PMID- 18006871 OWN - NLM STAT- MEDLINE DCOM- 20080228 LR - 20211020 IS - 8750-7587 (Print) IS - 0161-7567 (Linking) VI - 104 IP - 1 DP - 2008 Jan TI - Left ventricular dysfunction and associated cellular injury in rats exposed to chronic intermittent hypoxia. PG - 218-23 AB - Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality. We have reported that chronic intermittent hypoxia (CIH), a direct consequence during OSA, leads to left ventricular (LV) remodeling and dysfunction in rats. The present study is to determine LV myocardial cellular injury that is possibly associated with LV global dysfunction. Fifty-six rats were exposed either to CIH (nadir O(2) 4-5%) or sham (handled normoxic controls, HC), 8 h/day for 6 wk. At the end of the exposure, we studied LV global function by cardiac catheterization, and LV myocardial cellular injury by in vitro analyses. Compared with HC, CIH animals demonstrated elevations in mean arterial pressure and LV end-diastolic pressure, but reductions in cardiac output (CIH 141.3 +/- 33.1 vs. HC 184.4 +/- 21.2 ml x min(-1) x kg(-1), P < 0.01), maximal rate of LV pressure rise in systole (+dP/dt), and maximal rate of LV pressure fall in diastole (-dP/dt). CIH led to significant cell injury in the left myocardium, including elevated LV myocyte size, measured by cell surface area (CIH 3,564 +/- 354 vs. HC 2,628 +/- 242 microm(2), P < 0.05) and cell length (CIH 148 +/- 23 vs. HC 115 +/- 16 microm, P < 0.05), elevated terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-stained positive cell number (CIH 98 +/- 45 vs. HC 15 +/- 13, P < 0.01), elevated caspase-3 activity (906 +/- 249 vs. 2,275 +/- 1,169 pmol x min(-1) x mg(-1), P < 0.05), and elevated expression of several remodeling gene markers, including c-fos, atrial natriuretic peptide, beta-myosin heavy chain, and myosin light chain-2. However, there was no difference between groups in sarcomere contractility of isolated LV myocytes, or in LV collagen deposition on trichrome-stained slices. In conclusion, CIH-mediated LV global dysfunction is associated with myocyte hypertrophy and apoptosis at the cellular level. FAU - Chen, Ling AU - Chen L AD - Div. of Pulmonary and Critical Care Medicine, Univ. of Maryland, Baltimore, 685 West Baltimore St., MSTF 816, Baltimore, MD 21201, USA. Lchen@medicine.umaryland.edu FAU - Zhang, Jin AU - Zhang J FAU - Gan, Tracey X AU - Gan TX FAU - Chen-Izu, Ye AU - Chen-Izu Y FAU - Hasday, Jeffrey D AU - Hasday JD FAU - Karmazyn, Morris AU - Karmazyn M FAU - Balke, C William AU - Balke CW FAU - Scharf, Steven M AU - Scharf SM LA - eng GR - R03 AG031944/AG/NIA NIH HHS/United States GR - R03 AG031944-01A1/AG/NIA NIH HHS/United States GR - R03 AG031944-03/AG/NIA NIH HHS/United States GR - R01 HL-071865/HL/NHLBI NIH HHS/United States GR - R03 AG031944-02/AG/NIA NIH HHS/United States GR - R01 HL-68733/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20071115 PL - United States TA - J Appl Physiol (1985) JT - Journal of applied physiology (Bethesda, Md. : 1985) JID - 8502536 RN - 0 (MYH7 protein, rat) RN - 0 (Myosin Light Chains) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (RNA, Messenger) RN - 0 (myosin light chain 2) RN - 85637-73-6 (Atrial Natriuretic Factor) RN - 9007-34-5 (Collagen) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.6.1.- (Cardiac Myosins) RN - EC 3.6.4.1 (Myosin Heavy Chains) SB - IM MH - Animals MH - Apoptosis MH - Atrial Natriuretic Factor/genetics/metabolism MH - Blood Pressure MH - Body Weight MH - Cardiac Myosins/genetics/metabolism MH - Cardiac Output MH - Cardiomegaly/etiology/genetics/metabolism/pathology/*physiopathology MH - Caspase 3/metabolism MH - Cell Size MH - Chronic Disease MH - Collagen/metabolism MH - Disease Models, Animal MH - Hypertrophy MH - Hypoxia/*complications/genetics/metabolism/pathology/physiopathology MH - Male MH - Myocardial Contraction MH - Myocardium/enzymology/metabolism/*pathology MH - Myocytes, Cardiac/pathology MH - Myosin Heavy Chains/genetics/metabolism MH - Myosin Light Chains/genetics/metabolism MH - Proto-Oncogene Proteins c-fos/genetics/metabolism MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Research Design MH - Ventricular Dysfunction, Left/etiology/genetics/metabolism/pathology/*physiopathology MH - Ventricular Pressure MH - *Ventricular Remodeling/genetics EDAT- 2007/11/17 09:00 MHDA- 2008/02/29 09:00 CRDT- 2007/11/17 09:00 PHST- 2007/11/17 09:00 [pubmed] PHST- 2008/02/29 09:00 [medline] PHST- 2007/11/17 09:00 [entrez] AID - 00301.2007 [pii] AID - 10.1152/japplphysiol.00301.2007 [doi] PST - ppublish SO - J Appl Physiol (1985). 2008 Jan;104(1):218-23. doi: 10.1152/japplphysiol.00301.2007. Epub 2007 Nov 15.