ORIGINAL STUDIES
The renin-angiotensin-aldosterone system (RAAS) is involved in the pathogenesis of Coronary Heart Disease and myocardial infarction. The crucial component of the RAAS is angiotensin II and its effects are carried out by angiotensin II receptors 1st type (AT1R).
Aim of the study: determine the incidence of the mutant allele of the AT1R gene, estimate possible correlations between AT1R gene polymorphism and the extension of endothelial dysfunction in patients who have suffered MI in the age under 45.
Materials and methods: 122 men suffering myocardial infarction under the age of 45 have been examined. In all patients we measured a relative increase of brachial artery diameter during the test with reactive hyperemia, the number of circulating endotheliocytes. Identification of A1166C polymorphism of the AT1R gene was carried out by means of polymerase chain reaction (PCR).
Results: in patients with a history of myocardial infarction in the age under 45 we have found evidence of endothelial dysfunction: increased circulating endotheliocytes, decreased endothelium-mediated vasodilation. Among patients with a vasoconstrictive reaction the incidence of the C allele of the AT1R gene was higher than in patients exhibitng a vasodilative response during a test with reactive hyperemia (P<0.007). The incidence of the mutant allele of the AT1R gene was reliably lower in coronary patients with arterial hypertension than in those without hypertension.
The study is focused on the estimation of daily BP profiles in young patients with the syndrome of connective tissue displasia. A considerable party of them shows a strong evidence of altered balance between pressoric and depressoric mechanisms of BP regulation. We have verified two kinds of cardiovascular reactions in connective tissue displasia. Half of those examined, according to the postural test, exhibit altered adaptive potential.
We herewith present our experience of complex treatment with enalapril combined with б-tocopherol and endovascular laser blood radiation in 86 hypertensive patients with LVH. We have established complex therapy for a year to promote complete and earlier beginning LVH regression compared to monotherapy with enalapril.
To determine the influence of an individual year cycle (IYC) lasting from one birthday to another, on the clinical, laboratory and physiological values, we have studies case histories of 330 men with acute coronary pathology and also examined 146 men with Coronary Heart Disease admitted for CABG. 35 almost healthy young men were also examined during a year in different seasons.
We have found out that the number of patients developing MI in the XII month of the IYC, was reliably higher that the value for IV-VI months and almost twice as high as the number for the VI month. The severity of MI developing in the XII and I months of the IYC surpassed such in MI developing in other periods of the IYC. In the IV trimester of the IYC (X-XII months) the patients showed a relatively low number of T-cells, the highest cortisol concentration in the saliva, in the III and IV months – T-supressors; in the IV trimester coronary patients showed much less thyroxin, tri-iodothyronin and cortisol than in the I trimester. Blood values in the II trimester of the IYC were consistent with a better prognosis.
Healthy young men showed stressed adaptation mechanisms in the IV trimester of the IYC: increased personal alertness (the index of regulatory systems stressing was calculated from a mathematical analysis of heart rate), higher incidence of hypertension, decreased ability to work and immunity. The values in the II trimester were more favorable.
The data enable us to draw a conclusion about the universal nature of IYC changes of adaptive parameters of cardiovascular and endocrine systems, which is crucial for preventive cardiology.
We have examined 55 patients with vibrational disease II degree (a moderate form) with veloergometry to study cardiovascular reactions on dosed physical stress. We have found high tolerance to physical stress, including patients with concomitant cardiovascular diseases which is probably due to a professional adaptation to a heavy physical labor. In this sample we have found a tendency to hypotensive reaction to physical stress and unstable vascular tone in 83.6%. Patients with vibrational disease and essential hypertension showed a paradoxical reaction with no typical increase in diastolic blood pressure in response to increasing physical stress. Patients with concomitant Coronary Heart Disease showed evidence of delayed myocardial ischemia once the stress has been waived.
CLINICAL PHARMACOLOGY
The work has been carried out on myocardial bioptates, autopsy and experimental material. In chronic heart failure (CHF) it has been established the sharp decrease of ability of force generation, ATP hydrolysis and economy of energy transduction in myocardial contractile protein (MCPS) at the time of development of energy deficit state and disturbances in Ca-transport system are the key mechanism of CHF development and progression. In contradiction to early and acute HF in CHF myosin-based (as a result of damage of hydrolytic center of myosin head) decrease of intensity of ATP hydrolysis is deposited on the actin-based decrease of value and velocity of generated force and economy of energy transduction in MCPS. The described phenomena in CHF are conditioned on the molecular level by the changes of the structural-conformational state of monomer and protomer of actin and its interaction with myosin heads of thick filament in force generation process. This conclusion has been confirmed in experiments in which are studied the properties of hybrid fibers, reconstructed from failing heart thin filament and normal myosin and vice versa. The actomyosin hypothesis of the mechanism of force generation and energy transduction disturbances in CHF has been suggested. It has been shown that at the submolecular level in actin the distances between Lys61, Tyr69 in subdomain 2 and Cys374 and Cys10 are increased, the conformation mobility of these aminoacidic acids is decreased and microenviroment is changed. These leads to the loosening of outside doman of actin. According to these data together with the data of atomic structure of skeletal muscle actin and 3D reconstruction pattern of cardiac actin from normal and failing heart a hypothetic models for such actins have been reconstructed. The appointed faults have posttranslational character and under the creation of optimal conditions in vitro under the influence of cardiac glycosides (β-acetyldigoxine, β-methyldigoxine and strophantine K) are able to revert, though they are firm.
We have studied clinical efficacy and safety of a II generation calcium antagonist cordaflex-retard administered in a daily dose of 40 mg for 4 weeks to 40 patients with essential hypertension. Efficacy was estimated by clinical BP measuring and daily monitoring. The results indicate BP decrease in an overwhelming majority of patients. Treatment with cordaflex did not deteriorate daily BP rhythm, did not increase its variability. Adverse reactions were noted in a minor number of patients and did not require drug withdrawal as they were mild.
Condition of lipid peroxidation in hypertensives with a year-long treatment with mifebradil, fosinopril and doxasosine.
Paroxysmal supraventricular tachycardias: implications for β-blockers form the point of heart rate variability.
Betaxolol in the treatment of arterial hypertension in polycytemia vera.
Nebilet – is a new β-adrenoceptor blocking agent possessing both superseleсtive and NO-producing properties. Efficacy and safety of nebilet monotherapy of 5 mg/d were evaluated for 20 patients with mild and moderate essential hypertension during 8 weeks of treatment. Positive hypotensive effect was achieved in 79% of patients, average daily level of systolic and diastolic pressure decreased from 144,1±2,5 to 132,5±3,4 mm Hg and from 88,8±1,5 to 79,5±2,3 mm Hg respectively. A marked diminishing (by 80 %) of painful and painless myocardial ischemia overall duration was also observed.We didn’t reveal the inhibition of inotropic action, whereas good influencies to the remodelling of myocardium have oсcured. There were no serious adverse effects and laboratory deviations during the therapy.
EXPERIMENTAL STUDIES
Physical-chemical properties of very low density (VLDL) and two forms of high density lipoproteins (LP) - apo E-rich HDL and apo A-rich HDL in rat blood plasma after sympathetic and parasympathetic denervation of the liver, partial hepatectomy and intraportal atropine administration were investigated. Surface potential of VLDL and E-HDL in all experimental groups was significantly lower than in sham operated controls, but the most pronounced decrease was after intraportal atropine administration and in 7 days after partial hepatectomy. In A-HDL this parameter was essentially the same. VLDL and E-HDL particle radius significantly decreased after 70% hepatectomy and intraportal atropine administration, was slightly lower in 7 days after section of splanchnic nerves and vagotomy and was invariable in the case of A-HDL. VLDL and A-HDL lipid microviscosity increased after sympathetic denervation, partial hepatectomy and vagotomy. The degree of increase for VLDL under such conditions was higher than for A-HDL. As to E-HDL this parameter did not change. Percent of protein in water equipment in VLDL and E-HDL was greater after vagotomy and atropine administration and did not change in case of bilateral section of splanchnic nerves and hepatectomy. In A-HDL, this parameter was constant.
As all these parameters reflect the LP assembling, structure and transformation, our results confirm the suggestion that autonomic neuronal factors influence the LP production, acting on post-transcriptional processes.
REVIEW
Metabolic treatment of acute myocardial infarction. Glucose-insulin-potassium combination – mode of action, experience of usage.
NOVEL APPROACHES IN DIAGNOSTICS
Geometrical analysis of non-linear chaotic heart rate fluctuations as a novel method of functional diagnostics of the cardiovascular system.
LECTURE
Usage of cardioprotection principles in treating chronic heart failure.
ANNIVERSARY
SUPPORTING A PRACTITIONER
Role of nifedipin in contemporary treatment of cardiovascular diseases.
INFORMATION
The newsletter concerning the Russian National Congress of Cardiologists, Moscow, October 9-11 2001.
Russian Scientific Society of Cardiology working schedule for the year 2001.
List of materials published in the Russian Journal of cardiology for the year 2000.
ISSN 2618-7620 (Online)