scholarly journals High inborn aerobic capacity does not protect the heart following myocardial infarction

2013 ◽  
Vol 115 (12) ◽  
pp. 1788-1795 ◽  
Author(s):  
M. A. Høydal ◽  
G. Kaurstad ◽  
N. P. Rolim ◽  
A. B. Johnsen ◽  
M. Alves ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sarcoplasmic Reticulum ◽  
Protective Effect ◽  
Aerobic Capacity ◽  
Contractile Function ◽  
High Capacity ◽  
Dependent Protein Kinase ◽  
Global Cardiac Function ◽  
Dependent Protein ◽  
Cardio Protection

Maximal oxygen uptake (V̇o2max) is a strong prognostic marker for morbidity and mortality, but the cardio-protective effect of high inborn V̇o2max remains unresolved. We aimed to investigate whether rats with high inborn V̇o2max yield cardio-protection after myocardial infarction (MI) compared with rats with low inborn V̇o2max. Rats breed for high capacity of running (HCR) or low capacity of running (LCR) were randomized into HCR-SH (sham), HCR-MI, LCR-SH, and LCR-MI. V̇o2max was lower in HCR-MI and LCR-MI compared with respective sham ( P < 0.01), supported by a loss in global cardiac function, assessed by echocardiography. Fura 2-AM loaded cardiomyocyte experiments revealed that HCR-MI and LCR-MI decreased cardiomyocyte shortening (39%, and 34% reduction, respectively, both P < 0.01), lowered Ca2+ transient amplitude (37%, P < 0.01, and 20% reduction, respectively), and reduced sarcoplasmic reticulum (SR) Ca2+ content (both; 20%, P < 0.01) compared with respective sham. Diastolic Ca2+ cycling was impaired in HCR-MI and LCR-MI evidenced by prolonged time to 50% Ca2+ decay that was partly explained by the 47% ( P < 0.01) and 44% ( P < 0.05) decrease in SR Ca2+-ATPase Ca2+ removal, respectively. SR Ca2+ leak increased by 177% in HCR-MI ( P < 0.01) and 67% in LCR-MI ( P < 0.01), which was abolished by inhibition of Ca2+/calmodulin-dependent protein kinase II. This study demonstrates that the effect of MI in HCR rats was similar or even more pronounced on cardiac- and cardiomyocyte contractile function, as well as on Ca2+ handling properties compared with observations in LCR. Thus our data do not support a cardio-protective effect of higher inborn aerobic capacity.

scholarly journals Anti-phospholamban and protein kinase A alter the Ca2+ sensitivity and maximum velocity of Ca2+ uptake by the cardiac sarcoplasmic reticulum

1998 ◽  
Vol 331 (1) ◽  
pp. 245-249 ◽  
Author(s):  
Margaret E. KARGACIN ◽  
Zenobia ALI ◽  
Gary J. KARGACIN
Keyword(s):  
Protein Kinase ◽  
Sarcoplasmic Reticulum ◽  
Maximum Velocity ◽  
Functional Effect ◽  
Dependent Protein Kinase ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Dependent Protein ◽  
Uptake Velocity ◽  
Phospholamban Phosphorylation ◽  
Kinase A

The activity of the SERCA2a Ca2+ pump in the sarcoplasmic reticulum (SR) of cardiac muscle is inhibited by phospholamban. When phospholamban is phosphorylated by cyclic-AMP-dependent protein kinase (PKA) this inhibition is relieved. It is generally agreed that this results in an increase in the Ca2+ sensitivity of the SR Ca2+ pump; however, some investigators have also reported an increase in the maximum velocity of the pump. We have used a sensitive fluorescence method to measure net Ca2+ uptake by native cardiac SR vesicles and compared the effects of a constitutively active subunit of PKA (cPKA) with those of a monoclonal antibody (A1) that binds to phospholamban and is thought to mimic the effect of phosphorylation. Both the Ca2+ sensitivity and the maximum velocity of uptake were increased by cPKA and by A1. The effects of cPKA and A1 on uptake velocity were only slightly additive. No changes in uptake were detected with denatured cPKA or denatured A1. These results indicate that the functional effect of phospholamban phosphorylation is to increase both the Ca2+ sensitivity and the maximum velocity of net Ca2+ uptake into the SR.

