[Polypragmasia and interdrug interactions as risk factors of falling in elderly patients.]

This article presents the results of the analysis of data from patients over 75 years of age from a multidisciplinary hospital with cardiovascular disease and comorbid conditions. Pharmacotherapy of gerontological patients with multiple risk factors for falls was analysed in terms of the presence of polypragmasy and drug-drug interactions hazardous to the risk of falls. In the group of patients who experienced a fall in hospital compared to patients without a fall, the prescription lists audit showed a predominance of medicines (drugs) and drug combinations compromised by an increased risk of this serious adverse event. An audit of prescriptions of patients at increased risk of falls as a means of combating polypharmacy and identifying drugs that may cause falls can be conducted using the «Traffic light classification of FRIDs¼ and drug checkers to identify clinically relevant combinations. The use of these clinical and pharmacological tools can improve the quality and safety of medical care in a hospital setting.

[Initiation of pharmacotherapy as a risk factor for older patients.]

The article presents the literature and original data on the problems of falls in elderly patients. The connection of the fact of falling with initiation of therapy by a number of drugs known to have a negative impact on the risk of falling is considered. The article presents data on the frequency and structure of falls on the example of patients with cardiovascular diseases older than 75 years, treated in a multidisciplinary hospital. The analysis of the data showed a tendency of prevalence of the fact of falling in 1/3 patients (33,8%) in the first 5 days of hospital stay, which may be associated with high drug burden and the appointment of «new¼ drugs for the patient. The study noted that it was on the first day that the selection of therapy took place and additional drugs were often prescribed, leading to a state of polypragmasia. Analysis of individual groups of drugs was able to reliably confirm the relationship between the appointment of drugs that increase.

[Current ideas of a complex relationship between atrial fibrillation and ischemic heart disease and of optimum tactics for anticoagulant therapy to prevent embolism in systemic circulation].

The article discusses the issue of searching for optimum oral anticoagulants to prevent thrombosis and embolism induced by heart disease both in patients with atrial fibrillation and sinus rhythm. A complex bidirectional relationship between atrial fibrillation and coronary atherosclerosis is considered along with possible mechanisms for development of myocardial infarction in patients with atrial fibrillation. The authors provided evidence-based data which can be used in selecting an anticoagulant for prevention of heart disease induced thrombosis and embolism taking into account both the efficacy and safety established in randomized clinical studies.

[Clinico-Pharmacological and Clinical Basis of Multiplicity of Intake of Novel Oral Anticoagulants].

In this review we present comparison of pharmacokinetics of novel oral anticoagulants (NOAC) dabigatran, rivaroxaban, apixaban, and edoxaban, principles of selection of a regimen of their dosing for phase III clinical trials in patients with atrial fibrillation. Multiplicity of administration of NOAC depends on required level of anticoagulation, ability to maintain anticoagulation for 24 hours, relationship between minimal and maximal levels of equilibrium concentrations, efficacy and safety. Once a day administration of some drugs of this group is reasonable from positions of clinical pharmacology. It can provide not only better adherence to treatment but greater safety relative to development of bleeding.

[Potentialitis of phosphodiesterase inhibitors in management of patients with chronic heart failure complicating cardiac ischemia].

In spite of the advances in understanding the pathogenesis and approaches to the treatment of chronic heart failure, it remains one of the main causes of the patients invalidism and death, that makes the cardiologists all over the world develop new drugs for the treatment of the disease. The aim of the study was to show possible long-term use of enoximone, a new agent from the group of phosphodiesterase inhibitors, in doses of 75-150 mg a day in traditional combined pharmacotherapy of the patients with chronic heart failure. Thirty eight patients with chronic heart failure III-IV FC (NYHA) and 30% left ventrical efflux function were observed. The dynamics of the disease clinical signs, the heart hemodynamic and morphofunctional parameters, the heart bioelectric activity and the hospitalization frequency were investigated to estimate the therapy efficacy and safety. The use of enoximone in the traditional combined pharmacotherapy, including inhibitors of angiotensin-transforming enzymes, diuretics, beta-adrenoblockers and aldosterone antagonists, resulted in a reliable improvement as for the disease clinical signs, 17.8% increase of the left ventrical efflux function vs. the initial indices, less frequent hospitalization. The enoximone tolerability was good, no side effects requiring discontinuation of the drug use were recorded.

