FLOW-MEDIATED VASODILATATION

Objective: To assess whether flow-mediated dilatation (FMD) affectedcardiovascular (CV) parameters after consuming fructose or sucralose. Data source: Finometer.Design of study: Randomized, cross-over, single-blind design. Setting: School of biomedicalsciences, University of Nottingham, UK. Period: July, 2009. Materials and methods: Tenhealthy, white European males were studied twice. A Finometer continuously recorded CVparameters. Following 30 min baseline, a BP cuff, around mid-point of right arm was inflated 50mmHg above Systolic BP for 5 min. Upon deflation, FMD measurements were made. Volunteersthen consumed 500 ml of fructose or sucralose containing drink. Forty min later, 2nd FMD wasdone. Results: Pre-fructose FMD: SBP increased in late-occlusion and post-occlusion period(POP). HR and CO decreased and SV and TPR increased during POP (P < 0.01 & 0.001).Post-fructose: DBP rose (2 mmHg; P = 0.04) during occlusion; HR (P = 0.02) and CO (P <0.05) increased whereas TPR decreased (0.023; P < 0.04) in recovery period. Pre-sucralose:SBP, DBP and MAP increased in POP and thereafter. Decreased HR and CO and increasedTPR and SV were noted (P < 0.01 & 0.001). Post-sucralose: SBP rose in POP and thereafter (5mmHg; P < 0.01); MAP (3 mmHg; P = 0.04) and SV (P = 0.05) increased in POP. Conclusions:Attenuated BP and TPR, after fructose, indicate fructose’s possible vascular effects.

Characteristics of nervous tissue after modeling of focal cerebral ischemia in rats at different periods of reperfusion

The stroke-causing problems are extremely important in Ukraine. This makes a heavy burden not only on the health care system, but also on the whole society as a whole. That's why we've studied structural and ultrastructural changes of cortical neurons and striatum of the brain and the development of delayed death of nerve cells after the modeling of the middle cerebral artery occlusion (MCAO) and post ischemic period in rats. We've analyzed the data at different terms after modeling of MCAO. The purpose of the study was to investigate the changes in the nervous tissue in the modeling of focal cerebral ischemia by monofilament occlusion of MCAO in rats at different periods of reperfusion. The statistical processing of primary digital experimental data was carried out using the software Statistica 6.0. It was confirmed that the 60-minute occlusion of the MCAO is an adequate model of focal ischemic brain damage in rats. Changes of locomotor activity and a tactile sensitivity were determined in rats after occlusion and after reperfusion during the post-period period. It was found that in the experimental group with a reperfusion period of 72 hours, a clear increase of the volume of the ischemic area of the brain, accompanied by significant neurological deficiency, was observed. Reduced research activity of the rats was revealed, which was shown in the decrease of the number of squares they crossed, the number of racks, the increase of acts of grooming and the duration of acts of frizings. Following ischemic brain damage, there was also a disbalance of somato-sensory functions, as evidenced by an increase in the time during which the animal took a test stimulus ("Sticky tape") from both the anterior paws when tested for tactile sensitivity (adhesive removal test). An electron microscopic study of the cortex showed that dark wrinkled neurons and enlightened swollen neurons were observed at 72 hours of post-occlusion period, indicating different ways of death of these cells. Changes in striatum were similar to changes in the cortex, which progressed with an increase in the post-occlusion period. The protocol of the serial evaluation of neurological disorders used after MCAO modeling allowed detecting long-term stable functional disorders in laboratory rats. The obtained data indicate significant changes in the structure of the cortex and striatum in the post-ischemic period and the progressive nature of these changes.

Hemodynamic Environment and Occlusion Time of Tandem Intracranial Aneurysms Treated With Flow Diverters

The use of flow diverting devices to treat complex intracranial aneurysms difficult to treat with coils and clips has recently received substantial attention. Initial experiences with increasing numbers of patients have been carried out with promising results [1]. However, it is still difficult to predict the outcome and/or the aneurysm occlusion time after treatment with flow diverters. The purpose of this work was to relate the hemodynamic environment created immediately after treatment and the occlusion period of a pair of tandem aneurysms.

Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs

Transient episodes of ischemic preconditioning (PC) render myocardium protected against subsequent lethal injury after ischemia and reperfusion. Recent studies indicate that application of short, repetitive ischemia only during the onset of reperfusion after the lethal ischemic event may obtain equivalent protection. We assessed whether such ischemic postconditioning (Postcon) is cardioprotective in pigs by limiting lethal injury. Pentobarbital sodium-anesthetized, open-chest pigs underwent 30 min of complete occlusion of the left anterior descending coronary artery and 3-h reflow. PC was elicited by two cycles of 5-min occlusion plus 10-min reperfusion before the 30-min occlusion period. Postcon was elicited by three cycles of 30-s reperfusion, followed by 30-s reocclusion, after the 30-min occlusion period and before the 3-h reflow. Infarct size (%area-at-risk using triphenyltetrazolium chloride macrochemistry; means ± SE) after 30 min of ischemia was 26.5 ± 5.2% ( n = 7 hearts/treatment group). PC markedly limited myocardial infarct size (2.8 ± 1.2%, n = 7 hearts/treatment group, P < 0.05 vs. controls). However, Postcon had no effect on infarct size (37.8 ± 5.1%, n = 7 hearts/treatment group). Within the subendocardium, Postcon increased phosphorylation of Akt (74 ± 12%) and ERK1/2 (56 ± 10%) compared with control hearts subjected only to 30-min occlusion and 15-min reperfusion ( P ≤ 0.05), and these changes were not different from the response triggered by PC ( n = 5 hearts/treatment group). Phosphorylation of downstream p70S6K was also equivalent in PC and Postcon groups. These data do not support the hypothesis that application of 30-s cycles of repetitive ischemia during reperfusion exerts a protective effect on pig hearts subjected to lethal ischemia, but this is not due to a failure to phosphorylate ERK and Akt during early reperfusion.

Pretreatment with tyrosine kinase inhibitors partially attenuates ischemic preconditioning in rat hearts

Ischemic preconditioning (IPC) confers cardioprotection against a prolonged ischemic insult. Tyrosine kinase (TK) inhibitors have been shown to attenuate IPC; however, it is unclear whether TK is involved in the initiation of and/or the maintenance of this phenomenon. Thus the hypothesis that TK acts primarily during the initiation of IPC was examined in a rat model of myocardial infarction. Hearts were subjected to 30 min of coronary artery occlusion and 2 h of reperfusion. IPC was elicited by three 5-min occlusions interspersed with 5 min of reperfusion before the prolonged occlusion period. Genistein, a nonspecific TK inhibitor, was administered before or during the final 2 min of the first or third occlusion period of IPC. Daidzein, an inactive structural analog of genistein, and lavendustin A, a more specific TK inhibitor, were also tested in this model. IPC markedly reduced infarct size expressed as a percentage of the area at risk compared with control (56.3 ± 2.8 to 7.1 ± 2.0%). This cardioprotection was attenuated by genistein pretreatment (5 mg/kg: 34.7 ± 2.2%, 10 mg/kg: 33.5 ± 5.9%). However, genistein administered during the first or third occlusion period of IPC did not significantly attenuate cardioprotection (10.3 ± 2.9% and 6.4 ± 2.0%). Lavendustin A (1.0 mg/kg) pretreatment also attenuated IPC (30.1 ± 2.2%), whereas daidzein (5 mg/kg) had no effect (7.9 ± 2.4%). These results suggest that activation of a TK is involved in the initiation but not the maintenance of IPC in the rat myocardium.

