[Scintigraphic assessment of alterations in cardiopulmonary haemodynamics and renal functional activity in patients with endured coronary artery bypass grafting].

OBJECTIVE: By means of scintigraphic methods to assess alterations in cardiopulmonary haemodynamics and renal functional activity in patients with coronary artery disease (CAD) after endured coronary artery bypass grafting (CABG) performed in conditions of extracorporeal circulation (EC) and on the functioning heart. MATERIAL AND METHODS: We examined a total of 40 patients presenting with CAD (mean age 54.90±1.12 years) after endured CABG. All patients were subdivided into 2 groups: Group One consisting of 20 patients subjected to CABG performed on the beating heart with the use of myocardial "stabilizer" "Acrobat" (Study Group) and Group Two also comprising 20 patients but undergoing surgery with the use of extracorporeal circulation (Comparison Group). All patients included into the study were subjected to radiocardiopulmonography with (99m)Tc-pertechnetate and dynamic radionuclide renoscintigraphy with (99m)Tc-DTPA before and 6-7 days after operative treatment. RESULTS: In the early postoperative period after CABG, the patients of the both groups were found to have a significant increase in the minute volume, cardiac index, and circulation efficiency coefficient, accompanied by a significant decrease in the period of half-emptying of the left ventricle, thus suggesting improvement of LV contractility. Improved pulmonary microcirculation resulting from operative treatment in the compared groups of patients was confirmed by significantly shortened time of the indicator's passing through pulmonary vessels at the expense of both arterial (TAM) and venous (TVM) components. At the same time, a decrease in these parameters in the Study Group patients was more pronounced as compared with the Comparison Group patients. Thus, the means of the difference between the pre- and postoperative values of TAM and TVM in the Study Group amounted to 1.78 ± .40 s and 1.78 ± 0.32 s, and in the Comparison Group to 0.95 ± 0.22 s and 0.98 ± 0.16 s, respectively (p=0.029 and p=0.031 for TAM and TVM, respectively). The Comparison Group patients after CABG were found to have a significant decrease in the mean values of the total glomerular filtration rate (GFR) in combination with decelerated clearance of the indicator from blood. 30% of patients under the effect of nonpulsating blood flow developed relatively pronounced renal dysfunction (a decrease in the total GFR and/or GRF of one of the kidneys by 15% and more as compared with the initial level). Besides, these patients also demonstrated significant changes in the half-clearance of the radiopharmaceutical from the renal parenchyma and the index of cortical retention of the indicator on the both sides. Unlike the Comparison Group, in patients without EC the average values of the majority of parameters of renal filtration activity underwent no statistically significant alterations as compared with the baseline (prior to CABG) values. CONCLUSION: Coronary artery bypass grafting without cardiac arrest exerts less pronounced negative influence upon the state of the renal function as compared with the open-heart surgery with extracorporeal circulation, which may partially be conditioned by statistically more significant positive dynamics of microcirculation in the system of pulmonary circulation under the effect of myocardial revascularization with the use of the myocardial stabilizer "off-pump".

[Capabilities of 99mTc-pyrphotech single-photon emission computed tomography in combination with myocardial perfusion scintigraphy in the evaluation of inflammatory changes in the heart of patients with persistent atrial fibrillation].

AIM: To estimate the capabilities of 99mTc-pyrphotech single-photon emission computed tomography (SPECT) in the diagnosis of myocardial inflammatory changes in patients with persistent atrial fibrillation (AF). SUBJECTS AND METHODS: Nineteen patients (11 males and 8 females, mean age 47.46 ± 9.92 years) with persistent idiopathic AF underwent preoperative complete clinical and instrumental examination. 99mTc-pyrphotech SPECT was performed to identify foci of myocardial inflammatory changes. After completing 99mTC-pyrphotech scanning, resting myocardial perfusion scintigraphy with 99mTC-methoxyisobutylisonitrile (99mTc-MIBI) was performed in accordance with the standard protocol. The scintigrams obtained in both studies were then combined using the applied programs Jet Stream Workspace Release 2.5 (Philips) and the application Fusion. During invasive intervention, endomyocardial samples were intraoperatively taken from all the patients for histological and immunohistochemical examinations. RESULTS: Abnormal 99mTc-pyrphotech myocardial accumulation was found in 7 (36.8%) of the examinees, multiple foci in 3 cases and single foci in 4. Analysis of perfusion scintigrams indicated that the mean abnormal accumulation of 99mTc-MIBI in the left ventricle was 3.75 ± 0.88% (maximum 9%). Histological examination of endomyocardial samples from 19 patients with persistent AF verified myocarditis in 4 (21%) patients and myocardial sclerosis concurrent with other abnormalities in 15 (78.9%) patients. CONCLUSION: Latent lymphocytic or polymorphic cellular myocarditis of viral etiology is a cause of idiopathic AF in 20% of the cases. 99mTc-pyrphotech scintigraphy may be one of the primary noninvasive diagnostic techniques for the detection of myocardial inflammation in this form of arrhythmia.

