[123 I-MIBG scintigraphy in the assessment of heart failure prognosis and effectiveness of cardiac resynchronization therapy].

Cardiac resynchronization therapy (CRT) is one of the methods of treating patients with chronic heart failure, which can reduce the mortality rate of this group. Scintigraphic assessment of sympathetic myocardial innervation allows us to evaluate the heart failure prognosis and the effectiveness of interventional treatment. The method is based on use of the radiopharmaceutical 123 I-methiodiobenzylguanidine (123 I-MIBG), which is a structural analogue of norepinephrine and is able to selectively accumulate in the sympathetic nerve endings. This review includes a brief description of norepinephrine metabolism and pharmacokinetics of 123 I-MIBG in the sympathetic nerve ending, a brief description of the study methodology and the clinical significance of this method in patients with heart failure. Particular attention is paid to the possibilities of using this method in patients with severe chronic heart failure before and after CRT.

The Role of Endogenous Opioid System in the Regulation of Heart Tolerance to Stress-Induced Damage.

In Wistar rats, stress was modeled by 24-h immobilization in a supine posture and stress-induced damage to the heart was assessed by accumulation of 99mTc-pyrophosphate in the myocardium. The intensity of stress reaction was measured by serum levels of cortisol and insulin. Both stressinduced damage to the heart and intensity of stress reaction were examined under control conditions and in rats treated with opioid receptor antagonists naltrexone, methylnaltrexone bromide, MR2266, and ICI174.864. Activation of central µ-opioid receptors with endogenous opioids aggravated stress-induced cardiomyopathy, while stimulation of peripheral µ-opioid receptors produced a cardioprotective effect. The stress-induced damage to the heart was not directly related to up-regulation of cortisol secretion in response to 24-h immobilization. Blockade of the central opioid receptors promoted a decrease in cortisol level in stressed rats.

Role of ATP-Sensitive K+ Channels in Myocardial Infarct Size-Limiting Effect of Chronic Continuous Normobaric Hypoxia.

The role of KATP channels in myocardial infarct size-limiting effect of chronic continuous normobaric hypoxia was examined in a rat model based on a 20-min coronary occlusion and subsequent 3-h reperfusion. Rats were adapted to normobaric hypoxia (12% O2) for 21 days. This hypoxia produced a pronounced infarct size-limiting effect, which had been prevented by 0.3 mg/kg glibenclamide, a non-selective inhibitor of entire pool of KATP channels, or 5 mg/kg 5-hydroxydecanoate, an inhibitor of mitochondrial KATP channels. The study highlighted the important role of mitochondrial KATP channels in myocardial infarct size-limiting effect of chronic normobaric hypoxia.

Experimental Study of a Radiopharmaceutical Agent Based on Modified Fatty Acid Labeled with Technetium-99m.

Using rat model of coronary occlusion, we studied pharmacokinetics and the efficiency of a new radiopharmaceutical agent 99mTc-PDA-DTPA intended for diagnostics of changes in myocardial metabolism and its analogue 123I-PMPDA. 99mTc-PDA-DTPA was eliminated mostly by the kidneys and maximal concentration in the heart was attained within 60 min after intravenous injection; no accumulation in the area of myocardial infarction was observed. The studied substance was inferior to its analogue 123I-PMPDA by the quality of scintigraphic visualization of the heart.

[Current Possibilities of Using Radiopharmaceuticals to Evaluate Cerebral Blood Flow].

A comparison of the possibilities of using various neurotropic radiopharmaceuticals for scintigraphic evaluation of cerebral perfusion. In the whole range of radiopharmaceuticals used to diagnose cerebral blood flow disorders, there are Ceretec (99mTc-hexamethylpropyleneamine) and Neurolite (N,N-1,2-ethylenediylbis-L-cysteine-diethyl ether), which are the most optimal agents. Due to their high cost and related radiation exposure, the radiopharmaceuticals 123І-IMP (123I-isopropyl-iodoamphetamine) and 201Tl-DDC (diethyldithiocarbamate) labeled with thallium-201 virtually minimize the possibilities of being used in daily clinical practice. Fixation of 99mTc-DDC in the brain proves to be short-term, which is insufficient for tomoscintigraphy studies. Literature has been sought in the Scopus, Web of Scince, Pubmed, EMBASE, and Russian Science Citation Index databases.

Specific features of adaptation of rats to chronic cold treatment.

Permanent exposure of rats to four-week cold treatment at +4ºC for 24 h/day resulted in increased weights of the brown adipose tissue, adrenals, and spleen and had no effect on the levels of cortisol and corticosterone in the blood serum. Similar data were observed after exposure of rats to intermittent four-week cold treatment at +4ºC for 8 h/day. After short-term exposure of rats to intermittent cold treatment at +4ºC for 1.5 h/day, all indices studied were similar to those observed in intact animals.

