Differential depression of myocardial function and metabolism by lactate and H+

Michele Samaja, Sonia Allibardi, Giuseppina Milano, Gabriella Neri, Bruno Grassi, L. Bruce Gladden, Michael C. Hogan

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of both high blood H+ concentration ([H+]) and high blood lactate concentration ([lactate]) under ischemia-reperfusion conditions are receiving attention, but little is known about their effects in nonischemic hearts. Isolated rat hearts were Langendorff perfused at constant flow with media at two pH values (7.4 and 7.0) and two [lactate] (0 and 20 mM) in various sequences (n = 6/group). Coronary flow and arterial O2 content were kept constant at levels that allowed hearts to function without O2 supply limitation. We measured contractility, O2 uptake, diastolic pressure, and at the end of the protocol, tissue [lactate] and pH. Perfusion with high [lactate] raised tissue [lactate] from 5.5 ± 0.1 to 17.5 ± 2.6 μmol/heart (P <0.0001), whereas decreasing the pH of the medium decreased tissue pH from 6.94 ± 0.02 to 6.81 ± 0.06 (P = 0.002). Heart rate was not affected by high [lactate] but was reversibly depressed by high [H+] (P = 0.004). Developed pressure declined by 20% in response to high [lactate], high [H+], and high [lactate] + high [H+] (P = 0.002). After the high-[lactate] challenge was withdrawn, pressure continued to decline. In contrast, withdrawing the high [H+] challenge allowed partial recovery. The behavior of diastolic pressure mirrored that of developed pressure. Although unaffected by high [lactate], the O2 uptake was reversibly depressed by high [H+]. This suggests higher O2 cost per contraction in the presence of high [lactate]. We conclude that for similar acute contractility depression, high [lactate] induces irreversible damage, likely at some point in the pathway of O2 utilization. In contrast, the effect of high [H+] appears reversible. These differential behaviors may have implications for heart function during heavy exercise and ischemia-reperfusion events.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume276
Issue number1 45-1
Publication statusPublished - Jan 1999

Keywords

  • Isolated heart
  • Myocardial performance
  • pH

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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