Full analysis of the experiment on sheep part-funded by the British Heart Foundation

This macabre and truly repugnant experiment, financially supported by the British Heart Foundation (BHF)(1), formed part of a long running series conducted at Cambridge University, under the auspices of Professor Dino Giussani. It involved cutting open the bellies of sheep in late pregnancy, and placing tubes and monitors into the legs and major blood vessels of their babies. Both mother and young were then deprived of oxygen via the repeated suffocation of the mothers, and were killed several days later.

The suffering endured by the ewes, housed alone after extensive surgical mutilations, is heartbreaking to imagine. Several days after the surgery, they were forced to undergo two prolonged episodes of suffocation, essentially by having a bag put over their heads. This was in order to deprive their babies of oxygen, still in utero, who in turn had been connected to numerous invasive recording devices and given drugs to alter their physiology. As documented by heart and blood pressure monitoring, severe foetal distress was induced.

Professor Giussani has a track record of these kinds of gruesome experiments. The Home Office has allowed him to perform similar suffocation ‘procedures’ on pregnant ewes for at least a decade, in addition to grotesque brain damage experiments in which the umbilical cords of unborn sheep are clamped off. It is both tragic and mystifying as to how licences were repeatedly granted to such clinically irrelevant, manifestly unpleasant procedures – and this calls into question, yet again, exactly how the Home Office applies its ‘harm-benefit’ test when sanctioning animal experiments.

The experiment – Statin treatment depresses the fetal defence to acute hypoxia via increasing nitric oxide bioavailability

Financially supported by: British Heart Foundation
Performed at: Cambridge University
Published: 2012

Stated purpose

To investigate the effects of statins on the physiology of ‘chronically instrumented late gestation fetal sheep’, including during periods of hypoxia (lack of oxygen).


Statins are very widely prescribed to people at increased risk of cardiovascular disease. According to the researchers, rising levels of obesity and a tendency of women to delay childbirth has led to ‘growing clinical interest in treating pregnant women with statins’. To date, the recommendation has been (and remains) to stop statins during pregnancy due to a fear of their links to birth defects. The evidence for these side effects, however, is not conclusive. Indeed, recent trials investigating pre-eclampsia (a serious complication of late pregnancy) have recruited women with high-risk pregnancies and given them a daily dose of statins.

However, despite the large amount of data gathered from observational studies in pregnant women exposed to statins (which recorded not just birth defects, but pregnancy outcomes and condition of offspring), the researchers wished to investigate the effects of statins on the physiology of unborn sheep and whether or not those foetuses would be helped or hindered by statins after they had been deliberately starved of oxygen. The experiment was, thus, of a very basic exploratory nature, and its findings not required to have any medical relevance.

Experimental protocol

Twelve Welsh Mountain ewes, four-fifths of the way through their pregnancies, were starved for 24 hours, then anaesthetised before their abdomens and wombs were cut open. The legs of their foetuses were pulled out externally, so that various tubes could be inserted into the major blood vessels close to the foetal hearts. The incisions were sewn up, and all the tubes and devices were put through an incision in the side of the mother, inside a plastic pouch sewn onto the ewe’s skin.

After two to three days of ‘recovery’, during which the ewes were housed alone and given antibiotics – although the published scientific paper makes no mention of pain relief – they were transferred to a ‘metabolic crate’, a small cage in which they were experimented on and subsequently killed. The sheep, thus, spent their last days in solitary confinement in a cramped cage, unable to exercise or interact with others of their species.

The experiment itself consisted of subjecting all twelve ewes to acute oxygen starvation (hypoxia). A ‘respiratory hood’ was placed over the animals’ heads, and air pumped in for 60 minutes. The inhaled gas was then switched to a mixture composed mainly of nitrogen, which had the effect of suffocating both the mother and unborn lamb for 30 minutes. The ewes were then allowed to breathe air for 60 minutes of ‘recovery’. During this protocol, blood sampling and physiological monitoring was repeatedly carried out. Unsurprisingly, the heart rate and blood pressure of the ewes increased in response to suffocation, and the level of oxygen in their blood decreased dramatically. Monitoring of the foetuses showed severe distress, with their blood becoming more acidic, their heart rates dropping, and a massive release in stress hormones.

The following day, the statin drug, pravastatin, was given directly to the foetuses via an intravenous infusion. On the third and final day of the experiment, all the animals were suffocated for a second time with the respiratory hood, with six of the foetuses being treated intravenously with other drugs. These blocked the effects of nitric oxide (NO), a naturally occurring chemical that regulates blood flow to key organs including the brain and the circulatory system. The researchers believed that the blood regulatory actions of NO are mediated by statins, and it is the function of NO in such circumstances that they were seeking to explore. The sheep were all then killed by lethal injection, and post-mortems performed.

The researchers concluded at the end of the experiment that their initial hypothesis – that statins have an effect on the foetal circulation via their actions on nitric oxide – had been vindicated.

Scientific validity

Highly questionable. There would appear to be basic flaws in the methodology of the experiments, which render any extrapolation to human medicine highly suspect. Far more useful clinically are the number of observational studies of pregnant women, and newer trials in progress. Assessing the possibly subtle effects of oxygen deprivation on the foetal brain would take years of follow-up, something clearly not possible in animal studies. In addition, the experimenters put forward two seemingly contradictory ideas about how statins could influence foetal blood flow to the brain, both of which could be supported by their animal data.

Among the most striking problems regarding the approach of the sheep researchers relates to the actual administration of the statins. The researchers gave the drug intravenously to the unborn lambs, whereas in clinical practice, the drug would be taken orally by pregnant women. The research team claim their approach was necessary ‘to avoid confounding influences due to maternal effects of pravastatin and/or differences in transplacental passage of pravastatin’. However, these influences are precisely how the effects of the drug would be mediated in people. The team’s animal model is, therefore, manipulated for convenience of investigation – the all-important biological cycling between the maternal and foetal circulations is removed.

A second important point with regard to the experimental design is that pravastatin is a hydrophilic drug – one which tends to be dissolved by water, and not cross the fatty biological membranes found in living systems. Recent studies using human placentas have verified that it passes only slowly, and in small quantities, across the placenta. And so, the experimenters are reaching conclusions with regard to the effects of statins on the foetus, based on an animal model and using a drug that transfers in a highly limited fashion to the foetal circulation.

Obvious ethical concerns are raised by the fact that many human studies have reported on the safety profile of statins in pregnancy. Although the major outcome of interest has historically been birth defects, details of pregnancy outcomes, birthweights and neonatal complications have also been obtained. This data, while involving relatively small numbers of people, is still considerably better than any obtained through highly manipulated animal models. Data from a larger, multi-centre trial investigating pravastatin as a treatment for pre-eclampsia (that the researchers themselves reference in their paper) will include a whole range of neonatal health outcomes.

Meaningful enquiries into the effects of statins on the neurological health of the foetus must adopt a much longer time period than these animal experiments. A review article from 20122 references the experiment critiqued here, and points out that ‘these more subtle changes would require longer follow-up and assessment of cognitive function of offspring aged 2+ years’. This observation, by itself, amounts to a critical indictment of much of the Cambridge programme.

Tellingly, in common with much basic research, the team concludes with a series of speculations that would require further investigation, some of which are contradictory. They propose, for example, that the brains of foetuses of pregnant women taking statins may be more susceptible to injury during hypoxic periods, as foetal protective mechanisms mediated by NO may be diminished. On the other hand, they propose that the statin could increase blood flow to the foetal brain, also via its actions on nitric oxide. Both of these contrasting phenomena are apparently in accord with the results of this experiment. This makes it hard to see how any clinical advance can come from such animal suffering.

Lastly, the team’s recommendation that ‘the use of statins during pregnancy should be viewed with extreme caution’ is simply a reiteration of current good medical practice. The situation would change only if high quality human studies were to indicate a more favourable risk-benefit ratio.

In summary, it is hard to view this repulsive series of basic physiological animal experiments as anything other than superfluous. It has disturbing echoes of another scandalous, BHF-supported programme, conducted by researchers at Leeds University on more than 100 beagles. In particular, the use of one study to justify another, with a seemingly ever-present ‘urgent need for further research’, is strikingly similar.


  1. The published paper states that the work was supported by the BHF and Professor Dino Giussani – who heads the research programme of which the experiment was part – has received a Programme Grant from the BHF.
  2. Lecarpentier E, Morel O, Fournier T, Elefant E, Chavatte-Palmer P, Tsatsaris V (2012). Statins and Pregnancy, Between Supposed Risks and Theoretical Benefits. Drugs 2012; 72 (6): 773-788