Involvement of Protein Kinase C-δ in the Realization of Cardioprotective Effect of Ischemic Postconditioning.

Experiments on isolated perfused rat heart modeled 45-min global ischemia followed by 30-min reperfusion. Ischemic postconditioning was modeled by 3 cycles of reperfusion (30 sec) and ischemia (30 sec). Cardiomyocyte necrosis was assessed by the level of creatine phosphokinase in the perfusate. Postconditioning reduced the release of creatine phosphokinase from the heart by 30%. The cardioprotective effect of ischemic postconditioning was eliminated after inhibition of protein kinase C with cheleritrin or after blockade of δ-isoform of protein kinase C with rottlerin. These findings attest to participation of protein kinase C-δ in the realization of the cardioprotective effect of postconditioning.

Role of ß-Adrenoceptors and L-Type Ca(2+)-Channels in the Mechanism of Reperfusion-Induced Heart Injury.

We studied the effects of ß-adrenoceptor antagonists propranolol and nadolol and L-type Ca(2+)-channel blocker verapamil on cardiac reperfusion injury developed after 45-min coronary occlusion. The substances were injected intravenously 5 min before reperfusion. The results indicate that activation of ß-adrenoceptors and opening of L-type Ca(2+)-channels promote the development of cardiac reperfusion injury, while blockage of ß-adrenoceptors and/or L-type Ca(2+)-channels prevents reoxygenation-induced myocardial injury. Propranolol, nadolol, and verapamil can produce infraction-limiting effects after onset of ischemic heart injury.

Method for Studying the Myocardial Blood Flow Reserve by Load Dynamic Single-Photon Emission Computed Tomography.

We developed a method for collection and processing of scintigraphic data to estimate myocardial reserve in a gamma-chamber with cadmium-zinc-telluride detectors. Dynamic single-photon emission computed tomography of the heart with (99m)Tc-Technetril was performed in 16 coronary heart disease patients at rest and during pharmacological load. During data processing, regions of interest from the cavity and the myocardium of the left ventricle were formed and activity-time curves were constructed. The index of myocardial blood fl ow reserve was calculated as the difference between two ratios of the mean gamma-count from the myocardial area to the area under the left ventricle cavity curve (peak) during load and at rest. The mean indices of myocardial reserve in healthy volunteers and patients with coronary artery atherosclerosis were 1.86 (1.59; 2.20) and 1.39 (1.12; 1.69), respectively. The development of the method for studying myocardial reserve by single-photon emission computed tomography is an urgent problem and requires further investigations.

[ROLE OF ENDOGENOUS OPIOID SYSTEM IN THE REGULATION OF FUNCTIONAL STATE OF HEART].

The cardiovascular effects of opioid peptides may be associated with activation of opioid receptors located on the sarcolemma of cardiomyocytes, on the cell membrane of ICA and endothelial cells, on sympathetic and parasympathetic nerve terminals in the heart and in the adrenals. The cardiovascular effects of opioids penetrating the blood-brain barrier may be the result of their impact on central opioid receptors.

[INVOLVEMENT OF 5-OPIOID RECEPTORS IN THE INCREASED RESISTANCE OF HEART AND MITOCHONDRIA TO IMPACT OF ISCHEMIA-REPERFUSION AFTER ADAPTATION TO CHRONIC CONTINUOUS HYPOXIA].

It was investigated the involvement of cardiac Ϭ-opioid receptors (OR) in increasing the resistance of the heart and myocardial mitochondria to ischemia-reperfusion after adaptation rats to chronic continuous normobaric hypoxia (CCNH). Rats were subjected to CCNH for 21 days at 12 % O2. It was evoked global ischemia (45 minutes) and reperfusion (30 minutes) of the isolated perfused heart. Adaptation to CCNH promoted a reduction of creatine kinase release from necrotic cardiomyocytes during reperfusion and improved reperfusion recovery of heart contractility. Mitochondrial respiratory and state of MPT pore were more resistant to ischemia-reperfusion in adapting rats. Perfusion of isolated hearts with TIPP(0) (30 nM/l, a selective Ϭ-OR-antagonist) or naltriben (1 nM/l, a selective 52-OR-antagonist) completely eliminated the cardioprotective effect of CCNH. BNTX (1 nM/l, a selective Ϭ-OR-antagonist) had no effect on the cardioprotective effect of CCNH. This data suggest that cardiac 52-OR involved in the increased resistance of the heart and mitochondria to ischemia-reperfusion after adaptation rats to CCNH.

[CHRONIC CONTINUOUS NOR-MOBARIC HYPOXIA AUGMENTS CELL TOLERANCE TO ANOXIA(REOXYGE-NATION: THE ROLE OF PROTEIN KINASES].

