Orban, Marek

Tomas Konecny, 2012 Finalist and Presenting Author

AbstractBackgroundObstructive sleep apnea (OSA) imposes an afterload burden on the left ventricle and increases the pressure gradient across the aortic wall. Thus, OSA may increase the risk for aortic dissection (AD).MethodsThis study enrolled 40 subjects with acute AD from four institutions; 37 completed the modified Berlin Questionnaire and 31 underwent attended overnight polysomnography. Aortic diameter was measured on a computed tomography scan at seven locations from the sinotubular junction to the diaphragm.ResultsTwenty‐seven subjects had type A dissection; 13 had type B. In those who had polysomnography apnea–hypopnea index (AHI) ranged from 0.7 to 89. Prevalence of OSA (AHI ≥ 5) was 61%. Nocturnal presentation (10 p.m.–7 a.m.) did not differ by presence/absence of OSA. The modified Berlin Questionnaire was not predictive of the presence of OSA. Among type A subjects with polysomnography (n = 23), aortic diameters at all locations were greater in the OSA group though differences were not statistically significant. Summating aortic diameters at the seven locations also yielded a numerically larger mean value in the OSA group versus the non‐OSA group.ConclusionsIn this sample of patients with acute dissection, OSA was prevalent but was not associated with a nocturnal presentation. The presence of underlying OSA may be associated with larger aortic diameters at the time of dissection compared to patients without OSA. Though differences did not meet statistical significance the current series is limited by small numbers.

Background: Endothelial dysfunction assessed by flow mediated dilation (FMD) of the brachial artery has been identified as an independent predictor of cardiovascular events. However, whether weight gain impairs endothelial function is unknown. Methods: A randomized blinded controlled-trial to assess the effects of weight gain on endothelial function. After a weight maintenance period supervised by an experience dietitian, volunteers were randomized to gain weight (4 kg) or maintain weight. We recruited lean (BMI 18.5–24.9 kg/m 2 ) healthy volunteers (no diseases, medications and non-smokers) from the community. Using ultrasound, endothelial function was measured by FMD and non-flow mediated dilation (NFMD) of the brachial artery in the early morning (6:30 a.m.). Endothelial function was measured at baseline, after fat gain at 8 weeks and after weight loss at 16 weeks for fat-gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition techniques to measure body fat %, such as dual x-ray absorptiometry and abdominal CT scans were performed. Results: We recruited 35 fat-gainers and 8 weight maintainers. Mean age was 29 ± 6 years and 18 (42 %) were women. There were no differences in age, anthropometric and body composition measurements, blood pressure, heart rate or apnea hypopnea index at baseline between both groups. After an average gain of 4 kg, the fat-gainer group significantly increased their total, visceral and subcutaneous fat. Brachial artery FMD and NFMD remained unchanged in weight maintainers. However, it decreaed in fat-gainers (FMD=9.1 ± 3 vs. 7.6 ± 3.2, p=0.003 and NFMD=12.0 ± 4.9 vs. 10.1 ± 6.0, p=0.01), but recovered to baseline after subjects shed the gained weight (basleline vs. recovery: FMD=9.1 ± 3 vs. 9.0 ± 3, p=NS and NFMD =12.0 ± 4.9 vs.12.6 ± 5.0, p=NS). Visceral fat gain, but not subcutaneous fat gain was significantly correlated with the decrease in brachial artery FMD (rho =−0.42, p=0.004 and rho =−0.22, p=0.15, respectively). Conclusions: In lean healthy young subjects, modest weight gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial funcion recovers after weight loss. Viscerar rather than subcutaneous fat predicts endothelial dysfunction.

The ability to work efficiently at altitude is impaired by the reduced arterial oxygen tension. Acetazolamide may improve systemic saturation (SaO 2 ) by stimulating ventilation but increases the work of breathing. Efforts have focused on the potential role of sildenafil in improving exercise performance in high altitude environment. The purpose of this study was to determine the effects of acetazolamide and sildenafil on oxygen uptake (VO 2 ) and breathing efficiency during submaximal hypoxic exercise. Sixteen volunteers received sildenafil 40 mg (S), acetazolamide 125 mg (A) or matching placebo (P) tid × four doses in double‐blind fashion starting 8 hours prior to hypoxic exposure over 3 separate overnight stays in an altitude tent with an O 2 concentration of 12.5%, and then performed hypoxic submaximal exercise on a stationary bicycle for 10 min at a workload of 40% of VO 2 peak. SaO 2 decreased with exercise but there was no difference in exercising SaO 2 or VO 2 between conditions. As expected, acetazolamide increased ventilation compared to placebo and sildenafil. Breathing efficiency as measured by Ve/VCO 2 decreased with acetazolamide in comparison to placebo and sildenafil (P: 42.6±1.2, S: 41.9±1.6, A: 46.7±1.1, p<0.01). Sildenafil did not change breathing efficiency while acetazolamide reduced breathing efficiency during hypoxic exercise. This study was funded by Mayo Foundation and NIH Grant No. HL71478.

