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University of Ottawa Heart Institute Creates New Pfizer Chair in Hypertension Research
$2.4 million partnership to support innovative research into a condition that affects approximately five million Canadians
The University of Ottawa Heart Institute announced last month the creation of the Pfizer Chair in Hypertension Research.
The five-year agreement will advance the work of the Institute’s Hypertension Research Group in new and unexplored areas,such as brain function. The first recipient is Dr Frans Leenen, Director of the Hypertension Unit at the Ottawa Heart Institute.
The Heart Institute Foundation and Pfizer Canada will each invest $1 million, and the Canadian Institutes of Health Researchwill contribute $400,000. The total partnership will amount to $2.4 million in support of hypertension research.
The University of Ottawa Heart Institute is a global leader in the fight against heart disease. The Hypertension Research
Group at the Heart Institute explores the brain’s role in hypertension. By assessing the impact of salt on brain function, theresearch team is able to target specific areas affecting the nervous system, and therefore, blood pressure. The researchersbelieve that a better understanding of these brain mechanisms will help explain genetic links to hypertension and may leadto more effective preventative measures and new therapies.
Abstracts #450, #625, #704, #827 and #832 were printed incorrectly in the Can J Cardiol 2003;19(Suppl A):140A,192A,215A,252A,253A. The authors have been corrected for these abstracts, which are reprinted below.
usefulness of B-type Natriuretic Peptide (BNP) in the management of
DEPENDENCE OF THE ISCHEMIA-REPERFUSION
CHF patients. Though BNP was found to be supplemental in diagnosing
INDUCED CHANGES IN CARDIAC FUNCTION UPON
CHF in an emergency setting, its role in an inpatient population is not ful-
ly understood. Since its introduction, BNP continues to be used or per-
D Prajapati, NS Dhalla, PK Chohan
haps overused in the management of CHF. The aim of this study was to
evaluate and compare the clinical and economic benefit of BNP determi-nation in the management of heart failure in a community setting.
Although ischemia-reperfusion (I/R) of the isolated
In this retrospective study we compared and analyzed the
heart is known to depress cardiac performance, the mechanisms are not
length of stay (LOS), therapeutic differences and investigational
fully understood. In order to gain some information whether the
approach in the management of CHF in two groups of inpatients admit-
magnitude of I/R injury to the heart depends upon endothelial integrity,
ted with a primary diagnosis of CHF. Group I (n=191, mean age 65.5 ±
we compared the effects of I/R on changes in cardiac performance by
16.1, Male 89 and Females 102) included patients in whom BNP levels
perfusing the hearts either at constant flow or constant pressure.
were not tested, while Group II (n=171, mean age 66.2 ± 15.6, Male 94,
Isolated rat hearts were either perfused at a constant flow
Female 77) included those patients in whom BNP levels were tested.
(10 ml/min) or at constant pressure (80 mm Hg). Hearts were subjected
Both groups were matched for age, comorbidities and New York Heart
to global ischemia followed by reperfusion for 60 min at either constant
Association class (NYHA class III &IV).
flow or constant pressure and the contractile parameters were recorded.
There were no significant difference in the LOS (4.71±6 and
In hearts perfused at constant flow after 15 and 30 min of
4.39±5 days: p= 0.397) and no significant difference in the medications
ischemia, the recovery of contractile function was 70 and 25% of the con-
(p=0.41) and investigations ordered (p=0.36) between the two groups. A
trol, respectively. On the other hand, in hearts perfused at constant
total of 190 BNP determinations were made in group II which consisted
pressure after 30 and 60 min ischemia, the recovery of contractile func-
of 171 patients with a mean LOS of 4.39 days.
tion was 75 and 30%, respectively. The recovery of constant flow hearts
The results indicate that BNP measurement did not
by reperfusion after 30 min ischemia was improved by 3 mM L-arginine, a
influence the management of CHF patients with regards to the investiga-
precursor of NO, whereas that of constant pressure hearts after 30 min
tions, medications and interventions ordered in an inpatient setting. It
ischemia was attenuated by 100 µM L−NAME, an inhibitor of NO
also did not influence the length of stay. The lack of clinical benefit from
BNP measurement indicates that its utilization is of limited value while
Hearts perfused at constant flow are more sensitive to
managing CHF in an inpatient setting and undoubtedly increases the cost
I/R induced changes in cardiac performance than those perfused at con-
stant pressure and these differences appear to be dependent upon the abil-
ity of coronary endothelium to generate NO.DNCCIHR Group in Experimental Cardiology
ADRIAMYCIN-INDUCED APOPTOSIS AND
HETERODIMERIC ACTIVATION OF RETINOIC ACID
CLINICAL AND ECONOMIC INFLUENCE OF BNP IN THE
I Danelisen, S Thangirala, H Lou, P Singal
MANAGEMENT OF HEART FAILURE
JC Sebastian, G Kommareddy, SS Jacob, S Jacob, P Yelamanchili,
We have earlier shown that adriamycin-induced congestive heart failure
R Borra, M Korman
and cardiac pathology in rats was associated with no significant change in
the total retinol (Vitamin A) levels in heart and plasma but 3H retinol
An aging population and the increasing incidence of
was significantly increased in these tissues. This coincided with a signifi-
congestive heart failure (CHF) drives the need for advancements in the
