Docosahexaenoic acid-mediated protein aggregates may reduce proteasome activity and delay myotube degradation during muscle atrophy in vitro

Proteasomes are the primary degradation machinery for oxidatively damaged proteins that compose a class of misfolded protein substrates. Cellular levels of reactive oxygen species increase with age and this cellular propensity is particularly harmful when combined with the age-associated development of various human disorders including cancer, neurodegenerative disease and muscle atrophy. Proteasome activity is reportedly downregulated in these disease conditions. Herein, we report that docosahexaenoic acid (DHA), a major dietary omega-3 polyunsaturated fatty acid, mediates intermolecular protein cross-linkages through oxidation, and the resulting protein aggregates potently reduce proteasomal activity both in vitro and in cultured cells. Cellular models overexpressing aggregation-prone proteins such as tau showed significantly elevated levels of tau aggregates and total ubiquitin conjugates in the presence of DHA, thereby reflecting suppressed proteasome activity. Strong synergetic cytotoxicity was observed when the cells overexpressing tau were simultaneously treated with DHA. Antioxidant N-acetyl cysteine significantly desensitized the cells to DHA-induced oxidative stress. DHA significantly delayed the proteasomal degradation of muscle proteins in a cellular atrophy model. Thus, the results of our study identified DHA as a potent inducer of cellular protein aggregates that inhibit proteasome activity and potentially delay systemic muscle protein degradation in certain pathologic conditions.

Effect of Reperfusion Experimental Myocardial Infarction in Rats

The purpose of this study was to determine the effect of reperfusion about infarct size and infarct expansion by different duration of ischemic time. Temporary coronary ligation was performed in rats for 30min, 60min, 90min and 120min, followed by reflow. Rats with permanent ligation were used for comparison. After 7 days, transverse histologic heart sections were prepared for structual analysis. The results were as follows ; 1) Reperfusion after 30 min ischemic time 1.Infarct size of reperfusion (method 1 ; 16.5+/-8.3%, method 2 ; 20.9+/-8.0%) was smaller than that of permanent ligation (method 1 ; 29.8+/-8.9%, method 2 ; 33.5+/-12.1%)(p<0.01, p<0.05). 2. Expansion index of reperfusion (46.9+/-19.6) was smaller than that of permanent ligation (88.0+/-34.9)(p<0.01). 3. The infarct thickness of reperfusion (1.59+/-0.40mm) was larger than that of permanent ligation (1.10+/-0.21mm)(p<0.01). 4.The viable left ventricular tissue area of reperfusion (28.8+/-2.90mm2) was larger than that of permanent ligation (24.2+/-3.10mm2)(p<0.01). 2) Reperfusion after 60 min ischemic time 1. There was no difference in infarct size between reperfusion and permanent ligation. 2. Expansion ratio (27.2+/-5.9%) and expansion index (51.8+/-24.6) of reperfusion were smaller than those of peremanent ligation (35.7+/-7.4%, 88.0+/-34.9)(p<0.05, P<0.05). 3. The infarct thickness of reperfusion (1.48+/-0.32mm) was larger than that of permanent ligation (1.10+/-0.21mm)(p<0.01). 3) Reperfusion after 90~120 min ischemic time reduced neither infarct size nor infarct expansion. The results of this study in the rat preparation suggest a beneficial effect of reperfusion even in late on infarct expansion independent of myocardial salvage.

A Case of Normalized Hypertrophic Cardiomyopathy after Removal of Pheochromocytoma

The characterisitic finding of hypertrophic cardiomyopathy is left ventricular hypertrophy without dilated chamber. Echocardiographic studies of patients with pheochromocytoma in the past have revealed both dilated and hypertrophic cardiomyopathies, as well as obstruction of the left ventricular outflow tract. We report this case because we experienced a pheochromocytoma patient who had reversible hypertrophic cardiomyopathy which might be related with circulating catecholamine level.

Systolic Time Interval in Cardiac Pacing: Comparison of Atrioventricular, Ventriculoatrial and Ventricular Pacing

Permanent electrostimulation is the therapy of choice for syncope due to bradycardic rhythm disturbance. In maintaining optimal hemodynamic function, the role of atrial systole has been well recorgnized and the time relationship between atrial and ventricular systole have great relation with cardiac output. Assessment of optimal mode of cardiac pacing by nonivasive method is very important for the best hemodynamic effect. To evaluate the usefulness of systolic time interval for optimal pacing mode, we calculated systolic time interval by using ventricular pacing spike on electrocardiogram to aortic opening time/left ventricular ejection time by aortic pressure curve (invasive PEP/LVET) in various modes of cardiac pacing and measured cardiac output by thermodilution method simultaneously in 9 mongrel dogs. Basal pacing cycle length were 300 msec, and the atrioventricular (AV) and ventriculoatrial (VA) interval during AB & VA sequential pacing were set at 30 msec, 60 msec and 90 msec. The result were as follows: 1) The cardiac output at AV interval of 90 msec (1.65+/-0.23 L/min) is significantly higher than 30 msec (1.38+/-0.19 L/min) in AV sequential pacing. 2) The cardiac output in ventricular pacing is higher than VA sequential pacing, but no significant changes noted among VA interval 90 msec, 60 msec and 30 msec. 3) The invasive PEP/LVET at VA interval of 90 msec (0.85+/-0.17) is significantly lower than 60 msec (0.97+/-0.16) and 30 msec (1.01+/-0.16) in AV sequential pacing. 4) The invasive PEP/LVET among VA sequential pacing with 90 msec, 60 msec, 30 msec interval and ventricular pacing did not show any significant difference. 5) When AV interval changes from 90 msec to 30 msec during AV sequential pacing, cardiac output decreased and invasive PEP/LVET increased. 6) In VA sequential pacing, there were no changes of cardiac output and invasive PEP/LVET when VA interval changes from 90 msec to 30 msec. In conclusion, systolic time interval can be used for estimation of hemodynamic changes during AV sequential pacing considering our results and other authors' results of high correlation between invasive & noninvasive PEP/LVET.

