In the final part of this series, Joseph Parambil, MD, walks us through the approach of managing pulmonary hypertension, reviews the pathophysiology and digs into the mechanisms and the differences in the medications.

• Intro 0:12
• In this episode 0:17
• Interview with Joseph Parambil, MD 2:53
• Reviewing and clarifying pathophysiology prior to initiating therapeutics 4:13
• Evaluating patients in terms of their functional status and how does that play a role in initiating therapies 4:25
• Vasoreactivity testing 10:21
• The categories of medications 14:40
• Endothelin receptor antagonists 37:07
• TGF pathway 42:13
• Scleroderma patient and treatment 50:19
• Do patients get a repeat right-heart catheterization? 55:51
• What about the TGF-beta? 56:55
• Thank you, Dr. Parambil 58:34
• Thanks for listening 59:17

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.

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.

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.