[Coronary artery bypass grafting without extracorporeal circulation]. / Koszorúérmútétek extrakorporális keringés alkalmazása nélkül.

At the Department of Cardiovascular Surgery of Semmelweis University, Budapest we have performed 57 coronary bypass operations without using cardiopulmonary bypass between 1996 and September 2001. Due to the learning phase we preferred cases of 1-2 wessel diseases, and revascularisation necessary on the anterior surface of the heart. In the beginning the stabilization of the operative field was ensured by manual methods, then by applying mechanical stabilization devices (Octopus 2, Genzyme). As to the type of operative indication overwhelmingly elective operations were performed. REDO procedure, i.e. repeated coronary bypass operation was carried out in 2 cases. Forty-eight patients recovered without complication. Two patients died, one of them suffered perioperative infarction, the other died due to cerebral complication. Total mortality was 3.5%. As a consequence of cardiac ischaemia in the direct postoperative period, we performed emergent coronary ballon dilatation (PTCA) in two cases. In three cases we experienced perioperative infarction. We followed up our patients by way of interview and telephone interview. The follow-up is 95%, the average follow-up time is 15 months. Significant cardiac event (infarction, PTCA or REDO coronary operation) took place in the case of 7 patients. In the majority of our patients the operation resulted in an improvement of condition, 43 patients are free from angina.

[Atrial fibrillation after open-heart surgery--incidence, prevention and treatment]. / Posztoperatív pitvarfibrillàció okai, gyakorisága, megelözése és kezelése szívsebészeti betegeknél.

Atrial fibrillation is a common problem in the postoperative period following open-heart surgery. The pathogenesis of postoperative atrial fibrillation is likely to be multifactorial, however increased sympathetic activation may play a significant role. The aim of the study was to detect the incidence and possible reasons of atrial fibrillation in the first three postoperative days after open-heart surgery. Atrial fibrillation was detected in a total of 48 patients (mean age 64.8 +/- 8.8 years) of the 302 consecutive patients included in the study. The incidence of atrial fibrillation was 15.9%. In the history of patients with atrial fibrillation paroxysmal or persistent atrial fibrillation occurred in 18 cases. Acute ischaemia, hypopotassemia, high dose catecholamines contributed to the development of arrhythmias in 6, 4 and 4 cases, respectively. Lack of perioperative beta-blocker treatment was seen in 35 cases. Postoperative bleeding and reoperation occurred prior to the onset of atrial fibrillation in 9 instances. The applied antiarrhythmic therapy was metoprolol, amiodarone, propafenon and electrical cardioversion in 33, 21, 4 and 2 cases, respectively. Incidence of atrial fibrillation was found significantly lower in patients receiving beta-blocker premedication (13/181 [7.18%] versus 35/121 [28.9%]). There was no correlation between the incidence of atrial fibrillation and the length of the surgery, aortic-cross clamp time and the number of bypass grafts. Absence of preoperative beta-blocker treatment, previous atrial fibrillation and combined surgery were found to be strong predictors of atrial fibrillation. There was weaker association with increased age. On the basis of the outcome of our study beta-blocker premedication is suggested in most patients undergoing open-heart surgery.

Effects of non-depolarizing neuromuscular blocking agents on norepinephrine release from human atrial tissue obtained during cardiac surgery.

We have studied the effect of non-depolarizing neuromuscular blocking agents, at concentrations present in serum during anaesthesia, on release of [3H]-norepinephrine ([3H]NE) from superfused atrial appendage obtained during cardiac surgery from 48 patients. Three of the neuromuscular blocking agents (pancuronium, gallamine and rocuronium), which are known to cause an increase in heart rate during anaesthesia, increased stimulation-evoked release of [3H]NE. In contrast, (+)tubocurarine and pipecuronium, neuromuscular blocking agents that do not cause tachycardia, did not affect release of NE. Org 9487 significantly enhanced release while SZ1677 was ineffective, even at concentrations higher than those expected after administration of a 2 x ED95 dose. Atropine enhanced release. These data suggest that the axon terminals of sympathetic nerves in human heart have muscarinic heteroreceptors whose activation by acetylcholine (ACh) released from the vagal nerve reduces release of NE. This action contributes to lowering of heart rate. Therefore, any neuromuscular blocking agent with antimuscarinic actions and capable of increasing the release of NE may produce tachycardia.

