title: Intermittent v continuous ischemia decelerates adenylate breakdown and prevents norepinephrine release in reperfused rabbit heart.
abstract: Myocardium tolerates intermittent ischemia followed by short reperfusions better than continuous ischemia of the same duration. We attempted to delineate the differential mechanism(s) involved in intermittent v continuous ischemia. Isolated, paced rabbit hearts were perfused at 22 ml/min. Coronary flow was stopped intermittently 12 x for 2 or 4 min, with 3-min reperfusions (total reperfusion period: 36 min). In two other groups, flow was stopped continuously for 24 or 36 min followed by a flat 36-min reperfusion. Following the first intermittent 2-min ischemia, adenosine efflux increased ninefold; in all subsequent ischemia/reperfusion cycles, adenosine and total purine releases were substantially less despite identical heart rates, coronary flows and ischemic periods. The rate-pressure product prior to the intermittent ischemias exhibited exponential correlations with total purine efflux during the 3 min of reperfusion. When intermittent ischemia was extended to 4 min, the initial attenuation of ATP breakdown during the prior 2-min occlusions was overcome, but during subsequent 4-min ischemia/reperfusion cycles, ATP breakdown was again attenuated relative to the first 4-min ischemia. After the prolonged continuous ischemias, purine efflux was up to 6 x higher than with intermittent ischemias of the same total time of zero flow. Lactate release and hence cellular H+ export after intermittent ischemias remained consistently elevated, but following the continuous ischemia of 36 min, release of lactate, and thus H+, was subsequentially decreased. Glycogen mobilization occurred regardless of the ischemia's nature, but it was markedly enhanced during continuous ischemias, where no fall in proglycogen levels occurred. Similarly, myocardial norepinephrine release increased substantially only during the prolonged continuous ischemias. Thus short intermittent ischemia attenuates cardiac adenylate degradation and glycogen mobilization; such ischemic insult also provides for better lactate and H+ washouts immediately upon reperfusion. Another beneficial effect of intermittent ischemia was the near-complete absence of free interstitial norepinephrine, which exacerbates myocardial ischemic insults. In addition, the exponential correlations between preischemic rate-pressure product and postischemic purine release suggest that preischemic energy demand may determine ATP breakdown in ischemic rabbit myocardium.
authors.affiliation: Cardiochemical Laboratory, Thoraxcenter, Erasmus University Rotterdam, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: de Jong
authors.forename: A
authors.initials: A
authors.lastname: Cargnoni
authors.forename: S
authors.initials: S
authors.lastname: Bradamante
authors.forename: S
authors.initials: S
authors.lastname: Curello
authors.forename: M
authors.initials: M
authors.lastname: Janssen
authors.forename: E
authors.initials: E
authors.lastname: Pasini
authors.forename: C
authors.initials: C
authors.lastname: Ceconi
authors.forename: R
authors.initials: R
authors.lastname: Bünger
authors.forename: R
authors.initials: R
authors.lastname: Ferrari
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011687:Purines / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D000227:Adenine Nucleotides; D007042:Hypoxanthines; D011687:Purines; D019271:Hypoxanthine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine; D009638:Norepinephrine