title: Myocardial ischemia tolerance in the newborn rat involving opioid receptors and mitochondrial K+ channels.
abstract: Neonatal rat hearts are more tolerant to ischemia compared to adult rat hearts. We hypothesized that opioid receptors and mitochondrial potassium channels are involved in the elevated ischemia tolerance of neonatal rats. Newborn rats were treated by an intraperitoneal injection with sodium chloride (placebo, Pla; n = 7), naloxone (Nal; n = 8), or K+ (ATP) channel blocker 5-hydroxydecanoate (HD; n = 8), or were left untreated (sham; n = 8). Thirty minutes after injection, the rats were sacrificed and hearts were arrested cardioplegically and fixed with aldehyde fixative 90 min after global ischemia at room temperature. For control, newborn rat hearts were fixed immediately after sacrifice. Ventricular tissue blocks were prepared for electron microscopy. Mitochondrial (volume-weighted mean volume of mitochondria) and cardiomyocyte volume (cellular edema index, CEI) were estimated to quantify the ischemic injury. Compared to control myocardium, CEI was increased by 244% +/- 39% in sham, 173% +/- 28% in Nal, 142% +/- 25% in HD, and 101% +/- 24% in Pla (P < 0.05 between groups). Volume-weighted mean volume of mitochondria was increased by 514% +/- 235% in sham, 341% +/- 110% in Nal, 458% +/- 149% in HD, and 175% +/- 70% in Pla. Differences between Pla and other groups were significant (P < 0.01 for all). No significant difference was observed between the other groups. Thus, ischemic injury was smallest with placebo, indicating a mechanism similar to preconditioning induced by the intraperitoneal injection. This response was attenuated by blockade of opioid receptors and mitochondrial potassium channels, suggesting their involvement in the elevated ischemia tolerance of newborn rat hearts.
authors.affiliation: Division of Electron Microscopy, Department of Anatomy, University of Göttingen, Göttingen, Germany. cmuehlf@gwdg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Mühlfeld
authors.forename: Michele
authors.initials: M
authors.lastname: Urru
authors.forename: Randi
authors.initials: R
authors.lastname: Rümelin
authors.forename: Masoud
authors.initials: M
authors.lastname: Mirzaie
authors.forename: Friedrich
authors.initials: F
authors.lastname: Schöndube
authors.forename: Joachim
authors.initials: J
authors.lastname: Richter
authors.forename: Hilmar
authors.initials: H
authors.lastname: Dörge
mesh_terms: D000818:Animals; D003652:Decanoic Acids; D005947:Glucose; D006880:Hydroxy Acids; D008353:Mannitol; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000473:pathology / Q000648:ultrastructure; D009270:Naloxone; D015221:Potassium Channels / Q000502:physiology*; D011189:Potassium Chloride; D011343:Procaine; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology*; D012965:Sodium Chloride
chemical_list: C039984:Bretschneider cardioplegic solution; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; D011957:Receptors, Opioid; C117780:mitochondrial K(ATP) channel; D009270:Naloxone; D008353:Mannitol; D012965:Sodium Chloride; D011343:Procaine; C052853:5-hydroxydecanoic acid; D011189:Potassium Chloride; D005947:Glucose