Effect of blood flow occlusion on corticospinal excitability during sustained low-intensity isometric elbow flexion

Blood flow occlusion (BFO) has been used to study the influence of group III/IV muscle afferents after fatiguing exercise, but it is unknown how BFO-induced activity of these afferents affects motor cortical and motoneuronal excitability during low-intensity exercise. Therefore, the purpose of this study was to assess the acute effect of BFO on peripheral [maximal M wave (Mmax)], spinal [cervicomedullary motor evoked potential (CMEP) normalized to Mmax], and motor cortical [motor evoked potential (MEP) normalized to CMEP] excitability. Nine healthy men completed a sustained isometric contraction of the elbow flexors at 20% of maximal force under three conditions: 1) contractile failure with BFO, 2) a time-matched trial without restriction [free flow (FFiso)], and 3) contractile failure with free flow (FFfail). Time to failure for BFO (and FFiso) were ~80% shorter than that for FFfail ( P < 0.05). For FFfail and FFiso, Mmax area decreased ~17% and ~7%, respectively ( P < 0.05), with no change during BFO. CMEP/Mmax area increased ~226% and ~80% during BFO and FFfail, respectively ( P < 0.05), with no change during FFiso ( P > 0.05). The increase in normalized CMEP area was greater for BFO and FFfail compared with FFiso and for BFO compared with FFfail. MEP/CMEP area was not different among the protocols ( P > 0.05) and increased ~64% with time ( P < 0.05). It is likely that group III/IV muscle afferent feedback to the spinal cord modulates the large increase in motoneuronal excitability for the BFO compared with FFfail and FFiso protocols. NEW & NOTEWORTHY We have observed how blood flow occlusion modulates motor cortical, spinal, and peripheral excitability during and immediately after a sustained low-intensity isometric elbow flexion contraction to failure. We conclude that blood flow occlusion causes a greater and more rapid increase in motoneuronal excitability.

Acute disorders of metabolism of cardiomyocyte in cardiac contusion

New data on ultrastructural changes in cardiomyocytes in cardiac contusion in an experiment are submitted. The authors have identified the development of acute myocardial contractile failure that is associated with a statistically significant decrease in the content of ribosomes and glycogen in cardiomyocytes involved in the plastic and energy metabolism of the myocardium.

Abstract 5517: A Novel Tissue Engineered Skeletal Muscle Screening Platform to Assess the Myotoxic Potential of Statins

Our study had two objectives: to develop a novel tissue engineered skeletal muscle drug screening platform and to assess myotoxicity of various statins and identify underlying mechanisms. Methods: Engineered skeletal muscle tissue (SMT) was generated from adult rat skeletal myoblasts, rat fibroblasts (1.25x106 cells/SMT), matrigel, and collagen. Reconstitution-mixtures (450 μl) were poured into circular moulds yielding ring-shaped constructs after 5 days. SMTs were cultured for additional 10 days on stretch devices and treated with increasing concentrations of statins or vehicle for the last 5 culture days. Force of contraction (FOC) was measured and SMTs subjected to either immune fluorescence (IF), HE-staining or Western blotting (WB). Results: SMTs displayed differentiated muscle bundles (actin-IF and HE) and elicited tetanic contractions with maximal force at 60 Hz (1.3±0.2 mN; n=5). Carbachol (1 μM) induced a reversible block of muscle contraction which was antagonized by pancuronium (10 μM) indicating the presence and functionality of nicotinergic acetylcholine receptors. Statin treatment caused a concentration-dependent decrease in FOC in the following order of potency (EC50): cerivastatin (10 nM), simvastatin (100 nM), atorvastatin (350 nM), pravastatin (1860 nM; n=6–8/group and concentration). Contractile failure was paralleled by sarcomere breakdown and apoptosis (IF and WB: reduced actin, increased caspase 3). To assess the mechanism of statin myotoxicity, we investigated the protective effects of mevalonic acid (MEV, 100 μM), farnesyl-pyrophosphate (F-PP, 10 μM), squalene (S, 10 μM), and geranyl-geranyl-pyrophophate (G-PP, 10 μM) in the presence of maximally toxic cerivastatin concentrations (1 μM; complete contractile failure). MEV prevented cerivastatin toxicity completely (FOC: 102.3±16% of vehicle; n=7). GG-PP partially prevented cerivastatin-induced contractile failure (FOC: 53.3±14% of vehicle; n=4). S and F-PP had no protective effect (n=4/group). Conclusion: SMT can be used to identify and compare statin myotoxicity in vitro and may be useful to dissect its underlying mechanisms. In addition, our data suggests that statin myotoxicity is at least in part independent of cholesterol depletion.

Na+/Ca2+ exchange inhibition protects the rat heart from ischemia-reperfusion injury by blocking energy-wasting processes

We have recently reported that exposure of rat hearts to high Ca2+ produces a Ca2+ overload-induced contractile failure in rat hearts, which was associated with proteolysis of α-fodrin. We hypothesized that contractile failure after ischemia-reperfusion (I/R) is similar to that after high Ca2+ infusion. To test this hypothesis, we investigated left ventricular (LV) mechanical work and energetics in the cross-circulated rat hearts, which were subjected to 15 min global ischemia and 60 min reperfusion. Sixty minutes after I/R, mean systolic pressure-volume area (PVA; a total mechanical energy per beat) at midrange LV volume (mLVV) (PVAmLVV) was significantly decreased from 5.89 ± 1.55 to 3.83 ± 1.16 mmHg·ml·beat−1·g−1 ( n = 6). Mean myocardial oxygen consumption per beat (Vo2) intercept of (Vo2-PVA linear relation was significantly decreased from 0.21 ± 0.05 to 0.15 ± 0.03 μl O2·beat−1·g−1 without change in its slope. Initial 30-min reperfusion with a Na+/Ca2+ exchanger (NCX) inhibitor KB-R7943 (KBR; 10 μmol/l) significantly reduced the decrease in mean PVAmLVV and Vo2 intercept ( n = 6). Although Vo2 for the Ca2+ handling was finally decreased, it transiently but significantly increased from the control for 10–15 min after I/R. This increase in Vo2 for the Ca2+ handling was completely blocked by KBR, suggesting an inhibition of reverse-mode NCX by KBR. α-Fodrin proteolysis, which was significantly increased after I/R, was also significantly reduced by KBR. Our study shows that the contractile failure after I/R is similar to that after high Ca2+ infusion, although the contribution of reverse-mode NCX to the contractile failure is different. An inhibition of reverse-mode NCX during initial reperfusion protects the heart against reperfusion injury.