EFFECTS OF AE0047 ON CEREBRAL ISCHAEMIA AND OEDEMA AFTER MIDDLE CEREBRAL ARTERY OCCLUSION IN CATS

1. AE0047 is a new dihydropyridine calcium antagonist with protective effects against cerebral ischaemia and the occurrence of stroke in several animal models. 2. In the present study we investigated whether AE0047 would improve the reduced cerebral blood flow (CBF) and oedema formation in cats subjected to middle cerebral artery (MCA) occlusion and compared it for efficacy with other dihydropyridine calcium antagonists with different moieties, such as nilvadipine an. nicardipine. 3. Middle cerebral artery occlusion reduced local CBF (1CBF), as measured by the hydrogen clearance method, while dry weight measurement showed that water content in the cortical tissues surrounding each 1CBF measurement electrode had increased after 4 h ischaemia. 4. Both AE0047 (10 μg/kg) and nilvadipine (30 μg/kg), given intravenously 20min after MCA occlusion, produced an approximate 10. hypotensive response and significantly increased 1CBF in severely and moderately ischaemic regions, grouped according to the initial reduced flow values. However, nicardipine (5 μg/kg bolus followed by infusion of 3 μg/kg per min for 60 min) failed to mitigate the reduction in 1CBF despite an increase in the ICBF of the contralateral cortex. In addition, AE0047 tended to prevent an increase in cortical water content in severely ischaemic regions, whereas water content in both nilvadipine- and nicardipine-treated groups tended to increase. 5. These results suggest that dihydropyridine calcium antagonists act differently on cerebral ischaemia and oedema formation in a manner dependent on their side-chain structures and that AE0047 effectively attenuates ischaemic brain damage without aggravatin. oedema.     

Effects of NG-nitro-L-arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin-releasing hormone.

1. The effects of 300 mg kg-1 of the nitric oxide (NO) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the regional blood flow, on the flow response to 1 mg kg-1 of thyrotropin-releasing hormone (TRH) and on cerebral blood flow autoregulation were studied in urethane anesthetized rabbits subjected to unilateral sectioning of the cervical sympathetic claim. The blood flow measurements were performed by the tracer microspheres method. 2. The cerebral arteriovenous difference in oxygen saturation (CAVOD) was measured before and after the administration of L-NAME and TRH in order to ascertain whether the effects on cerebral blood flow that were observed were secondary to changes in cerebral metabolism. 3. L-NAME caused a significant decrease in blood flow in several cerebral regions; CBFtot decreased to 72 +/- 4% of control (P < 0.001). An increase in blood pressure and a concurrent decrease in heart rate and cardiac output were noted. 4. In the eye, L-NAME caused a reduction in uveal blood flow which was more pronounced on the sympathetically intact side; in the retina the blood flow decreased to 50% of control on both sides. 5. The administration of TRH in animals pretreated with L-NAME caused a significant increase in blood pressure and cerebral blood flow. 6. In L-NAME-treated animals the CBF was not affected when the mean arterial blood pressure was increased by ligation of the abdominal aorta. 7. The CAVOD increased from 56.0 +/- 5.2 to 73.6 +/- 3.5%, 20 min after the administration of L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protective effect of beraprost sodium, a new chemically stable prostacyclin analogue, against the deterioration of baroreceptor reflex following transient global cerebral ischaemia in dogs.

1. A possible cerebroprotective effect of a chemically stable prostacyclin analogue, beraprost sodium, was investigated in a canine model of cerebral ischaemia. Cerebral ischaemia was produced by the combined occlusions of the left subclavian and the brachiocephalic arteries with preceding ligations of the intercostal arteries. 2. The decrease in baroreceptor reflex sensitivity (BRS), measured by phenylephrine-induced reflex bradycardia, following 5 min ischaemia was used to assess the cerebroprotective effect. 3. Beraprost (1 microgram kg-1 min-1 i.v., infused for 15 min just before ischaemia) completely prevented the decrease in BRS. Although the lower dose of beraprost (0.1 microgram kg-1 min-1 i.v.) failed to show such a protective effect, its inhibitory effect on ADP-induced platelet aggregation was as potent as that of the higher dose. 4. The extent of decrease in BRS was inversely correlated with the extent of the residual blood flow in the medulla oblongata during ischaemia. Since beraprost did not affect the extent of the residual blood flow during ischaemia, its cerebroprotective effect could not be ascribed to the reduction of the degree of ischaemia by increasing collateral blood flow to the brain. 5. Post-ischaemic reduction of the regional blood flow in the medulla and the cerebral cortex was completely prevented by the higher dose of beraprost. 6. The present study suggests that the cerebroprotective effect of beraprost may be independent of its anti-aggregatory and vasodilator effects. It is possible that the protection may be due to a prostacyclin-like cytoprotective effect through membrane stabilization.     

