Is Doppler tissue velocity during early left ventricular filling preload independent?

BACKGROUND: Transmitral Doppler flow indices are used to evaluate diastolic function. Recently, velocities measured by Doppler tissue imaging have been used as an index of left ventricular relaxation. OBJECTIVE: To determine whether Doppler tissue velocities are influenced by alterations in preload. METHODS: Left ventricular preload was altered in 17 patients (all men, mean (SD) age, 49 (8) years) during echocardiographic measurements of left ventricular end diastolic volume, maximum left atrial area, peak early Doppler filling velocity, and left ventricular myocardial velocities during early filling. Preload altering manoeuvres included Trendelenberg (stage 1), reverse Trendelenberg (stage 2), and amyl nitrate (stage 3). Systolic blood pressure was measured at each stage. RESULTS: In comparison with baseline, left ventricular end diastolic volume (p = 0.001), left atrial area (p = 0.003), peak early mitral Doppler filling velocity (p = 0.01), and systolic blood pressures (p = 0.001) were all changed by preload altering manoeuvres. Only left ventricular myocardial velocity during early filling remained unchanged by these manoeuvres. CONCLUSIONS: In contrast to standard transmitral Doppler filling indices, Doppler tissue early diastolic velocities are not significantly affected by physiological manoeuvres that alter preload. Thus Doppler tissue velocities during early left ventricular diastole may provide a better index of diastolic function in cardiac patients by providing a preload independent assessment of left ventricular filling.

Cardiovascular safety of cocaine anaesthesia in the presence of adrenaline during septal surgery.

OBJECTIVE: The purpose of this study was to investigate the possible cardiovascular side effects of 4% cocaine solution in the presence of adrenaline during septal surgery. METHOD: Sixty adult patients undergoing elective septal surgery with local anaesthesia were included in the study. Noses were packed with 5-mL 4% cocaine (200-mg) solution on cotton pledgets, which were left in the nose for 15 minutes. Then, 10 mL of local anaesthetic (lidocaine 2% and adrenaline 1:100,000) were infiltrated in septal mucosa, and 15 minutes later, the surgical procedure was initiated. At the beginning of the operation, intervals from 12-lead surface electrocardiograms and vital signs including blood pressures and heart rate were recorded as a baseline. All measurements were repeated just before local anaesthetic infiltration, just before the beginning of the surgical procedure, and, finally, at the end of the operation. All four measurements and electrocardiographic tracings were examined. Systolic and diastolic blood pressures and QT parameters, RR intervals, and heart rates obtained from electrocardiogram were compared statistically with repeated-measures analysis of variance. RESULTS: No statistically significant difference was found among all four staged measurements. None of the patients developed tachycardia, hypertension, hypotension, or any chest pain. In electrocardiogram tracings, no sinus tachycardia depression, elevation, or bundle branch block was noted. CONCLUSION: This study shows that concomitant use of cocaine and adrenaline in the proper concentration and volume and in a carefully screened patient group was safe for the cardiovascular system.

Coronary artery disease and infection with chlamydia pneumonia.

The association between chlamydia pneumonia and coronary artery disease is well documented, however less is known about the correlation between chlamydia pneumonia infection and blood inflammatory markers or lipid levels. In 100 patients with proven coronary artery disease (25 females, 61.0 +/- 4.0 years old), and 60 healthy volunteer control cases (15 females, 60.6 +/- 3.4 years old), anti chlamydia pneumonia IgG, blood lipid, C-reactive protein and fibrinogen levels were detected. In cases with coronary artery disease seropositivity for IgG antibodies to chlamydia pneumonia (74% versus 34%, p < 0.0001), C-reactive protein (mg / l) (2.8 +/- 0.6 versus 1.4 +/- 0.6; p < 0.0001), fibrinogen (mg / dl) (317.4 +/- 38.2 versus 256.2 +/- 34.5, p < 0.0001), triglyceride (mg / dl) (217.5 +/- 39.0 versus 191.0 +/- 25.9, p < 0.0001), LDL-cholesterol (mg / dl) (126.9 +/- 19.2 versus 110.6 +/- 19.5, p < 0.0001) levels and total cholesterol / HDL-cholesterol ratio (7.7 +/- 1.8 versus 4.4 +/- 1.2, p < 0.0001) were higher but the level of HDL-cholesterol (mg / dl) (26.4 +/- 6.7 versus 47.0 +/- 11.2, p < 0.0001) was lower. The levels of total cholesterol did not differ between the two groups (p=0.9). Levels of triglyceride (r=0.60, p < 0.00001), LDL-cholesterol (r = 0.27, p = 0.0004), C-reactive protein (r = 0.69, p < 0.00001), fibrinogen (r = 0.60, p < 0.00001) and total cholesterol / HDL-cholesterol ratio (r = 0.74, p < 0.00001) had a direct relation, but the level of HDL-cholesterol had a negative (r= -0.80, p < 0.00001) relation with the seropositivity for chlamydia pneumonia. As a result, seropositivity for IgG antibodies to chlamydia pneumonia is considered as a risk factor for coronary artery disease by its association with the atherogenic lipid profile and procoagulant activity.