Cardio-Protection by Ginkgo biloba Extract 50 in Rats with Acute Myocardial Infarction is Related to Na+–Ca2+ Exchanger

2013 ◽  
Vol 41 (04) ◽  
pp. 789-800 ◽  
Author(s):  
Ai-Hua Liu ◽  
Yi-Min Bao ◽  
Xing-Yu Wang ◽  
Zhi-Xiong Zhang
Keyword(s):  
Myocardial Infarction ◽  
At Risk ◽  
Ginkgo Biloba ◽  
Myocardial Function ◽  
Contractile Function ◽  
Salvia Miltiorrhiza ◽  
Ginkgo Biloba Extract ◽  
Area At Risk ◽  
Ischemia Group ◽  
Cardio Protection

Ginkgo biloba has been used for medical purposes for centuries in traditional Chinese medicine. Ginkgo biloba extract 50 (GBE50) is a new standardized GBE product that matches the standardized German product as EGb761. This paper is aimed at studying the cardio-protection effects of GBE50 Salvia miltiorrhiza on myocardial function, area at risk, myocardial ultra-structure, and expression of calcium handling proteins in rat ischemic myocardium. Myocardium ischemia was induced by the left anterior descending (LAD) coronary artery occlusion and myocardial function was recorded by a transducer advanced into the left ventricle on a computer system. In vitro myocardial infarction was measured by 2,3,5-triphenyltetrazolium chloride (TTC) and Evans blue staining of heart sections. Morphological change was evaluated by electric microscopy and Western blotting was used for protein expression. Hemodynamic experiments in vivo showed that postischemic cardiac contractile function was reduced in ischemic rats. Salvia miltiorrhiza (7.5 g/kg/d×7) and Ginkgo biloba extract 50 (GBE50) (100 mg/kg/d×7) improved post-schemic cardiac diastolic dysfunction while not affecting the systolic function. In hearts of GBE50 group and Salvia miltiorrhiza (SM) group, the area at risk was significantly reduced and myocardial structure was better-preserved. Moreover, Na +– Ca 2+ exchanger (NCX) expression increase and sarcoplasmic reticulum Ca 2+– ATPase 2 (SERCA2), LTCC, and ryanodine receptor 2 (RyR2) expression decreases were smaller than those in ischemia group. There was a significant difference between the GBE50 and ischemia group in NCX expression. GBE50 could improve recovery in contractile function and prevent myocardium from ischemia damage, which may be caused by attenuating the abnormal expression of NCX.

Differential effects of phospholamban and Ca2+/calmodulin-dependent kinase II on [Ca2+]i transients in cardiac myocytes at physiological stimulation frequencies

2008 ◽  
Vol 294 (5) ◽  
pp. H2352-H2362 ◽  
Author(s):  
Andreas A. Werdich ◽  
Eduardo A. Lima ◽  
Igor Dzhura ◽  
Madhu V. Singh ◽  
Jingdong Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Wild Type ◽  
Dependent Protein Kinase ◽  
Frequency Dependent ◽  
Physiological Range ◽  
Dependent Protein ◽  
Isolated Cardiac Myocytes

In cardiac myocytes, the activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) is hypothesized to regulate Ca2+ release from and Ca2+ uptake into the sarcoplasmic reticulum via the phosphorylation of the ryanodine receptor 2 and phospholamban (PLN), respectively. We tested the role of CaMKII and PLN on the frequency adaptation of cytosolic Ca2+ concentration ([Ca2+]i) transients in nearly 500 isolated cardiac myocytes from transgenic mice chronically expressing a specific CaMKII inhibitor, interbred into wild-type or PLN null backgrounds under physiologically relevant pacing conditions (frequencies from 0.2 to 10 Hz and at 37°C). When compared with that of mice lacking PLN only, the combined chronic CaMKII inhibition and PLN ablation decreased the maximum Ca2+ release rate by more than 50% at 10 Hz. Although PLN ablation increased the rate of Ca2+ uptake at all frequencies, its combination with CaMKII inhibition did not prevent a frequency-dependent reduction of the amplitude and the duration of the [Ca2+]i transient. High stimulation frequencies in the physiological range diminished the effects of PLN ablation on the decay time constant and on the maximum decay rate of the [Ca2+]i transient, indicating that the PLN-mediated feedback on [Ca2+]i removal is limited by high stimulation frequencies. Taken together, our results suggest that in isolated mouse ventricular cardiac myocytes, the combined chronic CaMKII inhibition and PLN ablation slowed Ca2+ release at physiological frequencies: the frequency-dependent decay of the amplitude and shortening of the [Ca2+]i transient occurs independent of chronic CaMKII inhibition and PLN ablation, and the PLN-mediated regulation of Ca2+ uptake is diminished at higher stimulation frequencies within the physiological range.

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