Warren H. Johns is breathing hard this crisp September morning. The Loma Linda University special collections librarian--who holds a Ph.D. in systematic theology and a master's degree in library science--is on the home stretch of a 7.5-mile, mostly uphill, high-altitude run to the top of White Mountain near Bishop, California.
Dr. Johns started out, two hours ago, at an elevation of 11,680 feet. He should arrive, in another 25 minutes or so, at the 14,252-foot summit of this, the third highest peak in California. After that, he'll undergo a series of tests from a team of volunteer physicians and medical students to measure several of the physiologic effects of exertion at high altitude. The same group conducted a cardiac ultrasound on Dr. Johns and took his vital signs at the University of California's Barcroft research station, down at 12,470 feet.
At age 65, Dr. Johns embodies the Loma Linda Blue Zone lifestyle and looks decades younger than he is. Despite the fact that he's been running competitively for the last 30 years, today's run is no walk in the park. Besides the challenge of running uphill, other hazards abound: thin air can induce mountain sickness; sharp stones threaten falls and injuries; and fatigue is a constant danger. No matter that he was driven some 250 miles through the night to get here this morning, Dr. Johns must stay focused if he wants to finish the course.
As one of 14 runners recruited by cardiology and pulmonary researchers from Veteran's Administration Loma Linda Healthcare System (VALLHCS)--an affiliate of Loma University School of Medicine (LLUSM)--Dr. Johns is trying to better his time from last month when he first ran up the mountain. Today, he brought extra drinking water and intentionally started out slower. He hopes the two adjustments will shorten his time.
The tests he will undergo at the summit--as well as those he endured earlier at Barcroft station--will help researchers understand the effects, if any, of an unusual procedure called ischemic conditioning of the extremity (ICE) on high-altitude performance. The study Dr. Johns is participating in--titled "The Effects of Ischemic Pre-Conditioning on Pulmonary Vasoreactivity and Exercise Performance"--seeks to determine the extent to which ICE produces a systemic, or whole-body, effect on humans.
Defined as an experimental technique that protects many types of body tissues from the detrimental effects of low oxygen, ICE seems to defy logic. The procedure is performed by repetitively occluding blood flow to an extremity over the course of a 40-minute procedure.
While scientists know that ICE has protective effects, they would like to understand more about the underlying mechanism. By analyzing data gathered from this and other experiments, they hope to quantify ICE's influence on exercise performance, acute mountain sickness, cognitive function, molecular responses, and pulmonary artery pressures. Despite intriguing results from animal studies over the last decade, this is the first extensive test of the procedure on humans at high altitude.
James Anholm, M.D., chief of pulmonary and critical care medicine at VALLHCS and associate professor at LLUSM, and Gary Foster, M.D., staff cardiologist and director of cardiac imaging at VALLHCS and associate professor at LLUSM, work together as co-investigators on the study.
"Formally, I'm the principal invesigator," Dr. Foster says. "That's because the authorities want to have someone to blame if something goes wrong." Even so, he and Dr. Anholm are cautiously optimistic that ICE may provide significant benefits not only to high-altitude athletes, but also to the many patients suffering from the effects of pulmonary hypertension, or elevated blood pressure in the lungs.
If so, the study could have wide-ranging implications for both basic science and also translational research--that area of science where knowledge gained in the laboratory and, in this case, the mountains--is applied directly to patient care in a clinical setting. As responsible researchers, both investigators are cautious about asserting overly optimistic outcomes; yet they're excited about the possibility that findings of the study may one day contribute to improved treatment modalities for this, and perhaps other, deadly conditions.
They are not, of course, the only members of the study team. Besides themselves and the 14 runners, the study was supported by Paresh Giri, M.D., a pulmonary fellow at Loma Linda University Medical Center (LLUMC) and at VALLHCS; Laura Carnahan, RN, RCP, a pulmonary research nurse at VALLHCS; Michael Terry, RCP, RRT, manager of the pulmonary function laboratory at LLUMC; Bertha Jadowicz, RDCS, cardiac sonographer from VALLHCS; medical students from the summer research project of the Center for Health Disparities and Molecular Medicine at LLUSM; several high school students; family members; and assorted helpers and friends.
Medical students who participated in various aspects of the study included second-year students Douglas Rogers, Brenden Matus, and Mousa Saleh, third-year student Laura Foster, and fourth-year student Christina Tan.
Laura Carnahan says the medical students gained lots of practical experience during the five months of the study. "They were learning how to draw blood," she says, "doing echocardiograms, and looking at the vessels and the heart chambers. They were looking at pressures and taking measurements 90 minutes after the race, too. Back at the VA hospital, they were also collecting data on patients with heart catheters in place."
Dr. Anholm admits that the basic premise of ICE sounds a bit far-fetched. "It does seem preposterous," he says. "Initially, I thought, 'This is crazy; this can't work.' However, you look at the data that's been collected and it's pretty impressive. Then you look at our data, and it's pretty impressive, too."
The two categories of data he refers to are the aforementioned animal studies conducted at a variety of labs around the world, and an earlier study the team conducted last year using bicyclists, both at low altitudes and with high-altitude simulation.
Although the study was supposed to be a blinded test, it's pretty hard to conceal the fact that a blood pressure cuff around a runner's or cyclist's leg is suddenly being inflated to the point where blood flow to the extremity is curtailed.
"The placebo is partly a sham you try to set up," says Laura Carnahan. "In some studies, you can hide or blind it, but you can't blind this treatment because they can feel the blood pressure cuff being pumped up. We pumped it up for both runs, but didn't pump it as fully for the placebo run. We tested one time without the treatment and one time with it."
What isn't so obvious is the reason why the act of conditioning the athlete by five daily repetitions of the ICE procedure--the last typically being administered four to six hours before the run--results in a systemic effect. When asked to explain why it happens, Dr. Foster would only speculate based on prior animal studies. He did indicate, however, that the beneficial period occurs in two distinct waves.
"The first effect peaks at 90 minutes," he says, "and lasts about three hours. Then it recurs at around 24 hours and lasts until 72 hours."
As Dr. Johns rounds the bend for the last hundred yards of his journey, a group of enthusiastic supporters cheers him on. Some people have trouble even walking at 14,000 feet, but Dr. Johns breaks into a fast trot. When he finally crosses the finish line at 2 hours and 22 minutes, the crowd lets out a yell.
Dr. Johns is elated for three reasons. First, despite innumerable odds, he completed the arduous run. Second, he bested his previous time by several minutes. Third, he managed to beat most of the younger runners in the group. Not all, however: Matt Underwood, an emergency room physician at Riverside Community Medical Center and 1992 graduate of LLUSM, made the run in an amazing hour and a half.
"Once you make it to the top," Dr. Johns says, "there's a great feeling of accomplishment and a little bit of euphoria. You feel that way for about seven minutes."
Too bad the feeling didn't last longer. "After that," he says, "I was dehydrated; I was losing body salt in my sweat, and I started chilling and I got the shakes. What helped me was just plain hot water. Two cups. They put blankets around me, and in 45 minutes, my chilling was gone."
Fast forward to November 10, 2010, and members of the joint research team are gathering in a fourth-floor conference room at VALLHCS. It's 7:00 p.m. and people are talking excitedly in small groups.
Drs. Anholm and Foster are there along with Dr. Giri, Michael Terry, and Laura Carnahan. There are no less than 52 people in the room and to a one, they all seem to be having a wonderful time. Warren Johns has a grin half the size of White Mountain as he talks with other runners about their alpine ordeal.
As the group enjoys a potluck supper of haystacks, salads and cookies, Dr. Foster steps to the front of the room and talks about the study. He begins by explaining how the previous year's research--which tested the effects of prophylactic ICE at a simulated altitude of 13,000 feet--laid the groundwork for the 2010 study.
He tells the group that after the data from the 2009 project was analyzed, two primary questions came into focus: can ICE prevent or minimize high-altitude sickness related to increased pulmonary blood pressure, and can it improve human exercise performance?
For the next 45 minutes, Drs. Foster and Giri present an overview of how the 2010 study was designed to answer those questions. They talk about testing methods, share personal experiences, outline the goals and objectives of the study, thank everyone who participated in it, and confidentially discuss the study's remarkable preliminary findings.
Then they call Laura Carnahan forward to hand out a number of awards for people who put forth an exemplary amount of effort to make the ambitious project a reality.
When she comes to Warren Johns' award, she says that he could have been cited for being the oldest participant by far but instead chooses to give him the Energizer Bunny award. He, of course, is delighted.
When the meeting ends, Dr. Anholm reflects on the fact that the findings cannot be released until all of the numbers have been crunched and the study has been published in a peer-reviewed medical journal.
"The preliminary results," he says, "are very encouraging." In typical research talk, he underscores the fact that "further evaluation is still needed for all of the data," before concluding on a note of guarded optimism. "In the end," he says, "we will have significant new insights to report. As always, we now have more focused questions to address in next year's research effort."
For his part, Dr. Johns takes a thoughtful moment or two before responding to a question Michael Terry just raised.
"Would I do it again? That's a good question," he says. "If I knew there was the prospect to push the research to a whole new frontier, yes. I would want to be assured that it would help. But it is an experiment. There is a little risk in doing this."
Moments later, Dr. Johns tells Mr. Terry about the herd of deer he saw on the mountain, expresses regrets that he missed the big golden eagle other members of the expedition saw, talks passionately about how much he loves running, says he wishes he'd taken more time to enjoy the breathtaking scenery on top of the mountain and ....
It isn't hard to imagine he'll be putting on his running shoes next summer.
People wishing to contribute to these ongoing research efforts are invited to contact Gary Foster, M.D., by e-mail at gary.foster2@va.gov or gpfoster@llu.edu.
This story was originally published in the Dec. 17, 2010, edition of Today.