scholarly journals Why Pulmonary Vasodilation May Be Part of a Key Strategy to Improve Survival in COVID-19

Cureus ◽  
2021 ◽  
Author(s):  
Isaac Solaimanzadeh
Keyword(s):  
Pulmonary Vasodilation

Vasopressin-induced pulmonary vasodilation in rats

1989 ◽  
Vol 257 (2) ◽  
pp. H415-H422 ◽  
Author(s):  
B. R. Walker ◽  
J. Haynes ◽  
H. L. Wang ◽  
N. F. Voelkel
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Systemic Resistance ◽  
Constant Infusion ◽  
Bolus Administration ◽  
Pulmonary Hemodynamics ◽  
Pulmonary Vasodilation ◽  
Isolated Lung ◽  
Series Of Experiments

Experiments were performed to determine the pulmonary vascular responses to exogenous or endogenous arginine vasopressin (AVP) in rats. Both in vitro and in vivo approaches were used to examine the direct pulmonary vasoactive properties of AVP and how those properties affect pulmonary hemodynamics in the intact animal. In conscious, unrestrained rats, constant infusion of AVP (4.0 mU.kg-1.min-1 iv) resulted in a fall in mean pulmonary artery pressure (PAP), although systemic pressure was increased. Coincident with the fall in PAP were similar reductions in cardiac output and heart rate. Similarly, bolus administration of AVP reduced PAP, and this effect was augmented during hypoxia. Another series of experiments examined the effect of endogenous AVP released by arterial hypoxemia on pulmonary hemodynamics in conscious rats. Administration of a specific V1-vasopressinergic antagonist had no effect on the PAP response to hypoxia; however, systemic resistance tended to fall following V1-antagonism. To determine the vasoactive properties of AVP independent of these changes in blood flow, a series of experiments were performed on isolated, perfused rat lungs. Injection of 25, 200, or 2,000 mU of AVP into the circulation of the isolated lung was without effect under normoxic conditions. In contrast, 25 mU AVP elicited reproducible pulmonary vasodilation when injected during ongoing hypoxic pulmonary vasoconstriction. This vasodilatory response was unaffected by meclofenamate or by the platelet-activating factor receptor antagonist SRI 63-441, but was blocked by a specific V1-vasopressinergic antagonist. We conclude that although AVP exerts profound systemic vasoconstriction, the pulmonary circulation appears relatively unaffected by exogenous or endogenous AVP in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension

1998 ◽  
Vol 84 (2) ◽  
pp. 435-441 ◽  
Author(s):  
Christophe Adrie ◽  
Fumito Ichinose ◽  
Alexandra Holzmann ◽  
Larry Keefer ◽  
William E. Hurford ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Half Life ◽  
Hemodynamic Effects ◽  
Pulmonary Vasodilation ◽  
Short Half Life ◽  
Acute Pulmonary Hypertension ◽  
Inhaled No

Adrie, Christophe, Fumito Ichinose, Alexandra Holzmann, Larry Keefer, William E. Hurford, and Warren M. Zapol. Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension. J. Appl. Physiol. 84(2): 435–441, 1998.—Sodium 1-( N, N-diethylamino)diazen-1-ium-1,2-diolate {DEA/NO; Et2N[N(O)NO]Na} is a compound that spontaneously generates nitric oxide (NO). Because of its short half-life (2.1 min), we hypothesized that inhaling DEA/NO aerosol would selectively dilate the pulmonary circulation without decreasing systemic arterial pressure. We compared the pulmonary selectivity of this new NO donor with two other reference drugs: inhaled NO and inhaled sodium nitroprusside (SNP). In seven awake sheep with pulmonary hypertension induced by the infusion of U-46619, we compared the hemodynamic effects of DEA/NO with those of incremental doses of inhaled NO gas. In seven additional awake sheep, we examined the hemodynamic effects of incremental doses of inhaled nitroprusside (i.e., SNP). Inhaled NO gas selectively dilated the pulmonary vasculature. Inhaled DEA/NO produced nonselective vasodilation; both systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were reduced. Inhaled SNP selectively dilated the pulmonary circulation at low concentrations (≤10−2 M), inducing a decrease of PVR of up to 42% without any significant decrease of SVR (−5%), but nonselectively dilated the systemic circulation at larger doses (>10−2 M). In conclusion, despite its short half-life, DEA/NO is not a selective pulmonary vasodilator compared with inhaled NO. Inhaled SNP appears to be selective to the pulmonary circulation at low doses but not at higher levels.

scholarly journals Cinaciguat, a soluble guanylate cyclase activator, causes potent and sustained pulmonary vasodilation in the ovine fetus

