Effect of iloprost on contractile impairment and mitochondrial degeneration in ischemia-reperfusion of skeletal muscle.

Purpose Acute lower extremity ischemia is still a main cause of mortality and morbidity in orthopedic traumatology and reconstructive surgery. In acute lower extremity ischemia, the skeletal muscles are the tissues that are the most vulnerable to ischemia. The aim of this study was to evaluate the effects of iloprost (IL) therapy on skeletal muscle contractile impairment and mitochondrial degeneration in an acute lower extremity ischemia-reperfusion rat model. Main Methods Forty Wistar albino rats were randomly divided into a control group and four experimental groups. Experimental groups were either subjected to 2 h of lower extremity ischemia followed by a 4-h reperfusion period or to 4 h of ischemia followed by an 8-h reperfusion period. Except for the animals in the control group, all animals received IL (1 ng/kg/min) or saline (1 ml/kg) by intraperitoneal infusion for 10 min immediately before reperfusion. At the end of the recording of skeletal muscle electrical activity and contractility, all rats were sacrificed by decapitation and muscle samples of lower extremity were immediately harvested for histopathologic analyses. Results After ischemia-reperfusion, a breakdown in the force-frequency curves of extensor digitorum longus muscle was observed, showing the diminished muscle contractility. However, IL significantly improved muscle contractility following injury induced by 2 h of ischemia followed by a 4-h reperfusion period. In addition, IL partially ameliorated mitochondrial degeneration in the muscle cells of ischemia groups. Conclusion This study indicates that immediate IL therapy repairs muscle damage especially after 2 h of ischemia and 4 h of reperfusion and therefore that IL improves contractile function.

Hemodynamic effects of epinephrine in rats: evaluation by impedance cardiography.

BACKGROUND AND OBJECTIVES: This study was aimed to examine how inotropic effects of intravenously injected epinephrine change thoracic impedance measurements and to reveal the possible effects of this change on other hemodynamic parameters by using the technique of impedance cardiography. METHODS: 10 male Wistar Albino rats were divided into two equal groups: control and epinephrine. 0.2 mg/kg of epinephrine was administered to the rats in the epinephrine group via the tail vein. All hemodynamic parameters obtained by impedance cardiography [the base impedance (Z0), the maximum rate of change in impedance (dZmax/dt), the left ventricular ejection time (LVET), stroke volume (SV), cardiac output (CO), contractility index (IC), thoracic fluid content (TFC), heart rate (HR)] were recorded using the EBI 100C, DA 100 and ECG modules in the BIOPAC MP100 system. RESULTS: CO (p ≤ 0.05), HR (p ≤ 0.001), dZmax/dt (p ≤ 0.05) and IC (p ≤ 0.05) increased statistically significantly in the epinephrine group compared to the control group. However, LVET (p ≤ 0.001) decreased statistically significantly in the epinephrine group compared to the control group. CONCLUSION: Tachycardia was detected in the epinephrine group. There was an inverse correlation between LVET and dZmax/dt and IC. This is based on the fact that epinephrine increases inotropic effect (Tab. 2, Fig. 4, Ref. 30).

Clinical and histopathological relationship of sildenafil and bosentan treatments in rats with monocrotaline induced pulmonary hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a challenging disorder characterized by increasing pulmonary artery pressure, which is hard to treat. OBJECTIVE: This study was aimed to investigate the effects of bosentan, sildenafil and their combination. METHODS: Saline or MCT were applied to Wistar rats. By the development of PAH (4th week), MCT-given rats were treated orally with bosentan, sildenafil and combination of sildenafil and bosentan or placebo. ECHO examinations were performed. Tissues obtained from all of the rats were evaluated under an electron microscope. RESULTS: Left ventricular end diastolic diameter significantly increased in sildenafil and combined groups. Sildenafil group revealed a significant decrease in RV pressure and wall thickness. Examination of lung revealed a significant amount of connective tissue formation and increase in inflammatory cells in all the groups except controls in the interalveolar septum. Examination of PA revealed an increase in connective tissue volume, hypertrophic changes and expansions in granular endoplasmic reticulum cisternaes in smooth muscle cells in active groups rather than in the controls. Unlike the controls, the examination of the RV revealed an enlargement of the sarcoplasmic reticulum cisternaes in some cells, due to the calcium increase. CONCLUSION: Sildenafil and the combined therapy demonstrated to have more impact on pressure and the RV parameters in rats, with lower inflammatory findings in lung tissue (Fig. 6, Ref. 31).

Protective and therapeutic effects of swimming exercise training on diabetic peripheral neuropathy of streptozotocin-induced diabetic rats.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a typical complication of diabetes. No definitive treatment and prevention of DPN has been established, and very few data on the role of exercise training on DPN have been reported. AIM OF THE STUDY: The protective and therapeutic effects of aerobic physical activity on the development of DPN in Type 1 were investigated. METHODS: Rats were assigned to 5 groups: C (control), E (exercise), D (diabetic), DEx (exercise after diabetic), ExD (diabetic after exercise); C containing 10 animals and E, D, DEx, ExD containing 15 animals. Diabetes was induced with streptozotocin (STZ) (45 mg/kg, ip). Development of diabetes was confirmed by measuring blood glucose levels 2 days after STZ treatment. Body weights of all the animals were evaluated weekly throughout the experiment. Motor dysfunction defined by a significant increase in compound muscle action potential (CMAP) latency was recorded. The amplitude of CMAP which mainly reflects axonal dysfunction was also measured using standard techniques. Sciatic nerve morphometry and blood glucose levels were analyzed in all the groups. RESULTS: Blood glucose level significantly increased 2 days after STZ injection. All diabetic rats showed decreased body weight compared to control rats. An increase in motor latency of CMAP and a decrease in amplitude of CMAP, indicative of neuropathy, were seen in STZ rats. On the completion of the study (the 56th day post-STZ), histological examination revealed significant myelin loss (thinner myelin) in sciatic nerves of STZ rats. Treatment with swimming exercise had no effect on glycemic control but restored body weight, CMAP amplitude, CMAP latency or motor dysfunction in the diabetic animals. CONCLUSIONS: This study suggests that swimming exercise training has protective and therapeutic effects on DPN of STZ-induced diabetic rats.

No effect of GA-AS (904 nm) laser irradiation on the intact skin of the injured rat sciatic nerve.

We evaluated the electrophysiological and histopathological effects of low-energy gallium arsenide (904 nm) laser irradiation on the intact skin injured rat sciatic nerve. Twenty-four male Wistar rats were divided into three groups ( n=8 each). At the level of proximal third of the femur the sciatic nerve was crushed bilaterally with an aneurysm clip (Aesculap FE 751, Tuttingen, Germany) for half a second. A gallium arsenide laser (wavelength 904 nm, pulse duration 220 ns, peak power per pulse 27 W, spot size 0.28 cm2, pulse repetition rate 16, 128 and 1000 Hz; total applied energy density 0.31, 2.48 and 19 J/cm2) was applied to the right sciatic nerve for 15 min daily at the same time on 7 consecutive days. The same procedure was performed on the left sciatic nerve of same animal, but without radiation emission, and this was accepted as control. Compound muscle action potentials were recorded from right and left sides in all three groups before surgery, just at the end of injury, at the 24th hour and on the 14th and 21st days of injury in all rats using a BIOPAC MP 100 Acquisition System Version 3.5.7 (Santa Barbara, USA). BIOPAC Acknowledge Analysis Software (ACK 100 W) was used to measure CMAP amplitude, area, proximal and distal latency, total duration and conduction velocity. Twenty-one days after injury, the rats were sacrificed. The sciatic nerves of the operated parts were harvested from the right and left sides. Histopathological evaluation was performed by light microscopy. Statistical evaluation was done using analysis of variance for two factors (right and left sides) repeated-measures (CMAP variables within groups) and the Tukey-Kramer Honestly Significant Difference test (CMAP variables between laser groups). The significance was set at p < 0.05. No statistically significant difference (p > 0.05) was found regarding the amplitude, area, duration and conduction velocity of CMAP for each applied dose (0.31, 2.48 and 19 J/cm2) on the irradiated (right) side and the control (left) side, or between irradiated groups. Twenty-one days after injury there were no qualitative differences in the morphological pattern of the regenerated nerve fibres in either irradiated (0.31, 2.48 and 19 J/cm2) or control nerves when evaluated by light microscopy. This study showed that low-energy GaAs irradiation did not have any effect on the injured rat sciatic nerve.

Acute electrophysiological effect of pulsed gallium-arsenide low-energy laser irradiation on isolated frog sciatic nerve.

We evaluated the acute electrophysiological effects of low-energy pulsed laser irradiation on isolated frog sciatic nerve measured by extracellular recording technique. A pulsed gallium-arsenide (GaAs) laser (wavelength: 904 nm, pulse duration 220 ns, peak power per pulse: 27W, spot size: 0.28 cm(2), total applied energy density: 0.005-2.5J/cm(2)) was used for the experiment. Sixty isolated nerves were divided into six groups (n=10), each of which received a different laser dose. In each group, action potentials were recorded before laser irradiation which served as the control data. The extracellular action potentials were recorded for each combination of 1, 3, 5, 7, 10, 13 and 15 minutes of irradiation time and 4, 8, 16, 32, 64 and 128 repetition frequency by using a BIOPAC MP 100 Acquisition System Version 3.5.7 (Santa Barbara, USA). Action potential amplitude, area, duration and conduction velocity were measured. Statistical evaluation was performed using repeated measures variance analysis by SPSS 9.0. There were no statistically significant differences for action potential amplitude, area and conduction velocity among the laser groups and control data (p>0.05). The study showed that low-energy GaAs irradiation at 4-128 Hz repetition frequencies administered for irradiation times of 1-15 min generates no effect on action potential amplitude, area, duration and conduction velocity in isolated frog sciatic nerve.