M M Awan

Publications (3)17.41 Total impact

• Article: Opposing effects on infarction of delta and kappa opioid receptor activation in the isolated rat heart: implications for ischemic preconditioning.

  K A Aitchison, G F Baxter, M M Awan, R M Smith, D M Yellon, L H Opie
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  ABSTRACT: Delta-opioid receptors are known to participate in the protection found following ischemic preconditioning (IPC), but the role of kappa-receptors in IPC is currently controversial. Langendorff-perfused rat hearts received 35 min regional ischemia and 2 h reperfusion. PC (2 cycles 5 min global ischemia) substantially reduced infarct size. Pharmacological PC with the delta-agonist DADLE (10 nmol/L) had similar protective effects. However, higher dose DADLE (1 micromol/L) had a less beneficial effect, and in conjunction with the delta-antagonist naltrindole unexpectedly increased infarct size (61.5 +/- 2.0%, p<0.05 v 45.9 +/- 2.4% in controls) suggesting a non-delta effect. The universal kappa-opioid agonist bremazocine (30 nmol/L) increased infarct size (61.3 +/- 1.6%, p<0.05 v controls), an effect abrogated by the selective kappa1-antagonist nor-binaltorphimine (BNI). Since opiates are known to have anti-adrenergic effects, which hypothetically may help to mediate IPC, cyclic AMP levels were measured in DADLE and in bremazocine-treated hearts. Decreased levels of cyclic AMP at the start of the regional ischemic period were found in low dose DADLE hearts (0.485 +/- 0/020, n = 8, vs controls, 0.654 +/- 0.025 nmol/g wet weight, p<0.001), but not in high dose DADLE nor in bremazocine treated hearts. Thus, in the isolated rat heart kappa1-opioid receptor activation exacerbates infarct size through an as yet unknown mechanism, suggesting that there could be an "antipreconditioned state". In contrast, delta-activity mediates protection which may be associated with a reduction of tissue cyclic AMP levels.
  Archiv für Kreislaufforschung 02/2000; 95(1):1-10; discussion 11. · 7.35 Impact Factor
• Article: Normothermic transfer times up to 3 min will not precondition the isolated rat heart.

  M M Awan, C Taunyane, K A Aitchison, D M Yellon, L H Opie
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  ABSTRACT: Isolated, perfused heart preparations suffer an inevitable peri-operative delay (POD) before retrograde perfusion restores coronary flow. By varying this ischaemic period we investigated the threshold of POD-induced inadvertent preconditioning (PC) in the rat heart. Hearts subjected to POD at 37 degrees C increasing from 1, 2, 3, 5, 10 up to 15 min prior to 20 min retrograde perfusion were further subjected to 30 min global, normothermic ischaemia and 30 min reperfusion (index I/R). The functional recovery was 32 +/- 4.1% in hearts subject to 1 min POD. After 3 min POD functional recovery started to improve and peaked at 10 min POD (78 +/- 7.1%, P < 0.001). At 4 degrees C functional recovery started to improve after 5 min POD and peaked at 10 min POD. To demonstrate that the POD-mediated protection was true PC, two conventional models of PC were established. In both models, hearts were retrogradely perfused within 1 min POD prior to a standard PC protocol (one episode of 10 min ischaemia, or four episodes of 5 min ischaemia). In the conventional PC models protection against the index I/R was abolished using 100 microM 5-hydroxydecanoate (5-HD), the mitrochondrial KATP channel inhibitor. Likewise, 10 min POD-mediated recovery at 37 degrees C (70 +/- 3.2%) was reversed by 100 microM 5-HD perfusion (36 +/- 5.9%; NS v.s. 2 min POD). We conclude: (1) the threshold for PC is greater than 3 min at 37 degrees C and greater than 5 min at 4 degrees C: (2) blockade of the mitochondrial KATP channel abolishes protection in three models of PC in the rat heart, including prolonged POD.
  Journal of Molecular and Cellular Cardiology 04/1999; 31(3):503-11. · 5.17 Impact Factor
• Article: Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation.

  M M Awan, E D Saggerson
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  ABSTRACT: 1. Viable myocytes were obtained from rat hearts. Oxidation of [1-14C]palmitate by these cells could be decreased by the addition of glucose (5 mM) or lactate (2 mM). In the presence of glucose, insulin decreased and adrenaline increased palmitate oxidation. 2. The myocytes contained activities of ATP citrate-lyase, acetyl-CoA carboxylase and the condensing enzyme of the fatty acid elongation system. No fatty acid synthase activity was demonstrable in myocytes. 3. In rat hearts perfused with 5 mM glucose, malonyl-CoA content was acutely raised by insulin. In the presence of glucose+insulin, perfusion with palmitate or adrenaline decreased the malonyl-CoA content. 4. It is concluded that malonyl-CoA can be synthesized within cardiac myocytes and that the level of this metabolite can be acutely regulated. This is likely to have consequences for the regulation of carnitine palmitoyltransferase in the heart.
  Biochemical Journal 11/1993; 295 ( Pt 1):61-6. · 4.90 Impact Factor