2009 ◽  
Vol 297 (2) ◽  
pp. L318-L325 ◽  
Author(s):  
Marc Chester ◽  
Pierre Tourneux ◽  
Greg Seedorf ◽  
Theresa R. Grover ◽  
Jason Gien ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Left Pulmonary Artery ◽  
Flow Transducer ◽  
Pulmonary Vasodilation

Impaired nitric oxide-cGMP signaling contributes to severe pulmonary hypertension after birth, which may in part be due to decreased soluble guanylate cyclase (sGC) activity. Cinaciguat (BAY 58-2667) is a novel sGC activator that causes vasodilation, even in the presence of oxidized heme or heme-free sGC, but its hemodynamic effects have not been studied in the perinatal lung. We performed surgery on eight fetal (126 ± 2 days gestation) lambs (full term = 147 days) and placed catheters in the main pulmonary artery, aorta, and left atrium to measure pressures. An ultrasonic flow transducer was placed on the left pulmonary artery to measure blood flow, and a catheter was placed in the left pulmonary artery for drug infusion. Cinaciguat (0.1–100 μg over 10 min) caused dose-related increases in pulmonary blood flow greater than fourfold above baseline and reduced pulmonary vascular resistance by 80%. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an sGC-oxidizing inhibitor, enhanced cinaciguat-induced pulmonary vasodilation by >120%. The pulmonary vasodilator effect of cinaciguat was prolonged, decreasing pulmonary vascular resistance for >1.5 h after brief infusion. In vitro stimulation of ovine fetal pulmonary artery smooth muscle cells with cinaciguat after ODQ treatment resulted in a 14-fold increase in cGMP compared with non-ODQ-treated cells. We conclude that cinaciguat causes potent and sustained fetal pulmonary vasodilation that is augmented in the presence of oxidized sGC and speculate that cinaciguat may have therapeutic potential for severe neonatal pulmonary hypertension.

Abstract 257: Unselective Pulmonary Vasodilation is an Important Factor in Sodium Nitroprusside Enhanced Cardiopulmonary Resuscitation Improved Blood Flow

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Adrian Ripeckyj ◽  
Kadambari Chandra Shekar ◽  
Sebastian Voicu ◽  
Jennifer Rees ◽  
Timothy Matsuura ◽  
...  
Keyword(s):  
Blood Flow ◽  
Lactic Acid ◽  
Sodium Nitroprusside ◽  
Standard Technique ◽  
Tissue Perfusion ◽  
Right Atrial ◽  
Carotid Blood Flow ◽  
Oxygen Gradient ◽  
Pulmonary Vasodilation ◽  
Potent Vasodilator

Introduction: Sodium nitroprusside enhanced CPR (SNPeCPR) is a novel CPR method that includes a potent vasodilator, active compression-decompression CPR, an inspiratory impedance threshold device and abdominal binding. SNPeCPR has been shown to improve vital organ flow and functional survival outcomes compared to standard CPR methods in animals. We hypothesize that one of the main effects of SNPeCPR mediated increase in cardiac output during prolonged resuscitation is profound pulmonary artery vasodilation. Methods: After electrically induced VF was left untreated for 3 min, 20 (44-48Kg) pigs were randomized to receive SNPeCPR (10) or standard CPR (10) for a total of 30 min; the first 10 minutes were BLS CPR followed by twenty minutes of ACLS. During ACLS, animals were given IV SNP (1mg bolus) or standard epinephrine (0.5mg) q5 min until ROSC or 45 min total CPR. Shocks were delivered after 30 minutes of CPR at 300J. If ROSC was achieved, animal was monitored until 4-hour endpoint. Ventilations were provided with 10ml/kg at 10/min with a mechanical ventilator. Initially during CPR, room air was used and FiO2 was adjusted q5 minutes to maintain O 2 %saturation &gt 92% based on ABG. Lactic acid was also measured. Aortic, right atrial, and coronary artery pressures and carotid blood flow were recorded continuously. A-a oxygen gradient was measured with standard technique. Results: SNPeCPR animals documented a significantly higher mean CPP, lower lactic acid and 3x higher carotid blood flow over 30 minutes compared to standard CPR as previously documented. A-a oxygen gradient was dramatically increased in the SNPeCPR and coincided with a decreased lactate level (see Figure 1). Discussion: SNPeCPR causes profound pulmonary vasodilation and increases flow through non-ventilated lung areas. Despite that, the overall increase in forward flow leads to higher minute O 2 delivery and improved tissue perfusion. SNPeCPR should be used with 100% oxygen in the first human clinical trial.

