[Dynamic of cerebrovascular disorders in patients with carotid stenosis]. / Techenie tserebrovaskuliarnoi patologii u bol'nykh so stenoziruiushchim porazheniem sonnykh arterii.

AIM: To study the state of cerebral hemodynamics and platelet hemostasis in patients with carotid stenosis (CS). MATERIAL AND METHODS: The prospective study included 123 patients with atherosclerotic CS. The 1st group included 53 patients (mean age 52±12.5 yrs) who underwent carotid endarterectomy (CEA); the 2nd group - 70 patients who were treated conservatively (mean age 58.5±15.9 yrs). The state of blood flow through the main arteries of the head (Doppler flowmetry), platelet aggregation induced by adrenaline, the frequency of acute cardiovascular events that occurred during 12 months were evaluated. RESULTS AND CONCLUSION: The severity of neurological deficits and cognitive impairment increased with increasing of the degree of CS. CEA leads to an improvement of cerebral hemodynamics and stabilization of cognitive functions. The adverse course of the disease occurred in 23.6% of patients (stroke/heart attack during the year in 5.7%, progression of cerebral ischemia in 20%, restenosis within 5 years after CEA in 15%). Hyperaggregation of platelets induced by ADP and epinephrine and decreased aggregation of platelets induced by collagen in patients receiving ASA were identified in 53% of the operated and in 60% of non-operated patients. The use of combined antiplatelet therapy normalize the platelet hemostasis and reduce the frequency of acute cardiovascular events.

[Treatment tactics for patients with combined atherosclerotic lesions of brachiocephalic and coronary arteries].

OBJECTIVE: To evaluate the tactics of surgical treatment of patients with coronary heart disease and atherosclerotic lesions of cerebral vessels in dependence of risk stratification of heart and brain complications. MATERIAL AND METHODS: One hundred and fifty-six patients were examined. Cerebral and coronary blood flow and functional state of the brain and heart were studied. According to treatment characteristics, 3 groups were singled out: patients of the 1(st) group underwent simultaneous surgery of coronary and brachiocephalic arteries, patients of the 2(nd) group were first operated for brachiocephalic arteries, in the 3(rd) group, bypass graft was performed in the first stage. RESULTS AND CONCLUSION: A role of coronary and brachiocephalic arteries, functional state of the myocardium and brain in the postoperative risk was established. The authors suggest the algorithm for choosing the order of priority of surgical interventions on coronary and brachiocephalic arteries.

[Surgical prevention of stroke in patients with carotid stenosis]. / Khirurgicheskaia profilaktika ishemicheskogo insul'ta u bol'nykh so stenoziruiushchim porazheniem vnutrennikh sonnykh arterii

Objectives. To study the cerebral and central hemodynamics in patients with stenotic lesions of inner carotid arteries (ICA) before and after reconstructive surgery. Material and methods. Fifty-nine patients, aged from 46 to 78 years, with >50% atherosclerotic stenosis of ICA who underwent preventive carotid endarterectomy (CEAE) were examined. The isolate stenosis of ICA was identified in 13.6% of patients, concomitant lesions of brachiocephalic arteries in 86.4%. Atherosclerotic lesions of coronary arteries were found in 91.1% of patients and those of arteries of lower extremities in 45.8%. In 25.5% of patients, the heart surgery was performed before the current hospitalization. Heterogeneous atherosclerotic plaques with dense or hyperdense components were more frequents in symptomatic stenosis (63.3%). The maximal stenosis was identified in heterogeneous hyperechogenic plaques, the minimal ones in homogenous hypoechogenic plaques. Parameters of central hemodynamics were better in patients with 2nd stage of reconstructive surgeries. The emission fraction decreased proportionally to the degree of stenosis. The parameters of cerebral hemodynamics were significantly decreased in ICA stenosis and improved in the early post-surgery period. Results. CEAE promoted the improvement of cognitive functions and the recovery of motor functions. The best positive dynamics was recorded in asymptomatic ICA stenosis. Poor outcome (transitory ischemic attacks, urgent surgery, restenosis) was found in patients with low levels of central and cerebral hemodynamics 12-24 months after the discharge. Moreover, smoking and the degree of stenosis predicted poor outcome. Conclusions. Surgical treatment in combination with the complex pharmacotherapy (hypotensive drugs, antiaggregants and statins) had the maximal effect, including the remote period.

[Modern approaches to diagnostics and surgical correction of brachiocephalic arteries disorders in patients with ischemic heart disease].

The main causes of morbidity in Russia are ischemic heart and cerebrovascular disease. The mortality rate of these conditions accounts for almost 50% of all the lethality causes of the Russian population. The frequency of associated coronary and brachiocephalic arteries disorders varies from 18 to 54%. The complex evaluation of the anatomical and functional features of the disorder, as well as of the perfusion and functional heart and brain reserves allows to choose the appropriate methods of surgical treatment of patients with associated coronary and carotid disorders and to decrease the risk of intra- and postoperative cerebral and cardiac complications. The modern approaches of myocardium and cerebral revascularization enable to safely and effectively eliminate the myocardial and cerebral ischemia, to significantly decrease the risk of myocardial infarction and stroke development and to ensure the long ability to work among this group of patients. Over 500 patients with ischemic heart disease and associated brachiocephalic arteries disorders have been operated at the A.N. Bakoulev Scientific Centre for Cardiovascular Surgery for the last 5 years. The results of these operations are comparable to the ones of the leading European clinics.

[Changes in cognitive functions in patients with occlusive lesions of brachiocephalic arteries after reconstructive surgery on carotid arteries].

Seventy-six patients after the reconstructive surgery on carotid arteries underwent neuropsychological testing with the MMSE, the FAB, the Clock Drawing Test at baseline and 8-10 days and 3 months after the surgery. Patients were stratified into 3 groups: 20 patients with predominant lesions of one internal carotid artery (group 1), 22 patients with bilateral carotid stenosis (group 2) and 34 patients with the combination of lesions of carotid and vertebrobasilar system (group 3). The association between the rate of spreading of atherosclerotic processes in cerebral vessels and cognitive disorders was shown. The positive effect of reconstructive surgery on cognitive functions of patients was confirmed.

Cardiac contractility modulation with the impulse dynamics signal: studies in dogs with chronic heart failure.

The intravenous use of positive inotropic agents, such as sympathomimetics and phosphodiesterase inhibitors, in heart failure is limited by pro-arrhythmic and positive chronotropic effects. Chronic use of these agents, while eliciting an improvement in the quality of life of patients with advanced heart failure, has been abandoned because of marked increase in mortality when compared to placebo. Nevertheless, patients with advanced heart failure can benefit from long-term positive inotropic support if the therapy can be delivered 'on demand' and in a manner that is both safe and effective. In this review, we will examine the use of a novel, non-stimulatory electrical signal that can acutely modulate left ventricular (LV) contractility in dogs with chronic heart failure in such a way as to elicit a positive inotropic support. Cardiac contractility modulation (CCM) with the Impulse Dynamic(trade mark) signal was examined in dogs with chronic heart failure produced by intracoronary microembolizations. Delivery of the CCM signal from a lead placed in the great coronary vein for periods up to 10 minutes resulted in significant improvements in cardiac output, LV peak+dP/dt, LV fractional area of shortening and LV ejection fraction measured angiographically. Discontinuation of the signal resulted in a return of all functional parameters to baseline values. In cardiomyocytes isolated from dogs with chronic heart failure, application of the CCM signal resulted in improved shortening, rate of change of shortening and rate of change of relengthening suggesting that CCM application is associated with intrinsic improvement of cardiomyocyte function. The improvement in isolated cardiomyocyte function after application of the CCM signal was accompanied by an increase in the peak and integral of the Ca(2+) transient suggesting modulation of calcium cycling by CCM application. In a limited number of normal dogs, intermittent chronic delivery of the CCM signal for up to 7 days showed chronic maintenance of LV functional improvement. In conclusion, pre-clinical results to date with the Impulse Dynamics CCM signal indicate that this non-pharmacologic therapeutic modality can provide short-term positive inotropic support to the failing heart and as such, may be a useful adjunct in the treatment of advanced heart failure. Additional, long-term studies in dogs with heart failure are needed to establish the safety and efficacy of this therapeutic modality for the chronic treatment of this disease syndrome.

Electrical modulation of cardiac contractility: clinical aspects in congestive heart failure.