The study evaluated the role of protein kinase C, PI3-kinase and tyrosine kinases in the cardi-oprotective effect of the chronic continuous normobaric hypoxia (CCNH). Adaptation to CCNH was provided by placing the rats in an atmosphere with a low content of O2 (12 %) during 21 days. Anoxia-reoxygenation of isolated cardiomyocytes of intact rats caused the deaths of 16.5 % of the cells and the lactate dehydrogenase (LDH) release of them. A similar effect on isolated cardiomyocytes of adapted rats caused the death of only 6.8 % of the cells and less pronounced increase in LDH release. Preincubation of cells for 25 minutes with one of the protein kinases inhibitors: che-lerythrine (10 |mM/l); rottlerin (1 |j.M/l); genistein (50 |mM/l) eliminated the adaptive increase in cell survival and reduction of LDH release. Incubation of cells with PI3-kinase blocker wortman-nin (100 nM/l) had no effect on the percentage of cell death of adapted animals and LDH release from them after anoxia-reoxygenation. The authors believe that the cytoprotective effect of chronic normobaric hypoxia is realized through activation of protein kinase C-5 and tyrosine kinases. Kinase PI3 - is not involved in the implementation of protective actions CCNH.

[Dynamic single-photon emission computed tomography as a method of identification of multivessel coronary artery disease].

Objective: The aim of this study was to determine the informative value of dynamic tomoscintigraphy in detection of multivessel coronary artery disease (CAD). Material and Methods: Patients with multivessel CAD (n= 16) and healthy volunteers (n= 9) underwent dynamic cardiac single photon emission computed tomography with 99mТс-MIBI at rest and during pharmacological stress-test. Processing of acquired results involved the formation of regions of interest from the cavity and the myocardium of the left ventricle used to create activity-time curves. Coronary flow reserve index was defined as a quotient of two ratios of the mean counts from the myocardial region to the integral activity in the left ventricular cavity for the studies performed during pharmacological stress test and at rest. Results: The mean values of coronary flow reserve index were 1.86 (1.59; 2.2) in group of healthy volunteers and 1.39 (1.12; 1.69) in patients with multivessel CAD. When the value of this index was less than 1.77, the method allowed for detection of three-vessel CAD with the sensitivity and specificity rates of 81.8% and 66.7%, respectively. Conclusion: Performing the standard myocardial perfusion scintigraphy in combination with the method of coronary flow reserve index assessment allows for enhancement of the diagnostic value of scintigraphic approach in the evaluation of coronary circulation disturbances in multivessel CAD.

[STRESS AND INFARCT LIMITING EFFECTS OF EARLY HYPOXIC PRECONDITIONING].

It was established that early hypoxic preconditioning is an adaptive state different from eustress and distress. Hypoxic preconditioning has the cross effects, increasing the tolerance of the heart to ischemia-reperfusion and providing antiulcerogenic effect during immobilization stress.

[MIMICKING ISCHEMIC PRECONDITIONING PHENOMENON THROUGH THE IMPACT ON THE CANNABINOID RECEPTORS: ROLE OF PROTEIN KINASE AND NO-SYNTHASE].

It was established that CB 1-receptors stimulation mimic preconditioning phenomena. Since the cardioprotective effect of cannabinoid HU-210 is occurred both in the experiments in vivo and in the experiments in vitro there are reasons to believe that the protective effect of HU-210 is me- diated via an activation of cardiac CB1-receptors. It is established that the cardioprotective effect of cannabinoid HU-2 10 is depends upon a stimulation ofprotein kinase C whereas NO-synthase is not involved in protective impact of CB1-receptor stimulation.

[INVOLVEMENT OF NO-SYNTHASE IN THE INFARCT REDUCING EFFECT OF CONTINUOUS CHRONIC NORMOBARTC HYPOXTA].

It was investigated the role of inducible and endothelial NO-synthase (NOS) in the infaret reducing effect of chronic continuous normobaric hypoxia (CCNH) on the model of coronary artery occlusion and reperfusion in rats. Rats were subjected to hypoxic exposure (12% O2 during 21 days). It has found that CCNH causes an increase in total levels of nitrate and nitrite in deproteinized blood serum in 1.5-fold and 2-fold in myocardium compared with intact animals. This effect is manifested in intact animals and in rats with a 20 minute coronary artery occlusion and reperfusi- on. Chronic continuous normobaric hvoxia exhibited infarct soaring effect. which does not manifest after pretreatment with NO-synthase inhibitor NAME (10 mg/kg intravenously), the selective inhibitor of inducible NOS S-methylisothiourea (3 mg/kg intraperitoneally), but remained after blocking neuronal NOS with 7-nitronidazol (50 mg/kg intravenously). The findings suggest that the inducible NO-synthase and nitric oxide play an important role in the implementation of the infaret limiting effect of chronic continuous normobaric hvnoxia.

