The role of external Ca²âº in the action of Ca²âº-channel agonists and antagonists on isolated human thoracic arteries.

In systemic atherosclerosis develops the abnormal vascular tone which is associated with elevated calcium influx into smooth muscle cells and their calcification that may be proportional to the extent and severity of atherosclerotic disease. The goal of the present study was to investigate the responses of isolated human arterial samples to Ca²âº-channel agonists and antagonists by varying the external Ca²âº concentration. Two dihydropyridine type calcium-channel blockers, amlodipine and cerebrocrast, were used in this study. The benzodiazepine-type calcium-channel blocker diltiazem, the benzimidazole derivative 1-acetyl-5,6-dimethoxy-2-methylthiobenzimidazole and 3,4'-bipyridine derivative milrinone were also used. Experiments were carried out on isolated human thoracic artery samples obtained from 74 patients, aged 38-88 years, during conventional myocardial revascularisation operations. The contraction of artery samples was recorded using an iFOT10 force transducer. Cumulative concentration-contraction curves of the tested agents (10⁻7 to 10⁻4 M) were established by varying the external Ca²âº concentration from 0.9 mM to 2.7 mM. Cerebrocrast, regardless of the Ca²âº concentration significantly increased arterial contraction, particularly at the lower Ca²âº (≈77%). Diltiazem, the benzimidazole derivative and milrinone caused the artery samples to relax at 10⁻4 M concentrations by 55%, 55% and 44%, respectively, when the external Ca²âº corresponded to the physiological standard. Shifting to lower or higher Ca²âº concentrations significantly altered the response of vessel samples by increasing their contraction. In conclusion, the present study shows that the response of isolated human thoracic artery samples to both the slow calcium channel suppressant diltiazem and to agonists of that channel (milrinone and the benzimidazole derivative) is regulated by the amount of calcium present in the physiological solution. Treatment with a slow calcium channel inhibitor, the 1,4-dihydropyridine derivative cerebrocrast, resulted in a response that was independent of the external Ca²âº concentration.

Effects of intraoperative external head cooling on short-term cognitive function in patients after coronary artery bypass graft surgery.

The aim of study was to assess the effects of an intraoperative external head-cooling technique on cognitive dysfunction in the early postoperative period (at the 10th day) in patients after coronary artery bypass graft (CABG) surgery. Patients in Group H (n=25) were cooled with CPB and the intraoperative, external head-cooling technique, patients in Group C (n=25) were cooled only with cardiopulmonary bypass (CPB) to achieve mild hypothermia (33 - 34 °C). Cognitive function was analyzed before the operation and after the surgery using the Mini Mental State Examination (MMSE), the Modified Visual Reproduction Test from the Wechsler Memory Scale, Trail Making (A/B), WAIS--Digit Span (WDS) and WAIS Digit Symbol Substitution Test (WDSST). The incidence of cognitive impairment at the 10th day after the surgery was 36% (n=9) in Group H and 64% (n=16) in Group C (p=0.048). The temperature during the aortic cross-clamp period was associated with a lower rate of cognitive dysfunction (p=0.05, r(2)=0.09). The intraoperative, external head-cooling technique during the aortic cross-clamp period has a neuroprotective effect and leads to less short-term cognitive function impairment after CABG surgery.

The influence of mean arterial blood pressure during cardiopulmonary bypass on postoperative renal dysfunction in elderly patients.

The aim of the study was to find out if there is an optimal mean arterial blood pressure (MABP) during cardiopulmonary bypass (CPB) for renal function in elderly patients during the early postoperative period. We analysed the data of 122 patients >70 years of age with normal preoperative renal function who had been subjected to coronary artery bypass grafting (CABG) procedures on CPB. Patients were divided into 3 groups, according to MABP during CPB: group MP (n=50) included patients whose MABP was maintained between 60-70 mmHg; group LP (n=36), the MABP was <60 mmHg; and group HP (n=36) where the MABP was >70 mmHg. The patients' clinical data were evaluated during the first three postoperative days. The rate of renal impairment (urine output <50ml/h) in the early postoperative period after cardiac surgery did not differ among the groups. Oliguria developed in 3 patients (6%) of the MP group, in 2 patients (5.6%) in the LP group and in 6 patients (16.7%) in the HP group (χ(2)=3.6, df=2, p=0.161). Evaluation of MABP on renal excretion showed that there was no difference in urine output among the groups. Serum creatinine levels at the end of the first postoperative day in groups MP, LP and HP were 102.7±20.1, 116.4±58.6 and 113.2±39.8 µmol/L, respectively (F=0.5, df=2, p=0.640). There were no significant differences among the groups at the end of the second and the third day either. Volume balance at the end of surgery and during the early postoperative period was similar in all groups. The need for diuretics did not differ among the groups. The length of postoperative hospital stay was not significantly different among the groups. Our study did not reveal any relationship between a MABP of 48-80 and postoperative renal dysfunction in elderly patients after CABG surgery.

