Cardiac Preconditioning Protects against Irreversible Injury Rather Than Attenuating Stunning

Thomas F. Rehring, Elizabeth C. Brew, Randall S Friese, Anirban Banerjee, Alden H. Harken

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The purpose of this experiment was to determine if cardiac preconditioning (PC) mediates protection by attenuating stunning or preventing irreversible injury. Inherent in the definition of myocardial stunning is the ability to respond to catechol stimulation after ischemia/reperfusion (I/R). Irreversibly injured myocardium cannot respond to catechols. We hypothesized that α1-adrenergic-stimulated PC is mediated through a functional protection against reversible injury. We investigated this hypothesis in the isolated, buffer-perfused rat heart subjected to global ischemia (20 min, 37.5°C) and reperfusion (40 min). The PC group received an α1-adrenergic stimulus (norepinephrine, 0.5-1.0 μM, 2 min) 10 min prior to ischemia. Control hearts were perfused normoxically for 80 min. Developed pressure (DP) and heart rate were recorded continuously. To determine maximal myocellular function, all hearts received a β-adrenergic pathway stimulus (forskolin (FSK), 100 μM bolus) at end reperfusion. The ability to improve DP in response to FSK was indicative of reversible dysfunction (stunning). Failure to attain the maximal DP established in normoxic controls was utilized as a measure of irreversible dysfunction. Recovery was assessed as a percentage of initial DP. The results suggest that (1) PC protects against an I/R injury (recovery: I/R, 50.1%; PC + I/R, 76.0%; P < 0.05); (2) all groups exhibit reversible dysfunction (all increased DP in response to FSK); (3) when maximally stimulated, I/R hearts are unable to develop pressures similar to those of normoxic controls, suggesting irreversible injury; and (4) PC hearts, however, attained similar maximal pressures compared to controls. We conclude that α1-adrenergic PC improves postischemic cardiac function by preventing irreversible injury. Furthermore, α1-adrenergic PC improves the postischemic response to inotropic stimulation by 36.7%.

Original languageEnglish (US)
Pages (from-to)111-114
Number of pages4
JournalJournal of Surgical Research
Volume59
Issue number1
DOIs
StatePublished - Jul 1995
Externally publishedYes

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Reperfusion
Adrenergic Agents
Ischemia
Pressure
Wounds and Injuries
Colforsin
Catechols
Myocardial Stunning
Reperfusion Injury
Myocardium
Norepinephrine
Buffers
Heart Rate

ASJC Scopus subject areas

  • Surgery

Cite this

Cardiac Preconditioning Protects against Irreversible Injury Rather Than Attenuating Stunning. / Rehring, Thomas F.; Brew, Elizabeth C.; Friese, Randall S; Banerjee, Anirban; Harken, Alden H.

In: Journal of Surgical Research, Vol. 59, No. 1, 07.1995, p. 111-114.

Research output: Contribution to journalArticle

Rehring, Thomas F. ; Brew, Elizabeth C. ; Friese, Randall S ; Banerjee, Anirban ; Harken, Alden H. / Cardiac Preconditioning Protects against Irreversible Injury Rather Than Attenuating Stunning. In: Journal of Surgical Research. 1995 ; Vol. 59, No. 1. pp. 111-114.
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abstract = "The purpose of this experiment was to determine if cardiac preconditioning (PC) mediates protection by attenuating stunning or preventing irreversible injury. Inherent in the definition of myocardial stunning is the ability to respond to catechol stimulation after ischemia/reperfusion (I/R). Irreversibly injured myocardium cannot respond to catechols. We hypothesized that α1-adrenergic-stimulated PC is mediated through a functional protection against reversible injury. We investigated this hypothesis in the isolated, buffer-perfused rat heart subjected to global ischemia (20 min, 37.5°C) and reperfusion (40 min). The PC group received an α1-adrenergic stimulus (norepinephrine, 0.5-1.0 μM, 2 min) 10 min prior to ischemia. Control hearts were perfused normoxically for 80 min. Developed pressure (DP) and heart rate were recorded continuously. To determine maximal myocellular function, all hearts received a β-adrenergic pathway stimulus (forskolin (FSK), 100 μM bolus) at end reperfusion. The ability to improve DP in response to FSK was indicative of reversible dysfunction (stunning). Failure to attain the maximal DP established in normoxic controls was utilized as a measure of irreversible dysfunction. Recovery was assessed as a percentage of initial DP. The results suggest that (1) PC protects against an I/R injury (recovery: I/R, 50.1{\%}; PC + I/R, 76.0{\%}; P < 0.05); (2) all groups exhibit reversible dysfunction (all increased DP in response to FSK); (3) when maximally stimulated, I/R hearts are unable to develop pressures similar to those of normoxic controls, suggesting irreversible injury; and (4) PC hearts, however, attained similar maximal pressures compared to controls. We conclude that α1-adrenergic PC improves postischemic cardiac function by preventing irreversible injury. Furthermore, α1-adrenergic PC improves the postischemic response to inotropic stimulation by 36.7{\%}.",
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