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Pretreatment with Ro 5-4864 enhanced the bronchoconstrictor responses to histamine or carbachol in the anaesthetized artificially ventilated guinea pig. This suggests the involvement of a peripheral-type benzodiazepine receptor as also indicated by the lack of effect of clonazepam. PK 11195 did not antagonize the Ro 5-4864-induced enhancement, but itself enhanced the bronchoconstrictor responses to histamine or carbachol. The data indicate that Ro 5-4864 and PK 11195 behave as metactoid sensitizers of histamine or carbachol.

The potential additive protective effect provided by nifedipine to the University of Alabama Hospitals cardioplegia solution (ACS) was assessed with the use of a guinea pig heart-lung model of cardiopulmonary bypass and ischemic arrest. The addition of nifedipine consistently enhanced the protective properties of ACS infused at 37 degrees C; functional recovery was similar to that observed with cold ACS. Despite the additional protection under normothermic conditions, nifedipine did not improve recovery after infusion at 4 degrees C. The abolition by hypothermia of the protective effects of nifedipine suggests a similarity in action between nifedipine and hypothermic protection. The interaction between ACS and nifedipine was studied on bovine coronary arteries in vitro. Nifedipine caused a marked reduction in the coronary vasoconstricting effect of ACS, both under normothermic and hypothermic conditions. The use of nifedipine in cardioplegia may provide additional protection when uneven distribution of the cardioplegic solution is expected and hypothermic protection is unreliable.

In rats, adrenaline excretion is reduced and noradrenaline excretion is increased during the first two months after demedullation by either adrenal expression or adrenalectomy associated with cortical grafting. In rats demedullated by expression, this is followed by a substantial rise in adrenaline excretion and a simultaneous fall in noradrenaline excretion. In these animals, insulin, nicotine and phenoxybenzamine increase adrenaline excretion; these effects are lacking in rats demedullated by grafting. Indirect evidence suggests that these differences between the two types of demedullated rats are not due to differences in impairment of adrenocortical function. It is concluded that: a) demedullation by expression does not completely eliminate adrenomedullary activity; b) balance phenomena exist between the adrenergic and the noradrenergic function; c) the activity of the extra-adrenal chromaffin system is scarcely influenced by the sympathetic system. The possible central mechanism involved in the action of nicotine is discussed.

RECENTLY, the results of two separate groups of investigations have emphasized the importance of glucose metabolism via the pentose phosphate pathway.

Cold cardioplegia is currently the method of choice for providing myocardial protection during open-heart surgical procedures. Two components of protection, perfusion cooling and pharmacological cardiac arrest, were investigated in the guinea pig heart-lung model. The effects of two cardioplegic solutions, the University of Alabama Hospital solution and the St. Thomas' Hospital solution, and a control perfusate were compared. The results confirmed the efficacy of hypothermia as a protective agent and the additional protection afforded by pharmacological cardioplegia. Infusion temperature critically influenced the cardioprotective action of the Alabama solution: Striking protection was afforded only under hypothermic conditions, whereas myocardial damage was exacerbated by the infusion at 37 degrees C. The St. Thomas' Hospital solution provided substantial protection independent of infusion temperature. Thus, the safety margin of the Alabama solution was narrower than that of the St. Thomas' solution. It is suggested that the difference between the two cardioplegic solutions partially depends on their coronary vasoactivity, since the administration of the Alabama solution at 37 degrees C increased coronary perfusion pressure. It would seem worthwhile to use a temperature-independent cardioplegic solution devoid of coronary vasoconstricting action.

The effects of two cardioplegic solutions (CPSs) on isolated, superfused, bovine coronary arteries were compared with those produced by changes in composition of standard Krebs medium. High potassium, low sodium content or the addition of albumin produced vasoconstriction; high magnesium, high glucose content or the addition of mannitol led to vasodilatation. In most cases hypothermia slightly reduced vasoconstriction and enhanced vasodilatation. The action of the two CPSs is the result of the interaction of these basic effects. The results suggest that the vasomotor reactions of coronary arteries to CPS may affect the delivery of the CPS to the myocardium and exert a critical influence on successful cardioplegia.

The effects on the EEG tracings of a short lasting digital occlusion of the carotid artery in the neck has long since been used as a functional test in the clinical assessment on cerebrovascular patients. The occurance of EEG slowing during this manoeuvre is the expression of a cerebral ischemic anoxia and probably of a defective collateral circulation.

The values of cerebral circulation time were determined by means of rapid serial angiography in the chloralosed dog under control conditions, after administration of strychnine and after injection of ergotamine. These results were compared with those obtained by the simultaneous registration of the intracranial venous pressure. Confirming previous observations made by means of this latter technique, the angiographic results showed that strychnine reduces the cerebral circulation time by provoking an increase in cerebral blood flow, whereas ergotamine causes a cerebral vasoconstriction, thereby increasing intracranial circulation time. Moreover, a statistically significant inverse correlation exists between the values of the intracranial pressure and the cerebral circulation time. New evidence of the relationship between the extra- and the intracranial circulation was obtained by the angiographic observations; these latter data are discussed in relation with the problem of the lability of cerebral vasoconstrictor reactions.

1. Splanchnic nerve stimulation provokes a larger increase in blood pressure in intact rats than in rats previously demedullated by means of expression of the adrenals in situ and adrenalectomy followed by adrenocortical grafting. 2. Rats pretreated with guanethidine showed an attenuated albeit prolonged hypertensive response to splanchnic stimulation. Similar effects were exerted by guanethidine in rats demedullated by expression. In rats demedullated by grafting, smaller doses of guanethidine induced a more substantial depression of the blood pressure response without increasing its duration. 3. It is concluded that inhibition of the peripheral sympathetic endings induced by guanethidine was partially compensated by the enhancement of the cardiovascular effects of the mediators released by the adrenal medulla and that demedullation by expression did not completely eliminate chromaffin tissue.