QT intervals and heart rate variability in hypertensive patients.

Low heart rate variability and increased QT dispersion are risk factors for cardiac mortality in various patient populations. We studied dispersion of QT interval, i.e. an index of inhomogeneity of repolarization, and heart rate variability (HRV) i.e., a measure of cardiac autonomic modulation in 76 essential hypertension cases (45 women, 53.0 +/- 11.1 years, body mass index: 25.1 +/- 1.4 kg/m2) and 70 healthy cases (42 women, 54.0 +/- 10.2 years, body mass index: 25.5 +/- 1.6 kg/m2, p > 0.05). QT-corrected QT intervals and their dispersions were significantly higher in the hypertensive group (p < 0.0001), all showing a direct relation with the level of systolic and diastolic blood pressures, ventricular mass index and high Lown grade ventricular rhythm problems. Time domain measures like standard deviation of RR intervals, standard deviation of the means of all corrected RR intervals calculated at 5 min intervals (p < 0.0001), proportion of adjacent RR intervals differing by > 50 msec (p = 0.005), HRV triangular index (p = 0.007), the square root of the mean squared differences of successive RR intervals (p = 0.011), and the high frequency (HF, 0.16-0.40 Hz, p < 0.0001) part of the frequency domain measure of HRV were all decreased, whereas the low frequency (LF, 0.04-0.15 Hz, p = 0.013) part of the frequency domain measures and LF / HF ratio (p < 0.0001) were increased in hypertensive cases. Time domain and the HF part of frequency domain measures of heart rate variability showed an inverse relation with the increased levels of both systolic and diastolic blood pressures and Lown grading system of ventricular rhythm problems, whereas LF and LF / HF showed direct relations with high levels of systolic and diastolic blood pressures and high Lown grade ventricular rhythm problems. The measures of heart rate variability apart from LF and LF / HF were inversely related with the QT intervals and dispersions, whereas LF / HF was directly related with them. Therefore, we conclude that the levels of both systolic and diastolic blood pressures are related to the generation of ventricular rhythm problems either via increasing left ventricular mass which results in an increase in QT parameter measurements, or by altering heart rate variability measures indicating a disturbance in cardiac autonomic balance in essential hypertension.

6-Hydroxydopamine toxicity towards human SH-SY5Y dopaminergic neuroblastoma cells: independent of mitochondrial energy metabolism.

6-Hydroxydopamine (6-OHDA) is widely used to generate animal models of Parkinson's disease. However, little is known about the intracellular events leading to cell death of dopaminergic neurones. Here we correlate indices of energy production and cell viability in human dopaminergic neuroblastoma SH-SY5Y cells after exposure to 6-OHDA. The toxin induces a time and dose-dependent decrease in cell survival with an IC50 value of 25 microM after 24 h. In contrast to the mitochondrial complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+), 6-OHDA-induced reduction of cell viability is not associated with a decrease of intracellular ATP content, intracellular ATP/ADP ratio or NAD+ content. In addition, preventing or forcing glycolysis do not alter 6-OHDA toxicity. The antioxidant D-alpha-tocopherol can attenuate cell death induced by 6-OHDA. These results suggest that cell death induced by 6-OHDA is not due to an inhibition of mitochondrial energy supply, but probably involves production of free radicals.

1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism.

The endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3, 4-tetrahydroisoquinoline (salsolinol), which is structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been reported to inhibit mitochondrial complex I (NADH-Q reductase) activity as does the MPTP metabolite 1-methyl-4-phenylpyridinium ion (MPP(+)). However, the mechanism of salsolinol leading to neuronal cell death is still unknown. Thus, we correlated indices of cellular energy production and cell viability in human dopaminergic neuroblastoma SH-SY5Y cells after exposure to salsolinol and compared these results with data obtained with MPP(+). Both toxins induce time and dose-dependent decrease in cell survival with IC(50) values of 34 microM and 94 microM after 72 h for salsolinol and MPP(+), respectively. Furthermore, salsolinol and MPP(+) produce a decrease of intracellular net ATP content with IC(50) values of 62 microM and 66 microM after 48 h, respectively. In contrast to MPP(+), salsolinol does not induce an increase of intracellular net NADH content. In addition, enhancing glycolysis by adding D-glucose to the culture medium protects the cells against MPP(+) but not salsolinol induced cellular ATP depletion and cytotoxicity. These results suggest that cell death induced by salsolinol is due to impairment of cellular energy supply, caused in particular by inhibition of mitochondrial complex II (succinate-Q reductase), but not complex I.