Effects of hypercarbic acidotic reperfusion on recovery of myocardial function after cardioplegic ischemia in neonatal lambs

Fumikazu Nomura, Mitsuru Aoki, Joseph M. Forbess, John E. Mayer

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Background: There is continued controversy over the management of pH during ischemia and reperfusion. Calcium overload is an integral feature of the injury resulting from ischemia and reperfusion, and hydrogen ions are known to blunt Ca2+ influx into cells because H+ inhibits the Na+-Ca2+ exchange and the slow calcium channels. Hypercarbia is one source of H+, but elevated CO2 level is also known to be a potent coronary vasodilator, which may be beneficial during early reperfusion. This study was designed to explore the effect of respiratory and metabolic acidosis during the initial phases of reperfusion after hypothermic cardioplegic ischemia in the neonatal lamb. Methods and Results: Forty isolated, blood-perfused neonatal lamb hearts underwent 2 hours of cold cardioplegic ischemia followed by reperfusion with blood with various pH values. pH was controlled either by altering the FICO2 in the ventilating gas to the oxygenator (groups A through D) or by adding HCl to the reperfusate (group E). pH of the initial reperfusate was 6.8 in group A, 7.1 in group B, 7.5 in group C, and 7.8 in group D. In these groups, pH values were maintained for the initial 5 minutes of reperfusion and then corrected to 7.4 over 20 minutes by changing the FICO2 to the oxygenator. In group E, HCl was added to the reperfusate to give pH 6.8 (metabolic acidosis). pH was corrected after 5 minutes of reperfusion by administration of NaHCO3 and THAM over the next 15 minutes. At 30 and 60 minutes of reperfusion, left ventricular maximum developed pressure, dP/dt, -dP/dt, maximum developed pressure at V10 (volume that gave left ventricular end-diastolic pressure of 10 mm Hg during baseline measurements), and dP/dt at V10 were measured. Coronary blood flow and oxygen consumption (MV̇O2) were also measured to evaluate the metabolic recovery. Group A showed better functional recovery than groups B, C, or D (maximum dP/dt V10: group A, 88.3±7.7%; group B, 69.3±10.8%; group C, 74.6±10.3%; group D, 66.1±9.4%; and group E, 73.7±13.8% at 30 minutes [P<.05]; group A, 76.1±13.6%; group B, 61.9±8.6%; group C, 63.8±5.4%; group D, 57.9±9.4%; and group E, 62.6±12.7% at 60 minutes [P<.05]). Coronary blood flow was higher in group A than in other groups (A, 177.2±29.6%; B, 144.1±18.1%; C, 127.3±18.5%; D, 150.4±24.3%; and E, 106.0±20.0% [P<.05]). There were no significant differences in MV̇O2. Conclusions: These data indicate that hypercarbic reperfusion (pH 6.8) for a short period after ischemia improved functional recovery after cold cardioplegic ischemia in neonatal lamb hearts but that metabolic acidosis to an equivalent pH did not improve postischemic function. Possible mechanisms for this effect include reduction of calcium loading to the myocardium through H+ inhibition of calcium uptake or the induction of coronary vasodilation by hypercarbia.

Original languageEnglish (US)
JournalCirculation
Volume90
Issue number5 II
StatePublished - Nov 1994

Fingerprint

Recovery of Function
Reperfusion
Ischemia
Acidosis
Oxygenators
Cold Ischemia
Hypercapnia
Calcium
Respiratory Acidosis
Pressure
Calcium Channels
Reperfusion Injury
Vasodilator Agents
Vasodilation
Oxygen Consumption
Protons
Myocardium
Gases
Blood Pressure

Keywords

  • calcium acidosis
  • cardioplegia
  • hypercarbia
  • reperfusion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Effects of hypercarbic acidotic reperfusion on recovery of myocardial function after cardioplegic ischemia in neonatal lambs. / Nomura, Fumikazu; Aoki, Mitsuru; Forbess, Joseph M.; Mayer, John E.

In: Circulation, Vol. 90, No. 5 II, 11.1994.

