Zuhair Allebban

Technical aspects of diastology: why mitral inflow and tissue Doppler imaging are the preferred parameters?

Doppler methods for assessing left ventricular (LV) diastolic function have increased in number and complexity. However, time constraints may prevent measurement of all parameters during routine transthoracic echocardiography. Therefore, we designed a study to determine which Doppler parameters could be most successfully and quickly obtained. The recording success rate and time required to record different LV diastolic function parameters were evaluated in 80 patients. A specific recording protocol was followed by an experienced, credentialed sonographer and time intervals to record each parameter were measured. In comparison with color Doppler M‐mode of LV inflow propagation velocities (Vp) and pulmonary venous (PV) flow measurements, transmitral valve (MV) flow and tissue Doppler imaging (TDI) of the mitral annulus had the highest recording success rate and required the shortest time to record. PV flow and Vp took longer to obtain (80.1 ± 34.3 sec and 57.1 ± 29.1 sec, respectively) than did mitral valve inflow (36.3 ± 20.7sec) and mitral valve annular TDI (29.3 ± 18.4 sec for septal and 33.3 ± 14.5sec for lateral). MV flow velocities, Vp, and TDI were successfully recorded in virtually all patients (99–100%). In comparison, the PV flow velocities and durations were successfully recorded less often. The range of success rates for the six PV flow parameters was 49–84%. Since MV flow and TDI also have been shown by us to have the lowest interreader variability, measurement of these two parameters may be preferred for routine clinical evaluation of LV diastolic function in a busy echocardiography laboratory.

The effect of freezing and long-term storage on the stability of cardiac troponin T.

Cardiac troponin T (cTnT) levels are widely used to assess for evidence of myocardial infarction. We studied the effect of freezing and long-term storage on the stability of cTnT in blood samples from 178 patients with end-stage renal failure. The serum was separated and divided into multiple aliquots. Baseline cTnT levels were measured in the unfrozen aliquots. The remaining aliquots were frozen using standard techniques. The aliquots were thawed after 3, 6, 12, or 24 months and cTnT levels measured. There were no significant changes in the mean +/- SEM cTnT levels up to 12 months (0.111 +/- 0.098 microg/L) compared with baseline (0.114 +/- 0.098 microg/L); after 24 months, cTnT levels were significantly lower (0.107 +/- 0.095 microg/L) than baseline ( P = .004). The cTnT assay is a reliable method of measuring the cTnT level in human serum up to 12 months of frozen storage. However, after 24 months, the cTnT level was 0.007 microg/L lower than baseline, potentially causing erroneous interpretations. The clinical significance of the change in the cTnT level after long-term frozen storage is unclear. Further studies, including prospective analysis of patient outcomes, should be helpful.

Amino Acid Supplementation Differentially Modulates STAT1 and STAT3 Activation in the Myocardium Exposed to Ischemia/Reperfusion Injury

We have previously demonstrated that the transcription factor STAT1 plays a critical role in promoting apoptotic cell death, whereas the related STAT3 family member may antagonize STAT1 and protect cardiac myocytes from ischemia/reperfusion (I/R) injury. More recently we demonstrated that long-term nutritional supplementation with mixed amino acids (AAs) can enhance myocyte survival by preserving mitochondrial functional capacity during I/R injury. We therefore investigated whether short-term nutritional supplementation with the same AA mixture has any effects on STAT1 or STAT3 activation in the Langendorff perfused rat heart exposed to I/R injury. In Sprague-Dawley rats given a single oral dose of a mixture of mainly essential l-AA (1 g/kg), and exposed, after 6 hours, to 35 minutes of ischemia, followed by 120 minutes of reperfusion, AA supplementation prolonged STAT3 activation/phosphorylation, while STAT1 activation was reduced. Enhanced STAT3 phosphorylation paralleled a reduction in expression of Fas, a known STAT1 target gene and proapoptotic marker that is upregulated after I/R. Moreover, abrogation of STAT3 activation by means of the JAK inhibitor AG490, reduced, but did not abolish, the cardioprotective effects of AA supplementation after I/R. These results show that modulation of the functional balance between STAT3 and STAT1, with preferential activation of prosurvival STAT3 over the proapoptotic STAT1, represents a mechanism by means of which short-term oral supplementation with mixed AAs protects the heart from I/R injury.

