LOCAL RATE OF MYOCARDIAL AEROBIC METABOLIC IN RELATION TO LOCAL BLOOD FLOW

心肌血流分布不均匀，即使在 正常的心脏，并且在 心肌缺血 重要的是确定 局部血流分布不均的后果 有氧代谢率 然而，对于动物实验室， 测量几个小心肌的局部耗氧量， 区域同时可用。 最近，我们开发了一种 测定三羧酸循环局部速率的方法 (TCA循环;克雷布斯循环;柠檬酸循环）：我们注入5.0-5.5 13 C标记的乙酸盐（或乳酸盐或丙酮酸盐）进入心脏。 此后，左心室游离壁立即 冷冻夹紧并分成约0.5g湿重的区域（或 更小），从中提取代谢物。 非放射性 在TCA循环相关代谢物中检测到13 C标记，主要是 谷氨酸，使用提取物的13 C-NMR光谱。 消息是 谷氨酸的13 C-共振的多重精细结构， 用13 C标记分布的时间过程模型进行了分析， 谷氨酸盐的32种同位素异构体 一个简单的模型包含2 中间池和36个微分方程和更多 综合模型（6个中间池，132个微分方程） 已经被开发出来了。 微分方程的积分使用 一个ODE求解器下的资源仿真界面。 参数优化产生的局部速率的TCA循环在每个 小的组织区域，然后从该区域消耗局部氧气。 计算了 代谢率的估计独立于局部 基质传输 最多可以测量六个生理参数。 根据测量的9个13 C-NMR多个强度同时估计 冷冻心肌样本的提取物 局部灌注是 用标记的微球独立地测量。 我们发现， 解决了如何测量局部氧气的经典问题， 消费关系 局部血液流动。 我们将调查的假说，在 正常的心脏有一个密切的联系，局部代谢和血液 流量，但在心肌缺血期间， 需求变得更加多样化。 为了验证这一假设 将相对于局部氧测量局部血流量 猪心脏中的原位消耗（正常，由于 多巴酚丁胺、部分冠状动脉狭窄）。 苏本多什， 中层心肌和心外膜下心肌层将 但这些层内的显着异质性也是 密切调查。

Myocardial blood flow is heterogeneously distributed, even in the normal heart, and is redistributed very heterogeneously during myocardial ischemia. It is of importance to determine the consequences of the heterogeneous blood flow distribution for local aerobic metabolic rate. However, for the animal laboratory no method to measure local oxygen consumption in several small myocardial regions simultaneously was available. Very recently we developed a method to determine the local rate of the tricarboxylic acid cycle (TCA cycle; Krebs cycle; citric acid cycle): we infuse for 5.0-5.5 min 13C-labeled acetate (or lactate or pyruvate) into the heart. Thereafter the left ventricular free wall is immediately freeze-clamped and divided into regions of about 0.5 g wet weight (or smaller), from which metabolites are extracted. The non-radioactive 13C-label is detected in TCA-cycle-related metabolites, mainly glutamate, using 13C-NMR-spectroscopy of the extracts. New is that the multiple-fine-str ucture of the 13C-resonance of glutamate is analyzed with models of the time course of 13C label distribution in the 32 isotopic isomers of glutamate. A simple model containing 2 intermediate pools and 36 differential equations and a more comprehensive model (6 intermediate pools, 132 differential equations) have been developed. The differential equations are integrated using an ODE solver under the simulation interface of the Resource. Parameter optimization yields the local rate of the TCA cycle in each small tissue region, from which the local oxygen consumption is then calculated. The metabolic rate is estimated independently of local substrate transport. Up to six physiological parameters can be estimated simultaneously from 9 13C-NMR multiple intensities measured on extracts of frozen myocardial samples. Local perfusion is independently measured with labeled microspheres. Thus we have found a solution to the classic problem how to measure the local oxygen consumption in relation to local blood flow. We will investigate the hyothesis that in the normal heart there is a close link between local metabolism and blood flow, but that during myocardial ischemia this ratio between supply and demand becomes much more heterogeneous. To test this hypothesis the local blood flow will be measured in relation to the local oxygen consumption in situ in hearts of pigs (normal, high work state due to dobutamine, partial coronary stenosis). Subendocardial, mid-myocardial and subepicardial cardiac muscle layers will be compared, but the remarkable heterogeneity within these layers is also closely investigated.