Prospects of Using of κ-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia/Reperfusion.

We studied the ability of the agonist of κ1-opioid receptors U-50,488 in doses of 0.1 and 1 mg/kg to simulate ischemic pre- and postconditioning of the heart and κ-opioid receptors ICI 199,441 in a dose of 0.1 mg/kg to simulate the antiarrhythmic effect of heart preconditioning. The duration of ischemia was 10 or 45 min and the duration of reperfusion was 10 min or 2 h. Administration of 1 mg/kg U-50,488 both before ischemia and 5 min before reperfusion produced a pronounced antiarrhythmic effect. U-50,488 injected 5 min before reperfusion 2-fold reduced the ratio of infarction to risk area. Administration of ICI 199,441 in a dose of 0.1 mg/kg 15 min before ischemia produced a potent antiarrhythmic effect. Antiarrhythmic effect of κ-opioid receptor agonists depended on activation of κ-opioid receptors.

[Determination of the efficiency of single-photon emission computed tomography with 99mTc-HMPAO-labelled leukocytes in the diagnosis of myocarditis: Comparison of scintigraphic and histological data].

OBJECTIVE: to determine the efficiency of single-photon emission computed tomography (SPECT) with 99mTc-HMPAO- labelled leukocytes in diagnosing myocarditis, by comparing scintigraphic and histological data. MATERIAL AND METHODS: The investigation enrolled 35 patients with suspected myocarditis, who were planned to undergo coronaroventriculography or intervention with endomyocardial biopsy. Prior to endomyocardial biopsy, all the patients underwent myocardial scintigraphy using 99mTC-exametazime-labelled leukocytes. The results of myocardial scintigraphic and histological examinations were compared. RESULTS: Abnormal myocardial 99mTc-HMPAO-labelled leukocyte accumulation was detected in 7 (20%) examinees. Myocarditis was histologically verified in 9 (25.7%) persons. Our findings showed that the sensitivity of 99mTc-HMPAO-labelled leukocyte SPECT in diagnosing myocardial inflammatory changes was 62%; its specificity and diagnostic accuracy were 92% and 85%, respectively. Conclusion. 99mTc- HMPAO-labelled leukocyte scintigraphy is today one of a few procedures for the primary noninvasive diagnosis of myocardial inflammation. However, in view of its sufficiently low sensitivity and laboriousness and the sigh cost of consumables, the technique is irrationally used in routine clinical practice.

[PROBLEM OF END EFFECTOR OF ISCHEMIC POSTCONDITIONING OF THE HEART].

It is well known that cardiovascular disease and in particular acute myocardial infarction are a major cause of death among working-age population in Russia. Some of the patients die after successful recanalization of the infarct-related coronary artery as a result of ischemic and reperfusion injury of the heart. It is obvious that there is an urgent need to develop new approaches to prevention reoxygenation heart damages. In this regard the study of adaptive phenomenon postconditioning is of particular interest. This analysis of literature source preformed by authors of the article indicates that main pretenders to the role of end-effectors of ischemic postconditioning of the heart are: (1) Ca(2+)-dependent K+ channel of BK-type (big conductance K+ channel), (2) mitoKATp channel (mitochondrial ATP-sensitive K+ channel), (3) MPT pore (mitochondrial permeability transition pore). At the same time, some investigators consider that mitoK(ATP) channel is only an intermediate link in the series of signaling events ensured an increase in cardiac tolerance to impact of ischemia-reperfusion. The most likely end effector of these three structures is MPT pore. Alternatively, it is possible, that unique molecular complex appearing a single end effector of postconditioning does not exist. Perhaps, that there are several effectors ensured cardioprotective effect of an adaptive phenomenon of postconditioning.

Effect of Hypoxic Preconditioning on Stress Reaction in Rats.

In rats, immobilization stress (24 h) induced involution of the thymus and spleen, adrenal hypertrophy, and pronounced elevation (by 67%) of serum cortisol in comparison with intact animals; the mean number of stomach ulcers in rats subjected to stress was 6.9. Hypoxic preconditioning consisting of 6 sessions of 10-min hypoxia (8% O2) followed by 10-min reoxygenation with atmospheric air induced adrenal hypertrophy and spleen involution, but did not change blood cortisol level; no stomach ulcers were found in preconditioned rats. In rats subjected to both hypoxic preconditioning and immobilization, the weights of the thymus, adrenal glands, and spleen, as well as cortisol level did not differ from the corresponding parameters in rats subjected to immobilization stress alone. The number of stomach ulcers in experimental rats was 1.5-fold lower than in the stress-control ones. Thus, hypoxic preconditioning exerts a pronounced preventive anti-ulcer effect during immobilization, but it does not affect other indices of the stress reaction.