Oral Administration of Amino Acidic Supplements Improves Protein and Energy Profiles in Skeletal Muscle of Aged Rats: Elongation of Functional Performance and Acceleration of Mitochondrial Recovery in Adenosine Triphosphate After Exhaustive Exertion

Sarcopenia is an inevitable age-related degenerative process chiefly characterized by decreased synthesis of muscle proteins and impaired mitochondrial function, leading to progressive loss of muscle mass. Here, we sought to probe whether long-term administration of oral amino acids (AAs) can increase protein and adenosine triphosphate (ATP) content in the gastrocnemius muscle of aged rats, enhancing functional performance. To this end, 6- and 24-month-old male Fisher 344 rats were divided into 3 groups: group A (6-month-old rats) and group B (24-month-old rats) were used as adult and senescent control group, respectively, while group C (24-month-old rats) was used as senescent treated group and underwent 1-month oral treatment with a mixture of mainly essential AAs. Untreated senescent animals exhibited a 30% reduction in total and fractional protein content, as well as a 50% reduction in ATP content and production, compared with adult control rats (p <0.001). Long-term supplementation with mixed AAs significantly improved protein and high-energy phosphate content, as well as the rate of mitochondrial ATP production, conforming their values to those of adult control animals (p <0.001). The improved availability of protein and high-energy substrates in the gastrocnemius muscle of treated aged rats paralleled a significant enhancement in functional performance assessed by swim test, with dramatic elongation of maximal exertion times compared with untreated senescent rats (p <0.001). In line with these findings, we observed that, after 6 hours of rest following exhaustive swimming, the recovery in mitochondrial ATP content was approximately 70% in adult control rats, approximately 60% in senescent control rats, and normalized in treated rats as compared with animals of the same age unexposed to maximal exertion (p <0.001). In conclusion, nutritional supplementation with oral AAs improved protein and energy profiles in the gastrocnemius of treated rats, enhancing functional performance and accelerating high-energy phosphate recovery after exhaustive exertion.

A case of fatal ephedra intake associated with lipofuscin accumulation, caspase activation and cleavage of myofibrillary proteins

Ephedra, a herb reported to suppress appetite and stimulate the sympathetic nervous system as well as cardiac performance, has recently been related to several adverse events, including seizure, stroke, hypertension, myocardial infarction, and sudden death. Here, we describe the case of a 45‐year‐old woman who died of cardiovascular collapse while taking ephedra. Tissue analysis revealed non‐specific degenerative alterations in the myocardium (lipofuscin accumulation, basophilic degeneration and vacuolation of myocytes, as well as myofibrillary loss), associated with myocyte apoptosis, caspase activation, and extensive cleavage of miofibrillary proteins α‐actin, α‐actinin, and cardiac troponin T. Healthcare professionals are therefore urged to warn their patients about the risk of serious adverse effects, which may follow ephedra intake.

Endothelial function and urine albumin levels among asymptomatic Mexican-Americans and non-Hispanic whites

Background-Mexican-Americans (MA) exhibit increases in various cardiovascular disease (CVD) risk factors compared to non-Hispanic Whites (NHW), yet are reported to have lower CVD mortality rates. Our aim was to help explain this apparent paradox by evaluating endothelial function and urine albumin levels in MA and NHW.Methods-One hundred-five MA and 100 NHW adults were studied by brachial artery flow-mediated dilatation (FMD), blood and urine tests. Participants were studied by ultrasound-determined brachial artery flow-mediated dilatation (FMD), blood and urine tests, at a single visit.Results-Despite higher BMI and triglycerides in MA, MA demonstrated higher FMD than did NHW (9.1 ± 7.3% vs. 7.1 ± 6.3%, p < 0.04). Among MA, urinary albumin was consistently lower in participants with FMD ≥ 7% FMD versus < 7% FMD (p < 0.006). In multivariate analyses in MA men, urinary albumin was inversely related to FMD (r = -0.26, p < 0.05), as were BMI and systolic blood pressure. In MA women, urinary albumin:creatinine ratio was an independent inverse predictor of FMD (p < 0.05 ).Conclusion-To our knowledge, this is the first study to analyze, in asymptomatic adults, the relation of MA and NHW ethnicity to FMD and urine albumin levels. The findings confirm ethnic differences in these important subclinical CVD measures.