[Cardioprotective effect of remote postconditioning: mechanisms and possibility of clinical application].

Experimental data indicate that postconditioning at distance is an effective method of cardiac protection against reperfusion injury. Remote postconditioning prevents reperfusion necrosis and apoptosis of cardiomyocytes, decreases probability of postinfarction remodeling of the heart. Cardioprotective effect of remote postconditioning is depended on release from tissues after transient ischemia of humoral factor(s) increasing cardiac tolerance to long-term ischemia-reperfusion. Clinical studies show that postconditioning at distance is an effective method of prevention of reperfusion injury of the heart during coronary artery bypass surgery.

[Endogenous opioid system as a mediator of acute and long-term adaptation to stress. Prospects for clinical use of opioid peptides].

It has been well established that opioid peptides (OPs) affect various hormonal systems. Opioids exhibit stress-limiting and gastro-protective effects in stressed animals, acting via mu- and delta-opioid receptors (OR). Peripheral mu-OR stimulation by endogenous and exogenous opioids increases cardiac tolerance to pathological consequences of stress. Enhancement ofprostacyclin synthesis, decrease of thromboxane production as well as suppression of lipid peroxidation can be directly responsible for cardioprotective effects of OPs in stressed animals. Adaptive responses are accompanied by increased OP levels in blood and tissues. Reduction of ventricular arrhythmias induced by repeated short-term immobilization stress is mediated via mu-OR stimulation by endogenous opioids, while delta-OR account for an antiarrhythmic effect of adaptation to chronic intermittent hypobaric hypoxia. The mechanism of infarct size-limiting effect of continuous normobaric hypoxia involves both mu- and delta-OR stimulation. Peptide OR agonists can be considered in future clinical practice for treatment of withdrawal syndrome, stress-related cardiac disease or myocardial injury caused by ischemia-reperfusion insult.

[Mediated role of NO-syntase, protein kinase C and KATP-channels in realization of cardioprotective impact of cannabinoid HU-210].

It was shown that perfusion of the isolated heart of rat with solution containing the CB1- and CB2-receptor agonist HU-210 at concentrations of 0.1 or 1.0 microM/L for a duration of 10 min at 20 min before global ischemia (45 min) and reperfusion (30 min) promotes a twofold decrease in creatine kinase levels in coronary effluent. It was established that KATP channel blockade by glibenclamide (1 microM/L) or inhibition of protein kinase C (2 microM/L) by chelerythrine abolishes the cardioprotective effect of HU-210. The inhibitor of NO synthase L-NAME (1 microM/L) had no effect on the anti-necrotic effect of HU-210. Thus, the intracellular signaling mechanism of the cardioprotective effect of the CB-agonist HU-210 involves the activation of KATP channels and protein kinase C without the participation of NO-synthase.

[Perspective of creation of drugs on basis of opioids increasing cardiac tolerance to pathogenic impact of ischemia reperfusion].

It was established that delta- and kappa1-opioid receptor (OR) stimulation both in vivo and in vitro promotes a decrease of infarct size/area at risk (IS/AAR) ratio during ischemia and reperfusion of heart. mu-OR activation increases a tolerance of isolated perfused heart to impact of ischemia and reperfusion but has no effect on IS/AAR index in vivo. The ORL1-receptor agonist nociceptin does not exert IS/AAR ratio in vivo. Delta- and kappa1-OR stimulation prevents cardiomyocyte apoptosis during ischemia and reperfusion of heart. The delta- and kappa1-OR agonists mimic infarct-reducing effect of postconditioning. The OR inhibition does not impact IS/AAR index both in vivo and in vitro. The delta1-, delta2- and kappa1-OR agonists are the most perspective group of opioids for creation of drugs increasing cardiac tolerance to pathogenic impact of ischemia and reperfusion.

[The impact of antihypertensive therapy on cerebral hemodynamics in patients with metabolic syndrome].

The aim of this work was the scintigraphic study of brain perfusion and the elucidation of the relationship between daily variations of arterial pressure (AP) and the results of single photon emission computed tomography (SPCT) of the brain in patients with metabolic syndrome (MS). The secondary objective was to estimate effect of combined antihypertensive therapy on cerebral circulation. 24 patients with MS underwent SPCT with 99mTc HMPOA and 24 hr AP monitoring before and 6 mo after therapy with long-acting verapamil combined with slow-release indapamide or enalapril. It was shown that all the patients suffered disturbances of regional cerebral blood flow even in the absence of focal neurological symptoms. Perfusion was especially impaired in the temporal, occipital and superior frontal lobes. The degree of the night-time fall in AP was related to the level of perfusion in the right temporal region (r = -0.5; p = 0.04) which confirms the danger of extreme AD decrease in hypertonics during sleep. Combined antihypertensive therapy has positive influence on cerebral perfusion. Verapamil plus enalapril has more pronounced effect than verapamil plus indapamide on cerebral blood flow in many brain regions.

[Neuroprotective effect of ischemic postconditioning and remote preconditioning. Prospective of clinical use].

Ischemic postconditioning enhances brain and spinal cord tolerance to ischemia and reperfusion. There are no clinical data on the neuroprotective effect of postconditioning. It was established that foregoing effect of ischemic postconditioning depended upon an activation of PKCs, ERK, Akt kinases and a decrease in the activity of JNK kinase. Superoxide dismutase, Bax, Bal-2 and HSP proteins may be the end effector of postconditioning. Postconditioning phenomenon is mimicked by norepinephrine, diazoxide, sevoflurane, isoflurane and propofol. It is unknown before whether these pharmacological agents prevent brain reperfusion injury in human. Remote preconditioning improves brain and spinal cord tolerance to ischemic and reperfusion damages. There are no data on the neuroprotective effect of remote preconditioning in human at ischemic insult. The endogenous cannabinoids, reactive oxygen species are triggers of remote preconditioning. The neuroprotective effect of preconditioning at distance is depended on the activation of p38, ERK kinases and is attributed to enhancement of HSP-70 protein synthesis.

[Comparative characteristics of revealing hibernated myocardium by means of perfusion and metabolic scintigraphy].

OBJECTIVE: comparative assessment of the informative value of the methods of perfusion and metabolic single-photon emission computed tomography (SPECT) in detecting the hibernated myocardium. MATERIALS AND METHODS: the study included a total of twenty six patients diagnosed with coronary artery disease (CAD). Of these, there were 24 men and 2 women, mean age 52.0±7.0 years. All the patients in order to detect the viable myocardium were subjected to perfusion scintigraphy of the myocardium with (99)mTc-technitrile («Diamed¼, Russia) at rest and in a combination with the nitroglycerine test, as well as metabolic scintigraphy of the myocardium with (123)I-labelled beta-methyl-ρ-iodophenyl pentadecanic acid (BMIPP). RESULTS: the studies showed that sensitivity of myocardial scintigraphy with (99)mTc-technitrile on the background of the nitroglycerine test amounted to 89%, with specificity of 85% and diagnostic accuracy of 86%. While calculating the diagnostic significance of SPECT with (123)I-BMIPP, in turned out that the method's sensitivity amounted to 94%, specificity to 87%, and diagnostic accuracy to 91%. CONCLUSION: perfusion scintigraphy of the myocardium on the background of the nitroglycerine test and scintigraphic assessment of metabolism of fatty acids are highly informative tests for revealing viable portions of the ischemic myocardium, with the diagnostic parameters of SPECT with (123)I-BMIPP being slightly superior to those of perfusion scintigraphy with (99)mTc-technitrile on the background of sublingual administration of nitroglycerine.

[Assessment of the functional state of the right ventricle by radionuclide tomoventriculography].