Simultaneous coronary artery bypass grafting and vascular operations: early and mid-term results.

AIM: The purpose of this study was to estimate the results of surgical strategy for patients undergoing simultaneous coronary and peripheral artery surgical interventions and to compare their early and mid-term clinical results with the results of the isolated coronary artery bypass grafting (CABG) operations. METHODS: From 1999 to 2005, 78 patients underwent simultaneous vascular reconstructions following CABG. All the patients were divided into 3 groups: CABG and carotid artery group (CAG), CABG and peripheral vascular group (PVG), and CABG and abdominal aortic aneurysm group (AAAG). RESULTS: In CAG, early mortality was 2%, postoperative myocardial infarction and stroke rates were 2% and 6.1%, respectively. In PVG, one (4%) patient had postoperative stroke, and there were neither deaths nor myocardial infarctions. PVG and CAG did not differ significantly in postoperative complications and mortality rates from the isolated CABG group. The simultaneous abdominal aortic aneurysm operations were related to higher early mortality rate (2 out of 6). Using the Kaplan-Meier analysis, the 3-year overall survival probability in the simultaneous operation group was 82%; the 5-year overall survival probability, 74%. PVG and CAG did not differ in the survival probability from the isolated CABG group. The survival probability in AAAG was lower than in the isolated CABG group. CONCLUSION: The simultaneous CABG and vascular operations whenever indicated are feasible procedures to be performed on patients with concomitant carotid artery and/or peripheral vascular occlusive disease. The surgical management of coronary artery disease followed by abdominal aortic aneurysm repair remains still controversial.

Surgical treatment of congestive heart failure in coronary artery disease.

Heart failure (HF) is a pathophysiological condition, when the heart can not provide adequate blood flow to the body organs. The main cause of HF is now ischemic heart disease (IHD), and the number of patients with HF in aging society is growing. HF is becoming the leading cause of death. Medical therapy does not provide satisfactory results in respect of symptoms and survival (5 year survival 28-40%). Therefore there is a trend towards early invasive methods of IHD treatment: percutaneous or surgical revascularisation and surgical reconstruction of myocardial damage. Most common surgical procedure in IHD is coronary artery bypass grafting (CABG). This treatment is safe and effective in patients with normal ventricular function (operative mortality 0.5%, 5 year survival >92%). Results in patients with impaired left ventricular (LV) function are better than conservative therapy, but still not satisfactory (operative mortality 8.4%, 5 year survival 65%). The modern surgical concept for improvement of ventricular function is left ventricular (LV) shape and volume restoration (SVR) accompanied by CABG. In cases of severe damage of myocardium resulting in left ventricular aneurysm or akinesia, SVR improves LV function and prevents further LV remodeling. At present it is under investigation whether SVR is of benefit for moderate-sized ventricles and NYHA class II symptoms. In case of ischemic mitral insufficiency mitral valve repair is a method of choice. The results of combined procedures in Heart Failure group (CABG + MV reconstruction or SVR) are better than CABG alone. Other surgical alternatives for HF treatment are: heart transplantation, ventricular assist devices (VAD), dynamic cardiomyoplasty, constrictive devices and cellular transplantation therapy. Heart transplantation is reserved for younger patients with less comorbidities. Shortage of donor organs and poor long-term results remains a main problem of such a treatment. VAD at present is still very expensive, and serves particularly as a "bridge to heart transplantation" or "bridge to recovery" rather than destination therapy. Despite of all achievements in medical or invasive HF treatment further basic and clinical works as well as new organization systems are necessary to find optimal strategies to reduce cost of care, improve quality of life and survival.

Changes of beta2-adrenergic stimulation induced by hyperosmosis in human atrium.

