Perivascular tissue mediated relaxation - a novel player in human vascular tone regulation.

Perivascular tissue (PVT) modulates vascular tone, releasing adventitia/adipocyte derived relaxing factor (ADRF). Its physiological role remains unclear. We studied isolated internal thoracic artery (ITA) segments obtained from 132 patients subjected to coronary artery bypass grafting. The vessels were skeletonized in vitro and the ITA rings and PVT were incubated in separate isolated organ baths. Skeletonized ITA segments were first precontracted with 10(-5.5)mol/L 5-hydroxytryptamine hydrochloride. The PVT was next transferred to the ITA tissue bath. This resulted in relaxation of ITA, presumably related to ADRF release from PVT which was floating freely in the tissue bath. The in-vitro relaxation responses were then correlated to patients' characteristics - including demographics, clinical and laboratory data, as well as therapy. Perivascular tissue transfer resulted in 49.7 ± 26.2% relaxation of precontracted ITA segments. In multiple linear regression modelling, the relaxation of ITAto PVT was negatively related to patient age (ß = -0.67; 95% CI -1.17 - -0.17; P = 0.009), symptoms of CCS class 4 angina (ß = -20.11; 95%CI -32.25 - -7.97; P = 0.001), and positively to body mass (ß = 0.37; 95%CI 0.08 - 0.67; P = 0.01) and lack of heart failure symptoms (NYHA class 1) (ß = 9.06; 95%CI 0.33 - 17.79; P = 0.04). The relaxation response to PVT was not related to patients' sex, diabetes, hypertension, lipid profile or therapy in both univariate and multivariate analysis. PVT might play an important role in regulating vascular tone in humans as exemplified by its changing physiological function with age and in atherosclerosis.

Mechanisms of vasodilatatory effect of perivascular tissue of human internal thoracic artery.

It has beed showed that perivascular adipose tissue (PVAT) of human internal thoracic artery (ITA) releases adventitia/adipocyte-derived relaxing factor (ADRF). The precise mechanism of vasodilatatory effect of ADRF is still unknown. It was suggested that various potassium channels may be involved in the action of ADRF. The aim of this study was to assess the involvment of potassium channels in the vasorelaxing properties of ADRF in human internal thoracic artery. Human ITA rings were studied in vitro. First the ability of perivascular tissue of human ITA to release ADRF to the bath was checked. In subsequent experiments two fragments of skeletonised ITA were used to assess the involvement of various potassium channels in vasorelaxing action of PVAT. Segment of ITA, precontracted with serotonin (10(-5.5)M), was relaxed by adding PVAT to tissue bath, first without and then in the presence of appropriate potassium channel blocker. Second segment served as a control (no addition of PVAT). The magnitude of relaxation was measured and compared between preparations. This protocol was used to analyze the influence of iberiotoxin (100 nM), apamin (1 uM), 4-aminopyridine (1 mM, 5 mM), BaCl2 (100 uM) and glibenclamide (10 uM). The addition of PVAT to precontracted skeletonized ITA caused significant vasorelaxation (54.6±8.03 mN versus 33.7±6.58 mN p=0.03). Similar effect was seen when 5 ml of aliquot from separate incubation of PVAT was added (36.3±5.45 mN versus 20.7±3.02 mN; p<0.001). PVAT dependent relaxation was blocked in the presence of Ca⁺² dependent potassium channel blocker iberiotoxin (47.4±16.67 mN versus 43.3±14.54 mN; p=0.36) and 4-aminopyridine (5 mM) (59.3±3.54 mN versus 51.6±4.77 mN; p=0.12). We conclude that perivascular adipose tissue of human ITA releases relaxing factor that seems to act with the involvement of Ca⁺² dependent potassium channels.

Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy.

The goal of this experiment was to identify the presence of genetic variants in the adenosine receptor genes and assess their relationship to infarct size in a population of patients with ischemic cardiomyopathy. Adenosine receptors play an important role in protecting the heart during ischemia and in mediating the effects of ischemic preconditioning. We sequenced DNA samples from 273 individuals with ischemic cardiomyopathy and from 203 normal controls to identify the presence of genetic variants in the adenosine receptor genes. Subsequently, we analyzed the relationship between the identified genetic variants and infarct size, left ventricular size, and left ventricular function. Three variants in the 3'-untranslated region of the A(1)-adenosine gene (nt 1689 C/A, nt 2206 Tdel, nt 2683del36) and an informative polymorphism in the coding region of the A3-adenosine gene (nt 1509 A/C I248L) were associated with changes in infarct size. These results suggest that genetic variants in the adenosine receptor genes may predict the heart's response to ischemia or injury and might also influence an individual's response to adenosine therapy.