The aim of this work was to evaluate the potential of radionuclide tomoventriculography (RTVG) for the study of the functional state of right ventricle (RV) in patients with thromboembolism of branches of the pulmonary artery (TEPA) or ventricular arrhythmias. A total of 96 patients were admitted for examination to the clinics of Research Institute of Cardiology, Siberian Division of Russian Academy of Medical Sciences in 2006-2008. They were divided into 3 groups. Group 1 (n = 40) included patients of mean age 62 +/- 11 years with non-massive TEPA, group 2 (n = 15) patients with coronary heart disease NYHA class I-II (50 +/- 9 years), group 3 (n = 4) children and adolescents 13.2 +/- 3.7 years with ventricular extrasystole and/or monomorphic ventricular tachycardia. All patients were examined by ECG-synchronized RTVG. The study showed that this method can be used to efficaciously determine volume characteristics of right ventricle, ejection fraction, relationship between fast and slow filling phases, and intreventricular dyssynchronism. The functional ability of the right side of the heart in patients with minor lesions in the pulmonary vasculature should be regarded as a sign of acute thromboembolism and marked systole-diastolic dysfunction of right ventricle (under similar conditions) as a manifestation of chronic post-thromboembolic hypertension. The number of areas of asynchronous myocardial contractions and the degree of intraventricular dyssynchronism detected by RTVG positively correlate with the degree of contractile dysfunction of right ventricle. Scintiographic signs of intraventricular dyssynchronism suggest predominance of contractile heterogeneity of right ventricle over physiological one.

[Radionuclide methods for diagnostics of non-rheumatic myocarditis and postmyocarditic cardiosclerosis].

We compared the results of comprehensive scintigraphic examination of 35 patients with suspected myocarditis and the data of clinical, immunological, laboratory and instrumental studies. The patients were divided into 3 groups. Group 1 included 11 patients with preliminary diagnosis of acute myocarditis, group 2--11 patients with chronic myocarditis, group 3--13 patients with postmyocarditic cardiosclerosis. All patients were tested for antimyocardial antibodies, underwent 99mTc-HMPAO-labeled leukocyte and perfusion scintiography of myocardium. The study did not reveal significant differences between the three groups as regards the results of laboratory and instrumental studies. Elevated titers of antimyocardial antibodies were found in 70% of the patients in group 1, 100% in group 2, and 46% in group 3. Patients with chronic myocarditis had the highest titers of antibodies. Pathological accumulation of 99mTc-HMPAO-labeled leukocytes in myocardium was documented in 36.4 and 81.8% of the patients of groups 1 and 2 respectively. They were absent in the heart of group 3 patients. Disturbed myocardial perfusion was recorded in 45.5, 81.8 and 84.6% in groups 1, 2 and 3 respectively. The magnitude of accumulation of leukocytes was not significantly different between the groups. Results of the study suggest rather high specificity of radionuclide techniques for diagnostics of inflammatory lesions in myocardium. However, further studies are needed to confirm their sensitivity and accuracy.

[Radionuclide renal scintigraphy in assessment of nephroprotective effect of hypoxic preconditioning for myocardial revascularization under artificial circulation].

OBJECTIVE: Using renal scintigraphy to assess the nephroprotective efficacy of hypoxic preconditioning (HP) during myocardial revascularization under the conditions of artificial circulation (AC). MATERIALS AND METHODS: We examined a total of forty-seven patients with CAD (mean age 52.81 +/- 1.40 years) who endured coronary artery bypass grafting (CABG) under AC. All patients were randomly divided into 2 groups:patients (n = 16) who during CABG underwent HP (study group) and those (n = 31) without renal protection (comparison group). HP was performed in the mode of one cycle of 10-minute hypoxemia followed by a 5-minute period of reoxygenation. Dynamic radionuclide renal scintigraphy with 99mTc-DTPA was carried out before and 6-7 days after surgical treatment with calculating the parameters of the filtrating and excreting renal function. RESULTS: The comparison-group patients after CABG were found to have negative dynamics of the parameters of the renal filtration activity. Thus there was a significant decrease in the mean values of total and individually for each kidney glomerular filtration rate (GFR) combined with deceleration of the blood clearance. Besides patients of this group showed a significant increase in the mean value of the half-period of excretion of the indicator from the pelvicalyceal system of the left kidney and the parenchyma of the both kidneys. The study group patients showed no alterations in the values of the filtration activity of the kidneys as compared with the baseline measures, with the exception of the GFR of the right kidney. Thus a decrease in the filtration function of either one kidney or both kidneys under the influence of non-pulsating blood flow was observed only in three (19%) patients and was not pronounced. Alterations in the indices reflecting the excretory renal function in the study group were also insignificant. CONCLUSION: Radionuclide renal scintigraphy makes it possible to objectively and with a high level of the informative value to determine the degree and pattern of the effect of open-heart surgery on renal functional activity. HPC exerts a nephroprotective effect action on the renal functional activity in patients with endured open-heart surgery in the conditions of assisted circulation.

