In end-stage heart failure, cardiac beta-adrenoceptors are decreased and cardiac Gi protein is increased. We assessed beta-adrenoceptors, G proteins, and effects of several beta-adrenoceptor agonists, histamine, and 5-HT on adenylyl cyclase activity in right and left atria and left ventricles and on left ventricular contractility in six potential heart transplant donors (nonfailing hearts; NFHs) and in nine patients with end-stage dilated cardiomyopathy (DCM) and 11 patients with end-stage ischemic cardiomyopathy (ICM) to establish whether the functional responsiveness of all cardiac Gs-coupled receptors is reduced. Beta-adrenoceptors were reduced in all three tissues; in DCM, beta1-adrenoceptors were more markedly downregulated; in ICM, both beta1- and beta2-adrenoceptors were diminished. In all three tissues, isoprenaline-, terbutaline-, histamine- and 5-HT-induced adenylyl cyclase activation was reduced similarly in DCM and ICM. Moreover, in DCM and ICM, guanosine triphosphate (GTP)- (involving Gs and Gi) activated adenylyl cyclase was significantly diminished, whereas NaF-activated (involving only Gs) and Mn2+-activated (acting at the catalytic unit of the enzyme) adenylyl cyclase was unaltered. Left ventricular positive inotropic responses to beta1- (noradrenaline, dopamine, and dobutamine), beta2- (terbutaline), and beta1- and beta2-adrenoceptors (isoprenaline, adrenaline, and epinine), as well as H2-receptor (histamine) stimulation were significantly reduced. The extent of reduction was not different for each agonist in ICM and DCM. We conclude that in DCM and ICM, functional responsiveness of all cardiac Gs-coupled receptors is similarly reduced.

BACKGROUND In patients with chronic heart failure (CHF), plasma endothelin-1 (ET-1) levels are increased. We studied whether the cardiac ET-receptor system is altered in CHF patients. METHODS AND RESULTS We assessed ET-evoked inositol phosphate (IP) formation in slices from right atria and left ventricles from 6 potential heart transplant donors (NFH) and 15 patients with end-stage CHF; in membranes from the same tissues, we studied ET-induced inhibition of isoprenaline- and forskolin-stimulated adenylyl cyclase and ET-receptor density. ET (10[-9] to 10[-6] mol/L, ET-1 >>> ET-3) increased IP formation in right atria and left ventricles through ET(A)-receptor stimulation in a concentration-dependent manner; no difference in potency or efficacy between NFH and CHF hearts was observed. ET-1 (10[-10] to 10[-6] mol/L), via ET(A)-receptor stimulation, inhibited isoprenaline- and forskolin-stimulated adenylyl cyclase in right atria but not in left ventricles, whereas carbachol inhibited adenylyl cyclase in both tissues; again, the potency and efficacy of ET- or carbachol-induced adenylyl cyclase inhibition was not different between NFH and CHF hearts. [125I]ET-1 binding revealed the coexistence of ET(A) and ET(B) receptors in both tissues; however, the density of ET(A) receptors was not significantly different between NFH and CHF hearts. Finally, the immunodetectable amount of left ventricular Gq/11 protein did not differ between NFH and CHF hearts. CONCLUSIONS In the human heart, ET(A) and ET(B) receptors coexist; however, only ET(A) receptors are of functional importance. In right atria, ET(A) receptors couple to IP formation and inhibition of adenylyl cyclase; in left ventricles, they couple only to IP formation. In end-stage CHF, the functional responsiveness of the cardiac ET(A)-receptor system is not altered.

The aim of this study was to examine the influence of different incubation media on the morphology of the endothelium of great saphenous vein grafts and establish a suitable scoring system for the evaluation of damage caused by these media. Fifty specimens of saphenous veins from ten patients during elective aorto-coronary bypass surgery were used. Ten specimens served as controls; the others were assigned to test groups and exposed to heparinized whole blood, Bretschneider's HTK, human albumin or Ringer's solution. Specimens exposed to heparinized blood showed only slight morphological alterations, whereas the other three mediums caused severe damage. Thus, heparinized blood seems to be most suitable as a rinsing and incubation medium. A widely accepted scoring system for the quantification of endothelial damage caused by the incubation media did not adequately reflect the morphology alterations in the cytoskeleton and membrane topology. The proposed scoring system, which is based on endothelial cell separation, endothelial cell loss, amount of deposits, endothelial cell surface homogeneity, in addition to the frequency of spikes and blebs, seems to be suitable for characterizing differences in endothelial morphology.

