Optimal methods of the physical rehabilitation of patients with chronic ischemic heart disease with rhythm disorders

A study of 186 coronary patients with rhythm disturbance has shown that early incorporation of the elements of physical rehabilitation in combined treatment improves functioning of all the links of the blood circulation system, helps to raise cardiac rhythm stability and reduces the period of patients' stay in hospital.     

Intra-arterial <Emphasis Type="Italic">tert</Emphasis>-Butyl-Hydroperoxide Infusion Induces an Exacerbated Sensory Response in the Rat Hind Limb and is Associated with an Impaired Tissue Oxygen Uptake

The objective of this study was to investigate oxidative stress and oxygen extraction mechanisms in an animal model of continuous intra-arterial infusion of a free radical donor and in an in vitro model using isolated mitochondria. tert-Butyl-hydroperoxide (tert-BuOOH, 25 mM) was infused for 24 h in the left hind limb of rats to induce soft tissue damage (n = 8). After 7 days, we assessed local sensory response, tissue oxygen consumption, oxygen radicals, and antioxidant levels. In vitro mitochondrial function was measured after stimulation of isolated mitochondria of skeletal muscle cells with increasing doses of tert-BuOOH. tert-BuOOH infusion resulted in an increased skin temperature (p = 0.04), impaired function, and a significantly increased pain sensation (p = 0.03). Venous oxygen saturation levels (p = 0.01) and the antioxidant ceruloplasmin (p = 0.04) were increased. tert-BuOOH inhibited mitochondrial function in vitro. Induction of free radical formation in the rat hind limb results in an exacerbated sensory response and is associated with impaired oxygen extraction, which likely results from mitochondrial dysfunction caused by free radicals.     

Urgent Reaction of the Complement System to Hypoxic Exposure in Rats Sensitive to Hypoxia

Different modes of hypoxic exposure led to phasic changes in activities of the complement system components in rats sensitive to hypoxia starting from the first minutes of the posthypoxic period and persisting for 24 h and longer. The direction of shifts in the complement system depended on the duration and intensity of oxygen deficiency. Single one-hour interval hypoxia led to a moderate elevation of activities of virtually all the studied components. A more intense hypoxic exposure (1-h hypobaric hypoxia at a height of 5000 m) induced a biphasic response: reduction of activities of the majority of complement system components during the first hour of posthypoxic period and subsequent elevation of these activities above the normal. Exposure to severe hypobaric hypoxia (7000 m) led to a longer and more pronounced primary reduction of complement components activities, while the phase of their activity increase was blurred. Animal capacity to the formation of urgent tolerance of hypoxia was retained and increased with increasing the severity of hypoxic exposure. The complement consumption during the posthypoxic period was presumably a programmed reaction preventing hyperactivation of complement system components and essential for tolerance formation.     

Molecules to selectively target receptors for treatment of pain and neurogenic inflammation

Receptors that are involved in generation and transduction of pain signals attract much interest from the scientific and corporate communities. Good commercial prospects for successful development of effective analgesic drugs stimulate significantly the research. This article provides a brief overview of the key molecular targets, i.e. cell receptors, inhibition of which can lead to analgesia. Today transient receptor potential (TRP), purinergic (P2X) receptors and acidsensing ion channels (ASIC) are considered to be the most important proteins for perception of pain stimuli. These ionotropic receptors also participate in the development of inflammation; their hyperactivity leads to many pathological conditions and is closely associated with acute and inflammatory pain. Development of molecules capable to selectively modulate these receptors, their in vitro and in vivo effects, as well as perspectives for practical application described in patents and research articles are reviewed in this paper.     

