Biomedical subjects

S Hagl

Publications and source records attributed to S Hagl.

At least 55 records · Page 3Linked to original sources

PubMed2001

The role of endothelin-B receptors in myocardial and endothelial reperfusion injury after heart transplantation.

BACKGROUND: This study was designed to investigate the effects of the selective endothelin-B (ET-B) receptor agonist IRL1620 and the selective ET-B receptor antagonist BQ788 on myocardial and endothelial function after reversible deep hypothermic ischemia and reperfusion. METHODS: Isogenic intraabdominal heterotopic heart transplantation was performed on Lewis rats. After one hour of cold ischemic preservation, reperfusion was started either after application of saline vehicle or IRL1620 or BQ788 or both. Left ventricular pressure-volume relations and myocardial blood flow were assessed after one and 24 hours of reperfusion. Endothelium-dependent vasodilatation to acetylcholine (ACH) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) were also determined. RESULTS: IRL1620 attenuated and BQ788 improved myocardial contractility significantly as indicated by the left or upward shift of the systolic pressure-volume relation, respectively, and significantly changed myocardial blood flow during early reperfusion (p<0.05). Although myocardial function and baseline myocardial blood flow were similar in both groups after 24 hours of reperfusion, endothelium-dependent vasodilatation was still significantly lower in the IRL1620 and higher in the BQ788 group (p<0.05). CONCLUSIONS: These results suggest that activation of the ET-B receptors contributes to reperfusion injury after cardiac preservation in a rat heart transplant model.

Acetylcholine↗

PubMed2001

3D evaluation of myocardial edema: experimental study on 22 pigs using magnetic resonance and tissue analysis.

BACKGROUND: Myocardial edema (ME) adversely affects ventricular function. Thus, we performed an animal study to demonstrate (1) 3D-ME using magnetic resonance imaging (MRI), which can show ME depending on myocardial location, (2) type of cardioplegic solution, and (3) quantification tools. METHODS: Pig hearts (n = 22) were perfused using Bretschneider's solution (BRET, n = 8), butanedionemonoxime (BDM, n=8), or no cardioplegia as controls (CTRL, n = 6). Hearts underwent MRI (T(1)-inversion recovery). Myocardial water content (MWC, reference method) was determined from left ventricle anterior, posterior (PW), lateral wall, interventricular septum, papillary muscle, right ventricle wall. Images underwent 3D reconstruction using ray-tracing. Gray-value analysis was performed on "virtual" samples. For statistical analysis, ANOVA, Student's t-test, and the Student-Newman-Keuls test were used. RESULTS: (1) ME was induced (p < 0.0001 vs. control). Localization differed in MWC, p = 0.003 (BRET), p = 0.023 (BDM), highest at PW (p < 0.01). (2) Differences between the cardioplegia groups were not significant. (3) "Virtual" samples showed equal distribution (BRET: p = 0.007, BDM: p = 0.003), highest at PW (p < 0.01). CONCLUSIONS: We validated 3D assessment of induced ME in pig hearts using MRI. The method may therefore become an exact tool in monitoring cardioplegia.

Animals↗

PubMed2001

Near-fatal hemoptysis and emergency surgical repair after aortic patch-plasty.

A 38-year-old man presented with massive hemoptysis followed by hemorrhage shock. The patient's history revealed a Dacron patch repair for aortic coarctation and recoarctation carried out twice, once 23 and once 10 years ago. Diagnosis of a ruptured descending aortic aneurysm with an aortobronchial fistula into the left lower lobe was established using CT scan. Emergency surgery consisted of left pneumonectomy and descending aortic graft replacement during deep hypothermic circulatory arrest. The patient was discharged 12 days later.

Adult↗

PubMed2001

A novel perfusion catheter for hybrid procedures in minimally invasive bypass surgery.

