Sabiporide Improves Cardiovascular Function, Decreases the Inflammatory Response and Reduces Mortality in Acute Metabolic Acidosis in Pigs
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{"title"=>"Sabiporide Improves Cardiovascular Function, Decreases the Inflammatory Response and Reduces Mortality in Acute Metabolic Acidosis in Pigs", "type"=>"journal", "authors"=>[{"first_name"=>"Dongmei", "last_name"=>"Wu", "scopus_author_id"=>"35222544200"}, {"first_name"=>"Jeffrey A.", "last_name"=>"Kraut", "scopus_author_id"=>"7004460088"}, {"first_name"=>"William M.", "last_name"=>"Abraham", "scopus_author_id"=>"24391818000"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23326542", "doi"=>"10.1371/journal.pone.0053932", "sgr"=>"84872259027", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84872259027", "issn"=>"19326203", "pui"=>"368101385"}, "id"=>"ad65702f-6781-36ce-a758-fe943a34bb38", "abstract"=>"INTRODUCTION: Acute metabolic acidosis impairs cardiovascular function and increases the mortality of critically ill patients. However, the precise mechanism(s) underlying these effects remain unclear. We hypothesized that targeting pH-regulatory protein, Na(+)/H(+) exchanger (NHE1) could be a novel approach for the treatment of acute metabolic acidosis. The aim of the present study was to examine the impact of a novel NHE1 inhibitor, sabiporide, on cardiovascular function, blood oxygen transportation, and inflammatory response in an experimental model of metabolic acidosis produced by hemorrhage-induced hypovolemia followed by an infusion of lactic acid. METHODS AND RESULTS: Anesthetized pigs were subjected to hypovolemia for 30 minutes. The animals then received a bolus infusion of sabiporide (3 mg/kg) or vehicle, followed by an infusion of lactic acid for 2 hours. The animals were continuously monitored for additional 3 hours. Hypovolemia followed by a lactic acid infusion resulted in a severe metabolic acidosis with blood pH falling to 6.8. In association with production of the acidemia, there was an excessive increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Treatment with sabiporide significantly attenuated the increase in PAP by 38% and PVR by 67%, as well as significantly improved cardiac output by 51%. Sabiporide treatment also improved mixed venous blood oxygen saturation (55% in sabiporide group vs. 28% in control group), and improved systemic blood oxygen delivery by 36%. In addition, sabiporide treatment reduced plasma levels of TNF-alpha (by 33%), IL-6 (by 63%), troponin-I (by 54%), ALT (by 34%), AST (by 35%), and urea (by 40%). CONCLUSION: These findings support the possible beneficial effects of sabiporide in the treatment of acute metabolic acidosis and could have implications for the treatment of metabolic acidosis in man.", "link"=>"http://www.mendeley.com/research/sabiporide-improves-cardiovascular-function-decreases-inflammatory-response-reduces-mortality-acute", "reader_count"=>3, "reader_count_by_academic_status"=>{"Student > Ph. D. Student"=>1, "Other"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Student > Ph. D. Student"=>1, "Other"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/510043"], "description"=>"<p>All values are expressed as the mean ± SD (n = 5–6).</p>*<p>p<0.05 vs. the control group;</p>#<p>p<0.05 vs. the baseline value. BL: baseline; H30: at 30 minutes of hypovolemia; T30 min, –T300 min: at 30 min, –and 300 min from lactic acid infusion.</p>", "links"=>[], "tags"=>["acid-base", "parameters", "oxygenation", "hypovolemia", "lactic"], "article_id"=>180538, "categories"=>["Physiology", "Biochemistry", "Genetics", "Medicine"], "users"=>["Dongmei Wu", "Jeffrey A. Kraut", "William M. Abraham"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053932.t001", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_acid_base_parameters_and_blood_oxygenation_after_hypovolemia_and_lactic_acidosis_/180538", "title"=>"Changes in acid-base parameters and blood oxygenation after hypovolemia and lactic acidosis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 17:17:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/509974"], "description"=>"<p>All values are the mean ± SD (n = 5–6).</p>*<p>p<0.05 vs. the control group;</p>#<p>p<0.05 vs. the baseline value. BL: baseline; H30: at 30 minutes of hypovolemia; T30 min, –T300 min: at 30 min, –and 300 min from lactic acid infusion.</p>", "links"=>[], "tags"=>["hemodynamics", "hypovolemia", "lactic", "acidosis"], "article_id"=>180468, "categories"=>["Physiology", "Biochemistry", "Genetics", "Medicine"], "users"=>["Dongmei Wu", "Jeffrey A. Kraut", "William M. Abraham"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053932.t002", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_hemodynamics_after_hypovolemia_and_lactic_acidosis_in_pigs_/180468", "title"=>"Changes in hemodynamics after hypovolemia and lactic acidosis in pigs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 17:17:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/509770"], "description"=>"<p>Pulmonary arterial pressure and vascular resistance rose in controls with lactic acid infusions and remained elevated throughout the study. The increase in both parameters was blunted with sabiporide. All values are the mean ± SD. N = 5–6. *p<0.05 vs. the control group; #p<0.05 vs. the baseline value.</p>", "links"=>[], "tags"=>["pulmonary", "arterial", "vascular"], "article_id"=>180273, "categories"=>["Physiology", "Biochemistry", "Genetics", "Medicine"], "users"=>["Dongmei Wu", "Jeffrey A. Kraut", "William M. Abraham"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053932.g003", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_pulmonary_arterial_pressure_and_pulmonary_vascular_resistance_/180273", "title"=>"Changes in pulmonary arterial pressure and pulmonary vascular resistance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 17:16:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/509859"], "description"=>"<p>NHE1 inhibition with sabiporide prevented excessive fall in mixed-venous blood oxygen saturation following hypovolemia and lactic acidosis, and improved mixed-venous blood oxygen binding capacity of hemoglobin, resulting in improved oxygen delivery and decreased oxygen extraction ratio, suggesting improved tissue oxygenation. All values are the mean ± SD. N = 5–6. *p<0.05 vs. the control group; #p<0.05 vs. the baseline value.</p>", "links"=>[], "tags"=>["mixed-venous", "extraction", "oxygenated", "hb"], "article_id"=>180354, "categories"=>["Physiology", "Biochemistry", "Genetics", "Medicine"], "users"=>["Dongmei Wu", "Jeffrey A. Kraut", "William M. Abraham"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053932.g004", "stats"=>{"downloads"=>2, "page_views"=>70, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_mixed_venous_blood_oxygen_saturation_oxygen_delivery_oxygen_extraction_ratio_and_mixed_venous_blood_oxygenated_hemoglobin_total_Hb_ratio_FO_2_Hb_ratio_/180354", "title"=>"Changes in mixed-venous blood oxygen saturation, oxygen delivery, oxygen extraction ratio and mixed-venous blood oxygenated hemoglobin/total Hb ratio (FO<sub>2</sub>Hb) ratio.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 17:16:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/510009"], "description"=>"<p>All values are the mean ± SD (n = 5–6).</p>*<p>p<0.05 vs. the control group;</p>#<p>p<0.05 vs. the baseline value. BL: baseline; H30 min: end of hypovolemia; T120 min: end of lactic acid infusion; T180 min: end of fluid infusion; and T300 min: end of the experiment.</p>", "links"=>[], "tags"=>["ventricular", "ejection", "fractional", "shortening"], "article_id"=>180509, "categories"=>["Physiology", "Biochemistry", "Genetics", "Medicine"], "users"=>["Dongmei Wu", "Jeffrey A. Kraut", "William M. Abraham"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053932.t003", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Echocardiographic_measurements_of_left_ventricular_ejection_fraction_fractional_shortening_and_wall_motion_score_index_/180509", "title"=>"Echocardiographic measurements of left ventricular ejection fraction, fractional shortening and wall motion score index.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 17:17:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/509550"], "description"=>"<p>Anesthetized pigs were subjected to hypovolemia (30 ml/kg) for 30 minutes. The animals then received a bolus infusion of NHE1 inhibitor (3 mg/kg, sabiporide) or vehicle, followed by lactic acid infusion for 2 hours. The animals were continuously monitored for additional 3 hours.</p>", "links"=>[], "tags"=>["genetics and genomics", "physiology", "Critical care and emergency medicine", "Biochemistry"], "article_id"=>180046, "categories"=>["Physiology", "Biochemistry", "Genetics", "Medicine"], "users"=>["Dongmei Wu", "Jeffrey A. Kraut", "William M. Abraham"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053932.g001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Details_of_the_experimental_protocol_are_shown_/180046", "title"=>"Details of the experimental protocol are shown.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 17:15:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/509942"], "description"=>"<p>All values are the mean ± SD (n = 5–6).</p>*<p>p<0.05 vs. the control group;</p>#<p>p<0.05 vs. the baseline value. BL: baseline; H30: at 30 minutes of hypovolemia; T120 min: end of lactic acid infusion; and T300 min: end of the experiment.</p>", "links"=>[], "tags"=>["plasma", "levels", "ast", "urea", "lactic", "acidosis"], "article_id"=>180435, "categories"=>["Physiology", "Biochemistry", "Genetics", "Medicine"], "users"=>["Dongmei Wu", "Jeffrey A. Kraut", "William M. Abraham"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053932.t004", "stats"=>{"downloads"=>5, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_of_plasma_levels_of_TNF_945_IL_6_troponin_I_ALT_AST_and_urea_following_severe_lactic_acidosis_in_pigs_/180435", "title"=>"Changes of plasma levels of TNF-α, IL-6, troponin-I, ALT, AST and urea following severe lactic acidosis in pigs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 17:17:13"}

PMC Usage Stats | Further Information

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Relative Metric

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