The anti-diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dog

1. In the present study, we attempted to clarify whether the antidiabetic drug miglitol, an alpha-glucosidase inhibitor, has a protective effect against anginal ischaemia. We had reported previously that miglitol reduces myocardial infarct size through inhibition of glycogenolysis during ischaemia in rabbits. However, the effect of miglitol on anginal ischaemia remains unknown. 2. In open-chest beagle dogs with a severely stenosed left anterior descending coronary artery, an epicardial electrode was attached to the surface of the risk area of the left ventricle and a microdialysis probe was implanted into the myocardium to measure ST segment changes and interstitial lactate accumulation. The first episode of anginal ischaemia was induced by atrial pacing and phenylephrine infusion (50-100 microg/min) for 10 min. The second episode of anginal ischaemia was induced 210 min after the first episode. Miglitol (10 mg/kg, i.v.) was administered to the miglitol group (n = 10) 30 min before the second episode of anginal ischaemia, whereas saline was administered to the control group (n = 10). Regional myocardial blood flow was measured using coloured microspheres. 3. There was no significant difference in regional myocardial blood flow in the risk and non-risk areas between the first and second episodes of anginal ischaemia and between the miglitol and control groups. During the first and second episodes of anginal ischaemia, the ST segment was decreased to a similar extent in the control group. Although ST segment depression during the first episode of anginal ischaemia was similar in both groups, ST segment depression during the second episode of anginal ischaemia was significantly attenuated in the miglitol-treated group compared with the control group (1.3 +/- 0.4 vs 2.2 +/- 0.4 mV, respectively). Miglitol significantly attenuated myocardial interstitial lactate accumulation in the risk area. 4. In conclusion, in the present study miglitol improved ST segment depression and attenuated the accumulation of myocardial interstitial lactate during anginal ischaemia without altering regional myocardial blood flow. Miglitol has an anti-anginal ischaemia effect via a mechanism that is independent of regional myocardial blood flow.     

Effects of naftidrofuryl oxalate on microsphere embolism-induced decrease in regional blood flow of rat brain.

1. The purpose of the present study was to determine whether naftidrofuryl oxalate (naftidrofuryl), a vasodilator, is capable of improving brain regional blood flow of animals in sustained ischaemia. 2. Cerebral ischaemia was induced by injecting 900 microspheres (48 microns in diameter) into the right internal carotid artery of rats. Cerebral blood flow of brain regions was measured by a hydrogen clearance method on the 3rd, 7th and 28th days after the onset of ischaemia. Ischaemic animals were treated with naftidrofuryl, 15 mg kg-1 day-1 i.p., from the first to 28th day. 3. Microsphere-embolism caused a sustained decrease in cortical and striatal blood flow over a period of 28 days, whereas hippocampal blood flow was decreased on the 3rd day but not on the 7th or 28th day. On the 3rd day, the striatal and hippocampal but not cortical blood flow of naftidrofuryl-treated, microsphere-embolized rats was higher than untreated rats. On the 7th and 28th days, the cortical and striatal blood flow of the treated and untreated animals did not differ. 4. Brain slices from microsphere-embolized rats contained areas, which were not stained with triphenyltetrazolium chloride (TTC), to a similar degree on the 3rd, 7th and 28th days, indicating the genesis of cerebral infarction. TTC-unstained areas of microsphere-embolized rats that had received naftidrofuryl treatment were smaller than those of untreated rats on the 3rd and 7th days, but not on the 28th day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic naloxone enhances cerebral blood flow in anesthetized morphine-dependent rats

Laser-Doppler flowmetry was used to study cerebral cortical blood flow responses to morphine and naloxone in morphine-naive and -dependent rats. The experiments were performed in spontaneously breathing anesthetized rats. Morphine (10 mg/kg, i.p.) administration reduced regional cerebral blood flow in control, sham-operated and morphine-dependent rats, but the depressant effect of morphine in morphine-dependent animals was less than that in control and sham-operated groups. While naloxone (0.5 mg/kg, s.c.) had no considerable effect on regional cerebral blood flow in control and sham-operated groups, it increased regional blood flow in morphine dependent ones. The depressant effect of morphine in all groups and the enhancing effect of naloxone in morphine-dependent animals were not seen after local application of lidocaine at the recording site. This study may provide a framework to study the cellular and molecular mechanisms responsible for coupling neuronal electrical activity with regional alterations in blood flow during precipitation of morphine withdrawal.     