BACKGROUND: Combined off-pump bypass grafting and percutaneous coronary intervention (hybrid procedures) is supposed to be beneficial for high-risk patients. We developed a novel perfusion catheter to facilitate these hybrid interventions. METHODS: First, we tested coagulatory activation in vitro. Afterwards, 6 landrace pigs underwent active coronary perfusion of the LAD. In a second study, 15 pigs underwent off-pump bypass surgery (LIMA to LAD grafting) and the catheter was used to provide myocardial perfusion and prevent bleeding at the site of the coronary anastomosis. RESULTS: In the in vitro perfusion studies, no activation of coagulation or clotting occurred. Active coronary perfusion was feasible without signs of regional myocardial ischemia or coagulation over a 50-minute period. During off-pump bypass surgery, the catheter prevented bleeding in the operation field and facilitated the surgical procedure. CONCLUSION: The new perfusion catheter can optimize the conditions of off-pump bypass surgery by preventing bleeding in the operation field, maintaining myocardial perfusion and allowing direct angiographic control of the anastomosis. Therefore, this new technique could be an important tool to facilitate hybrid interventions.

Anastomosis, Surgical↗

PubMed2001

Does the completeness of revascularization contribute to an improved early survival in patients up to 70 years of age?

OBJECTIVE: In the era of a renewal of incomplete revascularization approaches, the controversy reappears as to whether the approach for complete revascularization is of prognostic value. The clear advantage of complete revascularization in elderly patients has recently been published. However, for the younger patient group, there is no conclusive information available so far. The aim of our study was to investigate the effect of complete vs. incomplete revascularization in patients up to 70 years of age. PATIENTS AND METHODS: 6531 patients underwent isolated CABG. 5003 of these patients were aged up to 70 years at the time of operation. RESULTS: Incomplete revascularization was performed in 534 (10.7 %) patients. The most common reasons for incomplete revascularization were small vessels and massive calcification. The differences in mortality up to the 180(th) day after CABG are statistically significant. By Kaplan-Meier analysis, the time relationship between incomplete revascularization and death affects predominantly the very early period after CABG. By logistical regression, incomplete revascularization was found to be an independent risk factor for death after CABG. CONCLUSION: Incomplete revascularization affects the early outcome after CABG in patients up to 70 years of age as an independent risk factor for death. In view of recent approaches for primarily incomplete CABG, our results indicate the necessity to reconsider the advantages of complete revascularization.

Age Factors↗

PubMed2001

[Preoperative administration of new GPIIb/IIIa inhibitors].

The influence of preoperative abciximab treatment on perioperative risks was analyzed. Six groups were formed in consecutive patients (n = 957, 1/1994-3/2000) operated upon for CABG according to the urgency of the intervention and the type of preoperative haemostaseological treatment. Thirty-one patients underwent urgent/emergency CABG with preceding abciximab treatment. After pretreatment with abciximab the surgical results did not differ from patients with other types of preoperative haemostaseological treatment. CABG can be performed with similar results in abciximab pretreated patients as in patients with other types of preoperative haemostaseological treatment.

Abciximab↗

PubMed2000

Three-dimensional color Doppler reconstruction of intracardiac blood flow in patients with different heart valve diseases.

An improved perception of the magnitude and dynamics of intracardiac flow disturbances has been made possible by the advent of 3-dimensional (3-D) color Doppler, a new diagnostic procedure developed at our institution. This study describes the new insights derived from 3-D reconstruction of color Doppler flow patterns in patients with different heart valve diseases. The color Doppler flow data from 153 multiplanar transesophageal or transthoracic echocardiographic examinations has been obtained from 133 patients with heart valve disease; 73 patients had mitral regurgitation, 15 had mitral stenosis, 18 had aortic regurgitation, 26 had aortic stenosis, and 21 patients had tricuspid regurgitation. Four patients had pulmonary regurgitation associated with mitral valve disease. The 3-D reconstructions of color Doppler flow signals were accomplished by means of the "Heidelberg Raytracing model," developed at our institution. The 3-D color Doppler reconstructions were obtained in all patients. The 3-D images revealed for the first time the complex spatial distribution of the blood flow abnormalities in the heart chambers caused by different heart valve diseases. New patterns of intracardiac blood flow disturbances were observed and classified. Three-dimensional color Doppler provides a unique noninvasive method that can be easily applied for studying intracardiac blood flow disturbances in clinical practice.