[Hypoxic preconditioning as novel approach to prophylaxis of ischemic and reperfusion damage of brain and heart].

Analysis of published data indicates that delayed hypoxic preconditioning essentially increases a cardiac and brain tolerance to ischemia-reperfusion. There are no experimental data in the literature on the neuroprotective effect of early hypoxic preconditioning in vivo. Clinical observations indicated that early hypoxic preconditioning exerts cardioprotective and neuroprotective effects. The single works testify that cardioprotective effect of delayed hypoxic preconditioning depend on the activation of inducible NO-synthase, KATP-channels and KCa-channels. Neuroprotective effect of hypoxic preconditioning is a consequence: (1) erythropoietin receptor stimulation and (2) an elevation of activity of PI3-Akt and ERK1/2 kinases. The supposed end effector of brain hypoxic preconditioning is MPT-pore.

[Parameters of perfusion pulmonoscintigraphy and radionuclide tomoventriculography in non-massive thromboembolism of pulmonary-artery branches].

OBJECTIVE: The present work was aimed at identifying the most informative parameters of perfusion pulmonoscintigraphy and radionuclide tomoventriculography in non-massive thromboembolism of the pulmonary-artery branches. MATERIALS AND METHODS: We examined a total of fifty-five patients. The Study Group was composed of 40 subjects (mean age 60.3 +/- 10.4 years) presenting with non-massive pulmonary artery thromboembolism (PATE). The Comparison Group comprised 15 patients with coronary heart disease (CAD) (average age 59.0 +/- 9.0 years, NYHA functional class I-IT circulatory insufficiency). All patients were subjected to perfusion-ventilatory pulmonoscintigraphy and radionuclide equilibrium tomoventriculography. The basic systolic and diastolic parameters of the right ventricle (RV) were determined using the obtained RESULTS: The Group of patients with non-massive PATE (i. e., damage to the pulmonary vascular bed up to 50%) turned out hypertension. quite heterogeneous by the severity degree of the RV contractility dysfunction. This Group included the patients with and without signs of RV contractility dysfunction. Taking into consideration small extension of the lesion, normal values of functional capability of the right portions of the heart may be interpreted as a sign of acute PATE, whereas the presence of pronounced systolicdiastolic dysfunction of the right ventricle should be regarded as apathognomonic sign of chronicpost-thromboembolic pulmonary hypertension. CONCLUSIONS: The most informative scintigraphic signs of right-ventricular dysfunction in thromboembolism of the pulmonary-artery branches are as follows: a decrease in the RV stroke volume, peak ejection rate and filling rate which are revealed even in insignificant embolisation of the lesser-circulation vessels. The preserved functional ability of the right portions of the heart in patients with a small scope of damage to the vascular bed of the lungs may be regarded as a sign of acute thromboembolism, while systolic-diastolic dysfunction of the right ventricle as one of the indices of chronic post-thromboembolic pulmonary hypertension.

[Radionuclide renoscintigraphy for the evaluation of nephroprotective action of acetylcysteine].

