Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Heusch, G; Post, H; Michel, MC; Kelm, M; Schulz, R.
Endogenous nitric oxide and myocardial adaptation to ischemia.
Circ Res. 2000; 87(2):146-152
Doi: 10.1161/01.RES.87.2.146
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- Post Heiner
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- Abstract:
- Ischemic myocardium does not inevitably undergo necrosis but rather can survive through downregulation of contractile function, ie, "hibernate." To study the role of endogenous NO in this adaptation, 41 enflurane-anesthetized swine were subjected to 90 minutes of moderate left anterior descending coronary artery hypoperfusion and assigned to placebo (P), to 30 mg/kg N(G)-nitro-L-arginine (L-NNA) IV to inhibit NO synthase, or to aortic constriction (AO) to match the increased left ventricular pressure observed with L-NNA. During normoperfusion, a regional myocardial external work index (WI, mm Hg. mm, sonomicrometry and micromanometry) was reduced with L-NNA (from 326+/-27 [SEM] to 250+/-19, P<0.05) but increased with AO (from 321+/-16 to 363+/-19, P<0.05 versus L-NNA). At 10 minutes of ischemia, WI was lower with L-NNA (109+/-10, P<0.05) than P (180+/-22) and AO (170+/-11) and did not change further at 85 minutes of ischemia. Relationships between WI and transmural myocardial blood flow and oxygen consumption were shifted rightward by L-NNA versus P and AO at both 10 and 85 minutes of ischemia. The maximal increment in calcium-activated external work was not different during normoperfusion among groups but was decreased during ischemia with L-NNA. L-NNA transiently increased myocardial contractile calcium sensitivity along with systemic pressure but reduced it during ongoing ischemia. The free-energy change of ATP hydrolysis after an early ischemic decrease recovered toward baseline values in all groups, and necrosis was absent after 2 (triphenyltetrazolium chloride staining) or 8 (histology) hours of reperfusion. Thus, endogenous NO contributes to hibernation by reducing oxygen consumption and preserving calcium sensitivity and contractile function without an energy cost during ischemia.
- Find related publications in this database (using NLM MeSH Indexing)
- Analysis of Variance -
- Animals -
- Aorta, Thoracic -
- Coronary Circulation - drug effects
- Heart - drug effects
- Hemodynamics - drug effects
- Lactates - metabolism
- Myocardial Ischemia - metabolism
- Myocardium - metabolism
- Nitric Oxide - physiology
- Nitroarginine - pharmacology
- Oxygen Consumption - drug effects
- Swine - drug effects
- Swine, Miniature - drug effects
- Ventricular Function, Left - drug effects
- Find related publications in this database (Keywords)
- contractile function
- oxygen consumption
- ischemia