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Myocardial substrate utilization and hemodynamics following repeated coronary flow reduction in pigs

Myokardialer Substratverbrauch und Hämodynamik während wiederholter Reduktion der Koronardurchströmung in Schweinen

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Summary

The effect of repeated local ischemia and reperfusion on myocardial metabolism and ventricular performance was studied in 12 open-chested pigs fasted overnight. Myocardial ischemia was induced by reduction of the flow in the left anterior descending coronary artery to 40% of control during 30 min. After 35 min of reperfusion a second 30-min occlusion period was started, again followed by a 35-min reperfusion period. At the end of both reperfusion periods coronary flow and coronary resistance had returned to control values. During control there was lactate uptake, but no significant uptake of glucose, free fatty acids (FFA), triglycerides, glycerol and inosine. During the first occlusion period the heart released lactate and inosine, and used glucose and FFA. At the end of the first reperfusion period lactate uptake approached control values, but inosine was still released by 10 of the 12 animals. In the second ischemic period, glucose and FFA were again taken up. Lactate and inosine were released, but the production was much smaller than during the first occlusion period. Depletion of myocardial glycogen and high-energy phosphates could be responsible for this quantitatively different response. Necrosis may have played a role, although enzyme release was minimal and only observed after the second occlusion period.

Heart rate, peripheral resistance and ventricular filling pressure were virtually unchanged throughout the course of the experiments. Maximum rate of fall of left ventricular pressure (min LVdP/dt) decreased during ischemia and did not recover during reperfusion. Changes in min LVdP/dt and cardiac output were more closely related than changes in max LVdP/dt and cardiac output.

This model cannot be used for the study of interventions during myocardial ischemia in which the animal serves as its own control.

Zusammenfassung

Der Effekt von wiederholter lokaler Ischämie und Reperfusion auf den myokardialen Energiestoffwechsel und Ventrikelfunktion wurde bei 12 narkotisierten Schweinen mit geöffnetem Thorax studiert. Die Schweine hatten 24 Stunden gefastet. Die myokardiale Ischämie wurde verursacht durch eine Reduktion der Blutdurchströmung in der linken Anterior Descending Koronar Arterie bis 40% vom Anfangswert während 30 Minuten. Eine zweite Reduktion wurde nach 35 Minuten Reperfusion angefangen. Die zweite Reduktion folgte wieder durch eine 35 Minuten dauernde Reperfusion. Am Ende der beiden Reperfusionen der Koronardurchströmung und Koronarwiderstand hatten sie wieder Anfangswerte angenommen. Während der Kontrolle gab es Laktat-Aufnahme, aber keine Aufnahme von Glukose, Freie Fettsäure (FFA), Triglyzeride, Glyzerol und Inosine. Während der ersten Okklusions-Periode wurde aus dem Herzen Lactat und Inosine freigemacht, es wurde Glukose und FFA aufgenommen. Am Ende der ersten Reperfusion wurde Laktat wieder aufgenommen, aber Inosine wurde noch immer an 10 von 12 Schweinen freigemacht. In der zweiten Okklusions-Periode gab es wieder Glukose und FFA-Aufnahme. Laktat und Inosine wurden freigemacht, aber die Produktion war viel kleiner als in der ersten Okklusions-Periode. Erschöpfung von myokardialen Glykogen und energiereichen Phosphaten können dafür verantwortlich sein. Nekrose könnte auch eine Rolle gespielt haben, obschon Enzym-Abgaben sehr gering waren und nur nach der zweiten Okklusions-Periode gefunden wurden. Herzfrequenz, Peripherewiderstand und ventrikulärer Füllungsdruck blieben so gut wie unverändert. Während der Experimente wurde die maximale Druckabfallgeschwindigkeit (minLVdP/dt) weniger, während Ischämie sich bei Reperfusion nicht herstellte. Veränderungen in minLVdP/dt und Herzminutenvolumen hatten einen höheren Korrelations-Koeffizient, als maxLVdP/dt und Herzminutenvolumen. Dieses Modell kann nicht für die Studien von Interventionen während myokardialer Ischämie benutzt werden.

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Author notes

  1. P. D. Verdouw

    Present address: Laboratories of Experimental Cardiology and Cardiochemistry, Thoraxcenter Medical Faculty, Erasmus University, P. O. Box 1738, Rotterdam, (The Netherlands)

Authors and Affiliations

  1. Laboratories of Experimental Cardiology and Cardiochemistry, Thoraxcenter Medical Faculty, Erasmus University, P. O. Box 1738, Rotterdam, (The Netherlands)

    W. J. Remme, J. W. de Jong & W. A. P. Breeman

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  1. P. D. Verdouw
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  3. J. W. de Jong
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With 7 figures and 2 tables

This investigation was supported by a grant from the Dutch Heart Foundation.

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Verdouw, P.D., Remme, W.J., de Jong, J.W. et al. Myocardial substrate utilization and hemodynamics following repeated coronary flow reduction in pigs. Basic Res Cardiol 74, 477–493 (1979). https://doi.org/10.1007/BF01907642

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