Early regional assessment of LV mass regression and function after stentless valve replacement: comparative randomized study.

Early regional performance and hypertrophy regression after stentless aortic valve replacement are still incompletely characterized. We compared early postoperative changes of segmental thickness and function after stentless and stented aortic valve replacement as assessed by cardiac magnetic resonance (CMR). In 16 patients randomly assigned to stented (Mosaic, 8 patients) and stentless (Freestyle, 8 patients) groups, 4 parallel short-axis images at the level of the apex (slice 4), midventricle (slices 2-3), and mitral valve (slice 1) were obtained with a 1.5 T CMR scanner (Magnetom Sonata, Siemens) before and 1 month after surgery. Cine images were obtained using an echo gradient sequence. Left ventricle mass was calculated as the difference between the left ventricular end-diastolic volume at the epicardial and endocardial borders multiplied by a myocardium density factor (1.05). Each slice was divided into 8 segments (octants) from anterior (octant I-II) to septal (octant V-VIII). A total of 32 segments encompassed the entire heart. From each of these elements end diastolic thickness and systolic function (fractional thickening) were calculated. In stentless valves significant reduction of septal octant thickness on the midventricular slice was noted. There was no difference in regional systolic function-segment thickening. In stented valves no segmental thickness changes were observed. In stentless valves there was early postoperative thickness reduction of septal segments at the midventricular level. However, this finding did not coincide with changes in segmental function.

Hemodynamic performance after stented vs stentless aortic valve replacement.

BACKGROUND: Stentless bioprostheses are anticipated to cause improved hemodynamics and increased longevity over stented bioprosthesis. We have compared echocardiographic analysis of stented bioprosthesis "Freestyle" with stented "Mosaic" bioprosthesis. Because of similar technology (0 pressure fixation, anticalcification) any differences may relate to stent. METHODS: Twenty-eight patients undergoing AVR were randomly assigned to receive either stented or stentless. Echocardiograms, by means of M-mode and Doppler were performed early, 3-6 months and 1 year postoperatively. RESULTS: The peak flow velocity was significantly lower in the stentless group, especially 1 week and 6 months after surgery. Mean transvalvular gradient dropped significantly in stentless group and did not change in stented group. EOA did not change significantly in either of groups. AoV velocity time integral was increasing in stentless group. LV mass had fallen significantly in both groups but degree of mass reduction was comparable. CONCLUSIONS: There are marked improvements of stentless valves hemodynamics. However it is not necessary equal to higher degree of LV mass reduction during 1 year follow-up.

[The physical capacity of men with ischaemic heart disease after cardiac rehabilitation]. / Ocena wydolnosci fizycznej mezczyzn rehabilitowanych z powodu choroby niedokrwiennej serca.

The aim of the study was the evaluation of physical capacity of cardiovascular system and the ability to perform permitted exercises in a group of 114 patients who underwent pharmacological or surgical treatment of ischaemic heart disease and subsequently were submitted to 12 month lasting cardiac rehabilitation. Rehabilitation programme comprised hospital, sanatorium and ambulatory periods. The control group comprised 29 patients without changes in coronary arteries. All patients underwent treadmill test, according to Bruce protocol. The efficacy of rehabilitation was estimated in the particular groups regarding to the method of treatment. 143 men, were enrolled in the study in following groups: A--patients with the history of myocardial infarction (MI) treated pharmacologically (n = 29) B--patients with the history of MI after surgical treatment (n = 29) C--patients without MI after surgical treatment (n = 28) D--patients without MI treated pharmacologically (n = 28) K--control group (n = 29). All men in groups A, B, C completed cardiac rehabilitation programme. The highest level of physical capacity was observed in group of operated (CABG) patients. Patients treated pharmacologically reached significantly lower level of physical capacity.

Comparison of retrograde vs simultaneous ante/retrograde cold blood cardioplegia.