Aortic Valve Insufficiency↗

PubMed2000

[Volumetric analysis and visualization of cardiologic ultrasound data].

BACKGROUND: Echocardiography is a standard imaging technique for the assessment of heart valve disease. The good spatial and temporal resolution is the basis for different methods which provide information about the severity of such defects. Dynamic colour visualisation and volumetric measurements of regurgitant jets are a new evaluating tool for the assessment of heart valve insufficiencies. METHODS: The regurgitant jet volume of 58 patients was evaluated on an external work-station after segmentation of the left atrium and compared to regurgitant volume; the correlation was good. This result is valid for central jets as well as for eccentric jets. CONCLUSIONS: Measurement of regurgitant jet volume is a method which considers the three-dimensional shape of the examined volume. Real-time visualisation techniques which support the interactive clipping of morphological structures provide dynamic visualisation of intracardiac flow during the heart cycle. Dynamic colour visualisation of jets together with myocardial structures allows the assignment of intracardiac flow to morphological structures.

Computer Graphics↗

PubMed2000

Dynamic cardiomyoplasty in a growing organism.

BACKGROUND: Until now cardiomyoplasty has been a treatment option for adults only. However, there may be a demand for cardiomyoplasty in children. The purpose of this study was to investigate the possibility of applying the method of cardiomyoplasty before growth is completed. METHODS: The latissimus dorsi muscle (LD) was wrapped around the heart of 20 Göttinger Minipigs (9.1 +/- 1.2 kg body weight). The LD was fixed to the pericardium in group 1 (n = 11) and to the epimyocardium in group 2 (n = 9) and stimulated with burst impulses. After 5.6 +/- 1.8 months hemodynamic and histologic follow-up-examinations were carried out in 13 surviving animals (weight 32.4 +/- 5.3 kg). RESULTS: In group 1 (n = 6) only the left ventricle was covered by the LD. In 4 animals the LD contracted strongly; in 2, the outer border of the muscle was atrophied. In group 2 (n = 7) both ventricles were covered by the LD in all animals and showed strong contractions. In 2 animals the outer border of the muscle was atrophied. In both groups the contracting parts of the LD showed an intact muscle structure, but compared with the contralateral LD, there was a higher percentage of interstitial fat and connective tissue. Hemodynamic measurements and the well-being of the animals suggest that restriction of cardiac chamber diameter did not occur. The electrical stimulation of the LD caused a minimal increase of left ventricular pressure and aortic peak flow in group 2. CONCLUSIONS: Cardiomyoplasty can be applied in a growing organism. There is growth of the LD with the heart. The muscle structure remains intact. To prevent dislocation of the LD, it seems to be important to fix the LD directly onto the epimyocardium.

Adult↗

PubMed2000

The endogenous pathway is a major route for deep sternal wound infection.

OBJECTIVE: Deep wound infections pose an increasing problem in cardiac surgery patients. Prospective infection monitoring is thus a means of identifying possible risk factors. METHODS: Within a period of 5 months, a total of 376 adult patients, 260 men and 116 women, with a mean age of 62.6 years (range 18-88), underwent coronary bypass grafting (n=281) or other cardiac surgery procedures (n=95). Nasal cultures were taken preoperatively from every patient, as well as cultures of the wound during surgery and when dressings were changed thereafter. In addition, nasal cultures were taken from all the medical and nursing staff. To differentiate endogenous and exogenous infection pathways, DNA fingerprint analysis was performed. RESULTS: A total of 38 patients (10.1%) developed a wound infection, in 14 patients this happened to be a deep wound infection, in 24 patients a superficial one. Five sternal wound infections were associated with mediastinitis (1.3%). The occurrence of a wound infection overall resulted in prolonged hospitalization (29.4+/-24 vs. 11.9+/-6.9 days, P=0.001), but not in increased hospital mortality (4.4% vs. 3.9%). Obesity, diabetes mellitus and nasal carriage of Staphylococcus aureus proved to be independent risk factors with an odds ratio of 2.07, 2.26 and 2.28, respectively. In all but one of the sternal colonizations with S. aureus, DNA fingerprint analysis demonstrated an identical pattern of S. aureus from the patient's nose and sternum, indicating an endogenous infection pathway. CONCLUSIONS: The determination of the endogenous pathway for severe wound infection makes prevention possible by means of preoperative local S. aureus eradication.

