Key points• Pulmonary transit of agitated contrast (PTAC) occurs during exercise in healthy individuals.• It has been suggested that positive PTAC reflects a greater pulmonary vascular reserve, allowing for the right ventricle to operate at a decreased afterload at high levels of exercise.• In this study, we determined whether individuals with highest maximal aerobic capacity have the greatest pulmonary vascular distensibility, highest PTAC and greatest increase in the capillary blood component of lung diffusing capacity during exercise.• We observed that individuals with highest maximal aerobic capacity have a more distensible pulmonary circulation as observed through greater pulmonary vascular distensibility, greater pulmonary capillary blood volume, and lowest pulmonary vascular resistance at maximal exercise.• Pulmonary vascular distensibility predicts aerobic capacity in healthy individuals.Abstract It has been suggested that shallow slopes of mean pulmonary artery pressure (MPPA)-cardiac output (Q ) relationships and pulmonary transit of agitated contrast during exercise may be associated with a higher maximal aerobic capacity (V O 2 max ). If so, individuals with a higherV O 2 max could also exhibit a higher pulmonary vascular distensibility and increased pulmonary capillary blood volume during exercise. Exercise stress echocardiography was performed with repetitive injections of agitated contrast and measurements of MPPA,Q and lung diffusing capacities for carbon monoxide (D L,CO ) and nitric oxide (D L,NO ) in 24 healthy individuals. A pulmonary vascular distensibility coefficient α was mathematically determined from the slight natural curvilinearity of multipoint MPPA-Q plots. Membrane (D m ) and capillary blood volume (V c ) components of lung diffusing capacity were calculated. Maximal exercise increased MPPA, cardiac index (CI), D L,CO and D L,NO . The slope of the linear best fit of MPPA-CI was 3.2 ± 0.5 mmHg min l −1 m 2 and α was 1.1 ± 0.3% mmHg −1 . A multivariable analysis showed that higher α and greater V c independently predictedV O 2 max . All individuals had markedly positive pulmonary transit of agitated contrast at maximal exercise, with increases proportional to increases in pulmonary capillary pressure and V c . Pulmonary transit of agitated contrast was not related to pulse oximetry arterial oxygen saturation. Therefore, a more distensible pulmonary circulation and a greater pulmonary capillary blood volume are associated with a higherV O 2 max in healthy individuals. Agitated contrast commonly transits through the pulmonary circulation at exercise, in proportion to increased pulmonary capillary pressures.

Aim/hypothesis This study was designed to determine whether type 2 diabetic adolescents have reduced aerobic capacity and to investigate the role of cardiac output and arteriovenous oxygen difference (a−vO 2 ) in their exercise response. Methods Female adolescents (age 12-18 years) with type 2 diabetes mellitus (n=8) and type 1 diabetes mellitus (n=12) and obese (n=10) and non-obese (n=10) non-diabetic controls were recruited for this study. Baseline data included maximal aerobic capacity (cycle ergometer) and body composition. Cardiac output and a−vO 2 were determined at rest and during submaximal exercise. Results Diabetic groups had lower aerobic capacity than nondiabetic groups (p<0.05). Adolescents with type 2 diabetes had lower aerobic capacity than the type 1 diabetic group. Maximal heart rate was lower in the type 2 diabetic group (p <0.05). Exercise stroke volume was 30-40% lower at 100 and 120 beats per min in the diabetic than in the nondiabetic groups (p<0.05). The a−vO 2 value was not different in any condition. Conclusions and interpretation Type 2 diabetic adolescents have reduced aerobic capacity and reduced heart rate response to maximal exercise. Furthermore, type 2 and type 1 diabetic adolescent girls have a blunted exercise stroke volume response compared with non-diabetic controls. Central rather than peripheral mechanisms contribute to the reduced aerobic capacity in diabetic adolescents. Although of short duration, type 2 diabetes in adolescence is already affecting cardiovascular function in adolescents.

These findings suggest that impaired femoral arterial blood flow, an indirect marker of muscle perfusion, affects low-intensity exercise performance in patients with type 2 diabetes. However, because of lower exercising stroke volume, we propose that femoral arterial blood flow and, possibly, cardiac output, limit V O(2 max) in patients with type 2 diabetes.

This study compared changes in cross-sectional area (CSA) and flow (Q) between the middle cerebral artery (MCA) and the internal carotid artery (ICA) at baseline and during 5 min of hypercapnia (HC; 6% CO2) and hypocapnia (HO; hyperventilation) and quantified how these changes contribute to estimates of cerebrovascular reactivity (CVR). Measures of MCA CSA were made using 3T magnetic resonance imaging. On a separate day, MCA flow velocity was measured with transcranial Doppler ultrasound and ICA diameters and flow velocity were measured with duplex ultrasound. Fourteen subjects (23 ± 3 yr, 7 females) participated, providing data for 11 subjects during HC and 9 subjects during HO. An increase in MCA CSA (P < 0.05) was observed within the first minute of HC. During HO, the decrease in MCA CSA (P < 0.05) was delayed until minute 4. No changes were observed in ICA CSA during HC or HO. The relative changes in QICA and QMCA were similar during HC and HO. Therefore, the MCA, but not ICA, dilates and constricts during 5 min of HC and HO, respectively. The consequent impact on QMCA significantly affects estimates of CVR, and reactivity cannot be attributed solely to changes in smaller arterioles.

