Mapacalcine specifically blocks hypoxia-induced calcium influx in rat hepatocytes.

Post ischaemic cell calcium invasion has been described as one of the main causes of graft failure. Protective effects of calcium antagonists have been investigated but are not convincing and their mechanisms of action remain unclear. In this work we tested the protective effect of a new calcium inhibitor described to block a calcium current insensitive to all known calcium blockers. Specific mapacalcine receptors were first characterized on rat hepatocytes membranes using the 125I-labeled mapacalcine. 45Ca fluxes were then measured on cultured hepatocytes submitted (or not) to an hypoxic period. The action of mapacalcine was investigated on the ischaemia-induced calcium influx. We demonstrate here that: (a) there are specific receptors for mapacalcine in rat hepatocytes; (b) Mapacalcine is able to specifically block ischaemia-induced calcium influx with an IC50 of 0.3 micro m and does not significantly interact with the basal calcium flux. Our work demonstrates that the mapacalcine receptor is a cellular structure directly involved in the phenomenon of postischaemic cell invasion by calcium. Specific block of ischaemia-induced Ca2+ influx by mapacalcine suggests that the development of a panel of pharmacological drugs acting on this receptor could lead to the discovery of therapeutic agents able to protect cells against one of the events responsible for organ failure after transplantation or simply after an ischaemic period. Moreover, identification of the cellular protein which binds mapacalcine may become an important step in the research of mechanisms involved in postischaemic cell invasion by calcium.     

Influence of ventilation of the face on thermoregulation in Man during hyper- and hypothermia

It has been suggested that a thermal countercurrent exchange may occur in the cerebral vascular bed of humans, thereby creating for the brain a state of relative thermal independence with regard to the rest of the body. However, worrying questions have arisen concerning this suggestion. Experiments were carried out on seven young male volunteers. Hyper- and hypothermic conditions were produced by immersion in water at 38.5 degrees C and 25 degrees C, respectively. During the last few minutes of immersion, the face was cooled or warmed by ventilation with a 200 l.min-1 air flow at 5 degrees C or 40 degrees C, respectively. Internal and peripheral temperatures were recorded. Blood flow in the anastomotic vessels between face and brain was measured by Doppler techniques associated with computerized frequency analysis. The general responses were as classically described, i.e. an increase in peripheral and central temperatures during immersion in the warm bath and a decrease in these variables in the cold bath. The reactions produced by cooling or warming the face were small and easily explained by the direct changes of the heat load they induced. Whatever the thermal conditions, the blood flow in the anastomotic vessels between the vascular bed of the face and that of the brain was never reversed. It was concluded that there was no experimental evidence for an efficient thermal counter-current exchange in the vascular bed of the human head.