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Relationship Between Endothelium-dependent and Independent Vasomotor and Platelet Dysfunction
S16
Heart, Lung and Circulation 2010;19S:S1–S268
Abstracts
ABSTRACTS
33
34
Relationship Between Endothelium-dependent and Independent Vasomotor and Platelet Dysfunction
Safety and Feasibility of Inhaled Iloprost on Exercise Capacity in Patients with Pulmonary Arterial Hypertension
A. Sverdlov ∗ , D. Ngo, W. Chan, Y. Chirkov, J. Horowitz University of Adelaide; The Queen Elizabeth Hospital, Australia Introduction: Endothelial dysfunction (EDF), defined on the basis of impaired eNOS-mediated vasodilatation, is a marker of atherogenic and coronary risk. Vascular nitric oxide (NO) resistance shares these prognostic implications, despite independence from NO generation. Furthermore, NO resistance at platelet level carries similar prognostic information. Nevertheless, previous data are limited as regards correlations between these parameters. Methods: In a population of randomly selected aging subjects (n = 177) (mean age 67 ± 6 years), we tested the hypotheses that (a) EDF predicts vascular NO resistance; (b) vascular NO resistance is correlated with platelet NO resistance. Vasomotor responsiveness was assessed utilizing applanation tonometry, with salbutamol and GTN as eNOS-dependent and independent dilators respectively, and platelet responsiveness to NO determined via inhibition of ADP-induced aggregation. Results: There was a significant (R = 0.3; p < 0.001) correlation between vascular eNOS-dependent and independent responses (Figure), but no significant correlation existed between vascular and platelet NO resistance (R = 0.1; p = 0.1).
A. Worthington ∗ , N. Collins, R. Haddad John Hunter Hospital, Newcastle, Australia Introduction: The use of inhaled prostanoids in pulmonary arterial hypertension (PAH) is limited by the need for frequent dosing, side effect profile and tachyphylaxis. The role of prostanoid therapy in patients on endothelin receptor antagonist (ERA) therapy is unclear. Aims: We sought to evaluate the acute hemodynamic effects of inhaled iloprost on exercise capacity in patients stabilised on oral ERA therapy for PAH. Methods: Patients with known PAH treated with ERA therapy underwent exercise treadmill testing after receiving both inhaled iloprost and placebo administered via nebulizer. Exercise tests were performed over two sessions, no closer than 7 days apart, with patients randomized to treatment order. Estimated pulmonary artery pressure data was obtained by echocardiography using tricuspid regurgitant velocity before and after exercise and then analysed by an investigator blinded to treatment. Results: Seven patients (all female; mean age 66 years) underwent exercise stress testing. Echocardiographic assessment confirmed improved post exercise pulmonary artery pressure (right ventricular systolic pressure 35.1 mmHg vs 27.5 mmHg). Change in 6 min walk test varied from −35 m to +75 m. Inhaled iloprost was well tolerated with no reported side effects. Conclusions: Single dose iloprost in patients maintained on ERA therapy is feasible and safe with demonstrable improvements in post exercise pulmonary artery pressure compared to placebo. Testing continues on another 15 patients, with results due in July 2010. doi:10.1016/j.hlc.2010.06.701 35 Sexual Dimorphism in the Relationship between Homocysteine and Arterial Stiffness in Healthy Children
Conclusions: Thus, vascular EDF appears to be determined substantially by biochemical factors distal to NO generation. On the other hand, the lack of correlation between vascular and platelet NO responsiveness suggests that the extent of modulation of NO response either by “scavenging” of NO or by soluble guanylate cyclase dysfunction varies significantly between tissues. doi:10.1016/j.hlc.2010.06.700
W. Abhayaratna 1,2,∗ , K. Hayes 1 , R. Telford 2 , S. Sakuragi 1,2 1 Canberra
Hospital, Australia National University, Australia
2 Australian
Background: Although an elevated homocysteine level is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease; a direct causal link is lacking. We hypothesized that a relationship between homocysteine and arterial stiffness may exist in healthy children. Aims: To evaluate the relationship between homocysteine levels and carotid-femoral pulse wave veloc-
