Nitrates for HAPE?

[Underwhelmed]

Greetings, all. I have a question that I cannot get answered, through research, and conversations with providers ALOT smarter than me--- so I challenge you to give me a satisfactory answer.

Let's say, hypothetically, that I may or may not be be taking a trip to a foreign land with altitudes exceeding 8,000 feet.

One of the main ailments that occur (30% give or take) in poorly acclimated individuals is HAPE, (High-altitude pulmonary edema).

Most texts refer to this as a poorly-understood process that ranges from cough, dyspnea on exertion (poor excercise tolerance) to life-threatening pulmonary edema. There are no specific numbers readily available to me for exactly how many servicemen have been evacuated as a result of this in the last ten years, so I'm going with the worst-case scenario assumption as I prepare for this trip.

In preperation, I have reviewed and considered each treatment that is suggested:

1: Descent ASAP
2: Supplimental oxygen
3: Oral Viagra
4: Oral or IV calcium-channel blockers (contraversial)

What I'm missing is how people describe this "phenomenon" as "poorly understood", because when I run over the physio in my head, it seems to make sense--so I'm going to run my theory by you guys, and my question about the treatment.

First and foremost, reducing the atmospheric pressure on the body (rapid ascent >8k feet) changes the concentration gradient for blood vessels; because PRESSURE is the primary driving force behind concentration gradient in the cardiovascular system. (HACE, anyone?) This applies to alot of stuff, and someone tells me that they understand a certian cardiac disease, but not how it affects pressure, or pressure affects IT, then they don't really understand it.

So the bottom line is, by reducing the outside pressure, you now make the pressure inside the blood vessels the driving force, (particularly the ones that line the aveoli like spider webs)which could trigger a shift of fluid from inside the vessels, to OUTSIDE the vessels and straight into the alveoli. Boom, pulmonary edema.

To compound this, the reduced oxygen concentration in the air causes pulmonary vasoconstriction. This one is easy, because if you look at all of the diseases that cause hypoxia, you'll also see pulmonary hypertension because the vessels in your lungs will tighten up in response to the drop in oxygen. This will cause all kinds of issues with the right side of your heart, because it has to now fight against a substantial increase in pressure. Conversely, if you INCREASE the oxygen taken in, the pulmonary vessels DILATE, which is why oxygen is extremely effective in treating HAPE.

So what happens if you have a pressure problem, and a container problem? The pressure on the inside of the blood vessels is now greater than the pressure on the outside of the vessels, and thanks to the decreased oxygen in the air, the pulmonary vasculature constricts... which further forces fluid out.

If you look at the treatment outlined, the first two are obvious then, because both will ultimately increase blood oxygen levels, which will dilate the vessels, which will make it easier for fluid to shift from the alveoli itself back into the capillaries. Descent is also great because it fixes the PRESSURE problem.

The next two are drug related, and we know the thinking behind this because both Viagra and CCB's are vasodilators. The approach is the same: If you can't do the first two, then pharmicologically dilate the pulmonary vessels to accomidate this fluid shift and reverse the pulmonary edema.

However... oooh, here comes the big one: I have NOT seen in any text or article, nitrates reccomended for HAPE, DESPITE the fact that nitroglycerin has surpassed furosemide in the first-line treatment for cardiogenic pulmonary edema. True, the mechanism by which nitro treats LV heart failure is different, but what is the difference between drugs like oral Viagra (phosphodiasterase inhibitors), or Diltiazem(Calcium channel blockers) and Nitroglycerin?

The fact that these two drugs work suggest that they both dilate pulmonary vessels. We know that nitro dilates CORONARY vessels, but what effect does it have on pulmonary vessels? If it does indeed dilate pulmonary vessels, then is it unreasonable to use it as an alternative to CCB's or oral viagra for its shorter half-life, ease of administration, and faster onset time?

Please, un-confuse me!

[Underwhelmed]

I suppose I could have picked a less-boring subject as my first post. Sorry. :P

[MTN Medic]

I recently got back from a high altitude exercise and have studied a lot about this exact issue. Turns out that Viagra doesn't really work that well; neither does Cialis. I brought Nifedipine and it turns out, it doesn't work either (all that well.)

Given the pharmokokinetics of Nifedipine, it would seem that it would be the perfect drug (ie it decreases pulmonary BP and decreases permeability of pulmonary tissue.) The fact that this drug doesn't work, leads me to believe that the best drug (cliche I know) is descent and, barring that, a Gamow bag and O2.

[Papa Zero Three]

This may not answer your question but it sheds some light on the fact that your concerns are not unfounded and DARPA is looking into it.

http://www.wired.com/dangerroom/2010...eme-altitudes/

Darpa’s Inhaled Drugs to Boost Troops at Extreme Altitudes
By Katie Drummond August 5, 2010 | 8:55 am | Categories: DarpaWatch


Extreme altitudes are a major barrier for troops fighting in the mountains of Afghanistan, and the military’s spent millions trying to minimize altitude’s impact on physical and cognitive ability. Now, Darpa-funded researchers are making impressive progress towards inhaled drugs that would pump up troop performance by fast-tracking the body’s natural adaptations to altitude.

The Pentagon’s blue sky research arm has awarded $4.7 million to scientists at the Case Western Reserve School of Medicine, to develop pharmaceuticals that can rapidly boost oxygen delivery. Blood carries less oxygen at high altitudes, leading to a lack of oxygen in bodily tissue, called hypoxia. That, in turn, can cause nausea, confusion and fatigue — hardly the attributes the military’s after in battle-ready troops. By augmenting blood flow to tissues, the research team hopes to enhance oxygen delivery too.

That’s an adaptive process the human body is already capable of, but the necessary acclimatization can take weeks. Dr. Jonathan Stamler, who’s leading the research at Case Western, says the drugs will essentially do what we already can.

“We’re essentially mimicking nature here,” he tells Danger Room. “Take people climbing mountains, who will set up base camps at varying altitudes to give their bodies time to adjust. We’re making these mechanisms much, much more acute — a matter of minutes, rather than days.”

The drugs will work by increasing blood levels of nitric oxide, which is naturally released by red blood cells to dilate vessels and increase blood flow.

Within three years, Darpa wants to see animal models and human subjects capable of immediately exercising more efficiently at altitude after taking the drugs. Stamler and co. are well on their way to meeting the ambitious goal: they’re already performing tests on animal models, and have applied for FDA approval to try the approach in people.

Stamler also anticipates widespread civilian applications for the drug, which will likely be dispensed in portable inhalers.

“A deficiency of nitric oxide has been observed in a number of conditions, from sickle cell disease to heart attacks and strokes,” he says.

Figuring out a quick way to increase nitric oxide levels might also help the military solve another major problem: donated blood that’s weeks old by the time it hits the front lines. Older blood is low on nitric oxide, which some scientists now suspect leads to risk of heart attack and stroke among transfusion recipients.

“If we can get this right for Darpa,” he says, “Then the actual approach could apply to much more than just altitude adaptations.”

Photo: National Guard

[MTN Medic]

also, 8 K is not really HAPE territory. If you are seeing HAPE at 8K, you should probably spend the rest of your days sipping mai tais on the coast. Honestly, I have only ever seen HAPE at 15,500+.

[Underwhelmed]

Wow, so the data reguarding the other vasodilators was largely unsubstantiated. The replies so far have been just the type of feedback I have been looking for.