69 research outputs found
A Sphingosine Kinase Form 2 Knockout Sensitizes Mouse Myocardium to Ischemia/Reoxygenation Injury and Diminishes Responsiveness to Ischemic Preconditioning
Sphingosine kinase (SphK) exhibits two isoforms, SphK1 and SphK2. Both forms catalyze the synthesis of sphingosine 1-phosphate (S1P), a sphingolipid involved in ischemic
preconditioning (IPC). Since the ratio of SphK1 : SphK2 changes dramatically with aging, it is important to assess the role of SphK2 in IR injury and IPC. Langendorff mouse hearts were subjected to IR (30 min
equilibration, 50 min global ischemia, and 40 min reperfusion). IPC consisted of 2 min of ischemia and 2 min of reperfusion for two cycles. At baseline, there were no differences in left ventricular developed pressure (LVDP), ± dP/dtmax, and heart rate between SphK2 null (KO)
and wild-type (WT) hearts. In KO hearts, SphK2 activity was undetectable, and SphK1 activity was unchanged compared to WT. Total SphK activity was reduced by 53%. SphK2 KO hearts subjected to IR exhibited significantly more cardiac damage (37 ± 1%
infarct size) compared with WT (28 ± 1% infarct size); postischemic recovery of LVDP
was lower in KO hearts. IPC exerted cardioprotection in WT hearts. The protective
effect of IPC against IR was diminished in KO hearts which had much higher infarction sizes (35 ± 2%) compared to the IPC/IR group in control hearts (12 ± 1%). Western analysis revealed that KO
hearts had substantial levels of phosphorylated p38 which could predispose the
heart to IR injury. Thus, deletion of the SphK2 gene sensitizes the myocardium to IR injury and
diminishes the protective effect of IPC
Accelerating pairwise statistical significance estimation for local alignment by harvesting GPU's power
Doxorubicin Cardiomyopathy
Established doxorubicin cardiomyopathy is a lethal disease. When congestive heart failure develops, mortality is approximately 50%. Extensive research has been done to understand the mechanism and pathophysiology of doxorubicin cardiomyopathy, and considerable knowledge and experience has been gained. Unfortunately, no effective treatment for established doxorubicin cardiomyopathy is presently available. Extensive research has been done and is being done to discover preventive treatments. However an effective and clinically applicable preventive treatment is yet to be discovered
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TECHNETIUM-99m FERRIC HYDROXIDE MACROAGGREGATES FOR PULMONARY SCINTIPHOTOGRAPHY
Effects of acute ischemia in the dog on myocardial blood flow, beta receptors and adenylate cyclase activity with and without chronic beta blockade
We ligated the left anterior descending coronary artery for 1 or 2 h in 31 purebred beagles. We did not detect any changes in,8-adrenergic receptor density or affinity when normal and isch-emic zones were compared, either in the subendocardium or in the subepicardium. In the ischemic zones, there was a signifi-cant decline in all measures of adenylate cyclase activity, in-cluding activity mediated by the,-adrenergic receptor. By contrast, after chronic fl-adrenergic blockade (1.5 mg/kg pro-pranolol i.v. twice daily for 7 d), there was an increase in ade-nylate cyclase activity stimulated by (-)-isoproterenol relative to adenylate cyclase activity stimulated by guanyl-5'imidodi-phosphate (GppNHp) in both normal and ischemic tissue, suggesting that one effect of chronic,B blockade may be to enchance coupling between the stimulatory guanine nucleotide regulatory protein (Gs) and the fl-adrenergic receptor, despite a reduction in the number or function of Gs units. Chronic,B blockade also led to up regulation of,-adrenergic receptor density in subepicardial regions. After 20 min of reperfusion following 2 h of ischemia, adenylate cyclase activity tended to return to control levels, particularly in the subepicardium, where (-)-isoproterenol-stimulated adenylate cyclase activity was not different from normal myocardium. We conclude that chronic f-adrenergic blockade may have beneficial effects during prolonged episodes of myocardial ischemia by preserv-ing signal transduction mediated by the,-adrenergic receptor
Recommended from our members
TECHNETIUM-99m FERRIC HYDROXIDE MACROAGGREGATES FOR PULMONARY SCINTIPHOTOGRAPHY
Effects of acute ischemia in the dog on myocardial blood flow, beta receptors, and adenylate cyclase activity with and without chronic beta blockade.
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