Letters to the Editor

PEDIATRICS ◽  
1973 ◽  
Vol 51 (5) ◽  
pp. 956-957
Author(s):  
G. C. Liggins ◽  
R. N. Howie
Keyword(s):  
Pulmonary Artery ◽  
Bronchial Artery ◽  
Letters To The Editor ◽  
Pulmonary Vasodilation ◽  
Arterial Responses

Dr. Holm's interesting hypothesis has as its core the action of catecholamines on the pulmonary and bronchial vasculature. Our perusal of the reference cited in support of the assertion that norepinephrine causes pulmonary artery vasoconstriction and bronchial artery vasodilation failed to find the expected evidence. In fetal lambs, the response to both methoxamine1 (an α-receptor stimulant) and isoprenaline2 (aβ-receptor stimulant) is pulmonary vasodilation. We are unaware of studies of fetal bronchial arterial responses to catecholamines.

scholarly journals Inhaled carbon monoxide does not cause pulmonary vasodilation in the late-gestation fetal lamb

2000 ◽  
Vol 278 (4) ◽  
pp. L779-L784 ◽  
Author(s):  
Theresa R. Grover ◽  
Robyn L. Rairigh ◽  
Jeanne P. Zenge ◽  
Steven H. Abman ◽  
John P. Kinsella
Keyword(s):  
Carbon Monoxide ◽  
Blood Flow ◽  
Pulmonary Artery ◽  
Vascular Tone ◽  
Ductus Arteriosus ◽  
Protoporphyrin Ix ◽  
Left Lung ◽  
Late Gestation ◽  
Zinc Protoporphyrin ◽  
Pulmonary Vasodilation

As observed with nitric oxide (NO), carbon monoxide (CO) binds and may activate soluble guanylate cyclase and increase cGMP levels in smooth muscle cells in vitro. Because inhaled NO (INO) causes potent and sustained pulmonary vasodilation, we hypothesized that inhaled CO (ICO) may have similar effects on the perinatal lung. To determine whether ICOcan lower pulmonary vascular resistance (PVR) during the perinatal period, we studied the effects of ICOon late-gestation fetal lambs. Catheters were placed in the main pulmonary artery, left pulmonary artery (LPA), aorta, and left atrium to measure pressure. An ultrasonic flow transducer was placed on the LPA to measure blood flow to the left lung. After baseline measurements, fetal lambs were mechanically ventilated with a hypoxic gas mixture (inspired O2fraction < 0.10) to maintain a constant fetal arterial [Formula: see text]. After 60 min (baseline), the lambs were treated with ICO[5–2,500 parts/million (ppm)]. Comparisons were made with INO(5 and 20 ppm) and combined INO(5 ppm) and ICO(100 and 2,500 ppm). We found that ICOdid not alter left lung blood flow or PVR at any of the study doses. In contrast, low-dose INOdecreased PVR by 47% ( P < 0.005). The combination of INOand ICOdid not enhance the vasodilator response to INO. To determine whether endogenous CO contributes to vascular tone in the fetal lung, zinc protoporphyrin IX, an inhibitor of heme oxygenase, was infused into the LPA in three lambs. Zinc protoporphyrin IX had no effect on baseline PVR, aortic pressure, or the pressure gradient across the ductus arteriosus. We conclude that ICOdoes not cause vasodilation in the near-term ovine transitional circulation, and endogenous CO does not contribute significantly to baseline pulmonary vascular tone or ductus arteriosus tone in the late-gestation ovine fetus.

Nitric oxide inhibits serotonin-induced calcium release in pulmonary artery smooth muscle cells

1997 ◽  
Vol 272 (1) ◽  
pp. L44-L50 ◽  
Author(s):  
X. J. Yuan ◽  
R. T. Bright ◽  
A. M. Aldinger ◽  
L. J. Rubin
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Calcium Release ◽  
Extracellular Fluid ◽  
Cyclopiazonic Acid ◽  
Muscle Cells ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilator

Nitric oxide (NO) is a potent endothelium-derived pulmonary vasodilator. Serotonin (5-HT; 10-50 microM) constricts pulmonary artery (PA) by releasing Ca2+ from intracellular stores and promoting Ca2+ influx through Ca2+ channels in PA smooth muscle cells (PASMC). The effect of NO on 5-HT-induced increase in cytosolic free Ca2+ concentration ([Ca2+]i) in rat PASMC was investigated to elucidate whether inhibition of agonist-mediated Ca2+ rise is involved in the NO-mediated pulmonary vasodilation. The 5-HT-induced increase in [Ca2+]i was characterized by a transient (because of Ca2+ release from intracellular stores) followed by a plateau (because of Ca2+ influx). Removal of extracellular Ca2+ eliminated the 5-HT-induced [Ca2+]i plateau, but insignificantly affected the [Ca2+]i transient. In some of the PASMC bathed in the Ca(2+)-containing or Ca(2+)-free solution, 5-HT also induced Ca2+ oscillations. Pretreatment of the cells with 10 microM cyclopiazonic acid (CPA) abolished, whereas 10 mM caffeine negligibly affected, the 5-HT-induced [Ca2+]i transients in the absence of external Ca2+. Authentic NO (approximately 0.3 microM) reversibly diminished 5-HT-induced [Ca2+]i transients but augmented CPA-induced Ca2+ release in the absence of extracellular Ca2+. NO also significantly inhibited 5-HT-induced [Ca2+]i plateau in PASMC bathed in Ca(2+)-containing solution, suggesting that NO inhibits both agonist-induced Ca2+ release from the CPA-sensitive Ca2+ stores and Ca2+ influx from extracellular fluid. These data suggest that NO-induced inhibition of the evoked increases in [Ca2+]i and augmentation of Ca2+ sequestration into intracellular stores in PASMC are involved in the mechanisms by which NO causes pulmonary vasodilation.