This report is about the angiographic follow-up, over 5 years, in a patient with urgent heart transplantation grafted with an atherosclerotic donor heart because of severe congestive heart failure due to dilative cardiomyopathy. Sequential quantitative angiography documented a regression of the luminal narrowing of a focal lesion in the right coronary artery with a minimal luminal diameter of 1.38 mm (56% diameter stenosis) in 1988 to 2.78 mm (13%) in 1993. During this catheterization in 1993 intravascular ultrasound imaging illustrated almost no atherosclerotic vessel wall abnormalities at the site of the previous angiographic luminal narrowing as well as in the adjacent segments. These findings might promote the potential acceptance of heart transplant donors with a certain extent of coronary artery disease in the case of urgent organ request, if close follow-up and strict guidance of the patient by the transplanting team is feasible.

Chylothorax may be a rare problem in thoracic and cardiovascular surgery, but it is one which is often difficult to handle. The therapeutic procedure required in each individual case is determined by the anatomy and physiology of the ductus thoracicus and the individual etiology of the chylothorax. The ductus thoracicus runs from the cysterna chilii through the right hemithorax in a dorsolateral position relative to the hiatus aortae, crossing over to the left at the height of the fourth thoracic vertebra and passing to the left supraclavicular venous angle. Major pathogenetic features of the duct are its variability, the large number of collaterals, and the variety of lymphaticovenous anastomoses found. Lymph flow at peak pressures up to 25 cm H2O is tolerated; at higher pressures the duct or its collaterals rupture. In terms of etiology, two groups may be distinguished: (a) traumatic or iatrogenic causes, i.e., direct punctual lesions, and (b) chylothorax of neoplastic origin, caused either by direct destruction by the tumor or by ruptures of the collaterals or intrathoracic lymphaticovenous anastomoses due to increased intraductal pressure. The absolute incidence of chylothorax remains at a constant low level. Over a period of 20 years the Mayo Clinic reports only 53 cases; at our clinic we have treated a total of 9 cases in the past 10 years. Our therapeutic approach, which is based on pathophysiological and anatomical considerations, is as follows: (a) Primary attempt at conservative treatment: parenteral feeding with a fat-free diet using a gastric tube (!) to relieve the stomach combined with Buelau drainage with a low suction. (b) In the case of traumatic or operative/iatrogenic chylothorax, the direct suture or supradiaphragmal ligature (Lampson) may be used; the possibility of the complication of chyloperitoneum must, however, be considered if there is a lack of collaterals. (c) In the case of severe localized obstruction due to tumor growth, relapse due to increased pressure in the collaterals is very probable. In such cases it is better to cover the rupture directly with autologous or xenogenic material and to seal it with fibrin glue. Fibrin glue appears helpful in providing an absolutely tight seal against fatty fluids in the area of the leakage for 1–2 days until the area is further sealed by cicatrization due to incipient healing and conversion processes. We see our concept as a promising additive to surgery, which can reduce the complication rate in the case of chylothorax caused by tumors with high secretion rates.

In the last three years forty mitral valve reconstruction (MR) procedures were performed in case of mitral insufficiency (MI). In three cases, anatomical changes made reconstruction impossible for us. One patient had to be re-operated because of unsatisfactory valve function. There was no operative mortality. In twelve of the patients, mitral insufficiency was the only problem, while in twenty eight others additional cardiac procedures (CABG, AVR) were performed. The patients' age ranged from 17 to 77 years. The aortic cross-clamping time for mitral reconstruction without additional cardiac procedures ranged from 35 to 134 minutes. With one exception, the post-operative TEE indicated no, or very little, insufficiency. We concluded that the mitral valve insufficiency can be corrected with very good results and with a very low rate of complications. Such corrections ought therefore be taken into consideration before valve replacement.

The effect of chronic beta-adrenoreceptor blockade (beta-blockade) on hemodynamics and oxygen consumption (VO2) during cardiopulmonary bypass (CPB) in mild hypothermia (34 degrees C) was studied in 34 patients. The study group included 17 patients who received beta-adrenergic blocking drugs for at least 1 mo prior to the study. Seventeen patients who did not receive beta-adrenergic blockers served as controls. Demographic data in the two groups were comparable. Prior to induction of anesthesia, the heart rate was slower in the beta-adrenergic blocker group as compared to the control group. During CPB, measurements were made at two pump flow rates: 2.4 L.min-1.m-2 and 3.0 L.min-1.m-2. Oxygen delivery was similar in the two groups (beta-adrenergic blocker vs control) but the oxygen consumption was significantly lower in the beta-adrenergic blocker group as compared to the control group at both flow rates (P = 0.009). Increasing the flow rate from 2.4 L.min-1.m-2 to 3.0 L.min-1.m-2 produced a similar increase (P = 0.0001) in oxygen consumption in both groups. Increasing flow rate increased mean arterial pressure (MAP) and central venous pressure (CVP) and decreased systemic vascular resistance index (SVRI) and reservoir volume similarly in both groups. Thus, compared to the control group, patients on chronic beta-adrenergic blocker medication have a lower VO2 during CPB.