KATP channels and memory of ischemic preconditioning in dogs: synergism between adenosine and KATP channels

Results from numerous studies have shown that there is an important link between adenosine A1 receptors and ATP-sensitive potassium (KATP) channels in mediating the cardioprotective effects of ischemic preconditioning (PC). The major aim of the present study was to determine whether occupation of A1 receptors and/or the opening of KATP channels is involved in the time delay between the PC stimulus and the prolonged ischemic insult or the “memory” of PC to reduce infarct size. Barbital sodium-anesthetized dogs were subjected to 1 h of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Ischemic PC was elicited by 10 min of LAD occlusion followed by 1 h of reperfusion (1-h memory) before the 1-h occlusion period. Either adenosine (800 g/min), bimakalim (3 g/min), a combination of two lower doses of each agent (400 g/min of adenosine and 0.3 g/min of bimakalim), or an equivalent volume of saline was infused into the LAD for 10 min followed by a 1-h drug-free period before the 1-h ischemic insult. In another series, glibenclamide, 8-cyclopentyl-1,3-dipropylxanthine (a selective A1-receptor blocker), or PD-115199 (a nonselective adenosine-receptor antagonist) was administered 50 min after ischemic PC (10 min before the 1-h occlusion period). Infarct size (IS) was expressed as a percentage of the area at risk. PC with 1 h of reperfusion resulted in a marked reduction in IS (8.1 +/- 6.5 vs. 29.8 +/- 5.8% in control dogs). Administration of adenosine or bimakalim followed by a 1-h drug-free period had no effect on IS; however, the simultaneous administration of adenosine and bimakalim resulted in a marked decrease in IS (11.5 +/- 2.7%). One hour after ischemic PC, administration of glibenclamide blocked the protective effect of ischemic PC, whereas 8-cyclopentyl-1,3-dipropylxanthine or PD-115199 did not affect it. These results provide evidence that the opening of myocardial KATP channels may play an important role in the memory of ischemic PC in the canine heart and also suggest that adenosine and the KATP channel may have a synergistic interaction that is important for the memory phase of PC.

MR Imaging of Gadolinium-DTPA-BMA-Enhanced Reperfused and Nonreperfused Porcine Myocardial Infarction

To investigate whether Gd-DTPA-BMA-enhanced MR imaging permits differentiation between reperfused and nonreperfused myocardial infarction, myocardial infarction was induced in 12 domestic pigs. In 6 pigs, Gd-DTPA-BMA, 0.3 mmol/kg b.w. was administered i.v. 60 min after the occlusion. In 6 other pigs, the infarctions were reperfused 80 min after the occlusion, followed by injection of Gd-DTPA-BMA after 20 min of reperfusion. Radiolabeled microspheres were used to confirm zero-flow during the occlusion period and reperfusion in the infarcted myocardium. All pigs were killed 20 min after injection of contrast medium, and the hearts were excised and imaged with MR. The Gd concentration was measured in infarcted and nonischemic myocardium by ICPAES. In the reperfused hearts, the infarctions were strongly highlighted, corresponding to a 5-fold higher Gd concentration in infarcted vis-à-vis nonischemic myocardium. In the hearts subjected to occlusion without reperfusion, there was only a rim of enhancement in the peripheral part of the infarctions.

Regulation of glycogenolysis in human skeletal muscle

The role of inorganic phosphate on the regulation of glycogenolysis in resting and contracting muscle was studied in human quadriceps muscle. Increased Pi content was achieved by intermittent electrical stimulation of the muscle followed by occlusion of the blood flow. Occlusion resulted in the maintenance of a high Pi content over a 60-s observation period during which the muscle was either at rest or was stimulated electrically. The study was performed with and without infusion of epinephrine (EPI). In the absence of EPI the phosphorylase a fraction was 50% immediately at the end of the initial stimulation period, declining to 22% after 60 s. With EPI corresponding values for phosphorylase a were 91% initially, 56% after 30 s, and 33% after 60 s, respectively. In both cases the Pi content was increased by approximately 35 mmol/kg dry muscle during the stimulation and remained constant during the occlusion. In neither of these situations was significant degradation of glycogen observed during the occlusion. In the study performed with electrical stimulation during the occlusion period, muscle glycogen degradation was observed both with and without EPI. Phosphorylase a fractions and Pi contents in this study were similar to those observed when muscle was rested over the 60-s occlusion period. The paradox of a high Pi content and extensive transformation of phosphorylase to the a form but low glycogenolytic activity points to additional factors in the regulation of glycogen breakdown.