In vivo mechanisms of myocardial functional stability during physiological interventions.
In vivo mechanisms of myocardial functional stability during physiological interventions.
复制标题
生理干预期间心肌功能稳定性的体内机制。
作者：
Osbakken,M;Blum,H;Wang,DJ;Doliba,N;Ivanics,T;Zhang,D;Mayevsky,A
代谢调节机制旨在维持稳定的心肌功能，在极端的生理损伤，他们现在可以在体内进行研究，并可能提供深入了解在疾病过程中改变心肌功能失代偿的机制。为探讨缺氧和急性压力负荷时心肌稳定性的机制，用~（31）P核磁共振（NMR）和烟酰胺腺嘌呤二核苷酸（NADH）荧光法分别测定磷酸肌酸（PCr）转化为三磷酸腺苷（ATP）的正向速率常数（Kf）和流量（PCr）和还原态（NADH），并与心脏作功进行相关分析（心率×收缩压，HR ×收缩压）、心输出量（CO）和耗氧量（MVO 2）。在吸入O2/N2为200/3，000的6只犬中产生缺氧（PaO 2为30-35 mm Hg）。通过给予去甲肾上腺素（NE，1 µg/kg/min）在9只犬中产生心脏负荷。每只狗都作为自己的对照。在每只犬中同时进行基线NADH荧光测定、31 P-NMR饱和转移和心功能测量，之后进行实验干预。两种干预期间发生的HR × SBP、CO和MVO 2的相似增加与不同的生物能量反应相关。NE灌注时CK的Kf较对照组升高，缺氧时Kf较对照组降低（p < 0.05）。缺氧时PCr → ATP的流量显著低于NE时（p < 0.05）。NE组PCr明显低于对照组（P < 0.05）。此外，NADH氧化还原状态在缺氧期间（140 ± 10%）增加（从基线100%），在NE输注期间降低（78 ± 6%）。这些数据表明，心肌对需求的反应并不普遍调节腺苷二磷酸（ADP）或氧化还原状态。此外，代谢调节剂可以诱导与干预类型相关的变化，而不管工作量的相似性如何。
Metabolic regulatory mechanisms are designed to maintain stable myocardial function during extremes in physiological insult; they can now be studied in vivo and may provide insight into mechanisms of altered myocardial functional decompensation during disease processes. To determine mechanisms of myocardial stability during hypoxia and acute pressure loading, creatine kinase (CK) kinetics (forward rate constant, Kf, and flux of phosphocreatine, PCr, to adenosine triphosphate, ATP), and nicotinamide adenine dinucleotide (NADH) redox state were determined with31P nuclear magnetic resonance (NMR) and NADH fluorometry, respectively, and correlated with heart work (heart rate × systolic blood pressure, HR × SBP), cardiac output (CO) and O2consumption (MVO2) in 15 anesthetized open chest dogs. Hypoxia (Pao2of 30-35 mm Hg) was produced in 6 dogs with an inspired O2/N2of 200/3,000. Cardiac loading was produced in 9 dogs by administration of norepinephrine (NE, 1 µg/kg/min). Each dog acted as its own control. Baseline NADH fluorometry,31P-NMR saturation transfer and cardiac function measurements were performed simultaneously in each dog, after which the experimental interventions were made. Similar increases in HR × SBP, CO, and MVO2 which occurred during both interventions were associated with different bioenergetic responses. During NE infusion, the Kfof CK increased from control; during hypoxia, the Kfdecreased from control (p < 0.05). Flux of PCr → ATP was significantly lower during hypoxia than during NE infusion (p < 0.05). PCr was decreased significantly during NE infusion (p < 0.05). In addition, NADH redox state increased (from baseline of 100%) during hypoxia (140 ± 10%) and decreased during NE infusion (78 ± 6%). These data indicate that the myocardial response to demand is not universally regulated by adenosine diphosphate (ADP) or redox state. In addition, metabolic regulators can induce changes related to the type of intervention irrespective of similarity of workload.