Modulation of norepinephrine release by ATP-dependent K(+)-channel activators and inhibitors in guinea-pig and human isolated right atrium.

OBJECTIVE: The aim of this study was to show, whether ATP sensitive K+ channels (KATP channels), are involved in the modulation of norepinephrine (NE) release from the sympathetic nerves innervating the guinea-pig and human right atrium. METHODS: The resting and stimulation-evoked release of [3H]norepinephrine ([3H]NE) was measured from the isolated guinea-pig and human right atrium and the effect of activators and inhibitors of ATP sensitive K+ channels was studied. RESULTS: Cromakalim (30-300 microM), a KATP channel-agonist decreased concentration-dependently the stimulation-evoked release of NE from the guinea-pig atrium, an effect, antagonized by glibenclamide, a KATP channel-antagonist (30 microM). Diazoxide (30-300 microM), another activator of the KATP channels reduced the resting release of NE, and also attenuated the evoked release at a single concentration (100 microM), and this latter action was also counteracted by glibenclamide (30 microM). Pinacidil, increased dose-dependently the resting and stimulation-evoked release of NE in a glibenclamide-sensitive manner and reversed the inhibitory effect of cromakalim (100 microM), suggesting that it acts as an antagonist. Glibenclamide (30-300 microM), by itself enhanced the stimulation-evoked release of [3H]NE, and also increased the resting release of NE. On the other hand, 5-hydroxydecanoate, an ischemia-selective inhibitor of cardiac KATP channels did not change NE release. Adenosine, (30-300 microM), an A1-receptor agonist, clonidine (3 microM), an alpha 2-adrenoceptor agonist and oxotremorine, a muscarinic receptor agonist (30 microM) all reduced the evoked release of [3H]NE, but these effects were not modified by glibenclamide (300 microM), indicating that neuronal adenosine (A1), adrenergic (alpha 2) and muscarinic (M3) receptors do not act on KATP channels. In the human right atrium, cromakalim, and diazoxide did not affect significantly the release of [3H]NE. However, glibenclamide (30-300 microM) and pinacidil (30-300 microM) enhanced dose-dependently the evoked-release of NE, and pinacidil also augmented the resting release. CONCLUSIONS: Our results indicate that sympathetic nerve endings of the human and guinea-pig atrium are endowed with ATP-sensitive K+ channels. These channels responded to agonists and antagonists under the experimental conditions applied and they could modulate the release of NE thereby affecting the autonomic control of cardiac function under various physiological and pathophysiological conditions.

[Experience with a transvenous pacemaker-cardioconverter-defibrillator without subcutaneous patch]. / Transzvénás, subcutan patch nélküli pacemaker-cardioverter-defibrillátorokkal szerzett tapasztalataink.

Sudden cardiac death caused by malignant ventricular arrhythmias is one of the main causes of cardiovascular mortality. Implantation of cardioverter-defibrillators has resulted in the reduction of the incidence of sudden cardiac death caused by malignant ventricular arrhythmias from the yearly 10-30% to 1%. For the very first time in Hungary, the authors applied only transvenous lead configuration for automatic cardioverter defibrillators in three patients. The indications of the implantation were ventricular fibrillation in one case, ventricular tachycardias refractory to drug treatment in two cases. Ventricular arrhythmias were secondary to coronary heart disease in two patients, dilatative cardiomyopathy in one patient. Preoperative, intraoperative and postoperative electrophysiological studies were regularly taken. Using Biotronik Phylax 03 device with a right ventricular electrode and a superior vena cava electrode and without subcutaneous patch the intraoperative defibrillation thresholds were 6, 11 and 12 J respectively. The fractally iridium coating increases the surface of the electrodes that has a very good effect on defibrillation threshold. During a mean follow-up of six months the occurring spontaneous ventricular arrhythmias (1 ventricular fibrillation and 5 ventricular tachycardias) were terminated by Phylax 03 with cardioversion-defibrillation or overdrive stimulation. The authors' results of intraoperative testing and clinical experiences show that the Phylax 03 biphasic system due to low defibrillation thresholds without subcutaneous patch can safely be applied with only transvenous implant technique in patients with major ventricular arrhythmias to prevent sudden cardiac death and to terminate ventricular tachycardia.