cant decrease in the total retinol and retinol palmitate (storage form of
management of heart failure. There has been mixed reviews regarding the
retinol) levels in the liver. The cardiac pathology was associated with
increased apoptosis stimulated by multiple factors. Retinoic acid, a meta-
bolic product of retinol, is known to regulate the expression of number of
CARDIOVASCULAR PROFILE OF TADALAFIL, A NEW PDE5
genes as well as it influences the process of apoptosis. In the current study
on isolated adult cardiomyocytes, retinoic acid (1000M-10:M) in low con-
G Brock, V Watkins, T Costigan, A Bedding, M Mitchell, J Emmick
centrations decreased apoptosis whereas at high concentration an opposite
effect was seen. Myocytes were also treated with adriamycin (10-40 :M) for
Tadalafil is a selective and potent inhibitor of PDE5, for
4 and 24 hours and protein levels of retinoic acid receptors RAR(∀,∃,()
the treatment of men with erectile dysfunction (ED). As the mecha-
and RXR (∀,∃,() in whole cell lysates were examined. Adriamycin treat-
nism of action of tadalafil and other PDE5 inhibitors involves vascular
ment resulted in a significant increase in RAR∀, RAR∃ and RAR( pro-
smooth muscle relaxation, there is a potential for effects on the cardio-
teins and RXR∃ was significantly decreased. These characteristic changes
vascular (CV) system. As previously reported, tadalafil has been shown
in the receptor proteins and in the heterodimeric nature of the activation
to augment the hypotensive effects of nitrates. This finding is consistent
of receptors in response to adriamycin may lead to proapoptotic state. Such
with the combined effects of nitrates and tadalafil on the nitric
a change in vivo may suggest a role of retinoic acid in adriamycin-induced
oxide/cGMP pathway. This report summarizes the overall CV profile of
tadalafil based on data from both clinical pharmacology and large-scale
Supported by the Heart and Stroke Foundation of Manitoba
Administration of 20 mg tadalafil in healthy
subjects resulted in no significant difference, compared to placebo, in
standing systolic and diastolic blood pressure (mean maximal decrease of
EVALUATION OF TADALAFIL IN MEN WITH ERECTILE
0.2/4.6 mm Hg, respectively), and no change in heart rate. The incidence
DYSFUNCTION (ED) TAKING SINGLE OR MULTIPLE
rate of myocardial infarction in tadalafil-treated patients across all clinical
studies (n > 4000) was 0.39 per 100 patient-years, vs 1.1 in placebo-treatedpatients (n > 1200) vs the prior published rate of 0.6 in age-standardized
G Brock, RW Lewis, J Denne, T Costigan, S Chang, JT Emmick
men (Sadovsky et al, Int J Clin Pract 2001;55:115-28). The phase 3 clini-
cal trials of tadalafil included patients with a wide variety of stable CV
ED and hypertension often coexist. We analyzed the efficacy
conditions, including patients taking multiple antihypertensive agents.
and safety of tadalafil in men with ED taking single or multiple antihyper-
The table shows the incidence of CV adverse events (AEs) in phase 3 clin-
ical trials involving 949 tadalafil-treated and 379 placebo-treated patients.
Tadalafil doses of 10 mg and 20 mg and placebo (not all
Overall, the incidence of CV AEs was low and tadalafil was not associated
treatments included in all studies) were evaluated in 7 randomized,
with a significant increase in these AEs, compared to placebo.
double-blind, placebo-controlled, phase 3 studies. For this integrated
Hypotension was reported in 1 placebo-treated patient compared to no
analysis, patients were categorized by concomitant use of aHT as follows:
1) no aHT; 2) single aHT; or 3) multiple (≥ 2) aHT. Efficacy was assessed
Tadalafil treatment has little effect on systemic arterial
by International Index of Erectile Function (IIEF) EF domain score and
pressure and has not been associated with an increased incidence of CV
percentage “yes” responses to Sexual Encounter Profile (SEP) diary ques-
tions 2 and 3 (SEP data not shown). Safety was assessed by incidence oftreatment-emergent adverse events (AE) and potentially clinically signifi-
CV AEs in Phase 3 Clinical Trialsa
cant changes in blood pressure (BP).
One thousand two hundred eighty-nine men with ED were
randomized to placebo or tadalafil 10 mg or 20 mg. Tadalafil 10 mg and
20 mg significantly improved EF vs placebo on all efficacy variables regard-less of aHT use. The incidences of commonly reported (≥ 5%) AE and car-
diovascular AE were not increased in tadalafil-treated patients taking
single and multiple aHT compared to tadalafil-treated patients not taking
aHT. The incidence of potentially clinically significant changes in BP for
patients taking single and multiple aHT was not increased in those treated
a All treatment-emergent CV AEs that occurred in at least 0.5% of patients
with tadalafil compared to those treated with placebo.
while on either placebo or tadalafil treatment; b Numbers of events too small
DCSupported by an unrestricted educational grant from Eli Lilly Canada Inc.
-Oxygenated Analogues of the 5-HT2A Serotonin Receptor Agonist 1-(4-Bromo-2,5-dimethoxyphenyl)-2-aminopropane Richard A. Glennon,* Mikhail L. Bondarev, Nantaka Khorana, and Richard Young Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298 Jesse A. May, Mark R. Hellberg, Marsha A. McLaughlin, and Najam A. Sharif Ophthalmic Pro
Pakistan J. Agric. Res. Vol. 26 No. 1, 2013GROWTH AND YIELD OF DIFFERENT BRASSICA GENOTYPES UNDER Arshad Ali, Imdad Ali Mahmood, Muhammad Salim, Muhammad Arshadullah* and Abdul Rasool Naseem**ABSTRACT:- A field study was conducted at farmer's salt-affected field (ECe=12.3 dS m ; pH=9.7; SAR=46.2) in Hafizabad to test growth and yield response of six Brassica cultivars (BARD-I, Dunkled, Rainbo