Radionuclide renoscintigraphy was used to evaluate efficiency of nephroprotection by N- acetylcholine in 36 patients subjected to coronaroangiography (CAG). The patients were randomly allocated to 2 groups, one undergoing CAG without nephroprotection, the other CAG in combination with N-acetylcholine nephroprotector. Dynamic radionuclide renoscintigraphy with 99m Tc-dtpa was performed before and 2-3 days after CAG; the results were used to estimate filtration and evacuation efficiency of the kidneys. Patients of group 1 showed negative dynamics of the renal function following CAG including decreased mean glomerular filtration rate and slowed down blood clearance. Mean half-time of 99mTc elimination from the pelvicalyceal system and parenchyma of the left kidney as well as its cortical retention index in bot kidneys increased. The filtration activity of the kidneys did not significantly change after CAF in patients of group 2; it was slightly impaired only in 5 (28%) of them. More patients suffered deterioration of 99mTc elimination but on the whole changes in the evacuation activity of both parenchyma and pelvicalyceal system were statistically insignificant. It is concluded that acetylcholine has nephroprotective action in patients subjected to radionuclide renoscintigraphy.

[Scintigraphic evaluation of cerebral circulation in prognosis of cerebrovascular complications of coronary artery bypass grafting].

The aim of the work was to study the possibility of using single-photon emission computed tomography (OECT) of brain using 99m Tc-hexamethyl propylene aminoxime for the evaluation of long-term prognosis of the development of neurocognitive deficit after coronary artery bypass grafting (CBG) and elucidation of relationship between variations of cognitive function and regional cerebral circulation. Surgical myocardial revascularization under artificial circulation was performed in 22 patients with CHD. All of them were examined for the assessment of neurologic and neuropsychological status, and OECT data before, 14 days and 6 months after CBg. Early cognitive deficit developed in 96% of the patients and persisted for 6 months in 55%. Cognitive dysfunction was manifest as post-operative impairment of short- and long-term memory, and general efficiency of remembering. Visual memory and psychomotor speed also deteriorated. Cerebral circulation decreased in frontal and parietal lobes of the right hemisphere. Deterioration of long-term memory 6 months postoperatively correlated with the early circulation decrease of in the right and left temporal lobes.

[Cardioprotective effect of remote ischemic preconditioning].

Authors of review analyze papers published in 1993-2008 on problem of remote ischemic preconditioning of the heart. The main manifestations of preconditioning at a distance are a decrease in infarct size, an improvement of cardiac contractility in reperfusion period, an enhancement of cardiac tolerance to arrhythmogenic impact of ischemia-reperfusion. The published data demonstrate that the humoral factors (endogenous opioids, bradykinin, calcitonin gene-related peptide, endogenous cannabinoids) play the main role in preconditioning at a distance. In the review, it is presented data that protein kinase C, mitochondrial ATP-sensitive K+ -channel, mitochondrial permeability transition pore, NO-synthase, reactive oxygen species are involved in signaling cascade of remote preconditioning.

[Pathophysiological mechanisms of bacterial endotoxicosis in disseminated peritonitis].

Using methods of nuclear medicine in experiment, we studied pathophysiologic mechanisms of bacteriemia in disseminated peritonitis in various laboratory animals. The results give grounds to consider regularities revealed to be universal.

[Vascular effects of ginseng compounds].

In the review it has been systematized data on the vascular effects of ginsenosides in vivo. It has been shown that ginsenosides increase a tolerance of isolated arteries to oxidative stress, hypoxia-reoxigenation, homocysteine and other pathogenic factors. It has been performed an analysis published works on the effects of triterpene saponines on the NO synthesis in the isolated endothelial cells, a proliferation of these cells, an apoptosis of endotheliocytes, a secretion of vascular endothelial growth factor by endothelial cells. It was exhibited data on the potency of ginsenosides to inhibit a proliferation of vascular smooth muscle cells. It has been discussed a molecular mechanisms of triterpene saponines action, their interaction with steroid hormone receptors, proteinkinases, NO-synthase, guanilyl cyclase, K(Ca)-channels, Ca(2+)-channels.

[Cardiovascular effects of D-ALA2, LEU5, ARG6-enkephalin (dalargin) are mediated by peripheral mu-opioid receptor activation].

It has been established that intravenous administration of dalargin at a dose of 0.1 mg/kg induced hypotensive, positive inotropic, and positive chronotropic response in patients with myocardial infarction, while not producing the "steal syndrome." The positive chronotropic effect of dalargin was mediated by peripheral mu-opioid receptors. Increase in the heart rate induced by dalargin had a reflex nature. Direct action of dalargin on the heart was accompanied by a decrease in the heart rate and a delay in the cardiac conductance in the atrioventricular junction region.