Effect of beta blocker treatment on platelet nitric oxide synthase, cyclic guanosine monophosphate...

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POSTER PRESENTATIONS S40 Heart, Lung and Circulation Poster Presentations 2008;17S:S4–S53 Conclusions: Measurement of plasma BNP to detect DHF is valid and important among those with various clinical presentation of HF. doi:10.1016/j.hlc.2007.11.101 Heart transplantation in patients with cardiac sarcoidosis in Japan Yusuke Sata , Satoshi Nakatani, Tomoko Kato, Akiko Mano, Masanobu Yanase, Noboru Oda National Cardiovascular Center, Japan Purpose: It is well-known that cardiac sarcoidosis is more often seen in Japanese. However, the tendency of requir- ing heart transplantation and outcome of post-transplant course has been unknown. We sought to review the ten- dency and the outcomes of cardiac sarcoidosis in Japanese heart transplant patients. Methods and materials: We retrospectively reviewed our single center experience of heart transplantation to eluci- date the tendency of requiring heart transplantation and post-transplant outcome in patients with cardiac sarcoido- sis. Results: Among 117 patients on the transplant wait- ing list due to end-stage heart failure during January 1997 to August 2007, none of them had been diag- nosed as cardiac sarcoidosis based on biopsy specimen prior to being on the list. However, 22 patients under- went heart transplantation during the same period (16 male and 6 female), two of them (9.1%) were finally diagnosed as cardiac sarcoidosis at the time of trans- plantation. They were 43- and 47-year-old male, and initially diagnosed as idiopathic dilated cardiomyopathy. The rest of the 20 patients included idiopathic dilated car- diomyopathy in 18 patients, dilated phase hypertrophic cardiomyopathy in one patient, and arrhythmogenic right ventricular dysplasia in one patient. The tendency of car- diac sarcoidosis in heart transplant recipients in Japan is significantly higher than that of United Nation of Organ Sharing Registry report in 2007 (9.1% vs. 0.17%, p < 0.0001). Both patients were under immunosuppres- sion therapy with cyclosporine, mycophenolate mofetil, and prednisolone, and showed no biopsy-proven rejec- tion, relapse or involvement of sarcoidosis of any organ for 1.5–2.5 years after heart transplantation. Conclusions: Although cardiac sarcoidosis was not diag- nosed prior to heart transplantation, quite a few transplant recipients might be cardiac sarcoidosis especially in Japanese. Mid-term outcomes of post-transplant course of cardiac sarcoidosis are satisfactory. The diagnosis of cardiac sarcoidosis should not be the factor for patient disqualification from potential transplant candidates. doi:10.1016/j.hlc.2007.11.102 Effect of beta blocker treatment on platelet nitric oxide synthase, cyclic guanosine monophosphate and oxidative stress, in patients with heart failure Ashish Shah a,, Eugenia Gkaliagkousi a , Julia DeCourcey b , Ruth Buckley b , James Ritter a , Albert Ferro a a King’s College London, London, UK b King’s College Hospital, London, UK Heart failure (HF) is characterised by impaired bioac- tive nitric oxide (NO), increased catecholamine and superoxide-anions. Platelet derived NO plays an impor- tant role in prevention of thrombosis. Beta-blocker (BB) treatment has been shown to improve outcome in HF patients. In the present work, we wished to deter- mine whether BB treatment influences platelet NO and superoxide-anion biosynthesis in HF patients. Ten HF patients (age 63.9 ± 5.1 years; 7 male, 3 female) were studied before and after 14 weeks of bisoprolol (4.4 ± 0.5 mg daily), along with standard HF medications. Platelet NO synthase (NOS) activity (both basal and stimu- lated with albuterol 10–5 M) was determined in gel-filtered platelets, from the rate of conversion of L-[3H] argi- nine to L-[3H] citrulline. Intraplatelet cGMP, an index of bioactive NO, was determined by radioimmunoassay. Platelet superoxide anion production was measured by pholasin-enhanced chemiluminescence. Data expressed as mean ± S.E.M., analyzed by student’s paired t test, with P < 0.05 as significant. After BB treatment, basal NOS activity was unaltered (pre: 211.7 ± 45.4, post: 241.1 ± 70.4 fmol L-citrulline/108 platelets, P > 0.05), whereas albuterol-stimulated NOS activity was increased as compared to baseline (percent rise, pre: 10.17 ± 7.23%, post: 23.74 ± 9.62%, P < 0.05). On the other hand, following BB treatment, both basal and albuterol-stimulated cGMP was increased in platelets. BB therapy decreased platelet superoxide anion production (pre: 15920.35 ± 2244.44, post: 8600.27 ± 1969.43 units of light/108 platelets, P < 0.05). Our results demonstrate that, in HF, BB therapy improves the ability of platelet NOS to synthesise NO, and decreases platelet superoxide anion generation, thereby leading to an increase in bioactive NO both basally and in response to stimulation. This effect is likely to attribute to a generalized improvement in HF status. Our findings may explain in part the ability of BB therapy to decrease thrombotic events in patients with HF. doi:10.1016/j.hlc.2007.11.103 LV remodelling features in athletes and hypertensive subjects Nino Sharashidze , Zurab Pagava, Guram Mamaladze, Tamar Kismareia, Giorgi Saatashvili Institute of Cardiology, Georgia It has been suggested, that LV remodelling in athletes is physiological phenomenon unlike in subjects with patho- logical heart hypertrophy.

Transcript of Effect of beta blocker treatment on platelet nitric oxide synthase, cyclic guanosine monophosphate...