Research output: Contribution to journalArticle

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title = "Effects of hypercarbic acidotic reperfusion on recovery of myocardial function after cardioplegic ischemia in neonatal lambs",
abstract = "Background: There is continued controversy over the management of pH during ischemia and reperfusion. Calcium overload is an integral feature of the injury resulting from ischemia and reperfusion, and hydrogen ions are known to blunt Ca2+ influx into cells because H+ inhibits the Na+-Ca2+ exchange and the slow calcium channels. Hypercarbia is one source of H+, but elevated CO2 level is also known to be a potent coronary vasodilator, which may be beneficial during early reperfusion. This study was designed to explore the effect of respiratory and metabolic acidosis during the initial phases of reperfusion after hypothermic cardioplegic ischemia in the neonatal lamb. Methods and Results: Forty isolated, blood-perfused neonatal lamb hearts underwent 2 hours of cold cardioplegic ischemia followed by reperfusion with blood with various pH values. pH was controlled either by altering the FICO2 in the ventilating gas to the oxygenator (groups A through D) or by adding HCl to the reperfusate (group E). pH of the initial reperfusate was 6.8 in group A, 7.1 in group B, 7.5 in group C, and 7.8 in group D. In these groups, pH values were maintained for the initial 5 minutes of reperfusion and then corrected to 7.4 over 20 minutes by changing the FICO2 to the oxygenator. In group E, HCl was added to the reperfusate to give pH 6.8 (metabolic acidosis). pH was corrected after 5 minutes of reperfusion by administration of NaHCO3 and THAM over the next 15 minutes. At 30 and 60 minutes of reperfusion, left ventricular maximum developed pressure, dP/dt, -dP/dt, maximum developed pressure at V10 (volume that gave left ventricular end-diastolic pressure of 10 mm Hg during baseline measurements), and dP/dt at V10 were measured. Coronary blood flow and oxygen consumption (MV̇O2) were also measured to evaluate the metabolic recovery. Group A showed better functional recovery than groups B, C, or D (maximum dP/dt V10: group A, 88.3±7.7{\%}; group B, 69.3±10.8{\%}; group C, 74.6±10.3{\%}; group D, 66.1±9.4{\%}; and group E, 73.7±13.8{\%} at 30 minutes [P<.05]; group A, 76.1±13.6{\%}; group B, 61.9±8.6{\%}; group C, 63.8±5.4{\%}; group D, 57.9±9.4{\%}; and group E, 62.6±12.7{\%} at 60 minutes [P<.05]). Coronary blood flow was higher in group A than in other groups (A, 177.2±29.6{\%}; B, 144.1±18.1{\%}; C, 127.3±18.5{\%}; D, 150.4±24.3{\%}; and E, 106.0±20.0{\%} [P<.05]). There were no significant differences in MV̇O2. Conclusions: These data indicate that hypercarbic reperfusion (pH 6.8) for a short period after ischemia improved functional recovery after cold cardioplegic ischemia in neonatal lamb hearts but that metabolic acidosis to an equivalent pH did not improve postischemic function. Possible mechanisms for this effect include reduction of calcium loading to the myocardium through H+ inhibition of calcium uptake or the induction of coronary vasodilation by hypercarbia.",
keywords = "calcium acidosis, cardioplegia, hypercarbia, reperfusion",
author = "Fumikazu Nomura and Mitsuru Aoki and Forbess, {Joseph M.} and Mayer, {John E.}",
year = "1994",
month = "11",
language = "English (US)",
volume = "90",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "5 II",

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TY - JOUR

T1 - Effects of hypercarbic acidotic reperfusion on recovery of myocardial function after cardioplegic ischemia in neonatal lambs

AU - Nomura, Fumikazu

AU - Aoki, Mitsuru

AU - Forbess, Joseph M.

AU - Mayer, John E.