BACKGROUND: To evaluate the homeostasis of myocardium during simultaneous continuous retrograde and antegrade cardioplegia vs retrograde continuous cardioplegia. METHODS: 40 patients who underwent elective operation of coronary arteries bypass grafting were randomly assigned to 2 groups: group one consisted of 24 patients who received retrograde continuous blood cardioplegia; group two consisted of 16 patients who received simultaneous continuous ante/retrograde cardioplegia. The following measurements were taken: acidosis, oxygen content, oxygen extraction and oxygen consumption; they were taken before and after cross-clamp releasing from coronary sinus effluent and from arterial line. Incidence of low cardiac output, ventricular fibrillation, raised cardiac enzymes and ischemic changes on ECG was noted. RESULTS: In simultaneous group such parameters as acidosis, oxygen content, oxygen extraction and myocardial oxygen consumption recovered after cross-clamping and changes of their values were respectively: 0.0005, 0.87 ml/100 ml, 0.098 and 1.4 ml/min. The same parameters didn't recovered in retrograde group and changes were respectively: 0.05 - p=0.2; 3.7 ml/100 ml - p=0.006, 0.29 p=0.006 and 7.4 ml/min - p=0.03. These changes were significant between groups. CONCLUSIONS: Metabolic viability of myocardium measured with oxygen utilisation is better preserved with simultaneous antegrade and retrograde cardioplegia.

Does simultaneous antegrade and retrograde cardioplegia improve functional recovery and myocardial homeostasis?

BACKGROUND: The purpose of our research was to evaluate the functional recovery and homeostasis of myocardium during simultaneous continuous retrograde and antegrade cardioplegia versus continuous retrograde cardioplegia. METHODS: Forty patients who underwent elective coronary artery bypass grafting (CABG) were prospectively assigned to two clinically matched groups and analyzed in respect to cardioplegia protocol. Group I consisted of 24 patients who received continuous retrograde blood cardioplegia; Group II consisted of 16 patients who received simultaneous continuous ante- and retrograde cardioplegia. Hydrogen ion release, carbon dioxide, lactate concentration oxygen content, and oxygen extraction were measured from coronary sinus effluent and from the arterial line before and after cross-clamping of the aorta. Median changes of these parameters were reported. Cardiac output was measured and left and right ventricle stroke works were calculated. Incidence of low cardiac output, ventricular fibrillation, raised cardiac enzymes, and ischemic changes on electrocardiogram (ECG) were noted. RESULTS: In the simultaneous group, oxygen content and oxygen extraction recovered well after cross-clamping. The same parameters did not recover to the same extent in the retrograde group. These changes were notable between groups. Hydrogen ion, carbon dioxide, and lactate releases were comparable between groups. Trend toward better recovery of left ventricle stroke work index was encountered in the simultaneous group. CONCLUSIONS: Viability of myocardium measured with oxygen utilization and functional recovery is better preserved with simultaneous antegrade and retrograde cardioplegia. However, there is no difference in anaerobic metabolism markers. Thus simultaneous ante- and retrograde cardioplegia is probably advantageous over retrograde alone.

[The evaluation of the coronary artery sufficiency in myocardial infarction patients after cardiac surgery and preventive therapy]. / Ocena wydolnosci wiencowej u chorych po zawale serca leczonych operacyjnie lub zachowawczo.

During 5 years period (1989-1993) the authors investigated a group of 40 patients with coronary artery disease after myocardial infarction treated in the Silesian Center of Cardiology in Katowice. 20 patients were operated on (CABG), 20 were medically-treated. It was evaluated the history, physical status, stress-test, echocardiography and 24-hours ECG. Stress test was estimated according to Mark's test. In the echocardiographic examination it was observed wall motion score index (WMSI) and the left ventricular abnormal contraction area (AA). In the operated group it was noticed higher physical ability and no influence of CABG on left ventricular contractability.

Intraoperative and laboratory evaluation of skeletonized versus pedicled internal thoracic artery.