(S)-emopamil, a novel calcium and serotonin antagonist for the treatment of cerebrovascular disorders. 3rd communication: effect on postischemic cerebral blood flow and metabolism, and ischemic neuronal cell death

The effect of (S)-emopamil ((2S)-2-isopropyl-5-(methylphenethylamino)-2-phenylvaleronitril e hydrochloride) treatment on postischemic cerebral blood flow and metabolism was investigated in nitrous oxide anesthetized, artificially ventilated rats. Forebrain ischemia was induced and maintained for 20 min by lowering arterial blood pressure to approximately 40 mmHg and clamping both carotid arteries. Local cerebral blood flow and glucose utilization were evaluated autoradiographically in 34 cerebral regions. In the cerebral blood flow studies intravenous infusion of 0.1 mg/(kg min) (S)-emopamil was begun 5 min after the end of ischemia. Local cerebral blood flow was determined 60 min later using [14C]iodoantipyrine. When the animals were treated with saline only, postischemic blood flow of 22 affected forebrain areas fell on average to 42 +/- 13% of nonischemic control. Treatment with (S)-emopamil increased perfusion of the same areas in a region-dependent fashion by an average of 54 +/- 19%, resulting in 63 +/- 17% of control values. The rise of blood flow in structures not directly affected by ischemia amounted to 52 +/- 27% (134 +/- 23% of control). In the studies on cerebral metabolism, the experimental animals received a total of 6 mg/kg (S)-emopamil by slow intravenous infusion before and during the ischemic episode. Determination of local cerebral glucose utilization was initiated after 50 min of postischemic recirculation using [14C]deoxyglucose. In the placebo-treated experimental group average glucose utilization of 14 forebrain areas was significantly lower (74 +/- 9% of control) than in the nonischemic control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

电针对摇头丸滥用者~(99m)Tc-ECD脑灌注显像及脑功能活动的影响

目的·· :用单光子发射计算机断层扫描 (SPECT)脑灌注显像 ,观察电针 (EA)对摇头丸滥用者局部脑血流量(rCBF)及脑功能活动的影响。方法·· :17例摇头丸滥用者和20例健康志愿者 (对照组 )在电针治疗前后进行SPECT检查 ,用脑血流功能变化率 (BCFR % )数学模型进行定量分析 ,评价电针对上述观察指标的影响。结果·· :与对照组相比 ,17例摇头丸滥用者的大脑皮质额叶、颞叶、脑岛、基底节均存在局部脑血流量不同程度的降低,而脑岛、基底节区功能亢进的病理表现 ;电针治疗可显著增加或调整局部脑血流量 ,并改善大脑的功能活动 (P<0.01 ,P<0.001)。结论·· :摇头丸滥用可以导致大脑血液供应减少或病理性增加 ,进而引起中枢神经系统的功能异常 ;针刺治疗对此有显著改善作用 ,提示针刺可以作为一种简便、有效、无副作用的方法用于治疗摇头丸滥用所导致的脑部病理损害     

维拉帕米改善实验性沙土鼠脑缺血后LCBF和脑水份含量

利用沙土鼠脑缺血再灌注模型,于缺血前或缺血后静脉注入钙通道阻滞剂维拉帕米0.5mg/kg,结果表明,维拉帕米显著地改善沙土鼠脑缺血后低灌注现象,增加缺血区脑血流量(P<0.01),同时减轻脑水份含量(P<0.01),对脑缺血后神经细胞将起保护作用,值得进一步研究及临床验证。     

The Development of Nao Li Shen and its Clinical Application

The traditional Chinese medicine Nao Li Shen (containing ginseng, gastrodia tuber, chuanxiong rhizome and red sage root) is used in craniocerebral injury, cervical spondylosis and cerebrovascular diseases. The preparation, as an orally administered liquid, was tested in Mongolian gerbils and shown to increase tolerance to ischaemia and anoxia. Clinical use of the preparation resulted in improvement in 96% of 202 patients, as judged by right cerebral blood flow, TCD and CT examination. We conclude that Nao Li Shen has a positive curative effect upon craniocerebral injury and sequelae of cerebrovascular diseases.     

