In this episode, we dive into the early therapies and how our understanding of vascular physiology drastically changed the management of pulmonary hypertension.

• Intro 0:12
• In this episode 0:18
• Recap of part 1 & 2 0:31
• What part 3 is about 2:31
• WHO conference in 1975: Treating pulmonary hypertension 3:48
• The Discovery of Non-Steroidal Anti-inflammatory Drugs (NSAIDs), Part 1 5:20
• Epoprostenol 6:18
• Prostacyclin 10:37
• Endothelin antagonists 11:41
• Phosphodiesterase type 5 (PDE5) inhibitors 14:08
• Interaction of nerves and blood vessels 15:06
• The Soups VS the Sparks 17:36
• A dreamed experiment 19:06
• Acetylcholine 23:23
• Enter “the calabar bean” 24:45
• Acetylcholine and vasodilation: 1976 26:01
• Rabbit aorta 27:45
• Nitric oxide 29:38
• Why are we using nitric oxide to treat pulmonary hypertension? 31:31
• Tachyphylaxis 33:48
• TNT factories 35:09
• Nitrous oxide and tachyphylaxis 36:52
• Pfizer in the 1980s 38:06
• Understanding the trigger of pulmonary hypertension 40:53
• PDE5 and nitric oxide and pulmonary hypertension 43:07
• The end of the ripping yarns 44:20
• Coming up in part 4 46:17
• Thanks for listening 47:29

We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum.

References:
Bernard C. C R Soc Biol. 1851;3:163-164.
Furchgott RF, et al. Nature. 1980;doi:10.1038/288373a0.
Galiè N, et al. N Engl J Med. 2005;doi:10.1056/NEJMoa050010.
Ghofrani HA, et al. Nat Rev Drug Discov. 2006;doi:10.1038/nrd2030.
Giordano D, et al. Biochim Biophys Acta. 2001;doi:10.1016/s0167-4889(01)00086-6.
Guthrie F. Q J Chem Soc. 1859;doi:10.1039/QJ8591100245.
Higenbottam T, et al. Lancet. 1984;doi:10.1016/s0140-6736(84)91452-1.
Marsh N, et al. Clin Exp Pharmacol Physiol. 2000;doi:10.1046/j.1440-1681.2000.03240.x.
Montastruc JL, et al. Clin Auton Res. 1996;doi:10.1007/BF02281906.
Nejad SH, et al. Future Cardiol. 2024;doi:10.1080/14796678.2024.2367390.
Tansey EM. C R Biol. 2006;doi:10.10116/j.crvi.2006.03.012.
Warren JV. Trans Am Clin Climatol Assoc. 1988;99:10-6.

Disclosures: Brown reports no relevant financial disclosures.

In part 2, we dig into the history of pulmonary hypertension. How did this strange diagnosis first get recognized, what does it have to do with cows with thick necks and urinary catheters in the heart?

• Intro 0:11
• In this episode 0:17
• Recap of part 1 0:26
• How was pulmonary hypertension discovered? 2:38
• 1891 3:51
• 1901 5:07
• 1935 7:02
• Hilar dance 12:58
• Cardiac catheterization: 1929 15:03
• When did cardiac catheterization become relevant? 20:10
• 1965: Aminorex 24:40
• World Health Organization: 1975 26:37
• 1980s: toxic oil syndrome of Spain 28:20
• Preview of part 3 33:15
• Back to cardiac catheterization 34:08
• Briskets disease 35:45
• 1947 37:56
• Pulmonary physiology and prostaglandin therapies (in the next episode) 38:41
• Schistosomiasis outbreaks in Egypt 1938 40:26
• Chronic thromboembolism 45:03
• Thanks for listening 48:16

We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum.

References:

Barst RJ. Ann Thorac Med. 2008;doi:10.4103/1817-1737.37832.

Bodo R. J Physiol. 1928;doi:10.1113/jphysiol.1928.sp002447.

Dresdale DT, et al. Am J Med. 1951;doi:10.1016/0002-9343(51)90020-4.

Egypt. Stanford.edu. Published 2015. https://schisto.stanford.edu/pdf/Egypt.pdf.

Hewes JL, et al. Pulm Circ. 2020;doi:10.1177/2045894019892801.

Johnson S, et al. Am J Respir Crit Care Med. 2023;doi:10.1164/rccm.202302-0327SO.

Newman JH. Am J Respir Crit Care Med. 2005;doi:10.1164/rccm.200505-684OE.

Weir EK, et al. Circulation. 1996;doi:10.1161/01.cir.94.9.2216.

Disclosures: Brown reports no relevant financial disclosures.

In this series, we dive into what rheumatologists should know about pulmonary hypertension, starting an interview with Joseph Parambil, MD, where we learn about the disease, when to suspect and how to work up!

• Intro 0:11
• In this episode 0:16
• Preview of the four-part series 4:46
• Interview with Joseph Parambil, MD 6:27
• How did you become interested in pulmonary hypertension? 7:02
• Brown and Parambil discuss the histology of pulmonary hypertension. 10:13
• Brown and Parambil discuss a case of pulmonary hypertension. 12:26
• What is pulmonary hypertension and what does that mean for a rheumatologist? Where is pulmonary hypertension happening? 13:25
• Describe the different groups of pulmonary hypertension. 19:51
• A note about Dr. Chatterjee 20:25
• Brown and Parambil discuss the groups of pulmonary hypertension. 23:35
• What should we know about evaluating patients with pulmonary hypertensions? 26:51
• Brown and Parambil discuss bendopnea and other signs of pulmonary hypertension. 29:58
• What about the heart sound? 33:06
• What should we look for in patients who we suspect to have pulmonary hypertension? 36:52
• What should we look for in the tricuspid jet? 38:18
• Brown and Parambil discuss the use of echocardiograms in pulmonary hypertension. 39:28
• Tell us about the threshold of diagnosis. 40:47
• What is the difference between the mean pressure and the wedge pressure? 41:41
• What about the role of the pulmonary function test? 43:55
• Summary 46:41
• Do you think the pulmonary hypertension in scleroderma and lupus are different entities? 48:37
• Brown and Parambil discuss the connection of autoimmune disease and pulmonary hypertension. 50:49
• Coming up in episode 91 51:50
• Thanks for listening 52:25

Disclosures: Brown and Parambil report no relevant financial disclosures.

Joseph Parambil, MD, is a staff member in the Respiratory Institute and the director of the HHT Center of Excellence and the Vascular Anomalies Center at the Cleveland Clinic. He is associate professor of medicine at Cleveland Clinic’s Lerner College of Medicine. He is certified by the American Board of Internal Medicine with additional specialty certification in pulmonary medicine and critical care medicine.

We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum.