T. Roberts

Relationship between Inflammatory Cytokines and Indices of Cardiac Dysfunction following Intense Endurance Exercise

Objectives Pro-inflammatory cytokines have been noted to increase following exercise but their relationship to exercise-induced cardiac dysfunction has not previously been investigated. We sought to evaluate whether exercise-induced cardiac dysfunction was associated with increases in cytokines, particularly the pro-inflammatory cytokines IL-1β, IL-12p70 and TNFα, which have been most implicated in cardiac pathology. Methods 40 well-trained endurance athletes underwent evaluation prior to and immediately following one of four endurance sporting events ranging from 3 to 11 hours duration. Cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNFα) were analyzed by flow cytometry from serum samples collected within 50 minutes of race completion. Cardiac troponin (cTnI) and B-type natriuretic peptide were combined with an echocardiographic assessment of cardiac function, and a composite of cTnI > 0.04 μg/L, BNP increase > 10 ng/L and a decrease in right ventricular ejection (RVEF) > 10% were prospectively defined as evidence of myocardial dysfunction. Results Relative to baseline, IL-6 IL-8 and IL-10 increased 8.5-, 2.9-, and 7.1-fold, respectively, P<0.0001. Thirty-one (78%), 19 (48%) and 18 (45%) of the athletes met the pre-specified criteria for significant cTnI, BNP and RVEF changes, respectively. TNFα, IL-12p70 were univariate predictors of ΔRVEF and ΔBNP whilst none of the anti-inflammatory cytokines were significantly associated with these measures. Ten athletes (25%, all athletes competing in the endurance event of longest duration) met criteria for exercise-induced myocardial dysfunction. In these 10 athletes with myocardial dysfunction, as compared to those without, there was significantly greater post-race expression of the pro-inflammatory cytokines IL-12p70 (8.1±3.8pg/ml vs. 2.5±2.6pg/ml, P<0.0001) and TNFα (6.5±3.1pg/ml vs. 2.0±2.5pg/ml, P<0.0001). Conclusion Cardiac dysfunction following intense endurance exercise was associated with increased expression of pro-inflammatory cytokines. This does not prove a causal relationship but provides rationale for further investigations into whether inflammation mediates exercise-induced myocardial dysfunction.

Abnormal right ventricular relaxation in pulmonary hypertension

Left ventricular diastolic dysfunction is a well-described complication of systemic hypertension. However, less is known regarding the effect of chronic pressure overload on right ventricular (RV) diastolic function. We hypothesized that pulmonary hypertension (PHT) is associated with abnormal RV early relaxation and that this would be best shown by invasive pressure measurement. Twenty-five patients undergoing right heart catheterization for investigation of breathlessness and/or suspected PHT were studied. In addition to standard measurements, RV pressure was sampled with a high-fidelity micromanometer, and RV pressure/time curves were analyzed. Patients were divided into a PHT group and a non-PHT group on the basis of a derived mean pulmonary artery systolic pressure of 25 mmHg. Eleven patients were classified to the PHT group. This group had significantly higher RV minimum diastolic pressure (5.1 ± 6.6 vs. −0.1 ± 3.3 mmHg, P = 0.03) and RV end-diastolic pressure (RVEDP; 11.0 ± 6.3 vs. 3.8 ± 3.7 mmHg, P = 0.004), and RV τ was significantly prolonged (53 ± 32 vs. 31 ± 13 ms, P = 0.04). There were strong correlations between RV τ and RV minimum diastolic pressure (r = 0.93, P < 0.0001) and between RV τ and RVEDP (r = 0.87, P < 0.0001). There was a trend toward increased RV contractility (end-systolic elastance) in the PHT group (0.73 ± 0.21 vs. 0.52 ± 0.21 mmHg/mL, P = 0.07) and a correlation between RV systolic pressure and first derivative of maximum pressure change (r = 0.58, P = 0.003). Stroke volumes were similar. Invasive measures of RV early relaxation are abnormal in patients with PHT, whereas measured contractility is static or increasing, which suggests that diastolic dysfunction may precede systolic dysfunction. Furthermore, there is a strong association between measures of RV relaxation and RV filling pressures.

Diagnosis and Significance of Pulmonary Microvascular Disease in Diabetes

OBJECTIVE To determine whether pulmonary microvascular disease is detectable in subjects with diabetes and associated with diminished exercise capacity using a novel echocardiographic marker quantifying the pulmonary transit of agitated contrast bubbles (PTAC). RESEARCH DESIGN AND METHODS Sixty participants (40 with diabetes and 20 control subjects) performed cardiopulmonary (maximal oxygen consumption [VO2peak]) and semisupine bicycle echocardiography exercise tests within a 1-week period. Pulmonary microvascular disease was assessed using PTAC (the number of bubbles traversing the pulmonary circulation to reach the left ventricle, categorized as low PTAC or high PTAC). Echocardiographic measures of cardiac output, pulmonary artery pressures, and biventricular function were obtained during exercise. RESULTS Subjects with diabetes and control subjects were of similar age (44 ± 13 vs. 43 ± 13 years, P = 0.87) and sex composition (70% vs. 65% male, P = 0.7). At peak exercise, low PTAC was present in more participants with diabetes than control subjects (41% vs. 12.5%, χ2 P = 0.041) and, in particular, in more subjects with diabetes with microvascular complications compared with both those without complications and control subjects (55% vs. 26% vs. 13%, χ2 P = 0.02). When compared with high PTAC, low PTAC was associated with a 24% lower VO2peak (P = 0.006), reduced right ventricular function (P = 0.015), and greater pulmonary artery pressures during exercise (P = 0.02). CONCLUSIONS PTAC is reduced in diabetes, particularly in the presence of microvascular pathology in other vascular beds, suggesting that it may be a meaningful indicator of pulmonary microvascular disease with important consequences for cardiovascular function and exercise capacity.