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In 1979, during my cardiology fellowship, a 16-year-old with primary pulmonary hypertension (PPH), a rare and severe condition at that time, spurred my research. There was limited literature then. My pediatric cardiology colleagues, who were experienced in dealing with pulmonary hypertension linked to congenital heart diseases, introduced me to vasoreactivity testing, a method involving the administration of oxygen and tolazoline to assess operability. Tolazoline administration resulted in a significant decrease in pulmonary artery (PA) pressure, suggesting potential therapeutic responsiveness, though diuretics were the only treatment for pulmonary hypertension and right heart failure at that time. This prompted my search for a viable solution. In 1980, I joined the Cardiology Faculty at the University of Illinois. Two years later, the patient I had previously treated experienced a critical decline, necessitating an urgent cardiac catheterization. This revealed an alarmingly low cardiac output of less than a liter/minute, explaining her hallucinations due to inadequate cerebral blood flow. I had previously considered the idea of creating an atrial septal defect as a palliative measure, but it was purely hypothetical and highly risky. However, with no other options left, I decided to attempt the shunt procedure as a last resort after discussing the risks with her mother and obtaining consent. This marked the first successful atrial septostomy for PPH. She was discharged on diuretics to manage her heart failure, and this experience inspired my pursuit of innovative treatments for PPH [1]. In the 1980s medical landscape, hope emerged with Nifedipine, a novel calcium channel blocker praised for its efficacy in hypertensive crises, filling me with the prospect of leveraging Nifedipine for treating PPH. At this time, Bruce Brundage, a pulmonary hypertension specialist and member of the NIH Registry for PPH steering committee, became Chief of Cardiology at the University of Illinois, setting the stage for a valuable mentorship opportunity. During what I consider the “golden age of academia,” I proposed an unconventional protocol involving escalating doses of Nifedipine to challenge patients with PPH. These types of proof-of-concept experiments were often conducted without oversight from an Institutional Review Board or sponsor funding, highlighting the flexible research environment of the era. Instead, I proposed this novel approach of incrementally challenging patients with Nifedipine based on the lessons from its use in patients with hypertensive crises under Brundage's guidance. The protocol aimed to test whether consecutive hourly doses of Nifedipine would be safe and effective in patients with PPH. Patients would be admitted to the intensive care unit for placement of a Swan-Ganz catheter to conduct hemodynamic monitoring during oral Nifedipine administration. The patient would be given hourly doses until they either responded or developed an adverse event, ending the study. In 1985, my first subject was a 38-year-old woman from New York, who consented to this trial, driven by a defiant resolve to defy her grim prognosis. When I explained the experimental nature of the protocol to her, she agreed without hesitation, saying, “Everyone told me I'm going to die in a year or two, so I'll do what you propose.” We began the treatment in the afternoon, administering 10 mg of Nifedipine each hour. Around 11 p.m., I head home but instructed the nurses to call me hourly with the patient's hemodynamic measurements. The initial PA pressure was ~90 systolic. As the night progressed, we observed a gradual decrease—first to 80, then to 75 and downward each hour. The patient's blood pressure remained stable and never went below 110 mmHg, which was encouraging. The pivotal moment came at 2 a.m. after her eighth dose. The nurse called to report that the patient's pulmonary pressure had dramatically dropped to 28/10. I was astounded and asked, “Are you kidding me?” The nurse confirmed that the patient's blood pressure remained stable. The significance of this finding overwhelmed me. I could hardly believe what we had stumbled upon. The next day, I rushed to the hospital to find the patient doing well, confirming the remarkable results of our experimental treatment. It seemed we had discovered the optimal dose after 8 h and 80 mg of Nifedipine. She went home on 80 mg of Nifedipine three times a day and had near-normal PA pressures for the next 30 years [2]. This experience marked a significant turning point in the management of pulmonary hypertension, opening up new avenues for treatment and research. A key lesson was recognizing that vasodilator doses effective in systemic circulation may need to be much higher for pulmonary circulation principle later confirmed with nitroprusside. I initially published my findings in Circulation, reporting a 62% responder rate among treated patients. However, I told Bruce Brundage I would not publish further until I had 5-year outcome data, arguing that success with one 38-year-old woman was not enough. Five years later, our results were published in the New England Journal of Medicine, showing an impressive 94% survival rate [3]. My work with high-dose calcium channel blockers in pulmonary hypertension has significantly impacted the field. Twenty years later, with the developing ability to study genetic signatures, the genotype for the calcium channel blocker responsiveness phenotype was discovered, making the channel currently the only truly personalized approach for PPH management [4]. The author has nothing to report. The author has nothing to report. The author declares no conflicts of interest.