The state of the vascular system in the children and adolescents presenting with metabolic syndrome

It was studied the state of the vascular wall at metabolic syndrome (MS) in children and adolescents. The study included two groups of children: 45 people with MS and 25 patients with simple obesity. With the help of the device Vasotens assessed indicators of vascular stiffness: pulse wave velocity in the aorta, the indices of stiffness and augmentation of the peripheral arteries and the aorta, the maximum rate of rise in blood pressure. The study showed that 70% of children with MS increased arterial stiffness and thickness of the vascular wall. The rigidity of the vascular wall in children with MS revealed a 3.5 times more likely than children with simple obesity. Pulse wave velocity is a predictor of hypertension and has a high correlation with SDS IMT.

Bromelain induces cardioprotection against ischemia-reperfusion injury through Akt/FOXO pathway in rat myocardium

Bromelain (Br), a proteolytic enzyme extracted from the stem of the pineapple, is known to possess anti-inflammatory activity and has been shown to reduce blood viscosity, prevent the aggregation of blood platelets, and improve ischemia-reperfusion (I/R) injury in a skeletal muscle model. We investigated the capacity of Br to limit myocardial injury in a global I/R model. Adult male Sprague-Dawley rats were divided into two groups: control (PBS) and Br at 10 mg/kg in PBS administered via intraperitoneal injection (twice/day) for 15 consecutive days. On day 16, the hearts were excised and subjected to 30 min of global ischemia followed by 2 h of reperfusion. Br treatment showed higher left ventricular functional recovery throughout reperfusion compared with the controls [maximum rate of rise in intraventricular pressure (dP/d tmax), 2,225 vs. 1,578 mmHg/s at 2 h reperfusion]. Aortic flow was also found to be increased in Br treatment when compared with that in untreated rats (11 vs. 1 ml). Furthermore, Br treatment reduced both the infarct size (34% vs. 43%) and the degree of apoptosis (28% vs. 37%) compared with the control animals. Western blot analysis showed an increased phosphorylation of both Akt and FOXO3A in the treatment group compared with the control. These results demonstrated for the first time that Br triggers an Akt-dependent survival pathway in the heart, revealing a novel mechanism of cardioprotective action and a potential therapeutic target against I/R injury.

A major role for P2X1 receptors in the early collagen-evoked intracellular Ca2+ responses of human platelets

SummaryIn the platelet, ATP-gated P2X1 receptors have been reported to amplify functional responses to collagen, however the relative importance of early Ca2+ mobilisation events is unknown. We now report that selective desensitisation of P2X1 receptor activity leads to a major reduction in the initial intracellular Ca2+ responses to a wide range of collagen concentrations (0.25–2 μg ml-1). Peak [Ca2+]i increases were reduced to 8.5 and 55% of control, and the maximum rate of rise was reduced to 12 and 33% of control, at low and high collagen concentrations, respectively. This P2X1-dependent acceleration and enhancement of collagen-stimulated Ca2+ responses was not observed in the absence of extracellular Ca2+. These results demonstrate a major role for ATP-gated Ca2+ influx in the early collagen-evoked Ca2+ signals and can at least partly explain the important contribution of P2X1 receptors to arterial thrombosis.

Acetaldehyde alters Ca2+-release channel gating and muscle contraction in a dose-dependent manner

We studied whether acetaldehyde, which is produced by alcohol consumption, impacts ryanodine receptor (RyR) activity and muscle force. Exposure to ∼50–200 μM acetaldehyde enhanced channel activity of frog RyR and rabbit RyR1 incorporated into lipid bilayers. An increase in acetaldehyde to 1 mM modified channel activity in a time-dependent manner, with a brief activation and then inhibition. Application of 200 μM acetaldehyde to frog fibers increased twitch tension. The maximum rate of rise of tetanus tension was accelerated to 1.5 and 1.74 times the control rate on exposure of fibers to 50 and 200 μM acetaldehyde, respectively. Fluorescence monitoring with fluo 3 demonstrated that 200–400 μM acetaldehyde induced Ca2+ release from the sarcoplasmic reticulum (SR) in frog muscles. Acetaldehyde at 1 mM inhibited twitch tension by ∼12%, with an increased relaxation time after a small, transient twitch potentiation. These results suggest that moderate concentrations of acetaldehyde can elicit Ca2+ release from the SR by increasing the open probability of the RyR channel, resulting in increased tension. However, the effects of acetaldehyde at clinical doses (1–30 μM) are unlikely to mediate alcohol-induced acute muscle dysfunction.

The Effects of Short Intravenous Infusions of Thiopentone on Myocardial Function, Blood Flow and Oxygen Consumption in Sheep

The cardiovascular effects of slow (over two minutes) intravenous infusions of thiopentone 750 mg in conscious instrumented sheep breathing 100% oxygen were examined for 30 minutes following the start of the infusion. The maximum rate of rise of left ventricular pressure (an index of myocardial contractility) decreased significantly from 1 to 10 minutes, to a minimum of 45% of baseline. Heart rate increased by up to 33% above baseline from 0.5 min onwards. Both mean arterial pressure and cardiac output were decreased from between 1 and 7 min. Left ventricular minute work was transiently decreased, but left coronary blood flow and myocardial oxygen consumption showed little or no change from baseline. We conclude that in vivo, thiopentone administered at a relatively slow rate caused large reductions in myocardial contractility, and therefore cardiac reserve, in the absence of significant changes in myocardial blood flow or oxygen consumption.

Activator calcium and myocardial contractility in fetal sheep exposed to long-term high-altitude hypoxia

We studied myocardial contractility in fetal sheep from ewes exposed to approximately 112 days of hypoxia at high altitude (3,820 m). We measured the inotropic response to extracellular Ca2+ concentration ([Ca2+]o, 0.2-10 mM) and ryanodine (10(-10) to 10(-4) M) in isometrically contracting papillary muscles and quantified dihydropyridine (DHPR) and ryanodine (RyR) receptors. In hypoxic fetuses, curves describing the force-[Ca2+]o relationship were shifted left, and the top plateaus were decreased by approximately 35% in both left and right ventricles. In normoxic and hypoxic fetuses, ryanodine (10(-4) M) reduced maximum active tension (Tmax) to approximately 25-40% of baseline values, indicating that the sarcoplasmic reticulum was the chief source of activator Ca2+ and that Ca2+ influx alone was not sufficient to activate a contraction of normal amplitude. Hypoxia resulted in a lower Tmax in the right ventricle and a lower maximum rate of rise in the left ventricle after treatment with ryanodine. DHPR number did not change, but RyR number and the RyR/DHPR in both ventricles were higher in hypoxic fetuses. We conclude that hypoxia decreases contractility, possibly by reducing the availability of activator Ca2+. Further studies are needed to directly measure the Ca2+ current and intracellular Ca2+ transient and to examine myofilament protein and adenosinetriphosphatase activity.

Prolongation and shortening of action potentials by electrical shocks in frog ventricular muscle

Effects of electrical shocks on myocardium are important for defibrillation. We measured effects of shocks (5 ms, 1–40 V/cm) in isolated frog ventricular strips. We recorded contraction strength and intracellular action potential (AP) with a shock-voltage cancellation technique to allow recordings immediately after shocks. Shocks of > or = 5 V/cm produced a dose- and latency-dependent prolongation of the AP ongoing during the shock. Stronger shocks of 28–40 V/cm decreased the duration, maximum diastolic potential, amplitude, and maximum rate of rise of the phase zero depolarization of paced APs that began after the shock. The contraction strength increased 43 and 59% during the 10 s after the stronger shocks. The transmembrane potential was shifted toward 0 mV immediately after the stronger shocks. We concluded that weak or strong shocks prolong the AP ongoing during the shock, whereas sufficiently strong shocks also shorten APs that begin after the shock. AP prolongation and shortening may be important for defibrillation and acceleration of tachycardia after failed cardioversion shocks.