摘要:

SUMMARY1. The postulate that the composition of solutions used to reperfuse ischaemic hearts may modulate their ability to synthesize high‐energy compounds was tested in isolated rat hearts subjected to 30 min normothermic ischaemia and then reperfused with either Krebs'‐Henseleit buffer (K‐H) for 20 min (control reperfusion, CR), or a ‘myocardial protective solution’ (MPS) for 5 min, followed by 15 min K‐H (modified reperfusion, MR). The ‘myocardial protective solution’ was designed to protect against damage caused by sodium and calcium accumulation and by free radicals. Metabolic precursors were also included to promote and support adenosine triphosphate (ATP) resynthesis during reperfusion under both aerobic and hypoxic conditions.2.31P nuclear magnetic resonance (NMR) was used to measure tissue ATP and creatine phosphate (CP), and atomic absorption spectrometry was used to measure Ca++. Early during CR, ATP recovered to 28% of the pre‐ischaemic value, but fell to 5.5% with continued perfusion. Similarly, CP recovered to 45.5% of the pre‐ischaemic level during early CR but fell to 25.5% with continued perfusion.3. Better maintenance of ATP was seen during MR with oxygenated MPS (O2‐MR), the final ATP remaining at 16.9% of the pre‐ischaemic level. During O2‐MR, CP recovered to 43.55 of the pre‐ischaemic level but was not maintained and fell to a final level of 29.5%.4. During MR with O2‐free MPS (non‐O2‐MR), there was no reperfusion‐associated fall in ATP or CP, with the levels maintained at 26.6% and 34.55, respectively.5. During 5 min CR, tissue Ca++was elevated but this did not happen during 5 min reperfusion with O2‐MR or non‐O2‐MR. After 20 min reperfusion there was no significant difference in Ca2+between the groups (CR 16.56±1.33; O2‐MR 13.48±1.2; non‐O2‐MR 15.97±2.4 μmol/g dry weight). When reperfused with O2‐free histidine‐containing MPS, tissue Ca1+increased substantially without any change in ATP (26.2 ± 1.65% at 20 min).6. Thus reperfusion injury, assessed by a secondary reduction in ATP, can be limited by the initial use of appropriately designed reperfusion ‘cocktails', and Ca++ov

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00425.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. We have previously demonstrated that cerebroventricular administration of potassium chloride (KCI) solutions produces dose‐dependent reductions in blood pressure and heart rate in anaesthetized rats and that these effects are significantly attenuated by ouabain, a selective inhibitor of the Na+‐pump. These observations suggest an important relationship between Na+, K+‐ATPase activity in the central nervous system (CNS) and neural mechanisms involved in the regulation of cardiovascular function.2. Since endothelin‐1 (ET‐1) has been shown to affect various ion transport mechanisms, including the Na+‐pump, the present studies were conducted to evaluate whether this peptide would antagonize central effects of KCI.3. The present studies demonstrate that cumulative doses of ET‐1 (0.8–3.2 pmol, intracerebrolateral ventricular administration, i.c.v.) produced significant attenuation of hypotension and bradycardia produced by i.c.v. injections of KCI (0.75 μmol/5 μL, i.c.v.); in a separate series, a single high dose of ET‐1 (4.0 pmol, i.c.v.) significantly reduced cardiovascular responses to various doses of KCI (0.375, 0.75, 1.25 μmol/5μL, i.c.v.).4. These studies suggest that endothelin may be involved in the regulation of arterial pressure since it is present in CNS and possesses a ouabain‐like effect. However, it is not conclusive that ET‐1 inhibits neuronal Na+‐pump, since alternative mechanisms can also account for the efficacy of the peptide to antagonize central ef

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00426.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. The forced oscillation technique is an effort‐independent method used to characterize the mechanical impedance of the respiratory system. To support the hypothesis that non‐invasive partitioning of total pulmonary resistance is possible by this technique, impedance was measured during air breathing and after equilibration with a mixture of 80% helium (He) and 20% oxygen (O2) in 21 chronic obstructive pulmonary disease (COPD) patients by means of a forced pseudo‐random noise pressure signal over a frequency spectrum from 4 to 52 Hz. Furthermore, during inhalation of both gas mixtures impedance was determined before and after inhalation of 0.400 mg Salbutamol.2. He + O2breathing caused less negative frequency dependence of resistance and a significant decrease in reactance over the range 16–52 Hz. Inhalation of Salbutamol caused a marked increase in reactance values over the range 8–40 Hz. However after equilibration with the He + O2mixture, Salbutamol caused a significant decrease in resistance and a significant increase in reactance at all frequencies.3. The results during He + O2breathing are in accordance with a partitioning of airways resistance into central and peripheral components. The decrease in reactance during He + O2can be explained by a density dependent decrease in inductive reactance. By comparing the impedance data during air and He + O2breathing, it can be concluded that a distribution of pulmonary resistance with minimal losses in the larger airways is more sensitive for detecting changes in the peripheral airways in COPD