Perioperative deterioration of the circulatory performance of patients undergoing heart surgery ranges from transitory impairment in cardiac output by deterioration of the compensation range of the oxygen transport system to manifest circulatory failure without previous myocardial damage and the acute decompensation of pre-existing chronic heart failure. On the basis of the current state of knowledge in this field, a concept for rational staged treatment should be based on the different myocardial beta-adrenoceptor conditions related to the type and stage of the individual underlying heart disease and on adrenoceptor subtype specific properties of positive inotropic drugs.1. The therapy of perioperative ''circulatory'' insufficiency after extra-corporal circulation consists of the use of drugs to adapt the performance of the oxygen transport system to increased overall oxygen demand. Simultaneous volume loading (by CVP) and positive inotropic support with dobutamine are the best means of treating this (normally transitory) dysregulation.2. In the case of manifest severe circulatory insufficiency (low cardiac output syndrome), sepsis or acute heart failure (e.g., following acute myocardial infarction), the use of a pulmonary artery catheter for determining perioperative cardiac output and resistance is essential. In such cases, positive inotropic therapy is based on catecholamines of medium (dobutamine) to high (adrenaline) efficacy, because it can be assumed that the beta-adrenoceptor pattern will remain normal with regular functioning and regulation of the (remaining) myocardium up to the onset of acute heart failure. To reduce the work load on the heart and to maintain adequate perfusion pressures, the peripheral vascular resistance is adjusted to 800 - 1200 dyn.s.cm(-5) using vasoconstrictors (phenylephrine, noradrenaline, depending on frequency) or dilators (nifedipine, nitroglycerine, possibly ACE inhibitors).3. Severe chronic heart failure with perioperative decompensation is accompanied by p-adrenoreceptor down-regulation of varying degress of severity and a capacity for postreceptor stimulation which is, from a clinical standpoint, largely unaffected. Except in the severest cases of cardiomyopathy, there is little impact on cAMP/PDE-III interaction. In this situation, we use PDE-III inhibitors as the sole therapy.4. If the hemodynamic improvement obtained is insufficient, the PDE-III inhibitors is supplemented by low doses of catecholamines (adrenaline). This almost always produces sufficient improvement in circulatory performance. In the overwhelming majority of cases, the situation can be brought under control by using this staged therapy program adapted to the cardiac and circulatory condition to be expected in each case (after problems requiring surgery have been rigorously excluded). If this therapy is unsuccessful, steps such as the use of mechanical support devices or a transplant should be discussed.

Perioperative deterioration of the circulatory performance of patients undergoing heart surgery ranges from transitory impairment in cardiac output by deterioration of the compensation range of the oxygen transport system to manifest circulatory failure without previous myocardial damage and the acute decompensation of pre-existing chronic heart failure. On the basis of the current state of knowledge in this field, a concept for rational staged treatment should be based on the different myocardial beta-adrenoceptor conditions related to the type and stage of the individual underlying heart disease and on adrenoceptor subtype specific properties of positive inotropic drugs. 1. The therapy of perioperative "circulatory" insufficiency after extra-corporal circulation consists of the use of drugs to adapt the performance of the oxygen transport system to increased overall oxygen demand. Simultaneous volume loading (by CVP) and positive inotropic support with dobutamine are the best means of treating this (normally transitory) dysregulation. 2. In the case of manifest severe circulatory insufficiency (low cardiac output syndrome), sepsis or acute heart failure (e.g., following acute myocardial infarction), the use of a pulmonary artery catheter for determining perioperative cardiac output and resistance is essential. In such cases, positive inotropic therapy is based on catecholamines of medium (dobutamine) to high (adrenaline) efficacy, because it can be assumed that the beta-adrenoceptor pattern will remain normal with regular functioning and regulation of the (remaining) myocardium up to the onset of acute heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

The classical triad of sudden devastating chest pain, electrocardiographic absence of acute myocardial infarction, and identification of an upstream flap in the ascending aorta by transesophageal echocardiography (TEE) indicates aortic type A dissection requiring emergent surgery. Among 34 patients presenting with clinical signs and symptoms of an aortic dissection, three did not show the mandatory flap in the upstream aorta. The only echocardiographic finding was aortic wall thickening indicating an intramural hematoma. Two of these patients showed early aortic ectasia and one showed a pericardial effusion. Despite the missing flap echocardiographically, surgery was performed in all three patients. The surgical approach was the same as that for patients with a type A dissection. Two patients are doing well after the procedure, and one patient died after reoperation. The postoperative histologic work-up confirmed that there was no intimal tear or dissection of the intimal layer. We conclude that the echocardiographic finding of an intramural hematoma combined with typical clinical signs of chest pain, with myocardial infarction ruled out, requires emergent surgical intervention.

