Alexander S. Clanachan

Biography

Professor Education: BSc Hons Pharmacology, University of Glasgow, 1972 PhD Pharmacology/Anesthesia, University of Glasgow, 1976 Teaching: PMCOL415, PMCOL337, PMCOL300*, PMCOL515*.

Research Interest

Research Interests / Laboratory Techniques Myocardial reperfusion is a common clinical event and occurs during the management of acute coronary syndrome or acute myocardial infarction when coronary perfusion of the affected region is re-established using drug, non-surgical, or surgical interventions. While reperfusion usually results in excellent recovery of LV contractile function, clinical outcomes are less than optimal in patients with hearts stressed by previous ischemia or other risk factors (smoking, diabetes, obesity, advanced age), or where reperfusion is delayed. We investigate mechanisms of reperfusion injury and aim to identify novel drug targets to improve recovery and limit longer-term adverse outcomes of ischemic injury. Our unique experimental approach uses model systems to examine key mechanisms that 1) affect recovery of LV mechanical and metabolic function, 2) regulate Na+ and Ca2+ homeostasis, and 3) influence infarct size. Drug-effects on mechanical function (LV work, O2 consumption, cardiac efficiency), metabolic function (rates of energy substrate metabolism), intracellular Ca2+ overload, and infarct size are measured along with cell signaling events that regulate pathways of glycogen and glucose utilization (GSK-3β, PFK, AMPK, NOS, p38MAPK, and PKB). Current Projects: Cardioprotection by adenosine: We are investigating the molecular mechanisms underlying the regulation of glycogen and glucose metabolism by adenosine receptors in normal hearts and in hearts altered by acute ischemic stress or by impaired insulin signaling. We also examine how attenuation of acidosis arising from excessive rates of glycolysis limits intracellular Ca2+ overload and thereby improves LV function. Cardioprotection by late INa inhibition: An additional mechanism that leads to intracellular Ca2+ overload is delayed inactivation of the voltage-gated Na+ channel that generates a persistent inward current (termed late INa) that leads to Na+ accumulation and activation of reverse mode Na+-Ca2+ exchange. We are investigating 1) metabolic and other mechanisms that augment late INa and, 2) the cardioprotective effectiveness of inhibitors of late INa.