BACKGROUND: The skeletonization of internal thoracic artery is postulated to improve graft length, early blood flow, sternal blood supply, and postoperative respiratory function. Concern exists that skeletonization may injure internal thoracic artery, precluding good results of surgery. Reports on endothelial function of skeletonized internal thoracic artery are lacking. METHODS: A prospective assessment of early clinical outcomes of 357 consecutive patients undergoing coronary artery bypass grafting was performed: 287 patients with nonskeletonized and 70 with skeletonized left internal thoracic artery (LITA). The lengths of LITA and of its discarded distal segment, as well as free LITA blood flow, were measured. The dose-effect relationship for relaxation to acetylcholine was studied in the organ bath. RESULTS: Apart from a higher incidence of breaching the pleura with nonskeletonized LITA the clinical outcomes were comparable. The length of skeletonized LITA was 17.8+/-1.14 cm versus 20.3+/-0.52 cm skeletonized (p = 0.11). The length of discarded LITA was shorter in nonskeletonized artery (0.8+/-0.28 cm versus 2.6+/-0.49 cm; p = 0.022). The free LITA blood flow was 66.3+/-7.42 mL/min in nonskeletonized vessel versus 100.3+/-14.84 mL/min in skeletonized (p = 0.048). The acetylcholine-induced relaxation was similar in both groups (maximal relaxation, 80.7%+/-5.95% in nonskeletonized versus 72.9%+/-9.11% in skeletonized; not significant; negative logarithm of half-maximal effect, 7.43+/-0.18 versus 7.1+/-0.10, respectively; p = 0.063). CONCLUSIONS: Skeletonization does not damage the endothelial function of the LITA. Higher free blood flow and available LITA length should encourage the use of skeletonized LITA in clinical practice.

Coronary artery bypass grafting without cardiopulmonary bypass--initial experience of 50 cases.

This study was undertaken to assess our experience with the first 50 patients who underwent CABG without cardiopulmonary bypass. In seven patients left internal mammary artery to left anterior descending artery (LIMA-LAD) grafting was performed through a short left anterior thoracotomy. In 43 other patients median sternotomy was used. Primary CABG was performed in 48 patients; there were two reoperations. Eleven patients had unstable angina. Three patients had left ventricular ejection fraction (LVEF) equal to or lower than 25%. One patient had carcinoma of the right lung coexisting with unstable angina and underwent also right lower lobectomy. In each patient the clinical course, 12-lead ECG, transthoracic echocardiography and the serum levels of creatine kinase (CPK), alanine aminotransferase (ALAT), aspartate aminotransferase (AspAT) were assessed. The need for inotropic or intraaortic balloon counterpulsation (IABP) support and blood transfusion was also recorded. There were three deaths, all in the sternotomy group (6%). A patient with systemic lupus erythemetodes (SLE) died of postoperative MI due to graft thrombosis. Another patient who was found to have porcelain aorta and had LIMA-LAD grafting as a rescue procedure died of MI with low cardiac output. The third patient with unstable angina and ejection fraction of 30% developed postoperative MI with ventricular arrhythmia. One patient with LIMA-LAD graft in whom percutaneous translaminal coronary angioplasty (PTCA) had been abandoned because of coronary spasm developed acute myocardial ischaemia 5 h postoperatively. He had a vein graft placed to LAD in cardiopulmonary bypass, his further course was uneventful. Six patients had IABP support. Nine patients needed inotropic support. Ten patients received blood transfusion. Twelve-lead ECG did not show acute ischaemia or MI, apart from the above described cases. Echocardiographic check showed improved IVS contractility in three patients and better apex motion in one case. In the other survivors the echocardiographic findings were the same as before the procedure. ALAT and AspAT serum levels were normal in all the survivors, and the CPK levels did not exceed 200 IU/ml. One patient from the mini-thoracotomy group had recurrent angina 2 months after the procedure. His left internal mammary artery (LIMA) graft was occluded; we replaced it with a vein graft. All 47 survivors remain asymptomatic, with the mean follow-up time of 6 months. Coronary surgery without cardiopulmonary bypass seems a valuable alternative for high-risk patients.

Comparison of retrograde versus antegrade cold blood cardioplegia: randomized trial in elective coronary artery bypass patients.