Receptor mediated presynaptic modulation of the release of noradrenaline in human papillary muscle.

OBJECTIVE: The aim was to determine the presynaptic modulation of noradrenaline (NA) release from the sympathetic nerve terminals in human isolated papillary muscle. METHODS: Papillary muscle and the right atrial appendage were obtained from operations on 22 patients (10 men and 12 women). The papillary muscle preparations were preincubated with [3H]NA and the release of [3H] at rest and in response to field stimulation was measured. RESULTS: Using an immunohistochemical method dopamine-beta-hydroxylase-positive neurones were found in the papillary muscle and right atrial appendage sample. The release of noradrenaline from the papillary muscle, associated with axonal activity, was enhanced by 7,8(methylenedioxy)-14-alpha-hydroxyalloberbane HCl (CH-38083), a selective alpha 2 adrenoceptor antagonist, and inhibited by xylazine, an alpha 2 adrenoceptor agonist, indicating that negative feedback modulation was functioning. In addition, the release of [3H]NA was enhanced by atropine, pancuronium, and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), a selective M3 muscarinic receptor antagonist, and reduced by oxotremorine, a selective muscarinic receptor agonist, indicating that acetylcholine released from the parasympathetic nerve ending was able to reach the varicose noradrenergic axon terminals that are equipped with inhibitory M3 muscarinic receptors. CONCLUSIONS: These findings, obtained for the first time in human papillary muscle, indicate that the release of noradrenaline is modulated by alpha 2 autoreceptors activated by noradrenaline and M3 muscarinic heteroreceptors. Thus during parasympathetic stimulation the release of noradrenaline from the sympathetic axon terminals is presynaptically controlled through muscarinic receptors.

Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia.

Between 1967 and 1976, 1,525 Slovenian patients with a histological diagnosis of intestinal metaplasia (IM) were classified according to subtype of IM based on morphology and mucin staining; 518 cases were diagnosed with type I, 197 with type II and 275 with type III, but in 291 the diagnosis of IM was not confirmed. Patients who had developed cancer or died up to 1986 were identified by record linkage at the Slovenia Cancer Registry and the Central Population Registry in Slovenia. A total of 34 incident cases of gastric cancer occurring at least 6 months after the diagnosis of IM were identified. The standardised incidence ratio (SIR) for stomach cancer was 2.23 in the whole cohort. It was highest for IM type III, followed by type II and IM-unconfirmed, but not increased for type I. The relative risk (RR) of developing gastric cancer based on Cox's proportional hazards model was 2.14 for type II and 4.58 for type III, compared with type I. The RR was especially increased for a subgroup of type III secreting sulphomucins in their goblet cells in comparison with types I-II negative to sulphomucins. Our results confirm that subtyping of IM is useful for identifying individuals at high risk for gastric cancer.

Disseminated hereditary gastrointestinal polyposis with orocutaneous hamartomatosis (Cowden's disease).

Cowden's disease, first described by Lloyd and Dennis in 1962, is a rare disseminated polyposis of the gastrointestinal tract with an autosomal dominant inheritance pattern, infrequently cited in the contemporary gastroenterological literature. In addition to multiple polyps, which are scattered throughout the gastrointestinal tract from the mouth to the anus, orocutaneous hamartomas and frequent benign and malignant cutaneous, thyroid and breast tumors are thought to represent the most common manifestations of the disease. Ectodermal lesions are most frequently reported as a salient feature, and represent the most consistent element in the definition of this condition in the majority of cases, most of which are recorded in the dermatological literature (multiple hamartoma syndrome or Cowden's disease). This article presents four cases of Cowden's disease, the patients being members of two genetically unrelated families. All four patients had disseminated polyposis of the gastrointestinal tract, extending from the oral mucosa to the anus, while the cutaneous lesions and the concomitant tumors were present either in a fully developed or only rudimentary form, or were even absent. The authors propose that the term "disseminated hereditary gastrointestinal polyposis with orocutaneous hamartomatosis " be introduced and consistently used in the gastroenterological literature when referring to Cowden's disease, which seems more common than previous reports in the literature would indicate.