Page 1: Effect of beta blocker treatment on platelet nitric oxide synthase, cyclic guanosine monophosphate and oxidative stress, in patients with heart failure

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S40 Heart, Lung and CirculationPoster Presentations 2008;17S:S4–S53

Conclusions: Measurement of plasma BNP to detect DHFis valid and important among those with various clinicalpresentation of HF.

doi:10.1016/j.hlc.2007.11.101

Heart transplantation in patients with cardiac sarcoidosisin Japan

Yusuke Sata ∗, Satoshi Nakatani, Tomoko Kato, AkikoMano, Masanobu Yanase, Noboru Oda

National Cardiovascular Center, Japan

Purpose: It is well-known that cardiac sarcoidosis is moreoften seen in Japanese. However, the tendency of requir-ing heart transplantation and outcome of post-transplantcourse has been unknown. We sought to review the ten-dency and the outcomes of cardiac sarcoidosis in Japaneseheart transplant patients.

Methods and materials: We retrospectively reviewed oursingle center experience of heart transplantation to eluci-date the tendency of requiring heart transplantation andpost-transplant outcome in patients with cardiac sarcoido-sis.

Results: Among 117 patients on the transplant wait-ing list due to end-stage heart failure during January1997 to August 2007, none of them had been diag-nosed as cardiac sarcoidosis based on biopsy specimen

Effect of beta blocker treatment on platelet nitric oxidesynthase, cyclic guanosine monophosphate and oxidativestress, in patients with heart failure

Ashish Shah a,∗, Eugenia Gkaliagkousi a, JuliaDeCourcey b, Ruth Buckley b, James Ritter a, AlbertFerro a

a King’s College London, London, UKb King’s College Hospital, London, UK

Heart failure (HF) is characterised by impaired bioac-tive nitric oxide (NO), increased catecholamine andsuperoxide-anions. Platelet derived NO plays an impor-tant role in prevention of thrombosis. Beta-blocker (BB)treatment has been shown to improve outcome in HFpatients. In the present work, we wished to deter-mine whether BB treatment influences platelet NO andsuperoxide-anion biosynthesis in HF patients.

Ten HF patients (age 63.9 ± 5.1 years; 7 male, 3 female)were studied before and after 14 weeks of bisoprolol(4.4 ± 0.5 mg daily), along with standard HF medications.Platelet NO synthase (NOS) activity (both basal and stimu-lated with albuterol 10–5 M) was determined in gel-filteredplatelets, from the rate of conversion of L-[3H] argi-nine to L-[3H] citrulline. Intraplatelet cGMP, an indexof bioactive NO, was determined by radioimmunoassay.Platelet superoxide anion production was measured bypholasin-enhanced chemiluminescence. Data expressed

prior to being on the list. However, 22 patients under-went heart transplantation during the same period (16male and 6 female), two of them (9.1%) were finallydiagnosed as cardiac sarcoidosis at the time of trans-plantation. They were 43- and 47-year-old male, andinitially diagnosed as idiopathic dilated cardiomyopathy.The rest of the 20 patients included idiopathic dilated car-diomyopathy in 18 patients, dilated phase hypertrophiccardiomyopathy in one patient, and arrhythmogenic rightventricular dysplasia in one patient. The tendency of car-diac sarcoidosis in heart transplant recipients in Japanis significantly higher than that of United Nation ofOrgan Sharing Registry report in 2007 (9.1% vs. 0.17%,p < 0.0001). Both patients were under immunosuppres-sion therapy with cyclosporine, mycophenolate mofetil,and prednisolone, and showed no biopsy-proven rejec-tion, relapse or involvement of sarcoidosis of any organfor 1.5–2.5 years after heart transplantation.

Conclusions: Although cardiac sarcoidosis was not diag-nosed prior to heart transplantation, quite a few transplantrecipients might be cardiac sarcoidosis especially inJapanese. Mid-term outcomes of post-transplant courseof cardiac sarcoidosis are satisfactory. The diagnosis ofcardiac sarcoidosis should not be the factor for patientdisqualification from potential transplant candidates.

doi:10.1016/j.hlc.2007.11.102

as mean ± S.E.M., analyzed by student’s paired t test, withP < 0.05 as significant.

After BB treatment, basal NOS activity was unaltered(pre: 211.7 ± 45.4, post: 241.1 ± 70.4 fmol L-citrulline/108platelets, P > 0.05), whereas albuterol-stimulated NOSactivity was increased as compared to baseline (percentrise, pre: −10.17 ± 7.23%, post: 23.74 ± 9.62%, P < 0.05). Onthe other hand, following BB treatment, both basal andalbuterol-stimulated cGMP was increased in platelets. BBtherapy decreased platelet superoxide anion production(pre: 15920.35 ± 2244.44, post: 8600.27 ± 1969.43 units oflight/108 platelets, P < 0.05).

Our results demonstrate that, in HF, BB therapyimproves the ability of platelet NOS to synthesise NO, anddecreases platelet superoxide anion generation, therebyleading to an increase in bioactive NO both basally andin response to stimulation. This effect is likely to attributeto a generalized improvement in HF status. Our findingsmay explain in part the ability of BB therapy to decreasethrombotic events in patients with HF.

doi:10.1016/j.hlc.2007.11.103

LV remodelling features in athletes and hypertensivesubjects

Nino Sharashidze ∗, Zurab Pagava, Guram Mamaladze,Tamar Kismareia, Giorgi Saatashvili

Institute of Cardiology, Georgia

It has been suggested, that LV remodelling in athletes isphysiological phenomenon unlike in subjects with patho-logical heart hypertrophy.