Effects of nisoldipine on recovery of coronary blood flow, sarcoplasmic reticulum function and other biochemical parameters in post-ischaemic porcine myocardium

The effects of nisoldipine (0.1 micrograms/kg/min; n = 9) or its solvent (n = 9) were studied in pigs, in which left anterior descending coronary artery (LADCA) blood flow in both groups was reduced to 20% of baseline for 60 min and reperfused for 2 hr. Infusions were started at 30 min of ischaemia and lasted throughout reperfusion. In both groups, flow reduction abolished regional contractile function and caused similar decreases in the level of creatine phosphate (CP; by 70%) and the energy charge (from 0.91 to 0.69), mean arterial blood pressure (by 25%), LVdP/dtmax (by 30%) and cardiac output (by 30%). During ischaemia LADCA blood flow slightly increased (from 14 +/- 8 to 24 +/- 6 mL/min/100 g; P less than 0.05) in the nisoldipine-treated animals, resulting in an increase in CP to 91 +/- 24% of baseline and preventing further decreases in energy charge, as observed in the solvent-treated animals. After 2 hr of reperfusion in neither group return of contractile function of the post-ischaemic myocardium was observed. Post-ischaemic blood flow in the nisoldipine-treated pigs increased from 24 +/- 6 mL/min/100 g to 76 +/- 14 mL/min/100 g and from 19 +/- 6 mL/min/100 g to 41 +/- 6 ml/min/100 g in the solvent-treated animals (P less than 0.05) after 2 hr of reperfusion. Myocardial work was significantly higher in the nisoldipine-treated animals (111 +/- 15 mmHg.L/min as compared to 69 +/- 14 mmHg.L/min in the solvent-treated pigs after 2 hr of ischaemia). The energy charge of the post-ischaemic myocardium was similar for both groups (0.84 +/- 0.02 for the nisoldipine-treated and 0.83 +/- 0.03 for the solvent-treated animals). The rate of sarcoplasmic reticular Ca2+ uptake of the non-ischaemic segment of the nisoldipine-treated animals was 61% higher (P less than 0.05) than that of the solvent-treated animals. In the post-ischaemic myocardium similar rates of Ca2+ uptake were found in both groups, but the activities were markedly lower as compared to the non-ischaemic myocardium. It is concluded that nisoldipine increases blood flow during reperfusion, which may have been caused by coronary vasodilatation. However, attenuation of the "no-reflow" phenomenon also contributed, since more rapid rephosphorylation of ADP leading to an increase in CP during ischaemia may have preserved jeopardized cells. Moreover, nisoldipine increases the sarcoplasmic reticular Ca2+ pump activity independent of ischaemia, which may have contributed in reducing the Ca2+ overload.     

Effects of mefenidil hydrochloride on cerebral blood flow in conscious and anesthetized rat

The purpose of this study was to determine the effects of the putative cerebral vasodilator, mefenidil hydrochloride (MF), on cardiocirculatory dynamics and the total distribution of cardiac output in the conscious rat. The radioactive microsphere technique was used to measure regional blood flow and cardiac output before (control) and during intravenous infusion of either MF (2.5, 5.0, 10.0 mg/kg) or vehicle (VH; saline, 0.0204, 0.0408. 0.0816 ml/min, respectively). Neither MF nor VH were found to have significant effects on cerebral blood flow or vascular resistance in conscious rats. MF significantly increased cerebral blood flow and lowered cerebral vascular resistance compared to VH in anesthetized animals without having significant effects in other circulatory regions.     