Ventilation-induced release of prostaglandinlike material from fetal lungs

1980 ◽  
Vol 238 (3) ◽  
pp. H282-H286 ◽  
Author(s):  
C. W. Leffler ◽  
J. R. Hessler ◽  
N. A. Terragno
Keyword(s):  
Pulmonary Blood Flow ◽  
Inferior Vena ◽  
Fetal Lung ◽  
Inferior Vena Caval ◽  
Pulmonary Vasodilation ◽  
Flow Characterization ◽  
Before And After ◽  
Pulmonary Arterial ◽  
Near Term ◽  
Layer Chromatography

Effects of indomethacin upon ventilation-induced pulmonary vasodilation of fetal goats suggest prostaglandins may be important in perinatal transition of the pulmonary circulation. To further test this hypothesis, left pulmonary arterial and pulmonary venous samples were taken before and after ventilation from anesthetized exteriorized fetal (near-term) goats and sheep utilizing, in different animals, either constant or variable left pulmonary blood flow. Characterization and quantification of prostaglandinlike compounds were accomplished utilizing extraction of acidic lipids, thin-layer chromatography, and tissue cascade bracket bioassay. The primary vascular prostaglandinlike material in both fetal and neonatal animals was PGI2-like (PGI). On passage through the fetal lung, concentrations of prostaglandin I- and E-like compounds decreased considerably. After ventilation and ligation of the umbilical cord, concentrations of both PGE2-like (PGE) and PGI in inferior vena caval blood fell, and there was net production of PGI by the newly ventilated lung. Production of PGI2 by newly ventilated lung could provide an important vasodilator influence that would establish and maintain the low pulmonary vascular resistance that is necessary for successful adaptation to extrauterine life.

Hyporesponsiveness to inhaled nitric oxide in isolated, perfused lungs from endotoxin-challenged rats

1996 ◽  
Vol 271 (6) ◽  
pp. L981-L986 ◽  
Author(s):  
A. Holzmann ◽  
K. D. Bloch ◽  
L. S. Sanchez ◽  
G. Filippov ◽  
W. M. Zapol
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Sepsis Syndrome ◽  
Inhaled Nitric Oxide ◽  
Pulmonary Vasculature ◽  
Cyclic Monophosphate ◽  
Pulmonary Vasodilation ◽  
Lps Challenge ◽  
And Control ◽  
Selective Pulmonary Vasodilation

Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in patients with the adult respiratory distress syndrome (ARDS). Approximately 30% of ARDS patients fail to respond to iNO. Because sepsis syndrome often accompanies a decreased response to iNO, we investigated NO responsiveness in isolated, perfused lungs from rats exposed to lipopolysaccharide (LPS). Eighteen hours after intraperitoneal injection of 0.5 mg/kg LPS, rat lungs were isolated, perfused, and preconstricted with U-46619. Ventilation with 0.4, 4, and 40 parts per million by volume NO vasodilated LPS-pretreated lungs 75, 47, and 42% less than control lungs (P < 0.01 value differs at each concentration). The diminished vasodilatory response to iNO was associated with decreased NO-stimulated guanosine 3',5'-cyclic monophosphate (cGMP) release into the perfusate. Soluble guanylate cyclase activity did not differ in lung extracts from LPS-pretreated and control rats. LPS increased pulmonary cGMP-phosphodiesterase (PDE) activity by 40%. The PDE-sensitive cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate vasodilated lungs from LPS-pretreated rats less than lungs from control rats. In contrast, the PDE-insensitive 8-para-chlorophenylthioguanosine 3',5'-cyclic monophosphate vasodilated lungs equally from both groups. After LPS challenge, the rat pulmonary vasculature becomes hyporesponsive to iNO. Hyporesponsiveness to iNO appears partly attributable to increased pulmonary cGMP-PDE activity.

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