Assessment of thromboplastins according to the WHO guidelines and the results of external quality control

The study was undertaken to assess commercial thromboplastins for compliance to the WHO guidelines and to substantiate the validity of the results of a prothrombin test carried out using these thromboplastins. The test thromboplastins were shown to meet the WHO guidelines for assessment of thromboplastins. Over 5-8 years of the authors'participation in two external quality control programs (Federal External Quality Control System, Russia; 72 trials; NEQAS, United Kingdom; 60 trials), the international normalized ratio derived through the use of assessed thromboplastins did not differ from that established due to the interlaboratory consensus value of both external quality control systems. It is concluded that correct thromboplastin assessment provide accurate results of determination of prothrombin time.     

Transient increase of free iron in rat livers following hemorrhagic-traumatic shock and reperfusion is independent of heme oxygenase 1 upregulation

Hemorrhagic-traumatic shock (HTS) followed by reperfusion induces heme oxygenase (HO) 1. Free iron (Fe2+) may cause oxidative stress, if not adequately sequestered. We aimed to characterize HO-1-mediated effects on Fe2+ levels in liver and transferrin-bound iron (TFBI) in plasma following HTS, including laparotomy, bleeding, and inadequate and adequate reperfusion. Anesthetized rats showed upregulated HO-1 mRNA at 40 min after HTS, which was followed by increased HO activity at 3 h after shock. Fe2+ levels were transiently increased at 40 min after shock, a time point when HO activity was not affected yet. Levels of plasma TFBI were higher in HTS animals, showing the highest levels at 40 min after shock, and decreased thereafter. In addition, we modulated HO activity 6 h before HTS by administering an inhibitor (zinc-protoporphyrin IX) or an activator (hemin) of HO. At 18 h after HTS in all shock groups, HO activity was increased, the highest being in the hemin-pretreated group. The zinc-protoporphyrin IX-treated HTS animals showed increased HO-1 mRNA and Fe2+ levels in the liver compared with the untreated HTS animals. Transferrin-bound iron levels were affected by pharmacological modulation before shock. All animals undergoing HTS displayed increased TFBI levels after reperfusion; however, in animals pretreated with hemin, TFBI levels increased less. Our data indicate that increase in Fe2+ levels in liver and plasma early after HTS is not mediated by HO-1 upregulation, but possibly reflects an increased mobilization from internal iron stores or increased cell damage. Thus, upregulation of HO activity by hemin does not increase Fe2+ levels following HTS and reperfusion.     

Adverse cerebrovascular effects of intraarterial CO2 injections: development of an in vitro/in vivo model for assessment of gas-based toxicity

PURPOSE: To assess whether and how CO(2) can cause ischemic injury in the central nervous system after internal carotid artery injection. MATERIALS AND METHODS: In 14 adult pigs, both internal carotid arteries were catheterized via a transfemoral approach. One carotid artery served as control and the other was injected via a prototype gas injector with defined volumes and pressures of gas. Effects were assessed by clinical observation, repeated magnetic resonance (MR) imaging, histopathology, and vital staining. An in vitro flow circuit was used to model injection parameters. RESULTS: Single injections of CO(2) did not produce persistent clinical symptomatology. In vitro conditions were created in which bubbles adhered to the tubing of the circuit, creating functional stenoses, or coalesced into larger bubbles that became trapped, thereby reducing flow and augmenting potential embologenic effects of subsequent injections. With in vitro-derived dual injection parameters, seven pigs underwent two sequential injections of CO(2). All did well after the first injections, but all had adverse effects after the second injections, including involuntary tonic-clonic muscular movements, cardiopulmonary arrest, recurrent intractable seizure activity during recovery, hemorrhagic venous infarcts on gross and histopathologic examination, and blood-brain barrier breakdown on vital staining. MR imaging was not sensitive even after symptomatic intraarterial air injection. CONCLUSIONS: Absence of adverse effects after single bolus injections in pigs does not prove the safety of intracranial CO(2) injections in human patients. Considering the possible deleterious effects of repeat intravascular injections in the highly sensitive system of the brain, it may be prudent for clinical application at other approved sites to let time pass between boluses sufficient to permit absorption of wall-adherent and coalescent bubbles that could cause gas embolic events.