The receptor systems through which serotonin (5-HT), histamine, angiotensin II and endothelin increase the force of contraction were studied in isolated right atria from patients without apparent heart failure. All agonists increased the atrial force of contraction in a concentration-dependent manner; maximal effects, however, were significantly less than those evoked by isoprenaline or Ca2+. 5-HT and histamine, but not angiotensin II and endothelin, activated adenylate cyclase, whereas endothelin and angiotensin II stimulated inositol phosphate generation. Experiments with subtype-selective antagonists revealed that histamine effects were mediated by H2-receptors (sensitive to ranitidine), 5-HT-effects by 5-HT4-receptors (sensitive to SDZ 205-557) and angiotensin II effects by AT1-receptors (sensitive to losartan). We conclude that in human right atria the force of contraction can be increased by cyclic AMP-dependent (histamine, 5-HT) and -independent (angiotensin II, endothelin) pathways. Compared to beta-adrenoceptors, however, all other receptor systems increase the force of contraction only submaximally indicating that the beta-adrenoceptor pathway is the most important physiological mechanism to regulate force of contraction and/or heart rate in the human heart.

A significant proportion of early graft occlusions after aortocoronary revascularization using autologous saphenous vein grafts (SVG) are due to mechanical and/or metabolic or biochemical endothelial lesions. The morphological examination of the endothelium, usually carried out using light microscopy or by various types of scanning electron microscopy (SEM), does not give any indication of the functioning of the endothelium (E). Functionally intact E is capable of producing endothelium-derived relaxing factor (EDRF); a practicable in vitro test is the relaxation of pre-contracted vein segments (VS) in response to acetylcholine (ACh) application. To study the effect of the solution used to rinse and store the SVG between removal and implantation on the functional characteristics of the E, we performed in vitro tests on macroscopically intact VS removed from the saphenous vein of 30 male patients who underwent elective CABG surgery. Isolated VS rings were incubated for 60 min in heparinized whole blood (HWB), Bretschneider's cardioplegic solution (HTK), human albumin solution (HAS), or Ringer's solution (RS) and compared with the results obtained immediately after the removal of untreated control samples (C) taken from the same patients. After equilibration in carbogen aerated Krebs-Henseleit solution and precontraction by 3 x 10(-7) M noradrenaline (NE), relaxation induced by 10(-6) M ACh was measured. Only the samples stored in HWB (13.4 +/- 0.4 mN) showed similar maximal contractions with NE to those in the control group (14.4 +/- 0.5 mN), i.e. all those segments which showed both contractions with NE and relaxation with ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with coronary artery disease undergoing coronary artery bypass grafting can develop perioperative low cardiac output failure requiring positive inotropic support. Commonly, the sympathetic amines, dopamine, dobutamine or adrenaline are used in low-output state. However, patients on long-term cardioselective beta-blocking therapy may experience problems with such a treatment. Dopexamine, a new synthetic amine, possesses positive inotropic effects by indirect stimulation of the beta1-receptors and direct stimulation of the beta2-receptors. We therefore studied the hemodynamic efficacy of dopexamine in patients with and without beta-receptor blockade.In 12 patients with coronary artery disease classed as NYHA II or III six without any beta-blocker medication, and six with beta1-blocker medication (bisoprolol 5 mg), anesthesia was induced with high-dose fentanyl (0.05 mg/kg) and pancuronium (0.1 mg/kg). The patients were normoventilated with a mask (O2:air 1:1, tidal volume 10 ml/kg with a rate of 10/min) for 5 min and then intubated. Following intubation anesthesia was continued with 0.025 mg/kg/h fentanyl. In anesthesia steady state the patients of both groups were treated with 2 mug/kg/min dopexamine over a period of 15 min and then with 4 mug/kg/min dopexamine over a further period of 15 min. Measurements of cardiovascular dynamics included heart rate (HR), cardiac index (CI), stroke volume index (SVI), mean arterial blood pressure (MAP), coronary perfusion pressure (CPP), systemic vascular resistance (SVR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrium pressure (RAP), pressure work index (PWI) and arterial-mixed venous oxygen content difference (AVDO2), which were monitored or calculated by standard formulas. Data and electrocardiogram were taken at the following times 1) before induction of anesthesia (W); 2) after induction of anesthesia and before administration of the catecholamine (K); 3) 15 min after continuous infusion of 2 mug/kg/min dopexamine (Dpx 2 mug); 4) 15 min after continuous infusion of 4 mug/kg/min dopexamine (Dpx 4 mug).Dopexamine induced significant increases of cardiac index, stroke volume index and heart rate, a small decrease of mean arterial pressure and a significant decrease of coronary perfusion pressure and systemic vascular resistance. Significant differences between both groups could not be evaluated. Pressure work index increased in both groups with dopexamine treatment, and the increase was more pronounced in patients with bisoprolol medication. Nevertheless, in both groups the levels of PWI with dopexamine were not greater in the awake and calm patient. In neither group did we observe any ST-segment changes in the ECG or an increase in pulmonary capillary wedge pressure.Dopexamine possesses a positive inotropic effect of nearly the same extent in patients with and without beta1-blockade pretreatment. Simultaneously, it induces an afterload reduction.The coronary perfusion pressure decreased, but did not change differently in either group, and there were no signs of myocardial ischemia, as shown in changes of left ventricular filling pressure or in the ECG. Probably, the lowered wall tension by arterial vasodilatation counterbalances the augmentation of myocardial oxygen consumption by the positive inotropic and chronotropic effects of dopexamine. In doses up to 4 mug/kg/min dopexamine acts mainly by stimulating beta2-receptors; therefore, its use seems suitable in such subtypes of heart failure where down-regulation of beta1-receptors or a pretreatment with beta1-receptor blockers exists.