PY - 1994/11

Y1 - 1994/11

N2 - Background: There is continued controversy over the management of pH during ischemia and reperfusion. Calcium overload is an integral feature of the injury resulting from ischemia and reperfusion, and hydrogen ions are known to blunt Ca2+ influx into cells because H+ inhibits the Na+-Ca2+ exchange and the slow calcium channels. Hypercarbia is one source of H+, but elevated CO2 level is also known to be a potent coronary vasodilator, which may be beneficial during early reperfusion. This study was designed to explore the effect of respiratory and metabolic acidosis during the initial phases of reperfusion after hypothermic cardioplegic ischemia in the neonatal lamb. Methods and Results: Forty isolated, blood-perfused neonatal lamb hearts underwent 2 hours of cold cardioplegic ischemia followed by reperfusion with blood with various pH values. pH was controlled either by altering the FICO2 in the ventilating gas to the oxygenator (groups A through D) or by adding HCl to the reperfusate (group E). pH of the initial reperfusate was 6.8 in group A, 7.1 in group B, 7.5 in group C, and 7.8 in group D. In these groups, pH values were maintained for the initial 5 minutes of reperfusion and then corrected to 7.4 over 20 minutes by changing the FICO2 to the oxygenator. In group E, HCl was added to the reperfusate to give pH 6.8 (metabolic acidosis). pH was corrected after 5 minutes of reperfusion by administration of NaHCO3 and THAM over the next 15 minutes. At 30 and 60 minutes of reperfusion, left ventricular maximum developed pressure, dP/dt, -dP/dt, maximum developed pressure at V10 (volume that gave left ventricular end-diastolic pressure of 10 mm Hg during baseline measurements), and dP/dt at V10 were measured. Coronary blood flow and oxygen consumption (MV̇O2) were also measured to evaluate the metabolic recovery. Group A showed better functional recovery than groups B, C, or D (maximum dP/dt V10: group A, 88.3±7.7%; group B, 69.3±10.8%; group C, 74.6±10.3%; group D, 66.1±9.4%; and group E, 73.7±13.8% at 30 minutes [P<.05]; group A, 76.1±13.6%; group B, 61.9±8.6%; group C, 63.8±5.4%; group D, 57.9±9.4%; and group E, 62.6±12.7% at 60 minutes [P<.05]). Coronary blood flow was higher in group A than in other groups (A, 177.2±29.6%; B, 144.1±18.1%; C, 127.3±18.5%; D, 150.4±24.3%; and E, 106.0±20.0% [P<.05]). There were no significant differences in MV̇O2. Conclusions: These data indicate that hypercarbic reperfusion (pH 6.8) for a short period after ischemia improved functional recovery after cold cardioplegic ischemia in neonatal lamb hearts but that metabolic acidosis to an equivalent pH did not improve postischemic function. Possible mechanisms for this effect include reduction of calcium loading to the myocardium through H+ inhibition of calcium uptake or the induction of coronary vasodilation by hypercarbia.

AB - Background: There is continued controversy over the management of pH during ischemia and reperfusion. Calcium overload is an integral feature of the injury resulting from ischemia and reperfusion, and hydrogen ions are known to blunt Ca2+ influx into cells because H+ inhibits the Na+-Ca2+ exchange and the slow calcium channels. Hypercarbia is one source of H+, but elevated CO2 level is also known to be a potent coronary vasodilator, which may be beneficial during early reperfusion. This study was designed to explore the effect of respiratory and metabolic acidosis during the initial phases of reperfusion after hypothermic cardioplegic ischemia in the neonatal lamb. Methods and Results: Forty isolated, blood-perfused neonatal lamb hearts underwent 2 hours of cold cardioplegic ischemia followed by reperfusion with blood with various pH values. pH was controlled either by altering the FICO2 in the ventilating gas to the oxygenator (groups A through D) or by adding HCl to the reperfusate (group E). pH of the initial reperfusate was 6.8 in group A, 7.1 in group B, 7.5 in group C, and 7.8 in group D. In these groups, pH values were maintained for the initial 5 minutes of reperfusion and then corrected to 7.4 over 20 minutes by changing the FICO2 to the oxygenator. In group E, HCl was added to the reperfusate to give pH 6.8 (metabolic acidosis). pH was corrected after 5 minutes of reperfusion by administration of NaHCO3 and THAM over the next 15 minutes. At 30 and 60 minutes of reperfusion, left ventricular maximum developed pressure, dP/dt, -dP/dt, maximum developed pressure at V10 (volume that gave left ventricular end-diastolic pressure of 10 mm Hg during baseline measurements), and dP/dt at V10 were measured. Coronary blood flow and oxygen consumption (MV̇O2) were also measured to evaluate the metabolic recovery. Group A showed better functional recovery than groups B, C, or D (maximum dP/dt V10: group A, 88.3±7.7%; group B, 69.3±10.8%; group C, 74.6±10.3%; group D, 66.1±9.4%; and group E, 73.7±13.8% at 30 minutes [P<.05]; group A, 76.1±13.6%; group B, 61.9±8.6%; group C, 63.8±5.4%; group D, 57.9±9.4%; and group E, 62.6±12.7% at 60 minutes [P<.05]). Coronary blood flow was higher in group A than in other groups (A, 177.2±29.6%; B, 144.1±18.1%; C, 127.3±18.5%; D, 150.4±24.3%; and E, 106.0±20.0% [P<.05]). There were no significant differences in MV̇O2. Conclusions: These data indicate that hypercarbic reperfusion (pH 6.8) for a short period after ischemia improved functional recovery after cold cardioplegic ischemia in neonatal lamb hearts but that metabolic acidosis to an equivalent pH did not improve postischemic function. Possible mechanisms for this effect include reduction of calcium loading to the myocardium through H+ inhibition of calcium uptake or the induction of coronary vasodilation by hypercarbia.

KW - calcium acidosis

KW - cardioplegia

KW - hypercarbia

KW - reperfusion

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