scholarly journals Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension

2019 ◽  
Vol 122 (4) ◽  
pp. 437-447 ◽  
Author(s):  
Yoh Sugawara ◽  
Yusuke Mizuno ◽  
Shinya Oku ◽  
Takahisa Goto
Keyword(s):  
Pulmonary Hypertension ◽  
Rat Model ◽  
Acute Hypoxia ◽  
Hypertensive Crisis ◽  
Pulmonary Hypertensive Crisis

Dead space ratio as a tool in nitric oxide weaning: a study in pulmonary hypertensive disease

2021 ◽  
pp. 1-5
Author(s):  
Alvaro D. Garcia ◽  
Wei Liu ◽  
William J. Hanna ◽  
Hemant Agarwal
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Dead Space ◽  
Hypertensive Crisis ◽  
Inhaled Nitric Oxide ◽  
Successful Weaning ◽  
Cardiac Intensive Care ◽  
Pulmonary Hypertensive Crisis ◽  
Nitric Oxide Therapy ◽  
Space Ratio

Abstract Objectives: To describe the association between successful weaning of inhaled nitric oxide and trends in dead space ratio during such weans in patients empirically initiated on nitric oxide therapy out of concern of pulmonary hypertensive crisis. Patients: Children in a cardiac intensive care unit initiated on inhaled nitric oxide out of clinical concern for pulmonary hypertensive crisis retrospectively over 2 years. Measurements and Main Results: Twenty-seven patients were included, and nitric oxide was successfully discontinued in 23/27. These patients exhibited decreases in dead space ratio (0.18 versus 0.11, p = 0.047) during nitric oxide weaning, and with no changes in dead space ratio between pre- and post-nitric oxide initiation (p = 0.88) and discontinuation (p = 0.63) phases. These successful patients had a median age of 10 months [4.0, 57.0] and had a pre-existent diagnosis of CHD in 6/23 and pulmonary hypertension in 2/23. Those who failed nitric oxide discontinuation trended with a higher dead space ratio at presentation (0.24 versus 0.10), were more likely to carry a prior diagnosis of pulmonary hypertension (50% versus 8.7%), and had longer mechanical ventilation days (5 versus 12). Conclusions: Patients empirically placed on nitric oxide out of concern of pulmonary hypertensive crisis and successfully weaned off showed unchanged or decreased dead space ratio throughout the initiation to discontinuation phases of nitric oxide therapy. Trends in dead space ratio may aid in determining true need for nitric oxide and facilitate effective weaning. Further studies are needed to directly compare trends between success and failure groups.

Pulmonary Hypertensive Crisis on Induction of Anesthesia

2016 ◽  
Vol 21 (1) ◽  
pp. 105-113 ◽  
Author(s):  
Travis Schisler ◽  
Jose M Marquez ◽  
Ibtesam Hilmi ◽  
Kathirvel Subramaniam
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Transplantation ◽  
Hypertensive Crisis ◽  
Positive Pressure ◽  
Metabolic Dysfunction ◽  
Anesthetic Induction ◽  
Severe Hypotension ◽  
Risk Patients ◽  
Pulmonary Hypertensive Crisis ◽  
End Stage

Anesthesia for lung transplantation remains one of the highest risk surgeries in the domain of the cardiothoracic anesthesiologist. End-stage lung disease, pulmonary hypertension, and right heart dysfunction as well as other comorbid disease factors predispose the patient to cardiovascular, respiratory and metabolic dysfunction during general anesthesia. Perhaps the highest risk phase of surgery in the patient with severe pulmonary hypertension is during the induction of anesthesia when the removal of intrinsic sympathetic tone and onset of positive pressure ventilation can decompensate a severely compromised cardiovascular system. Severe hypotension, cardiac arrest, and death have been reported previously. Here we present 2 high-risk patients for lung transplantation, their anesthetic induction course, and outcomes. We offer suggestions for the safe management of anesthetic induction to mitigate against hemodynamic and respiratory complications.

Serotonin transporter is not required for the development of severe pulmonary hypertension in the Sugen hypoxia rat model

2015 ◽  
Vol 309 (10) ◽  
pp. L1164-L1173 ◽  
Author(s):  
Michiel Alexander de Raaf ◽  
Yvet Kroeze ◽  
Anthonieke Middelman ◽  
Frances S. de Man ◽  
Helma de Jong ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Serotonin Transporter ◽  
Rat Model ◽  
Systolic Pressure ◽  
Serum Levels ◽  
Normal Function ◽  
Ventricular Systolic Pressure ◽  
Serotonin System ◽  
Pulmonary Arterial

