title: Vascular washout reduces Ca2+ overload and improves function of reperfused ischemic hearts.
abstract: Relationships between myocardial Ca2+ uptake, recovery of ventricular function, and restoration of tissue metabolites were determined during 30 min of reperfusion following ischemic and anoxic perfusion with either zero or low coronary flow, zero flow with intermittent perfusion, and low-flow perfusion without substrates. When zero-flow ischemia was maintained for 30 or 40 min, tissue lactate levels increased approximately 100-fold; with reperfusion of these hearts, developed pressure recovered to only 70 and 40% of preischemic function, respectively, and Ca2+ uptake increased by 7- and 15-fold. In contrast, 30 min of low-flow (1 ml/min) anoxic perfusion resulted in accumulation of less lactate (15-fold increase), less reperfusion Ca2+ uptake, and recovery of developed pressure to the preanoxic level. Omission of energy substrates during the low-flow anoxic perfusion caused a reduced recovery of heart rate with lower high-energy phosphate levels and increased Ca2+ uptake, but contractile function recovered to the same extent as in low-flow perfusion with substrate. Even very low flow rates (0.06-0.16 ml/min) of oxygen-deficient perfusate increased high-energy phosphate content and contractile function and decreased Ca2+ uptake. Intermittent perfusion with either oxygenated or anoxic buffer between four 10-min episodes of ischemia reduced lactate accumulation, maintained function, and left Ca2+ uptake essentially unchanged. Recovery of developed pressure during reperfusion was negatively correlated with the amount of lactate that accumulated during ischemia or anoxia and with reperfusion Ca2+ uptake, regardless of the duration or type of ischemia or anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822.
authors.forename: M
authors.initials: M
authors.lastname: Tani
authors.forename: J R
authors.initials: JR
authors.lastname: Neely
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism* / Q000502:physiology; D003971:Diastole; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion / Q000379:methods; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D013997:Time Factors
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D002118:Calcium