Heart, Lung and Circulation 2010;19S:S1–S268
Abstracts
ABSTRACTS
33
34
Relationship Between Endothelium-dependent and Independent Vasomotor and Platelet Dysfunction
Safety and Feasibility of Inhaled Iloprost on Exercise Capacity in Patients with Pulmonary Arterial Hypertension
A. Sverdlov ∗ , D. Ngo, W. Chan, Y. Chirkov, J. Horowitz University of Adelaide; The Queen Elizabeth Hospital, Australia Introduction: Endothelial dysfunction (EDF), defined on the basis of impaired eNOS-mediated vasodilatation, is a marker of atherogenic and coronary risk. Vascular nitric oxide (NO) resistance shares these prognostic implications, despite independence from NO generation. Furthermore, NO resistance at platelet level carries similar prognostic information. Nevertheless, previous data are limited as regards correlations between these parameters. Methods: In a population of randomly selected aging subjects (n = 177) (mean age 67 ± 6 years), we tested the hypotheses that (a) EDF predicts vascular NO resistance; (b) vascular NO resistance is correlated with platelet NO resistance. Vasomotor responsiveness was assessed utilizing applanation tonometry, with salbutamol and GTN as eNOS-dependent and independent dilators respectively, and platelet responsiveness to NO determined via inhibition of ADP-induced aggregation. Results: There was a significant (R = 0.3; p < 0.001) correlation between vascular eNOS-dependent and independent responses (Figure), but no significant correlation existed between vascular and platelet NO resistance (R = 0.1; p = 0.1).
A. Worthington ∗ , N. Collins, R. Haddad John Hunter Hospital, Newcastle, Australia Introduction: The use of inhaled prostanoids in pulmonary arterial hypertension (PAH) is limited by the need for frequent dosing, side effect profile and tachyphylaxis. The role of prostanoid therapy in patients on endothelin receptor antagonist (ERA) therapy is unclear. Aims: We sought to evaluate the acute hemodynamic effects of inhaled iloprost on exercise capacity in patients stabilised on oral ERA therapy for PAH. Methods: Patients with known PAH treated with ERA therapy underwent exercise treadmill testing after receiving both inhaled iloprost and placebo administered via nebulizer. Exercise tests were performed over two sessions, no closer than 7 days apart, with patients randomized to treatment order. Estimated pulmonary artery pressure data was obtained by echocardiography using tricuspid regurgitant velocity before and after exercise and then analysed by an investigator blinded to treatment. Results: Seven patients (all female; mean age 66 years) underwent exercise stress testing. Echocardiographic assessment confirmed improved post exercise pulmonary artery pressure (right ventricular systolic pressure 35.1 mmHg vs 27.5 mmHg). Change in 6 min walk test varied from −35 m to +75 m. Inhaled iloprost was well tolerated with no reported side effects. Conclusions: Single dose iloprost in patients maintained on ERA therapy is feasible and safe with demonstrable improvements in post exercise pulmonary artery pressure compared to placebo. Testing continues on another 15 patients, with results due in July 2010. doi:10.1016/j.hlc.2010.06.701 35 Sexual Dimorphism in the Relationship between Homocysteine and Arterial Stiffness in Healthy Children
Conclusions: Thus, vascular EDF appears to be determined substantially by biochemical factors distal to NO generation. On the other hand, the lack of correlation between vascular and platelet NO responsiveness suggests that the extent of modulation of NO response either by “scavenging” of NO or by soluble guanylate cyclase dysfunction varies significantly between tissues. doi:10.1016/j.hlc.2010.06.700
W. Abhayaratna 1,2,∗ , K. Hayes 1 , R. Telford 2 , S. Sakuragi 1,2 1 Canberra
Hospital, Australia National University, Australia
2 Australian
Background: Although an elevated homocysteine level is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease; a direct causal link is lacking. We hypothesized that a relationship between homocysteine and arterial stiffness may exist in healthy children. Aims: To evaluate the relationship between homocysteine levels and carotid-femoral pulse wave veloc-