OBJECTIVE: Myocardial areas distal to complete coronary artery occlusion are poorly protected by antegrade cardioplegia. Hence, retrograde cardioplegia becomes an important adjunct in myocardial protection. An aim of the study was to compare both methods prospectively. METHODS: 158 coronary artery bypass grafting (CABG) patients were randomly assigned to two groups according to myocardial protection technique: 89 patients to group 1--retrograde cold blood cardioplegia (RCBC); and 69 patients to group 2--antegrade cold blood cardioplegia (ACBC). Preoperative parameters were similar but cross-clamp time and volume of cardioplegia needed were higher in the retrograde group. The results were assessed on the basis of: (1) clinical outcome; (2) ECG and enzymatic parameters of ischemia; (3) assessment of early systolic function by means of cardiac output (CO), stroke work index (SWI), left ventricular stroke work index (LVSWI) and right ventricular stroke work index (RVSWI) taken before, and 1 and 5 h after coming off bypass; (4) late systolic and diastolic function by echo assessment of segmental contractility of 17 segments and indexes of peak transmitral flow (TMI) taken 7 days and 6 months after operation. RESULTS: Ischemic events, inotropes and ventricular fibrillation on reperfusion were significantly more frequent in the antegrade group. Sinus rhythm at an early stage postoperatively was found more frequently in the retrograde group. All these parameters became comparable 24 h after operation. Early myocardial recovery was better in the retrograde group where intraoperative improvement in CO and SWI was significant. At the same time, SWI decreased significantly in the antegrade group. RVSWI changes were similar in both groups. There were no differences in mortality and perioperative MI. Late myocardial performance by segmental contractility and diastolic transmitral flow were similar in both groups. CONCLUSIONS: Retrograde continuous blood cardioplegia reduces ischemic injury and permits better early recovery of myocardial function. There is no difference, however, regarding long-term assessment of myocardial recovery.

Internal mammary artery graft function is not affected in hypertensive patients on therapy.

Results are presented which assess the reactivity of isolated human internal mammary artery fragments from non-hypertensive and treated hypertensive patients in vitro. Material from three patient groups was examined: group I, no hypertension; group II, arterial hypertension treated with ACE inhibitors; and group III, arterial hypertension treated with nifedipine. Responses to KCl, norepinephrine and acetylcholine, as well as the influence of N(G)-monomethyl-L-arginine (L-NMMA) on the effects of norepinephrine were tested. Response to KCl was highest in group III, while the contractile reactivity to norepinephrine was depressed in group II. Relaxation after acetylcholine was enhanced in groups II and III. Incubation of vessel fragments with L-NMMA sensitized the tissue to norepinephrine in the order of potency group II>group III>group I. Internal mammary artery function as the graft, and particularly in terms of endothelial function, is not adversely affected in arterial hypertension, although proper antihypertensive treatment may be essential.

Gastric tonometry as a method of visceral oxygenation monitoring in patients undergoing coronary revascularisation.

OBJECTIVE: The aim of the study was to assess gastric mucosal pH during certain parts of a major cardiac procedure (hypo- and normothermic), and then throughout the first postoperative day. METHODS: Gastric mucosal pH was measured using a tonometer, in 15 patients subjected to elective CABG procedures. The patients were also assessed haemodynamically and serum lactate concentrations were measured. RESULTS: It was found that cardiopulmonary bypass did not suppress visceral perfusion. The most critical was the period between 4th and 12th postbypass hour when a tendency towards decreased cardiac output and oxygen delivery was noted. At the same time oxygen consumption was increasing which resulted in triggering of anaerobic metabolic pathways, that was mirrored by significant rise in serum lactate levels. During this period of time the lowest, although not critical levels of gastric mucosal pH were recorded, suggesting a relative decrease in splanchnic perfusion. CONCLUSION: Extracorporeal circulation does not significantly compromise splanchnic perfusion. Tonometry is a valuable, non-invasive method of visceral oxygenation monitoring. The first postoperative day is an especially critical time for a cardiac patient--a frequent control of haemodynamic and acid-base balance parameters is absolutely mandatory.

Results of mechanical prosthetic valve replacement in active valvular endocarditis.

