title: Circulatory consequences of reduced endogenous nitric oxide production during small-volume resuscitation.
abstract: Hypertonic small-volume resuscitation transiently restores the cardiovascular function during various circulatory disturbances. Nitric oxide (NO) is an important mediator of flow-induced peripheral and central hemodynamic changes, and therefore, we hypothesized that a decreased endogenous NO production could influence the consequences and the effectiveness of hypertonic fluid therapy. The main goal of this study was to outline and compare the circulatory effects small volume hypertonic saline-dextran (HSD, 7.5% NaCl-10% dextran; 4 ml/kg iv) infusion with (n=7) or without (n=7) artificially diminished NO production in normovolemic anesthetized dogs. HSD administration significantly increased cardiac index (CI), coronary flow (CF) and myocardial contractility, and elevated plasma nitrite/nitrate (NOx) and endothelin-1 (ET-1) levels. However, the late (2 h) postinfusion period was characterized by significantly decreased myocardial NO synthase (NOS) and enhanced myeloperoxidase activities. Pre-treatment with the non-selective NOS inhibitor N-nitro-L-arginine (NNA, 4 mg/kg) immediately increased cardiac contractility, and the HSD-induced CI and CF elevations and the positive inotropy were absent. Additionally, plasma ET-1 levels increased and NOx levels were significantly decreased. In conclusion, our results demonstrate that HSD infusion leads to preponderant vasoconstriction when endogenous NO synthesis is diminished, and this could explain the loss of effectiveness of HSD resuscitation in NO-deficient states.
authors.affiliation: Department of Surgery, Dr. István Bugyi Hospital, Szentes Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Molnár
authors.forename: E
authors.initials: E
authors.lastname: Csonka
authors.forename: A
authors.initials: A
authors.lastname: Vass
authors.forename: Mihály
authors.initials: M
authors.lastname: Boros
authors.forename: J
authors.initials: J
authors.lastname: Kaszaki
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003911:Dextrans / Q000494:pharmacology*; D004285:Dogs; D019332:Endothelin-1 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D012151:Resuscitation / Q000379:methods*; D012965:Sodium Chloride / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D003911:Dextrans; D019332:Endothelin-1; D004791:Enzyme Inhibitors; C104375:hypertonic saline-dextran solution; D019335:Nitroarginine; D009569:Nitric Oxide; D012965:Sodium Chloride; D052250:Nitric Oxide Synthase Type III