Cardiac and peripheral vasomotor factors contribute to the rapid pressor response at the onset of isometric handgrip exercise. We tested the hypothesis that age enhances the sympathetic and vasoconstrictor response at the onset of isometric handgrip exercise so that the pressor response is maintained, despite a diminished cardiac function. Twelve young and twelve older (24 ± 3 and 63 ± 8 yr) individuals performed 20-s isometric handgrip exercise at 30, 40, or 50% of maximal voluntary contraction force. Muscle sympathetic nerve activity (MSNA) was measured using microneurography. Mean arterial pressure (MAP) and cardiac output (Q) were assessed continuously by finger plethysmography and total peripheral resistance was calculated. MAP increased with the onset of handgrip; this increase was associated with handgrip intensity and was similar in both groups. Heart rate and Q increased with increasing handgrip intensity in both groups, but increases were greater in young vs. older individuals (age × handgrip intensity interaction, P < 0.05). MSNA burst frequency increased (P < 0.01), while MSNA burst incidence tended to increase (P = 0.06) with increasing handgrip intensity in both groups. The change in MSNA between baseline and handgrip, for both frequency and incidence, increased with increasing handgrip intensity for both groups. There was no effect of handgrip intensity or age on total peripheral resistance. The smaller heart rate and Q response during the first 20 s of handgrip exercise in older individuals was not accompanied by a greater sympathetic activation or vasoconstrictor response. However, increases in MAP were similar between groups, indicating that the pressor response at the onset of handgrip exercise is preserved with aging.

SummaryDiastolic heart failure is characterized by the symptoms and signs of heart failure, a preserved ejection fraction and abnormal left ventricular (LV) diastolic function caused by a decreased LV compliance and relaxation. The signs and symptoms of diastolic heart failure are indistinguishable from those of heart failure related to systolic dysfunction; therefore, the diagnosis of diastolic heart failure is often one of exclusion. The majority of patients with heart failure and preserved ejection fraction have a history of hypertension. Hypertension induces a compensatory thickening of the ventricular wall in an attempt to normalize wall stress, which results in LV concentric hypertrophy, which in turn decreases LV compliance and LV diastolic filling. There is an abnormal accumulation of fibrillar collagen accompanying the hypertension-induced LV hypertrophy, which is also associated with decreased compliance and LV diastolic dysfunction. There are no specific guidelines for treating diastolic heart failure, but pharmacological treatment should be directed at normalizing blood pressure, promoting regression of LV hypertrophy, preventing tachycardia and treating symptoms of congestion. Preventive strategies directed toward an early and aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of diastolic heart failure.

In response to acute physiological stress, the sympathetic nervous system modifies neural outflow through increased firing frequency of lower-threshold axons, recruitment of latent subpopulations of higher-threshold axons, and/or acute modifications of synaptic delays. Aging and coronary artery disease (CAD) often modify efferent muscle sympathetic nerve activity (MSNA). Therefore, we investigated whether CAD (n = 14; 61 ± 10 yr) and/or healthy aging without CAD (OH; n = 14; 59 ± 9 yr) modified these recruitment strategies that normally are observed in young healthy (YH; n = 14; 25 ± 3 yr) individuals. MSNA (microneurography) was measured at baseline and during maximal voluntary end-inspiratory (EI) and end-expiratory (EE) apneas. Action potential (AP) patterns were studied using a novel AP analysis technique. AP frequency increased in all groups during both EI- and EE-apnea (all P < 0.05). The mean AP content per integrated burst increased during EI- and EE-apnea in YH (EI: Δ6 ± 4 APs/burst; EE: Δ10 ± 6 APs/burst; both P < 0.01) and OH (EI: Δ3 ± 3 APs/burst; EE: Δ4 ± 5 APs/burst; both P < 0.01), but not in CAD (EI: Δ1 ± 3 APs/burst; EE: Δ2 ± 3 APs/burst; both P = NS). When APs were binned into "clusters" according to peak-to-peak amplitude, total clusters increased during EI- and EE-apnea in YH (EI: Δ5 ± 2; EE: Δ6 ± 4; both P < 0.01), during EI-apnea only in OH (EI: Δ1 ± 2; P < 0.01; EE: Δ1 ± 2; P = NS), and neither apnea in CAD (EI: Δ -2 ± 2; EE: Δ -1 ± 2; both P = NS). In all groups, the AP cluster size-latency profile was shifted downwards for every corresponding cluster during EI- and EE-apnea (all P < 0.01). As such, inherent dysregulation exists within the central features of apnea-related sympathetic outflow in aging and CAD.

Men with type 2 diabetes have an altered cardiac cycle and lower end-diastolic and stroke volume. A lower total blood volume and higher heart rate in men with type 2 diabetes suggest that changes in LV preload, independent of changes in LV relaxation or contractility, influence LV diastolic filling and stroke volume in this population.