淫羊藿甙扩张脑血管作用的研究

本实验用麻醉家兔和狗以电磁流量计测定了淫羊藿甙(EI)对脑血流的作用,结果表明,动脉和静脉给予EI均能显著增加脑血流量,降低腑血管阻力。EI增加脑血流的作用与罂粟碱(Pap)相似,作用强度虽弱于Pap,但作用时间较Pap长。     

Effect of hypoxia on vasodilator responses to S-nitroso-N-acetylpenicillamine and levcromakalim in guinea pig basilar artery

Ischaemic stroke is characterised by reduction of blood flow, tissue hypoxia, energy depletion and neuronal death. Drugs causing vasodilatation of cerebral arteries may potentially enhance blood supply to the ischaemic area and improve clinical outcome. However, vasodilators could also reduce cerebral blood flow in the ischaemic region by acting on blood vessels in non-ischaemic tissue, a phenomenon known as blood flow steal. To explore whether these drugs could act selectively on cerebral blood vessels in a hypoxic environment, we examined the effect of hypoxia on vasodilator responses to the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and the ATP-dependent potassium channel (K(ATP)) opener levcromakalim in guinea-pig basilar arteries contracted by endothelin-1. Hypoxia considerably enhanced the vasodilator responses to SNAP, while those to levcromakalim were unaffected. In the presence of the NO synthase inhibitor N(G)-nitro-L-arginine, hypoxia no longer enhanced the vasodilator response to SNAP and suppressed responses to levcromakalim. The results show that the NO donor SNAP, but not the K(ATP) opener levcromakalim, is a more effective vasodilator of cerebral arteries contracted by endothelin-1 during hypoxia than under control conditions. Hypoxia-induced inhibition of basal NO synthesis could explain this enhancement of the vasodilator response to SNAP. Thus, NO donors may have a selective effect on blood vessels in ischaemic brain areas and therefore warrant further evaluation as therapeutic agents in cerebral ischaemia.     

Excitatory amino acid antagonists and their potential for the treatment of ischaemic brain damage in man.

1. A wide range of therapeutic strategies has been explored in humans and experimental animals with the aim of improving outcome after brain ischaemia but few have shown convincing clinical benefit. 2. The massive increase in the extracellular concentration of glutamate which occurs in cerebral ischaemia is a key component in the sequence of neurochemical events which leads to neuronal death. Pharmacological blockade of the action of glutamate at the N-methyl-D-aspartate (NMDA) receptor, (the glutamate receptor subtype principally involved in the neurotoxic effects of the amino acid) provides a novel therapeutic approach to cerebral ischaemia. 3. The effects of NMDA receptor antagonists in animal models of focal cerebral ischaemia are uniquely consistent, viz, a marked reduction in the amount of irreversible ischaemic damage irrespective of the species, the model of cerebral ischaemia, when the animals are sacrificed after the ischaemic episode, whether ischaemia is permanent or temporary and followed by reperfusion and which particular NMDA antagonist was employed. 4. NMDA receptor antagonists have marked effects on brain function in normal animals. The balance between these potential adverse effects and the anti-ischaemic efficacy of these drugs will ultimately determine the clinical utility of this class of drugs. 5. The data which are reviewed provide the basis for the current clinical evaluation of NMDA receptor antagonists in stroke and head trauma.     

New models of focal cerebral ischaemia.

1. Studies in animal models of stroke have provided an invaluable contribution to our current understanding of the pathogenesis of cerebral ischaemia. The strengths of stroke research in animals are: 1) the ability to control the severity, duration, location and cause of the ischaemia, variables which confound interpretation of human stroke data; 2) co-existent disease states and variations in cerebrovascular anatomy are avoided; and 3) physiological parameters such as blood pressure, blood gases, temperature and plasma glucose (all of which influence the magnitude of the ischaemic lesion) can be closely monitored and controlled. Taking all these things on board, it is possible to induce a consistent focal ischaemic lesion in animal models of stroke (e.g. the permanent occlusion of the middle cerebral artery (MCA) in the rat). This has resulted in the wide use of animal models for assessment of anti-ischaemic drug efficacy as well as for research into the pathophysiological sequelae of stroke. 2. Traditionally focal ischaemia models involved permanent occlusion of a major cerebral artery such as the MCA. However, since vessel occlusion is seldom permanent in human stroke more recent developments have incorporated reperfusion (following ischaemia) into the design of the animal model. This has been achieved by reversible occlusion of cerebral vessels using 1) intraluminal filaments; 2) microclips; 3) the abluminal application of potent and prolonged vasoconstrictors; or 4) the introduction of emboli into the cerebral circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

通脉注射液抗缺血性脑血管疾病的实验研究

目的 研究通脉注射液治疗缺血性脑血管疾病的药理学基础.方法 采用去甲肾上腺素所致的脑血管阻力增加的麻醉猫及沙土鼠脑缺血再灌注损伤模型,了解其抗脑缺血的作用.结果 通脉注射液能明显促进再灌期EEG、电位幅度的恢复,并降低缺血区皮层细胞内钠、钙、水及脂质过氧化物的代谢物MDA的含量,对麻醉猫正常血压无影响,但可增加其脑血流量,同时降低脑血流阻力.延长小鼠常压缺氧的死亡时间和显著延缓注射异丙肾上腺素提高心肌耗氧量后小鼠缺氧的死亡时间.结论 通脉注射液有良好的抗脑缺血再灌注损伤所致的脑细胞内钠、钙潴留及抗脑水肿的药理作用.     

