved in group 2 with 72%, followed by group 1 with 44% and then group 3 with 28%. The most frequent complications in group 1 were bleeding (44%), multiple-organ failure (24%), neurologic disorders (18%), and acute renal failure (15%). In group 2, the major complications were bleeding (34%) and cerebrovascular disorders (22%) and in group 3, multiple-organ failure and sepsis (60%) and bleeding (32%).


Subject(s)
Heart Diseases/therapy , Heart-Assist Devices , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Treatment Outcome
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