Faculty Bibliography

This study examined the cardiac structure and function of a unique cohort of documented lifelong, competitive endurance veteran athletes (>50 yr). Twelve lifelong veteran male endurance athletes [mean ± SD (range) age: 56 ± 6 yr (50-67)], 20 age-matched veteran controls [60 ± 5 yr; (52-69)], and 17 younger male endurance athletes [31 ± 5 yr (26-40)] without significant comorbidities underwent cardiac magnetic resonance (CMR) imaging to assess cardiac morphology and function, as well as CMR imaging with late gadolinium enhancement (LGE) to assess myocardial fibrosis. Lifelong veteran athletes had smaller left (LV) and right ventricular (RV) end-diastolic and end-systolic volumes (P < 0.05), but maintained LV and RV systolic function compared with young athletes. However, veteran athletes had a significantly larger absolute and indexed LV and RV end-diastolic and systolic volumes, intraventricular septum thickness during diastole, posterior wall thickness during diastole, and LV and RV stroke volumes (P < 0.05), together with significantly reduced LV and RV ejection fractions (P < 0.05), compared with veteran controls. In six (50%) of the veteran athletes, LGE of CMR indicated the presence of myocardial fibrosis (4 veteran athletes with LGE of nonspecific cause, 1 probable previous myocarditis, and 1 probable previous silent myocardial infarction). There was no LGE in the age-matched veteran controls or young athletes. The prevalence of LGE in veteran athletes was not associated with age, height, weight, or body surface area (P > 0.05), but was significantly associated with the number of years spent training (P < 0.001), number of competitive marathons (P < 0.001), and ultraendurance (>50 miles) marathons (P < 0.007) completed. An unexpectedly high prevalence of myocardial fibrosis (50%) was observed in healthy, asymptomatic, lifelong veteran male athletes, compared with zero cases in age-matched veteran controls and young athletes. These data suggest a link between lifelong endurance exercise and myocardial fibrosis that requires further investigation.

The authors previously reported on an active, young male with normal coronaries who sustained an acute myocardial infarction (AMI). The acute cause was a coronary thrombus; however, the cause of this thrombus and a definitive diagnosis remained elusive for 18 months until a new series of events, including symptoms of breathlessness, dizziness and collapse led to acute hospital admission. CT scan revealed numerous deep venous thromboses in the right leg and bilateral pulmonary emboli (PE). Acute pharmacological thrombolysis eliminated breathlessness and significantly reduced the risk of mortality. Clinical consensus suggests a coagulopathy, requiring indefinite treatment with Warfarin. In young individuals presenting with AMI, lifestyle, personal, family and clinical history should be considered and coronary artery disease should not be assumed until further tests have eliminated coagulopathy. In those presenting with breathlessness and a history which includes AMI, a CT scan is indicated to eliminate concerns of venous thromboembolism generally and PE specifically where untreated survival times are short.

The cardiovascular benefits of exercise are well known. In contrast, the impact of lifelong endurance exercise is less well understood. Long-term high-intensity endurance exercise is associated with changes in cardiac morphology together with electrocardiographic alterations that are believed to be physiologic in nature. Recent data however has suggested a number of deleterious adaptive changes in cardiac structure, function and electrical activity, together with peripheral and cerebral vascular structure and function. This review serves to detail knowledge in relation to; (1) Cardiac structure and function in veteran endurance athletes focusing on the differentiation of physiological and pathological changes in cardiac remodelling; (2) Cardiac electrical activity and the veteran endurance athlete with attention to arrhythmias, the substrate for arrhythmia generation and the clinical significance of such arrhythmias; (3) Peripheral and cerebral vascular structure and function in ageing and endurance-trained individuals; and (4) directions for future research.

OBJECTIVE:To investigate the regulation of blood pressure in response to an orthostatic challenge in athletes running a marathon. METHODS:10 experienced male runners (mean (SD) age 29 (4) years) were tested on the day prior to the 2004 London Marathon, and again immediately postrace (race time 210 (36) min). In addition, 6 of the subjects were retested 24 h postrace. During each examination, beat-to-beat systolic arterial blood pressure (SBP) and heart rate (HR) were measured, and stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were estimated via arterial transmural pressure waveforms during 3 min in a supine position and then during 3 min of upright, unsupported standing. Data were averaged over 20 s epochs, and the final 20 s of each posture were compared prerace and postrace via repeated measures 2-way ANOVA. RESULTS:Prerace SBP in standing increased only moderately when compared with supine values (2 (9) mm Hg, NS). This was accompanied by an increase in HR (13 (7) beats/min, p<0.05), as well as a decrease in SV (16 (9) ml, p<0.05). However, there was little change in CO (-0.13 (0.97) litres/min, NS) or TPR (0.047 (0.280) medical units (MU), NS). Postrace SBP significantly decreased from supine to standing (-15 (20) mm Hg, p<0.05). The change in SBP was accompanied by an increase in HR (19 (6) beats/min, p<0.05) and a reduction in SV (26 (14) ml, p<0.05) and CO (-1.02 (1.39) litres/min, p = 0.05). Postrace there was no change in TPR (0.366 (0.607) MU, NS) upon standing. The orthostatic adjustments in SBP, HR and CO were greater than at prerace (p<0.05). The postrace orthostatic challenge resulted in only one subject experiencing presyncopal symptoms. At 24 h postrace, cardiovascular responses to an orthostatic challenge mirrored those at prerace. CONCLUSIONS:Following prolonged exercise, a fall in systolic blood pressure during orthostasis results from an inadequately compensated decrease in SV and resultant CO during standing.

