{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:31:13Z","timestamp":1787985073059,"version":"build-2784847793"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,9,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The right ventricle exposed to chronic pressure overload exhibits hypertrophy and decompensates when exposed to stress. We hypothesize that impaired ability to increase myocardial oxidative flux through pyruvate dehydrogenase leads to hypertrophied right ventricular (\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              ) dysfunction when exposed to hemodynamic stress, and pyruvate dehydrogenase stimulation can improve\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              function.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Infant male Yorkshire piglets (13.5\u00b10.6\u00a0kg weight, n=19) were used to assess substrate fractional contribution to the citric acid cycle after sustained pulmonary artery banding (\n              <jats:styled-content style=\"fixed-case\">PAB<\/jats:styled-content>\n              ). Carbon 13\u2013labeled glucose, lactate, and leucine, oxidative substrate tracers for the citric acid cycle, were infused into the right coronary artery on 7 to 10\u00a0days after\n              <jats:styled-content style=\"fixed-case\">PAB<\/jats:styled-content>\n              .\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              systolic pressure,\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              free wall thickness, and individual cardiomyocyte cell size after\n              <jats:styled-content style=\"fixed-case\">PAB<\/jats:styled-content>\n              were significantly elevated compared with the sham group. Both fractional glucose and lactate oxidations in the\n              <jats:styled-content style=\"fixed-case\">PAB<\/jats:styled-content>\n              group were &gt;2\u2010fold higher than in the sham group. Pigs with overdrive atrial pacing (\u224880% increase in heart rate) stress after\n              <jats:styled-content style=\"fixed-case\">PAB<\/jats:styled-content>\n              showed only a 22% increase in rate\u2010pressure product from baseline before atrial pacing and limited carbohydrate oxidation rate in the right ventricle. Intracoronary infusion of dichloroacetate, a pyruvate dehydrogenase agonist, produced higher rate\u2010pressure product (59% increase) in response to increased workload by atrial pacing in association with a marked increase in lactate oxidation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The immature hypertrophied right ventricle shows limited ability to increase carbohydrate oxidation in response to tachycardia stress leading to energy supply\/utilization imbalance and decreased systolic function. Enhanced pyruvate dehydrogenase activation by dichloroacetate increases energy supply and preserves hypertrophied\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              contractile function during hemodynamic stress.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.013169","type":"journal-article","created":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T09:00:16Z","timestamp":1566896416000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Metabolic Response to Stress by the Immature Right Ventricle Exposed to Chronic Pressure Overload"],"prefix":"10.1161","volume":"8","author":[{"given":"Masaki","family":"Kajimoto","sequence":"first","affiliation":[{"name":"Center for Integrative Brain Research Seattle Children's Research Institute Seattle 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