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00427.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

b1. Nicotine (10 μmol/L) produced rapidly developing but transient contractions of anococcygeus muscle isolated from rats. The magnitude of the response varied considerably between preparations. Tachyphylaxis occurred, such that no response was elicited by the same or a larger concentration in the continued presence of 10 μmol/L nicotine.2. Contractions produced by nicotine were not affected by atropine, but were abolished by Hexamethonium and the α‐adrenoceptor antagonists prazosin and phentolamine. Contractions were absent in the anococcygeus muscles of rats pretreated with reserpine.3. The (α‐adrenoceptor agonist UK 14304, or guanethidine, raised the tone of the anococcygeus muscle, and converted responses to field stimulation and nicotine to relaxations. Nicotine‐induced relaxations were more pronounced in the presence of UK14304 than guanethidine.4. Relaxations produced by nicotine (1–18 μmol/L) were transient, and tachyphylaxis occurred. When precautions were taken to avoid tachyphylaxis, concentration‐response curves could be constructed. The relaxations elicited by nicotine were abolished or greatly reduced by hexamethonium, tetrodotoxin or ω‐conotoxin GVIA.5. The nitric oxide synthase inhibitorl‐NG‐nitroarginine methyl ester (90 μmol/L) enhanced contractile responses to field stimulation and nicotine, and markedly reduced relaxations elicited by field stimulation and nicotine in the presence of UK14304. These relaxations were restored byl‐arginine (270 μmol/L).6. The results suggest that nicotine acts on nicotinic receptors of noradrenergic and nitrergic nerve terminals in the rat anococcygeus muscle, resulting in the release of noradrenaline and

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00428.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

b1. Phospholipase A2(PLA2) cleaves phospholipids to produce a lyso‐phospholipid and free fatty acid and, in view of the biological activity of the products, PLA2may play a role in many disease states. Lyso‐phospholipids and free arachidonic acid increase in ischaemic myocardium, indicating that ischaemia activates the enzyme.2. Plasma PLA2activity was measured in patients with acute myocardial infarction, based on the release of labelled arachidonic acid fromEscherichia colicell membrane. Fourteen males (peak serum creatine phosphokinase (CK) above twice upper normal) were studied on day 1 (within 6 h of chest pain onset), days 2–4, and days 6–9. Normal age matched males (n= 13) were also studied.3. Plasma PLA2in patients with uncomplicated myocardial infarction (n= 12) was, initially, 1.14±0.10 (s.e.m.) nmol/min per mL plasma, similar to that in the normal group (1.52 ± 0.14). On days 2–4, PLA2activity increased to 1.94±0.18(P<0.001) and this activity was correlated with the earlier peak CK level (P<0.02). On days 6–9, PLA2activity was 1.49±0.13 while in two patients who developed complications and underwent open‐heart surgery between the last two measurements, there were further increases to 4.22 and 4.04 nmol/min per mL.4. The increase in plasma PLA2in uncomplicated myocardial infarction is likely to be due to release from the damaged myocardium; whether it contributes to pathophysio

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00429.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. We assessed the effect of polyethylene glycol conjugated superoxide dismutase (PEG‐SOD) on myocardial stunning in the rabbit heart in which xanthine oxidase level is extremely low.2. In open‐chest anaesthetized rabbits, the left marginal branch of the coronary artery was occluded for 10 min and then reperfused for 30 min. A group of rabbits (PEG‐SOD group) received 1000 units/kg of PED‐SOD and another group (control group) was given saline 15 min before the coronary occlusion.3. Regional systolic thickening fraction (TF) was similarly reduced to approximately ‐ 25% of baseline value during ischaemia in both groups. However recovery of TF after reperfusion was significantly better in the PEG‐SOD group (n= 9) and TF at 30 min after reperfusion was 70.1 ±3.9% of baseline value compared with 44.9 ±3.4% in the control group (n= 9;P<0.05). Rate‐pressure products, left ventricular pressure, and LV dP/dt max were not significantly different between the PEG‐SOD treated and untreated control rabbits at any time during the experiment. PEG‐SOD did not modify the regional myocardial blood flow (coloured microsphere method) during ischaemia/reperfusion, which was assessed by using separate groups of rabbits.4. These findings indicate that oxygen free radicals are important in the pathogenesis of myocardial stunning in xanthine oxida