Adult↗

PubMed2000

Role of neural and humoral factors in hyperdynamic reaction and cardiac dysfunction following brain death.

BACKGROUND: Although hemodynamic instability and cardiac dysfunction after brain death are reported in the potential organ donor, the underlying mechanisms, for example, neurohumoral changes, myocardial injury, and altered loading conditions, have not been differentiated in clinical and experimental settings. In the present study, we performed a load-independent analysis of cardiac function, focusing on the influence of brain death-associated neural and humoral factors. METHODS: In a canine in situ cross-circulated heart model, brain death was induced by inflation of a subdural balloon catheter. Preload, afterload, and coronary perfusion pressure were kept identical in all hearts throughout the experiment. In Group H (humoral factors), the hearts of healthy dogs were perfused with blood from brain-dead support dogs (n = 6). In Group N (neural factors), the hearts of brain-dead dogs were perfused with blood from healthy support dogs (n = 6). In Group H + N (humoral and neural factors), the hearts of brain-dead dogs were perfused parabiotically in situ with the animals' own blood (n = 6). Systolic and diastolic pressure-volume relationships and coronary blood flow were measured. RESULTS: Induction of brain death led to a significant hyperdynamic response in all groups, with a maximal reaction in Group H + N followed by Group H and Group N. After the initial hyperdynamic phase, cardiac function returned to baseline within 15 minutes and remained stable in all groups for the 2-hour observation period. CONCLUSIONS: (1) Both neural and humoral factors contribute to the initial hyperdynamic reaction after brain death, and only in combination do they cause a maximal hemodynamic effect. (2) If loading conditions and perfusion pressure are kept constant, no cardiac dysfunction occurs after brain death. This indicates that poor cardiac function in the potential donor may reflect altered loading conditions and impaired coronary perfusion rather than neurohumorally mediated direct myocardial injury.

Animals↗

PubMed2000

Acute triiodothyronine administration does not reverse depressed contractile performance following catecholamine exposure in isolated rat cardiomyocytes.

BACKGROUND: It has been previously suggested that triiodothyronine (T3) may reverse depressed cardiac contractile performance occurring after excessive catecholamine stimulation. We therefore investigated the effects of T3 on intracellular calcium transients and contractile performance in isolated ventricular rat myocytes. METHODS: Isolated rat myocytes were loaded with the calcium indicator FURA-2/AM (50 micromol/L) and superfused with Krebs-Henseleit solution (pH 7.4). Cells were illuminated by ultraviolet light and fluorescent images obtained with a target camera at 340 nm and 380 nm excitation wavelengths (ratio method). Simultaneous measurements of calcium transients and cell shortening (35 degrees C, electrical field stimulation: 0.5 Hz) were done. At steady state conditions, FURA-2 loaded myocytes were superfused for 60 min with epinephrine (0.1 micromol/L). After 60 min the effect of T3 (10 micromol/L) on calcium transients and shortening were measured. As control, only the effect of 10 micromol/L T3 was analyzed. RESULTS: Epinephrine significantly increased cell shortening and FURA-2 signals to 148.6+/-8.8% and 109.5+/-3.1% (p < 0.01: n = 21; 5 min) respectively. With longer epinephrine exposure, the increase in cell shortening continuously declined to 134.6+/-7.9% with no change in FURA-2 fluorescence. Acute administration of T3 after epinephrine exposure lowered contractile performance from 136.2 +/- 15.5% to 102 +/- 8.2 %, after 10 minutes. In control experiments acute administration of T3 increased basal contractile response from 100% to 115.8+/-3.3% (p<0.01; n = 8; 5 min). CONCLUSIONS: This study confirms previous reports of impaired cardiac function after high catecholamine exposure. High catecholamine exposure is associated with a desensitization of contractile proteins for calcium. Acute T3 administration increased contractility in untreated myocytes, but further depressed myocyte shortening in epinephrine-treated cells. Our results show that T3 is ineffective at restoring myocardial contractility after excessive catecholamine stimulation.