Effect of low intravenous doses of TRH, acid-TRH and cyclo(His-Pro) on cerebral and peripheral blood flows.

Local cerebral and peripheral blood flow in conscious and anaesthetized rabbits were investigated with the microsphere method, before and after the i.v. administration of 25 or 50 micrograms kg-1 thyrotropin-releasing hormone (TRH). Before the experiment, the cervical sympathetic chain was sectioned on one side in order to evaluate the possible effect of the sympathetic nerves on cranial and extracranial blood flows. Blood flow was also determined in anaesthetized rabbits before and after the administration of the TRH metabolites cyclo(His-Pro) and acid-TRH and after subsequent administration of 50 micrograms kg-1 TRH. TRH caused an increase in mean arterial blood pressure (MAP) of about 1 to 2 kPa whereas cyclo(His-Pro) and acid-TRH had no effect on MAP. In the anaesthetized animal an increase in total cerebral blood flow (CBFtot), from 71 +/- 7 to 107 +/- 12 g min-1 100 g-1 (P less than 0.05) was observed on the sympathetic intact side after 25 micrograms kg-1 TRH and a further increase to 130 +/- 9 g min-1 100g-1 (P less than 0.01) after 50 micrograms kg-1 TRH. A similar effect was observed on the sympathotomized side. An effect on CBF in the conscious animal was not detected. The control CBFtot (104 +/- 8 g min-1 100g-1) was higher in these animals than in the anaesthetized animals (P less than 0.02). Neither cyclo(His-Pro) nor acid-TRH mimicked the effect of TRH on CBF. In several peripheral tissues, e.g. skin, pancreas and gastric mucosa, a reduction in blood flow was noted after the administration of TRH in both anaesthetized and conscious rabbits. It was concluded that TRH can induce cerebral vasodilatation in animals with a depressed CBF, whereas the vasoconstrictor effect of TRH in peripheral organs is not markedly affected by the state of consciousness.     

Ventricular fibrillation is reduced in hypothyroid rats with enhanced myocardial alpha-adrenoceptor responsiveness.

1. The severity of ventricular arrhythmias induced by coronary artery occlusion and reperfusion has been examined in control rats and animals made hypothyroid by pretreatment with 6-propylthiouracil (PTU). The maximal driving frequency and sensitivity of isolated left atria and papillary muscles to isoprenaline and to phenylephrine in the presence of propranolol, were also examined in tissues from control and hypothyroid animals. 2. Pretreatment with PTU resulted in a potentiation of responses to the alpha-adrenoceptor agonist phenylephrine in both left atria and papillary muscles, while responses to isoprenaline were depressed in left atria but unaltered in papillary muscles from hypothyroid animals. 3. In rats subject to coronary artery occlusion, PTU pretreatment reduced the incidence of ventricular fibrillation during acute myocardial ischaemia and abolished reperfusion-induced ventricular fibrillation. Mortality during myocardial ischaemia and reperfusion was also abolished. Diastolic blood pressure was similar in hypothyroid and control animals, but there was a small reduction in systolic blood pressure and a marked decrease in heart rate in PTU pretreated animals. 4. These results demonstrate that PTU-induced hypothyroidism represents a condition where cardiac alpha-adrenoceptor-mediated responses are enhanced but the severity of ischaemia- and reperfusion-induced arrhythmias is reduced.     

Effect of dimephosphon on the blood circulation and oxygen tension in the brain of normal waking rabbits and in motion sickness

By using methods of hydrogen clearance and polarography it was shown that rocking of conscious rabbits is followed by an increase of total cerebral blood flow, local blood flow and oxygen tension (pO2) in the frontal, occipital and temporal brain cortex during hypotension and a decrease of the heart rate. Dimephosphon causes a decrease of the cerebral blood flow both during the stationary position of animals and rocking, exerting a weak influence on pO2 in the cerebral cortex, arterial blood pressure and the heart work.