The differential effects of systemic vasoconstrictors on human pulmonary artery tension†

Hussain, Azar; Bennett, Robert T.; Haqzad, Yama; Qadri, S.; Chaudhry, Mubarak; Cowen, Michael E.; Loubani, Mahmoud; Morice, Alyn H.

doi:10.1093/ejcts/ezw410

Cited by 14 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These data are in accord with recent studies of vasopressin in pulmonary hypertension that, while noting a vasopressin‐induced decrease in the pulmonary‐to‐systemic pressure ratio, ascribe this improvement to a rise in aortic pressure rather to pulmonary vasodilation . Vasopressin may be unique among pressors in having no pulmonary constrictor effect, but we concur that it has no apparent pulmonary vasodilator effect . Indirect vasodilation has been postulated, for example, through vasopressin‐induced release of atrial natriuretic peptide; but these effects would fall outside of the timeframe of the present study.…”

Section: Discussionsupporting

confidence: 89%

Effect of vasopressin on a porcine model of persistent pulmonary hypertension of the newborn

Amer

Elsayed

Graham

et al. 2019

Pediatric Pulmonology

View full text Add to dashboard Cite

Background Persistent pulmonary hypertension of the newborn (PPHN) is due to a failure of pulmonary vascular relaxation. Vasopressin, a systemic vasoconstrictor acting on smooth muscle AVPR1a receptors, is used in treatment of PPHN. We sought to determine acute effects of vasopressin infusion on pulmonary hemodynamics in a large animal model of hypoxic PPHN. Methods PPHN was induced in 6 newborn piglets by 72 h normobaric hypoxia (FiO2 = 0.10); controls were 7 age‐matched 3‐day‐old piglets. Animals were anesthetized and ventilated with central venous and arterial lines, and after stabilization, randomized using a crossover design to normoxic or hypoxic ventilation, then 30 min infusion of 0.0012 U/kg/min vasopressin, followed by 45 min vasopressin washout period. Echocardiographic parameters and oxygen consumption were measured before and after vasopressin. Relaxation to vasopressin was tested in isolated PPHN and control pulmonary arteries by isometric myography. Expression of AVPR1a receptor mRNA was quantified in arterial and myocardial tissues. Results Vasopressin did not alleviate hypoxia‐responsiveness of PPHN pulmonary circuit. There were no significant differences in pulmonary hypertension, cardiac function indices, or oxygenation indices after vasopressin infusion. Vasopressin did not dilate control or PPHN pulmonary arteries, and AVPR1 was minimally expressed. Conclusions Vasopressin does not have a direct pulmonary vasodilator effect in PPHN, within the timeframe studied.

show abstract

Section: Discussionsupporting

confidence: 89%

Effect of vasopressin on a porcine model of persistent pulmonary hypertension of the newborn

Amer

Elsayed

Graham

et al. 2019

Pediatric Pulmonology

View full text Add to dashboard Cite

show abstract

“…Since 12 rings failed to contract to KCl, (37.6 mM [EC 80 ], calculated earlier [6]), they were eliminated from the study and the remaining 52 rings used. The effects of vasodilator agents on pulmonary artery tone (active tension to PGF 2α ) are summarised in Table 1 and …”

Section: Resultsmentioning

confidence: 99%

“…The vessels were then left to equilibrate with 21% O 2 : 5% CO 2 at 37˚C for 1 hour. PA rings were then pre-constricted with 11.21 µM PGF 2α (EC 80 ), calculated earlier from previous experiments [6]. When a stable active tension was achieved, a series of increasing concentration response curves were created for Sildenafil, Milrinone, Sodium Nitroprusside, Epoprostenol, Iloprost and Treprostinil by stepwise increases in agonist concentration in the myograph chamber when a plateau response was generated for the earlier concentration.…”

Section: Determination Of Agonist Induced Relaxationmentioning

confidence: 99%

“…Prostaglandin F2 acts via FP receptors and has been used in this study as a pre-constrictor. The reason we selected PGF 2α is that as it proved to be highly efficacious in previous experiments [6] and also activation of other prostanoid receptors by the prostacyclin analogues is not documented in the literature [26].…”

Section: A Hussain Et Al World Journal Of Cardiovascular Surgerymentioning

confidence: 99%

See 1 more Smart Citation

<i>In Vitro</i> Characterisation of Pharmacological Effect of Prostacyclin Analogues in Comparison to Phosphodiesterase Inhibitors on Small Human Pulmonary Vessels