Animals↗

PubMed2000

Vascular tracheobronchial compression syndromes-- experience in surgical treatment and literature review.

Between January 1988 and December 1997 a total of 22 patients (age: 8 days-46 years) were operated for vascular airway compression syndromes with respiratory insufficiency. Vascular anomalies in tracheal compression were double aortic arch in 7 patients, (2 previously operated elsewhere), right aortic arch + left ligamentum arteriosum in 1, and pulmonary artery sling in 3. Three of these patients had secondary long-segment tracheomalacia. Compression of trachea and a main bronchus existed in 2 patients with right aortic arch + left ligamentum. Isolated main bronchus obstruction was present in 9 patients (abnormal insertion of ligamentum arteriosum in 1, status post (s.p.) previous operation for PDA in 4, s. p. surgery for coarctation in 1, right aortic arch + left ligamentum arteriosum in 2, and right lung aplasia + left ligamentum in 1). 3 of these cases had secondary long-segment bronchomalacia. All patients had a complex respiratory anamnesis [long-term intubation in 7, s.p. tracheostomy in 2 (over 3 months - 3 years), and progressive respiratory insufficiency in 13). In tracheal compression, surgical correction included transsection of the underlying ring or sling components (with additional anterior aortic arch translocation in 5 patients resection-reimplantation of left pulmonary artery in 3, segmental tracheal resection in 1, and external tracheal suspension in 2). In the 2 cases with compression of the trachea and a main bronchus, aortic "extension" by a prosthetic tube was necessary. In isolated main bronchus obstruction, surgical decompression basically consisted of transsection of the ligamentum arteriosum or resection of its scarry remnant forming the "corner point" of a compression between aorta and pulmonary artery. In 3 patients with secondary long-segment malacia, additional external bronchus suspension was performed. Effective decompression and re-expansion of the airway segment concerned was achieved, and was demonstrated by intraoperative endoscopy in all patients. There were 3 postoperative deaths (sepsis 2; massive, irreversible edema of the tracheal mucosa 1). Of the 19 surviving patients 16 could be extubated between the 1st and 17th (mean = 7.5) postoperative day. In 1 case the preoperative long-term tracheostomy had to be left in place for inoperable additional laryngeal stricture. 2 patients had to be reoperated (segmental cervical tracheal resection after 5 months for primary long-term intubation-related subglottic stenosis in 1, esophageal decompression for residual dysphagia after 57 months related to a traction phenomenon at the right descending aorta in the other), both with gratifying results. In all other patients clinical, endoscopic, and radiographic examinations (follow-up = 2 months - 6 years) demonstrate good results.

Adolescent↗

PubMed2000

Sepsis and catecholamine support are the major risk factors for critical illness polyneuropathy after open heart surgery'.

BACKGROUND: Critical illness polyneuropathy (CIP) remains a problem after open heart surgery. Recently, we reported about a retrospectively performed study pointing out that sepsis, the application of higher amounts of catecholamines and intervention such as chronic venovenous hemodiafiltration may be involved in the onset of CIP. A prospectively performed study is presented in order to evaluate the significance of risk factors initially after open heart surgery. METHODS: From June 1997 until September 1998, patients undergoing open heart surgery and being ventilated beyond 3 days were prospectively enrolled in the study and underwent a standard protocol of electromyographic investigation in order to determine CIP. Several items were recorded: amount of catecholamines, serum levels of urea, creatinine, albumin, and glucose. The duration of sepsis and chronic venovenous hemodiafiltration were reevaluated. Additionally the age, the left ventricular end-diastolic pressure prior to the operation, the time of ICU stay and the time of ventilatory support were compared. RESULTS: Within the observation period, 37 adult patients could be enrolled in the study, whereas 12 patients did develop CIP and 7 patients did not. Patients developing CIP required significantly different amounts of epinephrine (0.17 +/- 0.02 vs. 0.09 +/- 0.01 mg/kg/day, p < 0.05, t-test) higher amounts of norepinephrine (0.06 +/- 0.02 vs. 0.02 +/- 0.01 mg/kg/day, p<0.05, t-test), and lesser dosages of dobutamine (2.2 +/- 0.5 vs. 4.9 +/- 0.7, p<0.05, t-test). After cardiac surgery, the plasma levels of urea was initially significantly elevated in patients developing CIP (127.4 +/- 10.5 vs 97.3 +/- 18.5, p<0.05, t-test) Patients suffering from CIP stayed significantly longer in the ICU (40.3 +/- 11.7 vs. 19.6 +/- 11.3 days, p < 0.05 t-test) with an extended time of ventilator support. (769.6 +/- 05.0 vs 295.0 +/- 134.0 hours, p<0.05, t-test). Patients of the CIP group were suffering significant longer from sepsis than patients without CIP. CONCLUSIONS: Sepsis and catecholamine support and an increased level of urea were associated with the development of CIP. The prevention of sepsis and a modulation of the catecholamine support in order to improve microcirculatory flow may reduce the onset of CIP in patients undergoing open heart surgery.

Aged↗

PubMed2000

Target, application, and interpretation of scores and alternative methods for risk assessment in cardiac surgery.

BACKGROUND: The more popular the use of different methods for risk adjustment becomes, the more often data are applied without any regard about the primary target and/or about important assumptions. Furthermore, risk adjustment is no longer restricted for quality assurance purposes, but became a "tool" of health policy. Few working groups currently use risk adjustment for the development of new therapeutic concepts. The aim of our study is to clarify possibilities and limitations of popular risk adjustment methods. PATIENTS AND METHODS: 4985 Patients underwent isolated CABG. Statistics was performed by calculating descriptive statistics, Parsonnet, and Higginsscores. Furthermore, the parametric, time-adjusted hazard function by Blackstone was used. RESULTS: Descriptive statistics allows intra-, and interinstitutional comparisons of single items to identify "outlying" results. Risk scores aim to predict preoperatively the risk category of the patient who undergoes cardiac surgery. However, since different scores are based on a score-specific combination of variables, and different definitions of the investigation interval, different results may occur, when different scores are calculated for a single patient. However, the use for example, of scores in patient groups allows description of changing risk structures. Most of the scores derive from univariate analyses and monophasic functions. However, survival curves are predominantly multiphasic and require a consideration of the time-dependency of "risk factors". DISCUSSION: An increasing number of patients with severe comorbidity undergoes cardiac surgery. To evaluate reliably present and futurous therapeutic options, risk adjustment is necessary. Since various tools for risk-adjustment are available, a serious discussion about reliability and application is necessary.

Aged↗

PubMed2000

Three-dimensional color Doppler flow reconstruction and its clinical applications.

The visualization and quantification of intracardiac blood flow have always been a challenging task for the cardiologist. The advent of color Doppler flow imaging substantially enhanced the clinical diagnosis of heart valve disease. Three-dimensional (3-D) color Doppler, a new diagnostic procedure, refines the diagnostic value of color Doppler by providing unique spatial and temporal information about the actual extension, direction, origin, and size of intracardiac flows. Here, we describe the procedure for 3-D color Doppler reconstruction of intracardiac blood flow velocities and reveal the varied findings in different heart pathologies that cause blood flow disturbances. An automated procedure for the segmentation of turbulent and laminar flows, which allows for the measurement of mitral regurgitant jet volumes, is one of the first 3-D quantitative approaches to the clinical assessment of mitral valve regurgitation. The major technical advances of this procedure include the direct use of digital color Doppler velocity data and an automatic voxel count of the turbulent jet flows. Three-dimensional color Doppler not only can disclose the spatial complex geometry of intracardiac blood flow disturbances but also can quantitatively assess the severity of mitral valve regurgitation.

Aortic Valve Stenosis↗

PubMed2000

Myocardial performance after brain death: studies in isolated hearts.

OBJECTIVES AND METHODS: Brain death related hemodynamic instability and/or cardiac dysfunction is frequently described in the potential organ donor which may lead to exclusion of the heart from transplantation. The underlying mechanisms are controversely discussed. Therefore, in the present study, potential brain death associated cardiodepressant factors were evaluated separately in cross-circulated canine heart models. Brain death was induced by inflation of a subdural balloon catheter. Loading conditions and coronary perfusion pressure were kept identical in all cross-circulated hearts throughout the experiment. RESULTS: Induction of brain death led to a significant hyperdynamic response in all groups, with a maximal effect by the combination of neural and humoral pathways. After the initial reaction all hemodynamic parameters returned to baseline and remained stable until the end of experiments. Even if the hearts were explanted from brain dead donors with typical hemodynamic deterioration in vivo, they showed no significant differences in comparison to the other groups including healthy controls ex vivo. CONCLUSIONS: Therefore we conclude, that hemodynamic instability in the potential donor may rather reflect altered loading conditions and impaired coronary perfusion than neuro-humorally mediated direct myocardial injury.

Animals↗

PubMed1999

Influence of Bretschneider's cardioplegia on norepinephrine release from isolated perfused guinea-pig hearts.

It was the aim of the present study to investigate the influence of Bretschneider's cardioplegia on norepinephrine (NE) release [determined by high pressure liquid chromatography (HPLC) and electrochemical detection] in isolated perfused guinea-pig hearts. The following resulted were noted. (1) Calcium-dependent exocytotic NE release evoked by electrical field stimulation (12 Hz, 1 min) was completely suppressed after only 3 min of normothermic (37.5 degrees C) Bretschneider's cardioplegia. (2) Stop-flow ischemia is associated with a substantial calcium-independent, non-exocytotic NE release, which is regarded as a sodium-dependent carrier-mediated process. Accordingly, it is inhibited by blockers of the sodium/proton-exchanger (e.g. amiloride) and the neuronal uptake1-carrier (e.g. desipramine). Compared with stop-flow ischemia alone, cardioplegia with 3 min of Bretschneider's histidine-tryptophan-ketoglutarate (HTK)-solution preceding stop-flow enhanced NE release at all stop-flow durations (10-90 min) investigated (e.g. after 30 min of normothermic Bretschneider's cardioplegia: 1070+/-41 pmol/g, n = 45, v stop-flow alone: 764+/-48 pmol/g, n = 27, P<0.05). The NE concentrations determined in the cardiac effluent upon reperfusion followed a typical first order kinetic indicating that the transmitter release had already occurred during stop-flow. Hypothermia reduced NE release in a temperature-dependent manner down to intramyocardial temperatures of 2 7.5 degrees C. NE release evoked by Bretschneider's cardioplegia still exceeded that induced by stop-flow ischemia alone by up to 60%. The NE release evoked by Bretschneider's cardioplegia and stop-flow ischemia was calcium-independent. However, it was significantly reduced by desipramine and amiloride, but both agents had a more pronounced inhibitory effect on NE release evoked by stop-flow ischemia alone. (3) This difference may be due to an intrinsic effect of Bretschneider's HTK-solution, as continuous administration of normothermic Bretschneider's HTK-solution induced a substantial NE release which was neither calcium-dependent nor inhibited by blockade of either uptake1 or sodium/proton-exchange. It is concluded that Bretschneider's cardioplegia is not neuroprotective, as it even augments the stop-flow ischemia-induced nonexocytotic NE release.

Adrenergic Uptake Inhibitors↗