Patients with coronary artery disease undergoing coronary artery bypass grafting can develop perioperative low cardiac output failure requiring positive inotropic support. Commonly, the sympathetic amines, dopamine, dobutamine or adrenaline are used in low-output state. However, patients on long-term cardioselective beta-blocking therapy may experience problems with such a treatment. Dopexamine, a new synthetic amine, possesses positive inotropic effects by indirect stimulation of the beta 1-receptors and direct stimulation of the beta 2-receptors. We therefore studied the hemodynamic efficacy of dopexamine in patients with and without beta-receptor blockade. In 12 patients with coronary artery disease classed as NYHA II or III, six without any beta-blocker medication, and six with beta 1-blocker medication (bisoprolol 5 mg), anesthesia was induced with high-dose fentanyl (0.05 mg/kg) and pancuronium (0.1 mg/kg). The patients were normoventilated with a mask (O2:air 1:1, tidal volume 10 ml/kg with a rate of 10/min) for 5 min and then intubated. Following intubation anesthesia was continued with 0.025 mg/kg/h fentanyl. In anesthesia steady state the patients of both groups were treated with 2 micrograms/kg/min dopexamine over a period of 15 min and then with 4 micrograms/kg/min dopexamine over a further period of 15 min. Measurements of cardiovascular dynamics included heart rate (HR), cardiac index (CI), stroke volume index (SVI), mean arterial blood pressure (MAP), coronary perfusion pressure (CPP), systemic vascular resistance (SVR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrium pressure (RAP), pressure work index (PWI) and arterial-mixed venous oxygen content difference (AVDO2), which were monitored or calculated by standard formulas.(ABSTRACT TRUNCATED AT 250 WORDS)

Traumatische Blutungen im Hals- und Thoraxbereich sind zu 80% Folge penetrierender Schuß- und Stichverletzungen. Die Letalität wird wesentlich durch Schnelligkeit und Effektivität der präklinischen und klinischen Versorgung beeinflußt. Im mittleren Halsbereich dominieren Verletzungen der A. carotis und V jugularis interna. Die Blutstillung erfolgt durch digitale Kompression und chirurgische Sofortversorgung in der Klinik. Bei Verletzungen der A. carotis interna oder der supraaortalen Gefäße hat sich die transfemorale Katheter-Angiographie zur genauen Lokalisation der Verletzung und temporären Blutstillung durch Ballon-Okklusion der Verletzungsstelle bewährt. Bei penetrierender Thorax-Verletzung und hämodynamischer Instabilität besteht die Indikation zur Notfall-Thorakotomie. Paramediane Lokalisation der Perforations-Verletzung, Schock und hämodynamische Instabilität sind Zeichen der Herz-Verletzung mit perikardialer Blutung oder Tamponade. Lebensrettend ist die Notfall-Peri-kardiotomie und primäre Naht der Myocardverletzung über eine mediane transsternale