Transient β adrenergic stimulation can precondition the rat heart against postischaemic contractile dysfunction

Gregory K. Asimakis, Karen Inners-Mcbride, Vincent Conti, Chun Jie Yang

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Abstract

Objective: The aim was to assess the abilities of exogenous noradrenaline, isoprenaline, and phenylephrine to precondition the isolated rat heart against ischaemic and reperfusion injury. Methods: The isovolumetric Langendorff rat heart model was used to determine postischaemic recovery of left ventricular function. The hearts were subjected to 30 min of normothermic global ischaemia followed by 30 min reperfusion. Treated hearts were perfused with noradrenaline (10-7 M), isoprenaline (10-8 M), or phenylephrine (10-6 M, 10-5 M, and 10-4 M) for 5 min followed by 5 min washout before the 30 min ischaemic period. Results: Control hearts recovered 47.6(SEM 4.3)% of baseline heart rate × developed pressure after 30 min reperfusion, whereas noradrenaline and isoprenaline treated hearts recovered 75.1(4.6) and 76.4(4.6)%, respectively (p< 0.001 v control). Left ventricular end diastolic pressures at the end of reperfusion were 48.8(4.0), 20.0(2.4), and 21.6(2.7) mm Hg for control, noradrenaline treated (p < 0.001 v control), and isoprenaline treated (p < 0.001 v control) hearts respectively. β Blockade with propranolol during noradrenaline treatment blocked the protective effects. No concentration of phenylephrine used was able to enhance postischaemic heart rate × developed pressure significantly, or result in improved (lower) postischaemic left ventricular end diastolic pressure. During treatment with noradrenaline and phenylephrine (10-5 M), lactate release was 13.0(1.0) and 11.0(0.9) μmol·5 min-1, respectively (p = NS); these values were significantly (p< 0.001) greater than baseline value of 3.7(0.5) μmol·5 min-1. Immediately before the 30 min ischaemic period, control and phenylephrine treated groups had glycogen levels of 132(14) and 128(5) nmol·mg-1 protein, respectively (p = NS), whereas the glycogen content of the noradrenaline treated group was only 96(5) nmol·mg-1 protein (p < 0.05 v control and phenylephrine treated). Conclusions: Transient β adrenergic but not α1 adrenergic stimulation can precondition the isolated perfused rat heart. The mechanism of protection may, at least in part, be due to transient demand ischaemia. Partial depletion of glycogen following treatment may play a role in the observed protective effects.Cardiovascular Research 1994;28:1726-1734.

Original languageEnglish (US)
Pages (from-to)1726-1734
Number of pages9
JournalCardiovascular Research
Volume28
Issue number11
DOIs
StatePublished - Jan 1 1994

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Keywords

  • Adrenergic receptors
  • Isolated rat heart
  • Myocardial ischaemia
  • Noradrenaline
  • Phenylephrine
  • Preconditioning

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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