UNLABELLED: To evaluate the results of mechanical prosthetic valve replacement for active endocarditis 71 patients were reviewed. They were treated surgically between 1988 and 1993 in our institution. Mechanical valves were used in 54 patients (group 1) and bioprosthetic valves were used in 17 patients (group 2). In terms of demographic, clinical and surgical variables prior to operation groups were statistically the same. Follow up ranged from 2-63 months averaged 21 months. This study was carried out to: asses cardiac status postoperatively and assess the rate of mortality, recurrency and reoperations. METHODS: Evaluation of cardiac status was assessed on the basis of symptoms and findings by examination, ECG, X-ray, echocardiography, and laboratory tests. Data analysis was done by means of statistical tests like: Student's "t"-test, Fisher exact test, one sided test of difference between two percentages, Kaplan Meyer survival analysis and Cox test. RESULTS: 4-year mortality was 20% in group 1 comparing to 28,6% in group 2, when early mortality were 13% in group 1 comparing to 17% in group 2. These differences were not significant. The recurrency rate was 8,5% in group 1 comparing to 28,6% in group 2 which was statistically significant (p=0.028). Especially early recurrency rates differed significantly between groups and were 4,2% in group 1 comparing to 21% in group 2 (p=0.022). The reoperations rate was 4,2% in group 1 comparing to 21% in group 2 which was statistically significant (p=0.022). Clinical status showed satisfactory values and significant improvement in both groups, slightly better after mechanical valve replacement. CONCLUSION: It is concluded that mechanical valve is recommended for valve replacement in active valvular endocarditis first of all due to low recurrency and reoperation rate.

Surgical treatment of atrial septal aneurysm.

The atrial septal aneurysm (ASA) is a morphologic abnormality known to cause peripheral and pulmonary embolism. 28-52% patients with ASA have embolic events. However ASA -- with no other concomittant cardiac patology has rarely been reported as the indication for open heart surgery. In this work, five cases of patients operated for ASA are presented. Embolic complications with cerebral symptoms were presented in three cases. The diagnosis of ASA was established with the use of transesophageal echocardiography. The surgical correction of the defect was performed in extracorporeal circulation. The aneurysmal part of interatrial septum was excised and replaced with a pericardial patch. The postoperative course was uneventful. The patients have no new embolic events during the follow up period of one year.

[Silent myocardial ischemia before and after revascularization]. / Nieme niedokrwienie miesnia serca przed i po rewaskularyzacji.

In 82 patients with unstable ischemic heart disease (IHD) before and after revascularisation (percutaneous transluminal coronary angioplasty-PTCA-in 11 patients and coronary artery bypass graft-CABG-in 71 patients) silent ischemia incidence was observed. In these patients before and after operation election fraction (EF) and wall motion score index (IK) were compared echocardiographically as well as physical ability according to Bruce protocol in treadmill exercise test. Data (EF and IK and exercise test) before and after operation didn't change significantly. Silent ischemia was directed before operation in 17 patients (21.8%) and in 15 patients (19.4%) one month after those procedures.

The dihydropyridines modulate neurotensin inotropic action paradoxically.

The interaction of neurotensin and calcium channel modulators is examined in isolated electrically driven guinea pig left atrial appendages. Left guinea pig atria exposed to diltiazem become desensitised to neurotensin. There is no significant influence of verapamil pretreatment on the neurotensin inotropic action. Nifedipine pretreatment causes increase in the inotropic response of guinea pig atria to neurotensin. The regression line of neurotensin after pretreatment with nifedipine compared to the regression line of neurotensin alone has higher slope and is shifted to the left. The ED50 of neurotensin after nifedipine pretreatment compared with the ED50 of neurotensin alone results in potency ratio of 2.24. Bay K8644 significantly decreases the inotropic effect of ED100 of neurotensin. Results suggest that: (1) the mechanism of interaction of calcium channel modulators and neurotensin in the atrium does not depend on the calcium influx through calcium channel nor does it on the calcium channel itself; (2) the interaction of nifedipine and neurotensin is possibly dependent on dihydropyridine receptors, (3) the dihydropyridine binding site, possibly different from voltage-sensitive calcium channel, is somehow involved in the neurotensin action in guinea pig atria.

Reactivity of isolated human right atria to norepinephrine in various disease states.

The reactivity of isolated, electrically driven, right human atrial muscle to norepinephrine was studied in patients with coronary heart disease, with and without proximal right coronary artery occlusion, and in patients with mitral valve disease. The dose-effect curves for norepinephrine and ED50 doses for each group were compared. We found no difference in reactivity of atria from both coronary artery disease groups. The mitral valve disease group dose-effect curve was shifted to the right (potency ratio 3.98), and the maximal effect was significantly higher than in both coronary artery disease groups. We suggest that adrenoreceptor down regulation could account for observed ED50 difference. The difference in maximal responses could depend on more effective contraction mechanism in mitral valve disease myocardium. We conclude that occlusion of proximal right coronary artery does not necessarily mean ischaemia of right atrium and/or ischaemia does not change myocardium reactivity to norepinephrine.