Do Differences in Subclinical Cardiovascular Disease in Mexican Americans Versus European Americans Help Explain the Hispanic Paradox

Mexican Americans have exhibited increases in various coronary heart disease risk factors compared to European Americans but have also had reportedly lower coronary heart disease mortality from vital statistics studies. We hypothesized this apparent paradox might relate to lower levels of subclinical disease in Mexican Americans. A total of 105 adult Mexican Americans (42 men and 63 women, age 46 +/- 14 years) and 100 European Americans (59 men and 41 women, age 50 +/- 11 years) were studied using blood tests, transthoracic echocardiography, and computed tomography coronary artery calcium (CAC) scans. Despite a greater body mass index and triglycerides in Mexican Americans (p <0.001), the Mexican Americans demonstrated less subclinical disease than did the European Americans (14.4% vs 25.7% with CAC scores >0, p <0.05 and mean left ventricular mass [LV] of 146 vs 160 g, p <0.05). Also, the LV mass was significantly greater in Mexican Americans with than in those without CAC (mean 172 vs 140 g, p <0.05). On logistic regression analysis, age and diastolic blood pressure were associated with an increased likelihood of CAC (p <0.001 and p <0.01, respectively), and Mexican-American ethnicity was associated with a decreased likelihood of CAC (odds ratio 0.33, 95% confidence interval 0.12 to 0.87, p <0.05). On multiple regression analysis, male gender, body surface area, and systolic blood pressure were independently associated with an increased LV mass (all p <0.001). The body mass index was less strongly related to the LV mass than was the body surface area and was not related to CAC. In conclusion, Mexican-American ethnicity is associated with both a lower LV mass and a lower prevalence of CAC, although the differences in LV mass did not remain after adjustment for other factors. Although systolic blood pressure, body surface area, and male gender were most strongly associated with the LV mass, age and diastolic blood pressure, in addition to Mexican-American ethnicity, were the most important indicators of CAC.

Relation of metabolic syndrome components to left ventricular mass in Mexican Americans versus non-Hispanic whites

Metabolic syndrome (MetS) is associated with increased risk for cardiovascular disease (CVD). Mexican Americans (MA) exhibit increases in CVD risk factors compared with non-Hispanic whites (NHW), but few data exist comparing the relation of MetS to subclinical CVD, for example, left ventricular (LV) mass. Asymptomatic subjects (104 MA and 101 NHW, 52.2% female, aged 48 ± 12 years) were studied by echocardiography (echo) and by blood and urine tests. Metabolic syndrome was defined based on the American Heart Association/National Heart, Lung, and Blood Institute definition. Echo LV mass was compared with the presence or absence of MetS and with the number of MetS components. Multiple linear regression also examined the association of MetS with LV mass adjusted for non-MetS risk factors. Left ventricular mass was lower in MA (145.5 ± 43.9 g) compared with NHW (160.2 ± 49.9 g) (P < .05), although this difference was attenuated after adjusting for MetS and other risk factors. Left ventricular mass was higher in those with vs without MetS in both MA and NHW men and women (P < .05 to P < .01). There was a significant (P < .001) graded increase in echo LV mass with increasing number of MetS components both in MA (108.3 to 153.8 g) and NHW (144.3 to 215.1 g). In multiple regression analysis, male sex and MetS remained independently associated (P < .0001) with LV mass; however, body mass index explained much of this association, indicating the strong association of obesity with LV mass. Mean LV mass in both MA and NHW adults was higher in those with vs without MetS and with increasing number of MetS components, with body mass index the principal component of MetS associated with LV mass. The prognostic significance of LV mass in persons with MetS requires further study.