This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objectives: HIV and protease inhibitor (PI)-based ART are associated with abnormal lipid metabolism and diastolic dysfunction. We used submaximal exercise to stimulate whole-body lipolysis and free fatty acid (FFA) oxidation and examined relationships among FFA kinetics, resting cardiac function, and PI use in HIV+ taking PI (ritonavir )-based ART (HIV+PI), HIV+ taking NRTI-based ART (HIVnoPI), and HIV-negative controls (Ctrl). We hypothesized that HIV+PI would have higher lipolytic rates and lower FFA oxidation rates during rest and exercise than HIVnoPI and Ctrl, and that FFA kinetics would be associated with abnormalities in cardiac function. Methods. 1-13C palmitate was infused during rest and 70min of submaximal exercise (50% peakVO2) to quantify basal and exercise-stimulated lipolytic rate (PalmRa) and palmitate oxidation rate (PalmOx) in 3 groups: HIV+PI (n=10), HIVnoPI (n=9), and Ctrl (n=5). Resting 2-D and Doppler echocardiography was used to quantify cardiac contractile and anatomic parameters. Results: In contrast to our hypothesis, PalmRa was similar among the 3 groups during rest and exercise. Resting PalmOx was higher in HIV+PI (1.0 0.5, p<0.05) than Ctrl (0.4 0.1), but was not different between Ctrl and HIVnoPI (0.8 0.4 mmol/kgFFM/min). When HIV+ groups were combined, PalmOx during rest (0.9 0.4 vs. 0.4 0.1) and during exercise (2.0 0.9 vs. 0.8 0.4 mmol/kgFFM/min, p<0.03) were higher than Ctrl. HIV+ subjects exhibited lower early diastolic velocity (global em: 12.0 4.0 vs. 16.4 3.8 m/s, p<0.02) and peak early (E) to peak late (A) diastolic flow velocity ratio (E/A ratio: 1.4 0.4 vs. 2.1 0.5, p<0.001) while left ventricular mass index (LVMI) tended to be greater (97.1 14.4 vs. 86.1 6.2 g/m2, p<0.09) than Ctrl. PalmOx during exercise was related to LVMI (r=0.46, p<0.05). Serum high-density lipoprotein (HDL) levels were positively related to global em (r=0.58, p<0.003), ejection fraction (r=0.37, p<0.08), flow propagation (r=0.56, p<0.006), E (r=0.44, p<0.03), E/A (r=0.55, p<0.006) and negatively related to mean arterial pressure (r= - 0.49, p<0.02) and diastolic BP (r= - 0.49, p<0.02). Conclusion: HIV infection regardless of PI use was associated with elevated whole-body FFA oxidation rates during rest and exercise. Elevated FFA oxidation and lower serum HDL levels were predictive of depressed cardiac, specifically diastolic, function.
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