PURPOSE: The purpose of the present study was to determine whether extracellular osmotic pressure modulates beta2-adrenergic stimulation of the contraction force and L-type Ca2+ current in human atrial myocytes. MATERIAL AND METHODS: Experiments were performed on human atrial trabeculae and myocytes isolated from the right atrium. The concentration dependent effect of salbutamol (SAL), a beta2-adrenoreceptor agonist, on peak tension (P) and L-type calcium current (ICaL) under isoosmolar (345 mOsm) and hyperosmolar (405 or 525 mOsm was achieved by adding of mannitol) conditions was studied. RESULTS: Salbutamol (10 nmol/L-10 micromol/L) added to the control solution increased P by 180.6 +/- 45.8% over control with a half-stimulation constant EC50 = 27 +/- 6 nmol/L. Under isoosmolar conditions SAL (0.1/10(3)nmol/L) increased ICaL by 182.3 +/- 19.8% over control with an EC50 2.9 +/- 0.9 nmol/L. In hyperosmolar solutions the same concentrations of SAL increased P and ICaL by 57.2 +/- 12.6% and 217.2 +/- 70.5% over control with EC50 = 640 +/- 260 nmol/L and 12 +/- 5 nmol/L respectively. CONCLUSIONS: These results indicated that hyperosmolarity reduced the effect of beta2-adrenergic stimulation, i.e. the dose-response curve of salbutamol on L-type calcium current was shifted to the higher concentration range and maximal increase in contraction force was diminished in human atrial cells.

Heart tissue viability monitoring in vivo by using combined fluorescence, thermography and electrical activity measurements.

A prototype system for in vivo monitoring of the heart tissue viability by using combined measurements of fluorescence, thermography and electrical activity has been elaborated for cardiac surgery. The fluorescence imaging of nicotinamide adenine dinucleotide NAD(P)H in the blue light range (lambda=467 nm) by using UV light (lambda=347 nm) excitation was used to detect metabolic disturbances. The method of the principal component analysis was used for the processing of the fluorescence image sequences. Far infrared (lambda=7.5-13 microm) imaging was used to evaluate temperature dynamics of the tissue surface during circulation disturbances. Evaluation of the epicardial electrogram shape by using continuous wavelet transform was used to detect and evaluate ischemia-caused disturbances of the electrical activity of the tissue. The combination of temperature, fluorescence and electrical activity estimates obtained from synchronically registered parameters during the experiments on model systems and experimental animals yielded qualitatively new results for the evaluation of cardiac tissue viability and enabled to achieve a versatile evaluation of the heart tissue viability.

Does alpha-1-proteinase inhibitor play a protective role in coronary atherosclerosis?

BACKGROUND: alpha-1-proteinase inhibitor (alpha-1-PI) might appear to be actively involved in atherogenesis as an important regulator protecting elastic tissue from damage by proteinases as well as lipid accumulation in arterial wall. MATERIALS AND METHODS: alpha-1-PI genetic variants were examined in 156 male coronary atherosclerosis patients (mean age 49+/-9 years). The frequency of alpha-1-PI phenotypes was determined in 1577 healthy individuals. Also, 108 long-survivors (mean age 92.7+/-4.3 years) were investigated for alpha-1-PI phenotype. The serum level of alpha-1-PI was examined in 43 coronary atherosclerosis patients (mean of age 49.6+/-8.1 years) and in different age groups of healthy males. A correlations between seruma-1-PI concentration and apoB, and apoA-1 were calculated. Relationship between serum alpha-1-PI and apolipoprotein B/apolipoprotein A-1 (apoB/apoA-1) ratio was determined. Isoelectric focusing of alpha-1-PI phenotypes was performed on thick polyacrylamide gels with ampholytes pH 3.5-5.0, 4.5-6.5 and 4.2-5.0. A quantitative assessment of alpha-1-PI, apoB and apoA-1 was performed by ELISA method using antibodies against human alpha-1-PI, apoB and apoA-1. RESULTS: The phenotype PI ZZ of alpha-1-PI associated with a severe congenital deficiency of alpha-1-PI in patients and long-lived subjects was not found. In population this phenotype (0.06%) as well as PI SS phenotype (0.06%) was detected once. No significant difference was found in the frequency of PI*M, PI*S and PI*Z genes in the coronary atherosclerosis group and population. The PI*Z gene was significantly more frequent in patients with coronary atherosclerosis than in long-survivors (P<0.01). The correlation between blood serum (-1-PI concentration and age in the control group of males was significant (r=-0.83, P<0.01). The alpha-1-PI concentration was found significantly higher in coronary atherosclerosis patients compared with control (2.14+/-0.6 and 1.68+/-0.3 g/l respectively, P<0.05). The alpha-1-PI concentration was found to dependent on the apoB/apoA-1 ratio: it was higher in patients having apoB/apoA-1>1.0 than in patients with apoB/apoA-1<1.0 (2.4+/-0.6 and 2.04+/-0.5 g/l respectively, P<0.05). There was a significant correlation between alpha-1-PI concentration and apoB/apoA-1 ratio in blood serum of patients suffering from coronary atherosclerosis (r=0.25, P<0.05). CONCLUSIONS: Derangements in the homeostasis of proteinase-antiproteinase system could be involved in destruction of the arterial wall connective tissue. The local as well as systemic inactivation of alpha-1-PI in atherosclerosis process could be related with hyperlipidemia. Investigation of long-survivors support the suggestion that they are important antiatherogenic control group for evaluating the role of genetic determinants in atherogenesis. Congenital (alpha-1-PI deficiency, hyperlipidemia) and acquired (related to smoking, aging) imbalance of proteinase-antiproteinase system is considered to one of the atherogenic factors. Authors discuss the possible mechanisms of atherogenesis related with imbalance of proteinase-antiproteinase system.

