What I Learned From the Study of Sex Differences in Pulmonary Hypertension: How Following the Data and the Kindness of Strangers Helped Me Overcome Self-Doubt and Imposter Syndrome
https://doi.org/10.1002/pul2.70168
Abstract
“Why is there more variation in the females? Could it be due to their estrous cycle?” This was the question my co-mentor, Dr. Irina Petrache, posed when I shared the first data I generated as a first-year research fellow. It was 2007, and was in the lab of cardiothoracic surgeon Dr. Dan Meldrum at Indiana University. Dan studied sex differences in cardiac ischemia–reperfusion injury in the left ventricle. With his model of isolated rat pulmonary artery rings, I joined to explore pulmonary vascular disease. Drawing on Dan's focus on sex biases in the left ventricle, I compared hypoxic pulmonary vasoconstriction in arteries from male and female rats. After gathering sufficient data, I was disappointed: no statistical difference. Before Dan's lab meeting, I consulted Irina. Her insight inspired a plan: a well-designed PowerPoint presentation, a literature review on the effects of the estrous cycle, and experiments on rats of both sexes, along with plans to assess the effects of the estrous cycle on hypoxic vasoconstriction in pulmonary arteries from female rats. Dan agreed to the study, which found that hypoxic pulmonary vasoconstriction varied with the cycle, attenuating at high estrogen levels. This yielded my first “first-author paper” in the American Journal of Physiology [1]. I was thrilled that I—a working-class German country boy with no lab experience and who had never held a pipette in his hand—could publish a research paper in this august journal.
This study on sex differences in pulmonary hypertension (PH) stemmed from experiences 2 years prior. As a second-year internal medicine resident on an elective in Kenya, I saw young women, not men, with severe right heart failure from indoor stove smoke-induced emphysema. Their EKGs showed extreme right ventricle remodeling. Researching sex differences felt like a natural progression of that prior observation.
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