Energy Expenditure was measured with doubly labelled water technique during heavy sustained exercise with an official finishing team in the Race Across America. Energy Intake was also calculated to produce an energy balance for the race. A team of 4 cyclists (Mean +/-SD age: 37+4 yr; body height: 182+8 cm; body mass: 80.8+6.6 kg) completed the race in a relay fashion. The team completed the race in 6 days 10 h and 51 min. Total mean energy expenditure was found to be 43,401 kcals (181,711 kJ) with a mean daily energy expenditure of 6,420 kcals (26,879 kJ). Total mean energy intake from all food and drink consumed was calculated at 29,506 kcals (123,536 kJ) with a mean daily energy intake of 4 918 kcals (20,591 kJ). This resulted in a total mean energy deficit of 13,878 kcals (58,104 kJ) with a mean daily energy deficit of 1,503 kcals (6,293 kJ). The high energy expenditure highlights the need for correct and practical dietary strategies and challenges nutritionists to devise high energy diets that not only contain the correct macronutrient balance, but are also palatable to the cyclists, thus encouraging a high energy intake.

There has been an increasing drive toward miniaturizing and accelerating experiments with droplet-based microfluidics across the chemical disciplines. Current applications take advantage of the numerous techniques for manipulating nano- to femtoliter droplets within microfluidic devices. To expand the range of possible applications, we have developed a method for compartmentalizing pure compounds within droplets, at a gradient of concentrations, starting from chemical mixtures. In this technique, a mixture is injected into an ultra performance liquid chromatography (UPLC) system, and droplets are generated from the LC output at a frequency high enough to fraction each compound into approximately 10(5) droplets, compartmentalizing pure compounds into a sequence of droplets with a range of concentrations spanning 2-3 orders of magnitude. Here we used fluorescent dyes to quantify the concentration profile of the droplet collections, and to demonstrate the correspondence between the concentration profile of the droplets and the compound elution profile monitored with a UV absorbance detector, allowing the use of compounds that are not fluorescently labeled but show UV absorbance. Hence this technique is applicable to a wide variety of applications that require both compound purity and the ability to probe a variety of concentrations, such as drug screening and titrations.

BACKGROUND:Ethnicity is an important determinant of cardiovascular adaptation in athletes. Studies in black male athletes reveal a higher prevalence of electric repolarization and left ventricular hypertrophy than observed in white males; these frequently overlap with those observed in cardiomyopathy and have important implications in the preparticipation cardiac screening era. There are no reports on cardiac adaptation in highly trained black females, who comprise an increasing population of elite competitors. METHODS AND RESULTS/RESULTS:Between 2004 and 2009, 240 nationally ranked black female athletes (mean age 21+/-4.6 years old) underwent 12-lead ECG and 2-dimensional echocardiography. The results were compared with 200 white female athletes of similar age and size participating in similar sports. Black athletes demonstrated greater left ventricular wall thickness (9.2+/-1.2 versus 8.6+/-1.2 mm, P<0.001) and left ventricular mass (187.2+/-42 versus 172.3+/-42 g, P=0.008) than white athletes. Eight black athletes (3%) exhibited a left ventricular wall thickness >11 mm (12 to 13 mm) compared with none of the white athletes. All athletes revealed normal indices of systolic and diastolic function. Black athletes exhibited a higher prevalence of T-wave inversions (14% versus 2%, P<0.001) and ST-segment elevation (11% versus 1%, P<0.001) than white athletes. Deep T-wave inversions (-0.2 mV) were observed only in black athletes and were confined to the anterior leads (V(1) through V(3)). CONCLUSIONS:Systematic physical exercise in black female athletes is associated with greater left ventricular hypertrophy and higher prevalence of repolarization changes than in white female athletes of similar age and size participating in identical sporting disciplines. However, a maximal left ventricular wall thickness >13 mm or deep T-wave inversions in the inferior and lateral leads are rare and warrant further investigation.

Using microfluidic techniques and a novel fluorous-tagged palladium catalyst, we generated droplet reactors with catalytically active walls and used these compartments for small molecule synthesis.

A microfluidic device capable of storing picoliter droplets containing single bacteria at constant volumes has been fabricated in PDMS. Once captured in droplets that remain static in the device, bacteria express both a red fluorescent protein (mRFP1) and the enzyme, alkaline phosphatase (AP), from a biscistronic construct. By measuring the fluorescence intensity of both the mRFP1 inside the cells and a fluorescent product formed as a result of the enzymatic activity outside the cells, gene expression and enzymatic activity can be simultaneously and continuously monitored. By collecting data from many individual cells, the distribution of activities in a cell is quantified and the difference in activity between two AP mutants is measured.