Objective Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease. However, acute cardiovascular effects of repetitive airway obstruction are poorly understood. While past research used a sustained Mueller manoeuver to simulate OSA we employed a series of gasping efforts to better simulate true obstructive apnoeas. This report describes acute changes in cardiac anatomy and flow related to sudden changes in intrathoracic pressure. Methods and results 26 healthy, normal weight participants performed 5–6 gasping efforts (target intrathoracic pressure −40 mm Hg) while undergoing Doppler echocardiography. 14 participants had sufficient echocardiographic images to allow comparison of atrial areas during the manoeuver with baseline measurements. Mitral and tricuspid E-wave and A-wave velocities postmanoeuver were compared with baseline in all participants. Average atrial areas changed little during the manoeuver, but variance in both atrial areas was significantly greater than baseline. Further, an inverse relationship was noted with left atrial collapse and right atrial enlargement at onset of inspiratory effort. Significant inverse changes were noted in Doppler flow when comparing the first beat postmanoeuver (pMM1) with baseline. Mitral E-wave velocity increased 9.1 cm/s while tricuspid E-wave velocity decreased 7.0 cm/s; by the eighth beat postmanoeuver (pMM8) values were not different from baseline. Mitral and tricuspid A-wave velocities were not different from baseline at pMM1, but both were significantly higher by pMM8. Conclusions Repetitive obstructive apnoeas produce dynamic, inverse changes in atrial size and Doppler flow across the atrioventricular valves. These observations have important implications for understanding the pathophysiology of OSA.

ObjectivesWe set to measure the interatrial pressure gradient during simulated obstructive sleep apnea (OSA).BackgroundOSA occurs when a sleeping patient attempts to inhale against an obstructed airway. How this event affects the interatrial pressure gradient has not been defined. We hypothesized that simulated OSA in a conscious subject (Mueller maneuver [MM], inspiration against obstruction) would promote increased right‐to‐left pressure gradient, and then the substrate for right‐to‐left atrial shunting.MethodsSelected patients underwent simultaneous measurement of airway and atrial pressures (both left and right atrium [LA, RA]) using high‐fidelity micromanometry at rest, during MM, and during VM, during right heart catheterization.ResultsTen patients (age 55 ± 11 years, two women) were successfully studied. During the onset of MM, RA pressure transiently but consistently exceeded LA pressure in response to the steep decline in intrathoracic pressure (maximum RA‐LA pressure gradient increased from 0.1 ± 1.4 mm Hg at baseline to 7.0 ± 4.3 mm Hg during MM, P < 0.001). The maximum right‐to‐left atrial pressure gradient during Mueller maneuver was higher than that achieved during the Valsalva maneuver release (P < 0.007).ConclusionsThe onset of MM increased right‐to‐left pressure gradient across the atrial septum, likely as a result of greater blood return to the RA from extrathoracic veins. The RA‐LA pressure gradient achieved during MM was greater than that observed during VM. These findings delineate the hemodynamic substrate for right to left shunting during OSA. © 2014 Wiley Periodicals, Inc.

Background— Obstructive sleep apnea is highly prevalent in patients with cardiovascular disease and has detrimental effects on systolic and diastolic function of the ventricles. In this research, the changes in strain (S) and strain rate (SR) during the performance of the Mueller maneuver (MM) in an effort to better understand how negative intrathoracic pressures affect ventricular mechanics. Methods and Results— The MM was performed to maintain a target intrathoracic pressure of −40 mm Hg. Echocardiography was used to measure various parameters of cardiac structure and function. Myocardial deformation measurements were performed using tissue speckle tracking. Twenty-four healthy subjects (9 women; mean age, 30�6 years) were studied. Global left ventricular longitudinal S in systole and SR in early filling were significantly decreased during the MM (S: baseline, −17.0�1.6%; MM, −14.5�2.2%; P <0.0001, SR: baseline, 1.09�0.20 s −1 ; MM, 0.92�0.21 s −1 ; P =0.01). Global right ventricular longitudinal S was also significantly decreased during the MM (baseline, −22.0�3.1%; MM, −17.2�2.5%; P <0.0001), as was global right ventricular longitudinal systolic SR (baseline, −1.34�0.35 s −1 ; MM, −1.02�0.21 s −1 ; P =0.0006). Conclusions— Left ventricular and right ventricular longitudinal deformation are significantly reduced during the MM. These results suggest that negative intrathoracic pressure during apnea may contribute to changes in myocardial mechanics. These results could help explain the observed changes in left ventricular and right ventricular mechanics in patients with obstructive sleep apnea.