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AN ACADEMIC BATTLE
text: © Sebastian Naslund
Have you ever wondered how a thesis for Ph. D is defended and approved?
In a globalized world knowledge flows across the borders, so when a new thesis on apnea is released it concerns the whole science world in that field. When Peter Lindholm (Sweden) was to defend his thesis on apnea the highly merited Italian Professor Massimo Ferrigno were flown in from Harvard Medical School (Boston, USA) to question its relevance and accuracy.
Proceedure -First Peter Lindholm was able to point out any faults that might be in the printed version of the thesis - there was none, he said. Then the opponent presented the work with its conclusions the way HE had understood it. Peter Lindholm then had one last chance to correct anything in that description. Which he did not want to (probably because Ferrigno explained Peter Lindholms work better than he himself usually is able to) - after that the opponent questioned details, analysis, methods e t c. After that the jury cimmity was let in with questions and finaly the assembly (all described below)

BACKGROUND

THE THESIS
Peter Lindholms thesis is built on four papers in different scientific journals. It was successfully defended on October the 4th at Karolinska Institutet, Stockholm.
Opponent (whose job was to question the relevance and accuracy, was Massimo Ferrigno, himself having done many studies concerning apnea.
In the jury was among others Erika Schagatay having studied apnea since late 80's at Lunds University (Sweden) and Hans Ornhagen, the number one authority on hyperbar medicine in Sweden.

Since many of these academic persons research in the same field, they are in one sense rivals for the same funding. Which made it interesting and sometimes apparent.

Peter Lindholms studies concerns Apnea - and the models are based on breath hold divers - even though results may further knowledge in fields like sleepapnea, sudden infant death sickness and general understanding of the human body.

KEYWORDS
DR = Diving response. HR = Heart rate. For more scientific terms check here.
More on Schagatays and Anderssons research in English,, in Swedish

His methods have mainly been breatholding while cycling a cycle ergometer. Sometimes this has been submerged in a water tank. Some of the usual parameters have been measured; ECG, blood pressure, oxygen saturation (venous and arterial), cardiac output AND the lung gases before and after, thus seeing how much oxygen and other gases there are left after a breath hold. The better diving response the more oxygen left was one hypothesis. In one part of the studies he let the subjects breath oxygen before breath hold, which could, compared to normal breath hold show the role of hypoxemia in the diving response. More about his research

HIS HYPOTHESES ARE AMONG OTHERS:

The diving response is in its full effect only during working apnea.
The diving response IS oxygen conserving.

INTERESTING RESULTS ARE:
That the diving reflex are among other factors initiated by the actual breath holding, that is, if you keep on breathing in a bag while "holding your breath" - the diving reflex is not as strong.
Hypoxemia actually enhances the diving response.
And above all the diving response delays the onset of hypoxemia.

THE DISSERTATION
This was the interesting part. Here the opponent and the jury tried to find faults in the thesis. All answers and questions are summarized. Ferrignos questions were in reality very long starting with a background leading up to a pointier question. Not all questions are presented here and they came in a somewhat different order.
Q (Ferrigno): How relevant is the research for the diving community? Most diving is done under water with pressure, your studies have been above water.
A (Lindholm): Claimed that since everything was done under exercise - it resembled the swimming diver better. Everything measured is magnified during working apnea. Thus the results become clearer.
(Which I guess sent a message to Schagatay in the audience who has done most of her studies on motionless people).
Q (Schagatay): Asked Lindholm what he considered a working diver - should all divers be considered working.
A (Lindholm): He pointed out that his studies only concerned some type of diving. Mainly working apnea as; UV-rugby and constant weight diving. They agreed that there is a difference between an UV-rugby player and a no limit record.
Q (Schagatay): By asking which specific divers Lindholm models concerned she implied that his work had much less relevance than for instance its title claimed (I guess this was a way of protecting results from her own studies in resting apnea).
A (Lindholm): Claimed that his test concerned apnoeic phenomena on the edge of unconsciousness (where for instance drowning occur). While her studies where in the initial phase of DR.
Q (Schagatay): Asked why he claimed that his research ultimately proved that DR gave an oxygen conservation - it had been proven before (read: in her and others tests)
A (Lindholm): The intriguing, and for the outsider, somewhat surprising answer was that journalists (including scientific journals) often want to present more straitforward claims as opposed to the academic world where you always find it wise to be humble and "beat about the bush a little". And also the traditions in scandinavia and the U.S differs somewhat. I guess he meant that sharper elbows are needed "over there". His studies, he pointed out again, concerned the state of hypoxemia, implying that this was necessary to really know something about oxygen conservation.
Q (Schagatay): asked if he found the studies of subjects with less hypoxemia useless
A (Lindholm): “If I did I would not refer to them, in my thesis”.
Q (Schagatay): Then took a few points by asking what the title meant: "severe hypoxemia during apnea in humans: influence of cardiovascular responses" - Why humans when there were only males tested.
A (Lindholm): Lindholm not expecting even his choice of title to be questioned explained that he had wanted the word human in the title and apnea and hypoxemia - avoiding the word diving since it might scare away future funding (his research might come across as being too narrow). He did not go for Schagatays rephrasing of his title: The influence of cardiovascular responses in preventing severe hypoxemia (in men).
Lindholm thought there was no reason to beleive there would be a difference between the resluts of men and women. There had been one or two women, but generally it was hard to find women wanting to take part in the tests (which are somewhat streneous).
Q (Ferrigno): Found the relevance issue interesting and "invited Lindholm to pursue this..." meaning him to explain what the results are good for. He implied that doing science that also tried to solve problems around sicknesses and disease would be more relevant.
A (Lindholm): Lindholm thought that research done on sleepapnea can be furthered if not narrowing in so much on the hypoxic state – the phase leading up to the hypoxemia could reveal clues on how to treat patients.
Q (Schagatay): questioned the relevance of drawing conclusions on sleepapnea when you only seek answers to working apnea. She was also concerned that Lindholm might have missed the point of having subjects forehead exposed to water when doing watertank studies. Her research has shown convincingly that this is a substancial trigger to the bradycardi.
SINCE a thesis is more or less approved before a dissertion like this (by the faculty scrutinizing it and articles being accepted for publication) this turned out to be more of a intriguing academic discussion, where the different parties battled with displaying their skills in rethory and showing that they were also knowledgeable in studies done in fields bordering to apnea. Even if you get approved you can do it well or less well, you can even lose your face.
Q (Ferrigno): Wanted to know why one specific amount of gas was choosen for inhalation (3,5 litres). Why not an amount relating to the percentage of the VC.
A (Lindholm): Sometimes a percentage of the VC had been used - other times not - since the volume had to be standardized. And 3.5 litres neither made the lungs over or under pressurized. And during a real deep dive the lung is anyhow compressed.
Q (Ferrigno): tried to argue that the oxymeter maybe wasn’t accurate below 80% because these machines are known to be useless at low levels.
A (Lindholm): The oxymeter was accurate down to 50%. And the signal was barely ever lost since he had used a lubrication on the ear that enhanced reception (This was received with approval and curiosity). Also the pulse meter read beat by beat, no averages, as most other pulse meters do.
Q (Ferrigno): questioned if 3 minutes was enough for recovery between apnea tests. CO2 and PH in the blood might still be high. He was concerned that the subjects might have started with different CO2. This was working apnea and thus needed more rest. And Ferrigno was curious why he had changed to 5 minutes in later tests.
A (Lindholm): It was a general feeling that 3 min was enough and the prep time before next test was another 60 seconds.
Q (Schagatay): pointed out that results in her tests had shown that the spleen letting go of blood cells is part of the DR and the spleen didn’t recover in 3-4 minutes.
A (Lindholm): Answered that the warm ups before the test would have put the spleen working at an even level.
Q (Ornhagen): was especially grateful for the warning text on freediving in the beginning of the thesis, but disappointed that matters like arterial pressure effect on HR weren’t dealt with more convincing (his own thesis dealt with HR - ECG)
Ornhagen then asked a most interesting question about HOW the subjects held their breath - with the diaphragm muscle or closing the epiglottis.
He also thought that diffeerent volume (of a breath) created differnt pressure and pressure can effect HR and in the end the DR.
A (Lindholm): my guess is that Lindholm had foreseen this but said he wanted to measure the DR - not HOW the subject acquires the DR.
And you cannot measure everything, all studies have their limitations.
Q (Ferrigno): How decide HR at arrhythmia
A (Lindholm): We averaged a beat by beat value. (5 second average during arrhythmia).
Q (Ferrigno): did you calculate the oxygen cost when rebreathing the same air in bag - (for some patients it actually taxes the oxygen some 15 % just the effort of breathing) (But normal exercising breath usually tax some 3%). A similar question was if the myoglobin storage of oxygen in the muscles had been included in calculations.
A (Lindholm): It had been thought of but considered negligible (at least the breathing taxing oxygen stores).And it is not an easy thing to measure.
Q (Ferrigno): did the subjects know that the breath they were given sometimes was oxygen. If so there was a psychological motive to hold longer.
A (Lindholm): Argued that one anyhow notices if its oxygen since the contractions becomes less sharp and deep
Q (Ferrigno): could it be that bradycardi is not mainly caused by vasoconstriction, maybe its because of high arterial pressure
A (Lindholm): Explained that HR goes up directly after apnea but blood pressure is still rising for some seconds after - thus we dont believe the baroreflex effects HR (during breathhold) since blood continues rising - that is is not mainly due to arterial pressure.
Q (Schagatay): Wanted to know why he didn’t measure contractions.
A (Lindholm): said they had to limit there studies somehow and pointed nicely out that "you have already done it in your studies - so why should I". And we did not have that machine.
(But the question if contractions enhances DR or bradycardi is still unanswered).
The last jury member had dug deep into some diagrams and found a part in the text that could contradict another part – he actually proposed that if put all together what Lindholm was saying was that heart rate – is a sign of heart rate – which one could say is not a piece of brilliant scientific work.
A (Lindholm): Peter had to admit that this part was a bit soft (as in hard evidence and soft evidence) but didn’t agree that there was a contradiction. (My guess, after asking around afterwards, is that Lindholm and his crew actually had foreseen something here; it concerned calculations dealing with MAP (mean arterial pressure) = HR x Stroke volume x TPR (total peripheral resistance).
(Generally one can say that non invasive measuremennts are not totally reliable).
Q (Schagatay): I have a feeling that Schagatay now feels Lindholm is somewhat in the defensive and finds it appropriate to ask him if it is wise to publish such ”soft evidence”? If it was research that were somewhat more controversial ( read: really important stuff like cures for disease e t c) would you have published it?
Schagatay continues to question the whole validity of one major part of the thesis. She claims that bradycardi and vasoconstriction does not always promote oxygen conservation. In fact she has seen contradictive results several times in her studies.
This is a severe accusation and the oxygen conservation thing is sort the centrepiece of Lindholms conclusions. Schagatay suggest that Lindholm has pushed to hard on certain individuals and their results (of which he had to few, she added).
In plain text he was accused of displaying the subjects that best suited his cause. Now he is also accused of being a questionable scientist.
A (Lindholm): Lindholm (just turning 30, fresh out of medical school) has all the time radiated a lot of self confidence (the three piece suit helped quite a lot here) and had most of the time a diagram on the overhead to defend his findings – he now kept his posture even here. He humbly suggested an explanation to Schagatays contradicting research. “Might it be when you measure oxygen saturation at the finger that the vasoconstriction in the arm does NOT let the blood come through to the measure point”. (Lindholm measures at the earlobe). The accusation was handed right back .
Lindholm is quite happy having as little as eight subjects (in some tests) since he claims the results are statisticly sound. But he wouldn´t mind having more subjects in the future.
In Lindholm last paper he claims that apnea during training and competition is different due to emotional stress. Claiming also that this is significant only in the easy phase and not in the struggle phase where DR usually occur.
Q (Ferrigno): questioned why emotional stress only played a part in the beginning.
A (Lindholm): had to seek for an answer and mentioned that the effect of the breathing reflex (contractions) distract you from emotional stress.

ANOTHER Ph D
Though questioned from every angle the jury and opponent found the work quite convincing and Lindholm can now call himself PhD, or doctor, as we say in Swedish. Congratulations doctor Lindholm and good luck with future research. And I know interesting tests are already planned – he and other scientists now has to find the hard evidence on what role pressure has in the DR and what the blood shift is and does.
A WEAK PART OF THE THESIS (editors comment)
The fourth and last (much thinner) part of the thesis I think is thrown in to link the studies to a realistic scenario – the competition.
This part mainly claims that HR are higher in a competition situation. And that that the subject is more prone to hypoxemia.
I would argue that too few subjects have been used, in too few tests. Some facts were based on the subjects’ own saying. As compared to other athletes in other sports having competed for years dousins of times, no freediver in the test could be considered experienced and of course there would be emotional stress. Nothing to build part of a thesis on, I would say.
On the other hand when measured in the training situation there was also a degree of stress since most freedivers are competitive and wants to perform when hooked up to a machine.
The emotional stress seems to have been decided based on the subjects HR. Which seems viable
But on a direct question if initial HR influenced the onset and development of DR Lindholm answered that it didn’t. Most subjects have a DR that is more or less an individual but consistent pattern. You get DR either you start at 120 or 80 in pulse. So why would freedivers at competition (as oppossed to training) have a higher risk of hypoxemia due to stress? Isn´t it natural to be tempted to push yourself harder once the competition is on – in spite of what you promised yourself before the competition.
Therefore you risk hypoxemia.
HOW IMPORTANT IS THE DIVING RESPONSE FOR THE FREEDIVER
I (the editor) would argue that since DR is part of an emergency reaction in the body, it kicks in very late. Usually after breathing reflexes. And that the DR is more enhanced without packing and with low oxygen and high CO2.
It is a reflex to save your life in the last part of the dive - that last part that only person pursuing personal bests need and will get whatever his preparations.

The DR will help you. But desiring a strong DR early can be opposed to what makes a dive easier and longer and deeper. High CO2 is a nuisance, low oxygen should come as late as possible. Packing gives more oxygen and better equalization.

A low pulse out of other reasons than the bradycardi is desirable. A low metabolism in the muscles out of other reasons than vasoconstriction is needed. A freediver should look to postpone his DR end lengthen the easy phase.
To that we cannot look for answers in thesis like this one only in our mental training and ability to relax.

And Lindholm also defines this at the end by saying that the breath hold abilities are most dependent on technique – then lung volume and after that a good DR.

The author of this text is one of the subjects and confess to beeing quite enthusiastic about the research (any apnea research in fact).
Breathold test - seven sambas - Lindholm pictures - More scientific links