title: Hyperosmotic perfusion of the beating rat heart and the role of the Na+/K+/2Cl- co-transporter and the Na+/H+ exchanger.
abstract: The aim of the present study was to investigate the role of the Na+/K+/2Cl- co-transporter and the Na+/H+ exchanger on contractile function and electrolyte regulation during hyperosmotic perfusion of the heart. Langendorff perfused rat hearts were subjected to hyperosmolal perfusion in 10-min intervals. Perfusates were made hyperosmotic by adding mannitol to the buffer (370, 450 and 600 mOsmol/kg H2O). Cardiac contractile function was monitored with a balloon in the left ventricle (LV) coupled to a pressure transducer. Cardiac effluent was sampled repeatedly throughout and after hyperosmotic perfusion and analysed for content of Na+, K+, and Cl-. All three hyperosmotic perfusates initially reduced LV developed pressure (LVDP), but for 370 and 450 mOsmol/kg H2O, LVDP recovered to baseline within 4 min of perfusion. With 600 mOsmol/kg H2O, LVDP recovered slowly and was 50% below baseline after 10 min of hyperosmotic perfusion. Inhibition of the Na+/H+ exchanger with 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694) abolished the recovery of LVDP to the 600 mOsmol/kg H2O perfusate, whereas inhibition of the Na+/K+/2Cl- co-transporter had no impact on LVDP. Potassium was taken up by the heart during hyperosmotic perfusion and this uptake was significantly reduced with inhibition of the Na+/H+ exchanger. Intracellular pH was assessed with 31p magnetic resonance spectroscopy and hyperosmolality induced a significant alkalosis that was dependent upon the Na+/H+ exchanger. The rat heart responds to moderate elevations in osmolality with a transient reduction in contractile function, whereas an elevation of 300 mOsmol/kg H2O persistently reduces contractile function. The Na+/H+ exchanger, but not the Na+/K+/2Cl- co-transporter, is of importance in contractile recovery and electrolyte regulation during hyperosmotic perfusion in the rat heart.
authors.affiliation: Department of Physiology and Biomedical Engineering Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Geir.Falck@medisin.ntnu.no
authors.forename: G
authors.initials: G
authors.lastname: Falck
authors.forename: J
authors.initials: J
authors.lastname: Schjøtt
authors.forename: M
authors.initials: M
authors.lastname: Bruvold
authors.forename: J
authors.initials: J
authors.lastname: Krane
authors.forename: S
authors.initials: S
authors.lastname: Skarra
authors.forename: P
authors.initials: P
authors.lastname: Jynge
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009200:Myocardial Contraction; D009995:Osmosis; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D014882:Water-Electrolyte Balance
chemical_list: D018118:Chloride Channels; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase