Martin Claus, Schulz Rainer, Post Heiner, Boengler Kerstin, Kelm Malte, Kleinbongard Petra, Gres Petra, Skyschally Andreas, Konietzka Ina, Heusch Gerd
Institut für Pathophysiologie, Zentrum für Innere Medizin des Universitätsklinikums, Essen, Germany.
Cardiovasc Res. 2007 Apr 1;74(1):46-55. doi: 10.1016/j.cardiores.2006.12.020. Epub 2007 Jan 3.
Nitric oxide (NO) synthesis by NO synthases (NOS) requires oxygen. However, although counterintuitive, NO synthesis is increased in ischemic myocardium. Accordingly, mechanisms independent of the NOS pathway have been suggested to contribute to NO synthesis during ischemia. NO initiates detrimental as well as protective mechanisms in a concentration-dependent manner, thus aggravating or improving the outcome of ischemia. The aim of this study was to measure in situ interstitial NO concentrations in parallel to infarct size in anaesthetized pigs subjected to myocardial ischemia/reperfusion. The contribution of NOS-independent pathways to NO synthesis was studied using NOS blockade.
Interstitial NO measurements, based on microdialysis combined with the oxyhemoglobin method, were made during 90 min of moderate or severe ischemia and subsequent reperfusion. To examine the effect of NOS inhibition, an initial 30-min ischemic period was followed 60 min later by a second 30-min ischemic period with intracoronary infusion of S-ethyl-isothiourea.
During ischemia, the interstitial NO concentration increased for about 30 min and then remained constant at this elevated level. The increase in NO concentration by 253+/-82 nmol/L during moderate and 565+/-169 nmol/L during severe ischemia correlated inversely with subendocardial blood flow (r=-0.76). NOS inhibition increased coronary arterial pressure and decreased the interstitial basal NO concentration and tissue nitrite content. However, it did not diminish the increase in interstitial NO concentration during ischemia.
NOS-independent pathways are significantly involved in NO synthesis during myocardial ischemia.
一氧化氮合酶（NOS）合成一氧化氮（NO）需要氧气。然而，尽管有悖常理，但缺血心肌中的NO合成却增加。因此，有人提出独立于NOS途径的机制在缺血期间有助于NO的合成。NO以浓度依赖的方式引发有害和保护机制，从而加重或改善缺血的后果。本研究的目的是在接受心肌缺血/再灌注的麻醉猪中，并行测量梗死面积与原位组织间隙NO浓度。使用NOS阻断来研究不依赖于NOS的途径对NO合成的贡献。
基于微透析结合氧合血红蛋白法，在中度或重度缺血90分钟及随后的再灌注期间进行组织间隙NO测量。为了检验NOS抑制的效果，在最初30分钟的缺血期后60分钟，进行第二次30分钟的缺血期，同时冠状动脉内输注S-乙基异硫脲。
在缺血期间，组织间隙NO浓度升高约30分钟，然后在该升高水平保持恒定。中度缺血时NO浓度升高253±82 nmol/L，重度缺血时升高565±169 nmol/L，与心内膜下血流量呈负相关（r = -0.76）。抑制NOS可增加冠状动脉压力，降低组织间隙基础NO浓度和组织亚硝酸盐含量。然而，它并未减少缺血期间组织间隙NO浓度的升高。
不依赖于NOS的途径在心肌缺血期间的NO合成中起重要作用。