Mitral valve procedures in ischemic regurgitation.

A restrictive definition of ischemic mitral regurgitation (IMR) has allowed us to select a more uniform cohort of 41 patients having undergone mitral valve surgery for IMR between January 1993 and March 1995. Thirty-six patients (88%) presented with chronic and five with acute IMR. All patients had at least one significant stenosis in the circumflex area. Left ventricular ejection fraction averaged 35%. Transesophageal echocardiography (TEE) revealed a > or = 3+ MR in 30 patients and an intermittent, fluctuating or grade 2+ MR in 11 (27%). Annulus dilatation was found in all cases, and it was the only mechanism in 10 (24.4%). Leaflet restrictive motion was clearly seen in 17 cases (41.5%) and leaflet prolapse in 14 (34%). In doubtful cases, an intra-operative dynamic testing using TEE, and associating a loading test and an afterload test, led to the indication of a valve procedure in 11/19 patients (58%). An average of three distal coronary anastomoses per patient were constructed. Mitral valve replacement (MVR) was unavoidable in four patients (9.8%); at least the posterior leaflet subvalvular apparatus was preserved in all. Repair of the mitral valve (Mvrep) was achieved in 37 cases (90%). Ring annuloplasty alone was performed in 27 cases (73%). In the remaining 10 cases, leaflet prolapse was corrected by various artifices such as flip-over technique, quadrangular resection, papillary muscle plication or commissuroplasty. At the 10th postoperative day, a residual MR was found in 4/34 cases (11.8%), only after isolated ring annuloplasty. The four patients who have died in the ICU after MVrep belonged to the same group of isolated ring annuloplasty; this mortality of 4/27 (14.8%) illustrates the mediocre prognosis of marked annulus dilatation and impaired LV function with restrictive leaflet motion. Overall, the hospital mortality (14.6%) more reflected the mode of presentation of the patients than the type of operative technique: when a short and definitive procedure is required by a precarious general condition, one should not hesitate to prefer a rapid MVR to a complicated repair. At 4.5 months, there was no significant improvement in LV dimensions. At six months, 80.5% of the patients survived, with 88% of them being in NYHA class I or II.

A posteroseptal accessory pathway located in a coronary sinus aneurysm: diagnosis and radiofrequency catheter ablation.

A coronary sinus aneurysm was diagnosed by means of echocardiography, coronary sinus contrast angiography, coronary angiography, and nuclear magnetic resonance imaging in a patient with Wolff-Parkinson-White syndrome caused by a posteroseptal accessory pathway. Percutaneous radiofrequency current catheter ablation performed in the isthmus of the coronary sinus aneurysm was successful.

Diagnosis and surgical treatment of ectopic atrial tachycardia.

Eighty-two patients with ectopic atrial tachycardia (EAT) were subjected to radical closed heart surgery (without cardiopulmonary bypass). The age of the patients ranged from 1 to 51 years. Permanent EAT was present in 19 patients, incessant EAT in 14, and paroxysmal EAT in 49 patients. Preoperative electrophysiological study included computed analysis of the P wave vector. Ectopic foci were established in the right atrium in 34 patients, in the left atrium in 11, in the interatrial septum in 32, and extracardially in 5 patients. For ablation or isolation of the foci, the cryogenic technique was used in 74 patients, cryo- and laser techniques in 4, and the laser technique alone in 1 patient. In 3 patients resection of the atrial auricles including the ectopic focus was undertaken. In 4 patients complete AV block was induced and a cardiac pacemaker implanted. After primary surgery, favourable results were obtained in 71 patients. In 11 patients recurrences were observed; 8 of these patients underwent successful repeat surgery. In 3 patients medical treatment was effective. Finally, the follow-up results have been promising-79 patients (96.4%) (including 4 patients in whom a complete AV block was created) have become arrhythmia-free. When EAT is resistant to medical treatment, closed heart ablation of the ectopic focus has proved to be safe (no mortality or morbidity) and effective. It can therefore be recommended not only for the termination of EAT but also for the prevention of dilated cardiomyopathy.