Hussain¹,

Bennett²,

Tahir³

et al. 2017

WJCS

Self Cite

View full text Add to dashboard Cite

Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 -4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC 50 : 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies How to cite this paper:

show abstract

“…Dysregulated Ca 2+ homeostasis, and increased Ca 2+ spark frequency promotes arrhythmogenesis of PV cardiomyocytes in HF, which may play an important role in the development of AF [19]. Interestingly, in vitro and in vivo studies showed that AVP produces relatively less vasoconstriction in pulmonary circulation [20, 21]. However, the role of AVP in PV arrhythmogenesis was not clear.…”

Section: Introductionmentioning

confidence: 99%

Arginine vasopressin modulates electrical activity and calcium homeostasis in pulmonary vein cardiomyocytes

Huang

Chen

et al. 2019

J Biomed Sci

View full text Add to dashboard Cite

Background Atrial fibrillation (AF) frequently coexists with congestive heart failure (HF) and arginine vasopressin (AVP) V1 receptor antagonists are used to treat hyponatremia in HF. However, the role of AVP in HF-induced AF still remains unclear. Pulmonary veins (PVs) are central in the genesis of AF. The purpose of this study was to determine if AVP is directly involved in the regulation of PV electrophysiological properties and calcium (Ca2+) homeostasis as well as the identification of the underlying mechanisms. Methods Patch clamp, confocal microscopy with Fluo-3 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, Ca2+ homeostasis, and Ca2+ regulatory proteins in isolated rabbit single PV cardiomyocytes incubated with and without AVP (1 μM), OPC 21268 (0.1 μM, AVP V1 antagonist), or OPC 41061 (10 nM, AVP V2 antagonist) for 4–6 h. Results AVP (0.1 and 1 μM)-treated PV cardiomyocytes had a faster beating rate (108 to 152%) than the control cells. AVP (1 μM) treated PV cardiomyocytes had higher late sodium (Na+) and Na+/Ca2+ exchanger (NCX) currents than control PV cardiomyocytes. AVP (1 μM) treated PV cardiomyocytes had smaller Ca2+i transients, and sarcoplasmic reticulum (SR) Ca2+ content as well as higher Ca2+ leak. However, combined AVP (1 μM) and OPC 21268 (0.1 μM) treated PV cardiomyocytes had a slower PV beating rate, larger Ca2+i transients and SR Ca2+ content, smaller late Na+ and NCX currents than AVP (1 μM)-treated PV cardiomyocytes. Western blot experiments showed that AVP (1 μM) treated PV cardiomyocytes had higher expression of NCX and p-CaMKII, and a higher ratio of p-CaMKII/CaMKII. Conclusions AVP increases PV arrhythmogenesis with dysregulated Ca2+ homeostasis through vasopressin V1 signaling.

show abstract

The differential effects of systemic vasoconstrictors on human pulmonary artery tension†

Cited by 14 publications

References 25 publications

Effect of vasopressin on a porcine model of persistent pulmonary hypertension of the newborn

Effect of vasopressin on a porcine model of persistent pulmonary hypertension of the newborn

<i>In Vitro</i> Characterisation of Pharmacological Effect of Prostacyclin Analogues in Comparison to Phosphodiesterase Inhibitors on Small Human Pulmonary Vessels

Arginine vasopressin modulates electrical activity and calcium homeostasis in pulmonary vein cardiomyocytes

Contact Info

Product

Resources

About

The differential effects of systemic vasoconstrictors on human pulmonary artery tension†

Cited by 14 publications

References 25 publications

Effect of vasopressin on a porcine model of persistent pulmonary hypertension of the newborn

Effect of vasopressin on a porcine model of persistent pulmonary hypertension of the newborn

&lt;i&gt;In Vitro&lt;/i&gt; Characterisation of Pharmacological Effect of Prostacyclin Analogues in Comparison to Phosphodiesterase Inhibitors on Small Human Pulmonary Vessels

Arginine vasopressin modulates electrical activity and calcium homeostasis in pulmonary vein cardiomyocytes

Contact Info

Product

Resources

About

<i>In Vitro</i> Characterisation of Pharmacological Effect of Prostacyclin Analogues in Comparison to Phosphodiesterase Inhibitors on Small Human Pulmonary Vessels