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00430.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. Superficial fibres of frog skeletal muscle were electrically stimulated in Ringer solution where the chloride content had been replaced by various weakly permeant anions. Changes of the membrane potential were recorded at three different time scales. The complex response was initiated by a volley of fast repetitive action potentials (10–20 ms cycle length) superimposed on the ascending phase of a transient depolarization to ‐ 35 mV. The transient depolarization was followed by a membrane potential oscillation (0.3–0.6 s cycle length). The parameters of the volley and membrane potential oscillation were not greatly affected by the substituent anion.2. The transient depolarization was fully abolished by tetrodotoxin (3 μmol/L), but left unaffected by nifedipine (5 μmol/L), or by the replacement of extracellular Ca for Ni or Co. Tetraethylammonium (20–40 mmol/L) increased the duration and amplitude of the transient depolarization. The shape of transient depolarization was uniform in a given fibre, in spite of its marked variability under different experimental conditions.3. Single outward current pulses applied in chloride‐free solution containing tetraethylammonium (20–40 mmol/L) evoked prolonged depolarizations to positive membrane potentials accompanied by increases in the specific membrane conductance. This slow response, which was also frequently observed in the absence of TEA, was mediated by Ca ions, as it was insensitive to tetrodotoxin (3 μmol/L) but abolished by nifedipine (10 4mUmol/L).4. Two populations of the muscle fibres were observed during the slow response. Some fibres repolarized completely, while others failed to produce complete repolarization but formed a plateau between ‐ 20 and ‐ 30 mV, lasting for several minutes. When the external K concentration was abruptly increased to 5 or 10 mmol/L during the plateau of the slow response, repolarization and increase in membrane conductance were observed.5. In muscle fibres, having osmotically disrupted T‐system, the duration of transient depolarization was in the range of minutes, in contrast to the range of seconds observed in intact fibres. The volley was preserved in glycerol treated fibres, however, the baseline of discharges was close to the resting potential and the rate of depolarization of the baseline was significantly less in glycerol treated than in intact fibres.6. These results are consistent with the existence of a second stable membrane potential level in skeletal muscle between ‐ 40 and ‐ 30 mV. The depolarization and repolarization during the membrane potential oscillation and transient depolarization can be regarded as a partial or full transition, respectively, between these two stable membrane potential levels, possibly due to the conductance changes of the inward rectifier K channels. It seems likely that the various types of repetitive activity are also linked to these conductance changes indicating that they are endogenous properties of the

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00431.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. It has been suggested that prolonged exposure to a rigorous bed rest regimen (hypokinesia) may induce greater serum carbohydrate and electrolyte changes in physically conditioned than unconditional subjects and that chronic hyperhydration may normalize or attenuate the development of these biochemical alterations in physically conditioned subjects.2. Serum carbohydrate and electrolyte changes were determined in 18 physically healthy male volunteers aged 19–24 years during 30 days of a rigorous bed rest regimen. The subjects were divided into three equal groups. The first g oup consisted of six unconditioned subjects with V̇o2 maxof 44 mL/kg bodyweight/min, the second group consisted of six conditioned subjects with V̇o2 maxof 69 mL/ kg bodyweight/ min and the third group consisted of six conditioned subjects with V̇o2 maxof 69 mL/kg body weight/min who consumed daily an additional amount of 26 mL water/kg bodyweight and 0.10 mg sodium chloride/kg bodyweight.3. For the simulation of the hypokinetic effect all volunteers were kept under a rigorous bed rest regimen for 30 days. During the pre hypokinetic period of 15 days and during the bed rest period of 30 days the concentrations of cortsol, aldosterone, testosterone, tri‐idothyronine (T3), thyroxine (total; T4), glucose, potassium, sodium and chloride were determined in blood serum of volunteers.4. During the bed rest period of 30 days serum carbohydrate and electrolyte changes were more pronounced in physically conditioned than unconditioned hypokinetic subjects. In physically conditioned hyperhydrated subjects serum carbohydrate and electrolyte changes were less pronounced than in physically conditioned and unconditioned hypokinetic subjects.5. It was concluded that exposure to a rigorous bed rest regimen over a prolonged period of time induced significantly more changes in serum carbohydrate and electrolyte concentrations in physically conditioned than in unconditioned subjects and that chronic hyperhydration may be used to normalize or stabilize all serum biochemical changes in physically conditioned subjects during prolonged exposure to a rigorous bed rest r

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00432.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY