David J. Hearse

Learn More
We have investigated the possibility that xanthine oxidase-linked free radical production has a role in the genesis of arrhythmias during ischemia and reperfusion. In this study, rats were treated with allopurinol (20 mg/kg, orally, 24 hours before study, plus 20 mg/kg, iv, 15 minutes prior to study). Using an anesthetized open-chest preparation with either(More)
Using the isolated perfused rat heart with transient (10-minute) regional ischemia induced by coronary artery ligation, we have shown that PBN (N-tert-butyl-alpha-phenylnitrone), an organic spin trap agent designed specifically to form "stable" adducts with free radicals in electron spin resonance studies, can dramatically reduce the vulnerability of the(More)
The objective of this study was to determine whether reactive oxygen intermediates (e.g., singlet oxygen and the superoxide radical) can rapidly induce electrophysiological disturbances leading to the genesis of arrhythmias, even in the absence of ischemia and reperfusion. Rat hearts (n = 6 per group) were perfused aerobically at 37 degrees C for 10 minutes(More)
OBJECTIVE To characterise the effects of exogenous H(2)O(2) on sarcolemmal Na(+)/H(+) exchanger (NHE) activity and determine the roles of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase C (PKC) in observed effects. METHODS Sarcolemmal H(+) efflux rate (J(H)) was determined by(More)
OBJECTIVE A brief period of ischaemia (5 min) and reperfusion (5 min), prior to a longer period of ischaemia and reperfusion, has been shown to reduce the extent of injury (necrosis, arrhythmias, or postischaemic contractile malfunction) caused by a subsequent longer period of ischaemia and reperfusion. Adenosine has been identified as a factor in the(More)
During cardiac surgery or cardiac transplantation, the heart is subjected to varying periods of global ischemia. The heart must be protected during this ischemic period to avoid additional injury, and techniques have been developed that delay ischemic injury and minimize reperfusion injury. Almost universally, this involves using a hyperkalemic cardioplegic(More)
BACKGROUND Although there are many factors that might contribute to tissue injury during ischemia and reperfusion, the loss of adenine nucleotides has long been considered to be of importance. This has led to the study of interventions designed to limit the loss of nucleotides or to enhance the rate of nucleotide resynthesis during reperfusion.(More)
  • Y Kusama, M Bernier, D J Hearse
  • 1990
A burst of free oxygen radical production has been demonstrated during the early moments of reperfusion, coincident with the onset of reperfusion arrhythmias, which can be attenuated by antioxidants. We have investigated whether a sudden burst of oxidant stress, superimposed on that occurring during reperfusion, can exacerbate reperfusion arrhythmias. Rat(More)
OBJECTIVES Arrhythmias, including ventricular fibrillation (VF), occur in two phases after coronary obstruction, the first during the reversible stage of acute myocardial ischaemia (phase 1) and the second during evolution of the infarct (phase 2). We tested the hypothesis that phase 2 arrhythmias are mediated by actions of neutrophils accumulating within(More)
BACKGROUND We have shown that acadesine (AICAr: 5-amino-4-imidazole carboxamide riboside) improves the early recovery of function of the ischemic and reperfused rat heart. In the present studies we used the transplanted rat heart, with reperfusion for up to 24 hours, to assess whether the beneficial effect of acadesine is a transient or a sustained(More)