Increased serotonin serum levels have been proposed to play a key role in pulmonary arterial hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is required for the development of experimental pulmonary hypertension in rodents exposed to hypoxia or monocrotaline. While these animal models resemble human PAH only with respect to vascular media remodeling, we hypothesized that SERT is likewise required for the presence of lumen-obliterating intima remodeling, a hallmark of human PAH reproduced in the Sugen hypoxia (SuHx) rat model of severe angioproliferative pulmonary hypertension. Therefore, SERT wild-type (WT) and knockout (KO) rats were exposed to the SuHx protocol. SERT KO rats, while completely lacking SERT, were hemodynamically indistinguishable from WT rats. After exposure to SuHx, similar degrees of severe angioproliferative pulmonary hypertension and right ventricular hypertrophy developed in WT and KO rats (right ventricular systolic pressure 60 vs. 55 mmHg, intima thickness 38 vs. 30%, respectively). In conclusion, despite its implicated importance in PAH, SERT does not play an essential role in the pathogenesis of severe angioobliterative pulmonary hypertension in rats exposed to SuHx.

Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and systemic blood pressure

1993 ◽  
Vol 75 (4) ◽  
pp. 1748-1757 ◽  
Author(s):  
V. Hampl ◽  
S. L. Archer ◽  
D. P. Nelson ◽  
E. K. Weir
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Systemic Blood Pressure ◽  
Systemic Circulation ◽  
Systemic Arterial Pressure ◽  
Hypoxic Pulmonary Hypertension ◽  
Basal Tone ◽  
Isolated Lungs

It has been suggested that chronic hypoxic pulmonary hypertension results from chronic hypoxic inhibition of endothelium-derived relaxing factor (EDRF) synthesis. We tested this hypothesis by studying whether chronic EDRF inhibition by N omega-nitro-L-arginine methyl ester (L-NAME) would induce pulmonary hypertension similar to that found in chronic hypoxia. L-NAME (1.85 mM) was given for 3 wk in drinking water to rats living in normoxia or hypoxia. Unlike chronic hypoxia, chronic L-NAME treatment did not increase pulmonary arterial pressure. Cardiac output was reduced and mean systemic arterial pressure was increased by chronic L-NAME treatment. The vascular pressure-flow relationship in isolated lungs was shifted toward higher pressures by chronic hypoxia and, to a lesser degree, by L-NAME intake. In isolated lungs, vasoconstriction in response to angiotensin II and acute hypoxia and vasodilation in response to sodium nitroprusside were increased by chronic L-NAME treatment in normoxia and chronic hypoxia. Chronic hypoxia, but not L-NAME, induced hypertensive pulmonary vascular remodeling. Chronic supplementation with the EDRF precursor L-arginine did not have any significant effect on chronic hypoxic pulmonary hypertension. We conclude that the chronic EDRF deficiency state, induced by L-NAME, does not mimic chronic hypoxic pulmonary hypertension in our model. In addition, EDRF proved to be less important for basal tone regulation in the pulmonary than in the systemic circulation.

Peptide Blocking Self-Polymerization of Extracellular Calcium-Sensing Receptor Attenuates Hypoxia-Induced Pulmonary Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Rui Xiao ◽  
Shengquan Luo ◽  
Ting Zhang ◽  
Yankai Lv ◽  
Tao Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Disulfide Bonds ◽  
Acute Hypoxia ◽  
Extracellular Domain ◽  
Left Ventricular ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

Activation of the CaSR (extracellular calcium-sensing receptor) has been recognized as a critical mediator of hypoxia-induced pulmonary hypertension. Preventive targeting of the early initiating phase as well as downstream events after CaSR activation remains unexplored. As a representative of the G protein-coupled receptor family, CaSR polymerizes on cell surface upon stimulation. Immunoblotting together with MAL-PEG technique identified a reactive oxygen species-sensitive CaSR polymerization through its extracellular domain in pulmonary artery smooth muscle cells upon exposure to acute hypoxia. Fluorescence resonance energy transfer screening employing blocking peptides determined that cycteine129/131 residues in the extracellular domain of CaSR formed intermolecular disulfide bonds to promote CaSR polymerization. The monitoring of intracellular Ca 2+ signal highlighted the pivotal role of CaSR polymerization in its activation. In contrast, the blockade of disulfide bonds formation using a peptide decreased both CaSR and hypoxia-induced mitogenic factor expression as well as other hypoxic-related genes in vitro and in vivo and attenuated pulmonary hypertension development in rats. The blocking peptide did not affect systemic arterial oxygenation in vivo but inhibited acute hypoxia-induced pulmonary vasoconstriction. Pharmacokinetic analyses revealed a more efficient lung delivery of peptide by inhaled nebulizer compared to intravenous injection. In addition, the blocking peptide did not affect systemic arterial pressure, body weight, left ventricular function, liver, or kidney function or plasma Ca 2+ level. In conclusion, a peptide blocking CaSR polymerization reduces its hypoxia-induced activation and downstream events leading to pulmonary hypertension and represents an attractive inhaled preventive alternative worthy of further development.

Sign in / Sign up

Export Citation Format

Share Document