This study observed the protective effect of hypercapnic acidosis preconditioning on rabbit heart suffered from ischemia-reperfusion injury. Hypercapnic acidosis was established in animals with mechanical hypoventilat...This study observed the protective effect of hypercapnic acidosis preconditioning on rabbit heart suffered from ischemia-reperfusion injury. Hypercapnic acidosis was established in animals with mechanical hypoventilation before ischemia-reperfusion. Thirty-two rabbits were randomly divided into 4 groups, with each having 8 aminals in term of the degree of acidification： hypercapnic acidosis group A （group A）, hypercapnic acidosis group B （group B）, hypercapnic acidosis group C （group C）, ischemia and reperfusion group （group IR）. Animals in group IR were ventilated normally （tidal volume： 15 mL/kg, breathing rate 35 bpm）. The PETCO2 was maintained at the level of 40-50 mmHg for 30 min. Animals in groups A, B, C received low-frequency, low-volume ventilation to achieve hypercarbonic acidosis and the target levels of PETCO2 were 75-85 ,65-75, 55-65 mmHg, respectively, with levels being maintained for 5 min. The animals then were ventilated normally to lower PETCO2 to 40-50 mmHg. The left anterior branch artery of all the animals was ligated for 30 min and reperfused for 180 min. Then the infarct size was calculated. The cardiomyocytes were morphologically observed and ECG and hemodynamics were monitored on continuous basis. Acid-base balance was measured during procedure. Our results showed that the infarct size was （48.5±11.5）% of the risk area in the control group and （42.4±7.9）% in group C （P〉0.05）. Mean infarct size was significantly smaller in group B （34.5%±9.4%） （P〈0.05 vs control group） and group A （31.0%±9.1%） （P〈0.01 vs control group）. It is concluded that HA-preconditioning can effectively protect the myocardium.展开更多
The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.T...The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.The present study was designed to address whether stimulation of Phox2 b-expressing LC(Phox2 b~(LC)) neurons affects breathing and to reveal the putative circuit mechanism.A Cre-dependent viral vector encoding a Gqcoupled human M3 muscarinic receptor(hM3 Dq) was delivered into the LC of Phox2 b-Cre mice.The hM3 Dqtransduced neurons were pharmacologically activated while respiratory function was measured by plethysmography.We demonstrated that selective stimulation of Phox2 b~(LC) neurons significantly increased basal ventilation in conscious mice.Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses.Moreover,stimulation of Phox2 b~(LC) neurons enhanced the activity of preBotzinger complex neurons.Finally,axons of Phox2 b~(LC) neurons projected to the preBotzinger complex.Collectively,Phox2 b~(LC) neurons contribute to the control of breathing most likely via an LC-preBotzinger complex circuit.展开更多
基金supported by a grant from the Special Foundation for Doctoral Program of the Ministry of Education of People's Republic of China (No. 20050533022).
文摘This study observed the protective effect of hypercapnic acidosis preconditioning on rabbit heart suffered from ischemia-reperfusion injury. Hypercapnic acidosis was established in animals with mechanical hypoventilation before ischemia-reperfusion. Thirty-two rabbits were randomly divided into 4 groups, with each having 8 aminals in term of the degree of acidification： hypercapnic acidosis group A （group A）, hypercapnic acidosis group B （group B）, hypercapnic acidosis group C （group C）, ischemia and reperfusion group （group IR）. Animals in group IR were ventilated normally （tidal volume： 15 mL/kg, breathing rate 35 bpm）. The PETCO2 was maintained at the level of 40-50 mmHg for 30 min. Animals in groups A, B, C received low-frequency, low-volume ventilation to achieve hypercarbonic acidosis and the target levels of PETCO2 were 75-85 ,65-75, 55-65 mmHg, respectively, with levels being maintained for 5 min. The animals then were ventilated normally to lower PETCO2 to 40-50 mmHg. The left anterior branch artery of all the animals was ligated for 30 min and reperfused for 180 min. Then the infarct size was calculated. The cardiomyocytes were morphologically observed and ECG and hemodynamics were monitored on continuous basis. Acid-base balance was measured during procedure. Our results showed that the infarct size was （48.5±11.5）% of the risk area in the control group and （42.4±7.9）% in group C （P〉0.05）. Mean infarct size was significantly smaller in group B （34.5%±9.4%） （P〈0.05 vs control group） and group A （31.0%±9.1%） （P〈0.01 vs control group）. It is concluded that HA-preconditioning can effectively protect the myocardium.
基金supported by the National Natural Science Foundation of China(31971058 and 31571174)the Youth Fund for Scientific and Technological Research in Higher Education Institutions of Hebei Province(QN2019019)the Youth Science and Technology Talent Support Program of Natural Science in Hebei Medical University(CYQD201907)。
文摘The locus coeruleus(LC) has been implicated in the control of breathing.Congenital central hypoventilation syndrome results from mutation of the paired-like homeobox 2 b(Phox2 b) gene that is expressed in LC neurons.The present study was designed to address whether stimulation of Phox2 b-expressing LC(Phox2 b~(LC)) neurons affects breathing and to reveal the putative circuit mechanism.A Cre-dependent viral vector encoding a Gqcoupled human M3 muscarinic receptor(hM3 Dq) was delivered into the LC of Phox2 b-Cre mice.The hM3 Dqtransduced neurons were pharmacologically activated while respiratory function was measured by plethysmography.We demonstrated that selective stimulation of Phox2 b~(LC) neurons significantly increased basal ventilation in conscious mice.Genetic ablation of these neurons markedly impaired hypercapnic ventilatory responses.Moreover,stimulation of Phox2 b~(LC) neurons enhanced the activity of preBotzinger complex neurons.Finally,axons of Phox2 b~(LC) neurons projected to the preBotzinger complex.Collectively,Phox2 b~(LC) neurons contribute to the control of breathing most likely via an LC-preBotzinger complex circuit.