Heart failure is a highly prevalent disease in western society. Drug therapies aimed at increasing myocardial contractility have been associated with decreased survival. Several short and mid term clinical studies have suggested adjuvant or alternative therapies to congestive heart failure using modified pacing techniques that were aimed to increase contractility (e.g. Paired pacing) or restore synchrony of contraction (biventricular pacing). While delivery of paired pacing was abandoned during the early 70's, biventricular pacing has recently emerged as an adjuvant treatment to limited group of congestive heart failure patients with aberrant left ventricular conduction. In this brief review, we describe our initial safety and efficacy experience in patients with heart failure using a novel non-stimulatory electrical approach to the delivery of positive inotropic therapy to the failing myocardium. The study suggests that unlike modified pacing techniques, delivery of the signal to the left ventricle during the refractory period resulted in a rapid increase in myocardial contractility and improved hemodynamic performance. The near instantaneous contractility improvement achieved by this type of stimulus was shown to be safe and effective independently of the primary cause of heart failure or the function of the conduction system. Unlike pharmacologic treatments, which have a relatively constant effect, use of electrical stimuli may prove useful as a new therapeutic modality in the treatment of heart failure with which contractility can be improved when and as needed.

Neurotransmitter-induced novel modulation of a nonselective cation channel by a cAMP-dependent mechanism in rat pineal cells.

In the rat, circadian rhythm in melatonin is regulated by noradrenergic and neuropeptide inputs to the pineal via adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca2+-dependent mechanisms. We have identified a large conductance (170 pS), voltage-dependent, nonselective cation channel on rat pineal cells in culture that shows a novel mode of modulation by cAMP. Pituitary adenylate cyclase activating peptide (PACAP), norepinephrine, or 8-Br-cAMP increase channel open probability (Po) with a hyperpolarizing shift in voltage dependence such that the channel becomes active at resting membrane potentials. The increase in Po was accompanied by a change in current rectification properties such that the channel was transformed from being inactive at rest to an inwardly rectifying cation conductance in the presence of agonist, which depolarizes the cell. This channel is calcium insensitive, is blocked by Cs+, and shows a permeability sequence: K+ > Na+ >/= NH+4 > Li+. The data suggest that PACAP and norepinephrine acting through a cAMP-dependent mechanism modulate this nonselective cation channel, resulting in a slow onset depolarization that may be important in regulation of pineal cell excitability.

A novel cGMP-activated Cl- channel in renal proximal tubules.

Cl- channels activated by natriuretic peptides were detected in cultured rat proximal convoluted tubule (PCT) cells with the use of patch-clamp methodology. Bath application of atrial natriuretic peptide (ANP) activates a 150-pS Cl- channel with the open probability (Po) of the channel increasing from 0.0008 +/- 0.0003 to 0.021 +/- 0.008. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), a membrane-permeable analogue of cGMP, increased channel activity in the on-cell mode. In inside-out patches the channel was activated by cGMP in a dose-dependent manner. Channel activity decreased after washing out and increased on reapplication of cGMP. A similar activation was observed also in presence of either of two protein kinase inhibitors, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride or KT5823, or a phosphatase inhibitor. Bath application of urodilatin mimicked the action of ANP. Po of the channel was found to be independent of both voltage and Ca2+, and gating activity could be blocked by the stilbene, 4,4-dinitrostilbene-2,2-disulfonic acid. These results demonstrate a Cl- conductance in PCT cells modulated by ANP and urodilatin via their second messenger, cGMP.

Diverse modulations of chloride channels in renal proximal tubules.

Cl- selective channels were detected and characterized in apical membranes of cultured rat renal proximal convoluted tubule cells (PCT) using patch-clamping methods. Subpopulations of Cl- channels modulated by cyclic nucleotides, Ca2+, or voltage were identified. Two different 30-pS, voltage-independent, Cl- channels modulated by adenosine 3',5'-cyclic monophosphate (cAMP) or Ca2+ were seen most frequently. The cAMP-dependent channel was activated by membrane-permeable analogues of cAMP, dibutyryl-cAMP or 8-bromo-cAMP. Catalytic subunit of protein kinase A (PKA) applied to detached inside-out patches, activated the channel as well, suggesting activation via phosphorylation. Channel activity was blocked by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, by 4,4-dinitrostilbene-2,2-disulfonic acid, and by SCN-. Permeability sequence for different halides was Cl- > I > F with a Cl(-)-to-cation permeability ratio (PCl/Pcation) of 7:1. The Ca(2+)-sensitive channel was not activated by cAMP nor by PKA. A third anionic selective channel encountered infrequently is voltage dependent and has a unitary conductance of 145 pS, with a PCl/Pcation value of 9:1. This diversity of Cl- channels may underlie the rich repertoire of physiological functions attributed to Cl- channels.