Prediction of Pulmonary Arterial Pressure by Pulsed Doppler Echocardiography

Noninvasive prediction of pulmonary arterial pressure is of paramount importance in heart disease. To estimate pulmonary arterial pressure, several echocardiographic techniques, including abnormal pulmonary valve motion, prolongation of RV preejection period/RV ejection time ratio and contrast echocardiography have been proposed. Recently Doppler echocardiography has been known to detect intracardiac blood quantitatively. For assessment of the benefit of several indices by Pulsed Doppler echocardiography for mean pulmonary arterial pressure, 22 patients(mean pulmonary pressure> or =20mmHg; 11, <20mmHg; 11) were compared with the mean pulmonary arterial pressure by cardiac catheterization. In comparison of mean pulmonary arterial pressure(MPAP); 1) Right preejection period / RV ejection time RPEP/RVET;r=0.278 2) Right preejection period / Acceleration time RPEP/AT : r=0.654 3) Acceleration time(AT) AT=-1.55(MPAP)+154.37(r=-0.763) AT=-92.99(log MPAP)+239.41(r=-0.752) AT is less than 105 msec in 9 or 11 pulmonary hypertension and one of 11 normal individual. 4) Acceleration time/ RV ejection time AT/RVET=-136.36(MPAP)+83.31(r=-0.817) AT/RVET=-0.29(log MPAP)+0.81(r=-0.803) 5) (Right preejection period+Decceleration time) / AT (RPEP+DT)/AT=9.6(MPAP)-0.16(r=0.806) (RPEP+DT)/AT=3.86(log MPAP)-2.46(r=0.789) In conclusion AT/RVET, (RPEP+DT)/AT and Acceleration time of 105 msec are valuable indices to estimate mean pulmonary arterial pressure by Pulsed Doppler echocardiogram.

A Case of Complete A-V Block due to Intra-His Block

His bundle recordings enable us to diagnose conduction disturbances not discernable in the standard leads, and to localize conduction block in the subdivisions of the conduction system. Cases of intra-His bundle block were first reported in 1970 by Narula and Samet. Thereafter many additional reports and studies were made. We report a case of 3degrees A-V block due to conduction block at the His bundle level. A 71-year-old woman was admitted because of dizziness. Surface ECG showed 3degrees A-V block. His bundle electrogram revealed typical split His potential. A-H intervals were 80 msec and H'-V intervals 50~70 msec. And there found no relation between AH and H'A. Atrial pacing resulted only prolongation of A-H to 90 msec but dissociation between h and H' was consistent. We implanted a permanent endocardial pacemaker in her chest.

Clinical Application of Esophageal Electrocardiogram

The esophageal electrocardiogram is of increasing significance in the study and diagnosis of cardiac arrhythmia and of posterior myocardial disease. We used both bipolar and unipolar esophageal recording leads and standard electrocardiogram equipment, and compared the effectiveness of esophageal electrocardiogram with co nventional electrocardiogram. The effectiveness of esophageal electrocardiogram were as follows: 1) Differentiation of sinus, atrial, junctional, or ventricular rhythm. 2) Differentiation of origin of premature beats. 3) Differentiation of atrial flutter and fibrillation. 4) Detection of retrograde atrial conduction of extraventricular systole. 5) Detection of electrical alternance of QRS amplitude. 6) Diagnosis of posterior myocardial infarction. The results reported here indicate that the esophageal electrocardiogrm seems to be a valid method in the diagnosis of cardiac arrhythmias without invasiveness.

Echocardiographic Study of the Aortic Root and Valve in Dilated Cardiomyopathy

Echocardiographic study was performed in 31 cases with dilated cardiomyopathy and 31 normal persons. measurement values of the aortic valve and root echocardiogram were compared with those in normal. The resuts were followings. 1. There were 22 males and 9 females of 31 cases with dilated cardiomyopathy whose average ages were 53 years. 2. LAD 3.86+/-0.76cm, AoD/LAD ratio 0.74+/-0.21 in dilated cardiomyopathy were significantly changed with those in normal(p<0.01). 3. C-E slope 2.14+/-0.68 cm in dilated cardiomyopathy was significantly decreased with that in normal(p<0.01). 4. cAoD 3.24+/-0.50 cm, AoPWT 0.46+/-0.14 cm in dilated cardiomyopathy were significantly decreased with those in normal(p<0.01). 5. cAVD 1.56+/-0.29cm, cAvD/mAvD ratio 0.79+/-0.10 in dilated cardiomyopathy were significantly decreased with those in normal(p<0.01). 6. AvOT or ET 0.24+/-0.03 sec. in dilated cardiomyopathy was significantly shortened with that in normal(p<0.01).