S. M. M. Karim

INDUCTION OF LABOUR WITH PROSTAGLANDIN E2

The effect of prostaglandin E2 on the activity of the pregnant human uterus in vivo has been studied in 50 women at or near term and in need of induction. Labour was successfully induced in all cases with a continuous infusion of 0·5 μg./min. The uterine activity produced by prostaglandin infusion resembled that of normal spontaneous labour. No unphysiological increase in uterine tonus was observed. The average infusion time was 5·5 hours and the average infusion‐delivery interval was 10 hours.

THERAPEUTIC ABORTION AND INDUCTION OF LABOUR BY THE INTRAVAGINAL ADMINISTRATION OF PROSTAGLANDINS E2 AND F2α

In 45 women pregnancy was terminated in the first and second trimesters and in 10 labour was induced at term by the intravaginal administration of prosta‐glandins E2 and F2α. With prostglandin E2 the average induction‐abortion interval in 30 women was 12½ hours, and in the 15 women in whom abortion was induced with prostaglandin F2α the average induction‐abortion interval was 14 hours 50 minutes.

THE ACTION OF PROSTAGLANDINS ON THE HUMAN ISOLATED NON‐PREGNANT CERVIX

The isolated non‐pregnant cervix has been shown to exhibit spontaneous isotonic and isometric contractility and to respond to drugs. PGE2 causes a marked relaxation whilst the effect of PGF2α is more variable. Oxytocin and adrenaline cause contraction of the muscle.

THE EFFECTS OF PROSTAGLANDINS E2 AND F2α ADMINISTERED BY DIFFERENT ROUTES ON UTERINE ACTIVITY AND THE CARDIOVASCULAR SYSTEM IN PREGNANT AND NON‐PREGNANT WOMEN

Prostaglandin E2 and prostaglandin F2α both stimulate the intact non‐pregnant and pregnant human uterus. Doses required to provide long lasting stimulation when given by intravenous, subcutaneous and intramuscular routes had no effect on the cardiovascular system. Both the non‐pregnant and the pregnant uterus during early pregnancy showed a similar sensitivity to prostaglandin E2 and prostaglandin F2α. The non‐pregnant uterus was not inhibited by prostaglandin E2at any dose level.

EFFECTS OF ORAL ADMINISTRATION OF PROSTAGLANDINS E2 AND F2α ON THE HUMAN UTERUS

The effects of oral administration of prostaglandins E2 and F2α have been studied in 42 male and non‐pregnant female volunteers and in pregnant women.

THE EFFECT OF ETHYL ALCOHOL ON PROSTAGLANDINS E2 AND F2α INDUCED UTERINE ACTIVITY IN PREGNANT WOMEN

Intravenous infusion of 500 ml. of 10 per cent ethanol per hour for one hour inhibited uterine activity initiated and maintained by an infusion of either prostaglandin E2 or prostaglandin F2α.This study was carried out in seven women with intrauterine death of the fetus in the third trimester of pregnancy and in four women in whom therapeutic termination of pregnancy in the second trimester was planned. The significance of these findings in relation to the physiological role of prostaglandins in parturition is discussed.

Cardiovascular actions of prostaglandin F2α infusion in man

Abstract The effect of PGF 2α on the cardiovascular system in six normal volunteers was studied by intravenous infusion of 0.01–2.0 μg/kg/min. This prostaglandin had no effect on the systolic and diastolic blood pressures, heart rate, ECG or the respiration rate. Similarly rapid single intravenous injections of 1–40 μg of PGF 2α did not alter any of these parameters. One volunteer was also infused with 0.2 μg/kg/min of prostaglandin E 1 for 30 min. This produced an increase in heart rate and a fall in systolic and diastolic pressures.

Prostaglandins and Human Reproduction: Physiological Roles and Clinical Uses of Prostaglandins in Relation to Human Reproduction

The history of prostaglandins is very closely associated with the human reproductive system. What was described as a smooth muscle stimulating substance found in human seminal fluid (Kurzrok and Lieb, 1930; von Euler, 1934, 1935 and Goldblatt 1933), was later shown to consist of a group of modified long chain 20 carbon fatty acids (see Chapter 9 for the Chemistry of Prostaglandins). Subsequent studies have been directed in three main areas. (1) Towards the isolation and identification of prostaglandins in human reproductive organs and in fluids. (2) Towards a study of the pharmacological actions of these compounds on various reproductive organs. (3) Towards establishing physiological roles for prostaglandins in various reproductive processes.

Cardiovascular and Renal Actions of Prostaglandins

Von Euler defined prostaglandin as a ‘lipid soluble smooth muscle stimulating and blood pressure lowering factor with acidic properties in human seminal fluid and some accessory genital glands of man and sheep’ (von Euler, 1935a, 1935b). This definition of prostaglandin was based on the observation that extracts of seminal fluid when injected into animals characteristically lowered the blood pressure of many species including the rabbit, cat and dog (Euler, 1935a, 1935b, 1936, 1963; Goldblatt, 1933 1935). Since the separation and identification of many different naturally occurring prostaglandins, the cardiovascular actions of these compounds have been investigated in many species. From these studies it has become evident that there are marked qualitative as well as quantitative differences in response between species as well as between various prostaglandins.

General Introduction and Some Pharmacological Actions of Prostaglandins

The prostaglandins are a family of closely related unsaturated hydroxy fatty acids. They were first found in male accessory glands and their secretions and are now known to occur with widespread distribution in animal and human tissues and body fluids. The term ‘Prostaglandin’ was coined by von Euler (1935a) in the belief that the biologically active substance found in human semen was a secretion of the prostate gland.