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BACKGROUND: Xenon induces early myocardial preconditioning of the rat heart in vivo, but whether xenon induces late cardioprotection is not known. Cyclooxygenase-2 (COX-2) has been shown to be an important mediator in the signal transduction of myocardial ischemic late preconditioning (i-LPC). We investigated whether xenon induces late preconditioning (Xe-LPC) and whether COX-2 activity and/or expression are involved in mediating this effect.

METHODS: Anesthetized male Wistar rats were instrumented with a coronary artery occluder. After 7 d of recovery, animals were randomized to 1 of 5 groups each containing 8 animals. The i-LPC group underwent 5 min of coronary occlusion to induce i-LPC. Xe-LPC was achieved by administration of xenon (70 volume%) for 15 min. Additional rats were pretreated with the COX-2 inhibitor NS-398 (5 mg kg^–1 body weight i.p.) with and without Xe-LPC. A group of sham operated animals not undergoing i-LPC or Xe-LPC served as controls (Con). After 24 h, all animals were anesthetized and underwent 25 min of myocardial ischemia induced by tightening of the coronary artery occluder followed by 2 h of reperfusion. Myocardial infarct size was assessed by triphenyltetrazolium chloride staining. In additional experiments, hearts were excised at different time points after preconditioning to investigate COX-2 mRNA and protein expression by polymerase chain reaction and infrared Western blot, respectively.

RESULTS: Both i-LPC and Xe-LPC reduced myocardial infarct size (% of the area at risk) compared with Con (i-LPC: 29 ± 7%; Xe-LPC 31 ± 8%, both P < 0.05 vs Con 64 ± 6%). NS-398 abolished the cardioprotective effect of Xe-LPC (61 ± 6%, P < 0.05 vs Xe-LPC). COX-2 mRNA and protein expression was only increased in the i-LPC group, but not in the Xe-LPC group.

CONCLUSION: Xenon induces late myocardial preconditioning that is abolished by functional blockade of COX-2 activity. In contrast to i-LPC, Xe-LPC did not lead to an increased expression of COX-2 mRNA and protein. These data suggest differences in COX-2 regulation in i-LPC and Xe-LPC.

The Age of Entanglement When Quantum Physics Was Reborn
Written by Louisa Gilder

A brilliantly original and richly illuminating exploration of entanglement, the seemingly telepathic communication between two separated particles—one of the fundamental concepts of quantum physics.

In 1935, in what would become the most cited of all of his papers, Albert Einstein showed that quantum mechanics predicted such a correlation, which he dubbed “spooky action at a distance.” In that same year, Erwin Schrödinger christened this spooky correlation “entanglement.” Yet its existence wasn’t firmly established until 1964, in a groundbreaking paper by the Irish physicist John Bell. What happened during those years and what has happened since to refine the understanding of this phenomenon is the fascinating story told here.

We move from a coffee shop in Zurich, where Einstein and Max von Laue discuss the madness of quantum theory, to a bar in Brazil, as David Bohm and Richard Feynman chat over cervejas. We travel to the campuses of American universities—from J. Robert Oppenheimer’s Berkeley to the Princeton of Einstein and Bohm to Bell’s Stanford sabbatical—and we visit centers of European physics: Copenhagen, home to Bohr’s famous institute, and Munich, where Werner Heisenberg and Wolfgang Pauli picnic on cheese and heady discussions of electron orbits.

Drawing on the papers, letters, and memoirs of the twentieth century’s greatest physicists, Louisa Gilder both humanizes and dramatizes the story by employing their own words in imagined face-to-face dialogues. Here are Bohr and Einstein clashing, and Heisenberg and Pauli deciding which mysteries to pursue. We see Schrödinger and Louis de Broglie pave the way for Bell, whose work is here given a long-overdue revisiting. And with his characteristic matter-of-fact eloquence, Richard Feynman challenges his contemporaries to make something of this entanglement.