Intravital fluorescence microscopy and phototocicity: effects on leukocytes.

The purpose of this investigation was to clarify whether the light exposure of fluorescently marked leukocytes and/or plasma influences the leukocyte behavior (rolling and firm adhesion). Anaesthetized Balb/c mice were laparotomized to expose the mesentery of the terminal ileum. Animals were randomly assigned to 5 experimental groups. One group was studied in trans-illumination mode, the other four groups received iv-bolus injections of either FITC-dextran (FITC-dx) 150 kD, rhodamine 6 G (rh6G), a combination of FITC-dx and rh6G, or acridine orange, respectively, and were then studied in epi-illumination mode. In each animal, eight vessels (6 venules, 2 arterioles) were exposed five times for 60 sec. to continuous light of the appropriate excitation wavelength with a 20-min. interval between exposures. The vessel diameters and leukocyte-endothelial cell interactions were quantified using intravital fluorescence microscopy. The diameters of arterioles and postcapillary venules remained unchanged in all groups studied. Rolling and adherent leukocytes were observed in postcapillary venules only and there were no significant differences between all groups. Under these conditions, the exposure of fluorescently labeled leukocytes and/or plasma to standard light levels for up to 300 seconds has no significant impact on leukocyte-endothelial cell interactions in mesenteric postcapillary venules.

Validation of OPS imaging for microvascular measurements during isovolumic hemodilution and low hematocrits.

Orthogonal polarization spectral (OPS) imaging is a new technique that can be used to visualize the microcirculation with reflected light. It uses hemoglobin absorption to visualize the red blood cells (RBCs). Thus the method could fail at low hematocrit (Hct). The aim of this study was to validate OPS imaging for quantitative measurements of diameter and functional capillary density (FCD) under conditions of hemodilution of varying degrees to achieve a wide range of Hcts. The validation was performed in the dorsal skinfold chamber of nine awake Syrian golden hamsters. Measurements of vessel diameter and FCD were performed off-line using Cap-Image on video sequences captured using OPS imaging and standard intravital fluorescence microscopy at baseline, 85, 70, 55, and 40% of the initial Hct. For hemodilution, isovolumic exchange of blood for 6% Dextran 60 was performed. Bland-Altman plots for the vessel diameter and FCD show good agreement between the two methods for both parameters at all studied Hcts. As expected, there was a systematic bias of approximately 4 microm in the diameter measurements since the RBC column was measured and not the intravascular diameter. In conclusion, OPS imaging can be used to measure diameter and FCD at a wide range of Hcts.

The Cytoscan Model E-II, a new reflectance microscope for intravital microscopy: comparison with the standard fluorescence method.

The Cytoscan Model E-II (Cytometrics Inc., Philadelphia, Pa., USA) is a newly developed instrument which functions as an intravital microscope and is small and easily portable. Through the use of orthogonal polarization spectral (OPS) imaging, the Cytoscan Model E-II delivers images of the microcirculation which are comparable to those achieved with intravital fluorescence videomicroscopy (IFM), but without the use of fluorescent dyes. The purpose of this study was to validate the Cytoscan Model E-II instrument against IFM. The experiments were carried out on striated muscle in the dorsal skinfold chamber of the awake Syrian hamster. The following parameters were measured in identical regions of interest in the same animal under baseline conditions and 0.5 and 2 h after a 4-hour period of pressure-induced ischemia: arteriolar diameter, venular diameter and venular red blood cell velocity. Bland-Altman plots showed good agreement between the two techniques for venular red blood cell velocity. As expected, arteriolar and venular diameters as measured by the Cytoscan were on average 5 microm smaller than the values from IFM, since the Cytoscan measures the red blood cell column width and IFM measures luminal diameter. Thus, OPS imaging can be used to make valid measurements of microvascular diameter and red blood cell velocity in tissues.