Pamela Garlick

Widening participation in medicine

The extended medical degree programme at King’s College London shows that widening participation in medicine can be successful, but requires appreciable extra commitment by academic staff

The synthesis, release and action of leukotrienes in the isolated, unstimulated, buffer-perfused rat heart.

When the perfusion medium of an isolated, non-recirculating, Langendorff rat heart is changed from Krebs buffer to coronary effluent, a significant vasoconstriction (23%, P less than 0.005) is observed. In this study we have investigated the involvement of leukotrienes in this phenomenon. We have extracted and quantified leukotrienes C4, D4 and E4 in samples of coronary effluent taken at different times during the first 2 h of perfusion; the total amounts released during this time were 9, 5 and 32 pmol of LTC4, LTD4 and LTE4 respectively. We have used two different methods to prevent the action of the effluent leukotrienes on the heart. Firstly, we have blocked the leukotriene receptors in the heart, with FPL 55712 (3.8 microM), during perfusion with effluent and, secondly, we have perfused with coronary effluent which was collected in the presence of a leukotriene synthesis inhibitor, AA861 (1 microM). The addition of FPL 55712 to the effluent decreased the normally observed vasoconstriction such that after 30 min the coronary flow rate (CFR) was 114 +/- 3% (n = 6) compared with 66 +/- 1% (n = 7) with effluent alone (P less than 0.005). Effluent collected in the presence of AA861 also caused a decrease in the normally observed vasoconstriction such that by 30 min the CFR was still 88 +/- 2% (n = 6, P less than 0.005 compared to controls). We have confirmed the proposed involvement of leukotrienes in the effluent-induced vasoconstriction by investigating the effect of a mixture of the synthetic leukotrienes C4, D4 and E4, when each of them was present at the same concentration as measured in the coronary effluent; the vasoconstriction observed was superimposable upon that seen with effluent. This vasoactive effect of the leukotriene mixture was not secondary to a change in contractility, since this only decreased to 97 +/- 5% (n = 9) during the 30 min of the leukotriene infusion. Finally, we have studied the effects of the same two leukotriene blockers in normal, buffer-perfused hearts after an initial perfusion of either 30 or 120 min. Application of either AA861 or FPL 55712 resulted in a dramatic vasodilatation (25 to 45% increase), a larger effect always being observed after the shorter initial period of perfusion. Our conclusions are two-fold. Firstly, isolated, buffer-perfused rat hearts synthesize leukotrienes C4, D4 and E4 in considerable amounts and release them into the coronary effluent and secondly, the coronary flow rates of isolated, buffer-perfused rat hearts are partly controlled by the action of internally produced leukotrienes.

Broadening access to medicine

We would like to comment on Ip and McManus’s editorial on our extended medical degree programme (EMDP) at King’s College London.1 Firstly, our aim in setting up the programme was to enable bright motivated pupils from inner …

Broadening access to medicine: The extended medical degree programme at King's.

We would like to comment on Ip and McManus’s editorial on our extended medical degree programme (EMDP) at King’s College London.1 Firstly, our aim in setting up the programme was to enable bright motivated pupils from inner …

The extended medical degree programme at King's

We would like to comment on Ip and McManus’s editorial on our extended medical degree programme (EMDP) at King’s College London.1 Firstly, our aim in setting up the programme was to enable bright motivated pupils from inner …