Manganese (Mn) dipyridoxyl diphosphate (MnDPDP) is the active component of a contrast medium for liver MRI. By being metabolized, MnDPDP releases Mn 2 , which is taken up and retained in hepatocytes. The study examined whether MnDPDP elevates Mn content and enhances proton relaxivity in normal myocardium, but not in ischemic myocardium with reduced coronary flow and impaired metabolism. Isolated guinea pig hearts were perfused at normal flow or low flow, inducing global subtotal ischemia. Ventricular ATP and Mn contents, T 1 and T 2 were measured. At normal flow tissue Mn content increased from the control level of 4.1 to 70.4 mmol/100g dry wt with MnDPDP (3000 mM), while low-flow perfusion with MnDPDP (3000 mM) resulted in a Mn content of 16.6 mmol/ 100 g dry wt. Prolonged ischemia (35 and 90 min) reduced tissue Mn down to the control level. T 1 shortening closely paralleled myocardial Mn elevations during both normal and low-flow perfusion. The use of a Mn 2 -releasing contrast agent like MnDPDP may be a promising principle in MRI assessments of myocardial function and viability in coronary heart disease by revealing a differential pattern of changes in T 1 relative to coronary flow, cell Mn uptake and retention, ion channel function and metabolism.
Background. Soluble guanylate cyclase (sGC) plays multiple, conflicting roles during sepsis (Am.J. Physiol.,2009;297:H654-663). Here we studied the impact of sGC deficiency on cardiac calcium (Ca 2þ ) handling in sepsis-induced cardiomyopathy (SIC). Methods and Results. Cardiomyocyes were isolated from mice deficient in the a 1 subunit of sGC (sGCa 1 -/-) and wild-type (WT), at baseline and 12h after administration of lipopolysacharide (LPS, 25 mg/g, ip). In sGCa 1 -/cells (vs. WT), LPS induced a more marked decrease in externally paced Ca 2þ transients (DCa i , fura-2AM, Table ), sarcoplasmic reticulum Ca 2þ load (Ca SR , using caffeine applications), fractional release (FR, DCa i / Ca SR ) and trans-sarcolemmal Ca 2þ entry (Ca E , from the first DCa i after caffeine removal). Ca 2þ transient decay (t Ca ) was slower in sGCa 1 -/vs. WT after LPS, while Ca 2þ decay during caffeine (t Caff , measuring Na þ /Ca 2þ exchange) and L-type Ca 2þ currents (I Ca,L ) were similar (Table ; for all, n> 25 cells from >4 mice). Conclusions. LPS induces a decrease in I Ca ,L , Ca E , FR, Ca SR and DCa i that does not require sGCa 1 . Moreover, sGC partially protects against Ca 2þ handling alteration in SIC, through yet unidentified mechanisms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.