The high conservation of Popdc genes and their inferred role

in muscle cell injury and repair suggest that these novel proteins

may have an important function in heart and skeletal muscle.

doi:10.1016/j.yjmcc.2006.03.159

145. Post-ischaem ic administra tion of a3 adenosi ne

receptor agonis t amel iorates myocar dial

ischaemia–reperfusion injury via ERK 1/2

A. Hussain, H. Al-Rajaibi, P. Karjian, H.L. Maddock. Faculty

of Health and Life Sc., Coventry University, CV1 5FB, UK

A3 adenosine receptor (A3R) agonist, 2-Cl-IBMECA has

previously been reported to limit lethal reperfusion injury

through anti-apoptotic and anti-necrotic mechanisms. The

consequence of activating A3Rs at different time points during

reperfusion has not been studied before in a model of myocardial

ischaemia–reperfusion. Rat hearts were subjected to 35 min left

coronary artery occlusion followed by 120 min reperfusion.

Treatment groups (n = 5) were perfused with 2-Cl-IBMECA (1

nM) in the presence and absence of U0126 (10 AM) (MEK 1/2-

Erk 1/2 inhibitor) and introduced at different time intervals

during reperfusion (R), either at start of R, 15 min, 30 min after

start of R. Results are show in the table. Hearts underwent

triphenyl tetrazolium staining for infarct size assessment.

Administration of 2-Cl-IBMECA at R, 15 and 30 min after

initiation of R led to a significant reduction in infarcted

myocardium. The protection afford by 2-Cl-IBMECA was

abrogated by U0126 at all time points. This study is the first to

show that A3R activation at various time points post-reperfusion

can still reduce myocardial injury and is dependent on ERK 1/2.

Table: Effect of administering A3 agonist in the absence and presence of U0126

(10 AM) at different time points during reperfusion on I/R

doi:10.1016/j.yjmcc.2006.03.160

146. Effect of chronic atorvastatin therapy in the

mitochondrial function in an ex-vivo animal model of

global myocardial ischemia–reperfusion

Pedro Monteiro, Marta Paiva, Raquel Carreira, Lino

Goncalves, Luıs A. Providencia. Basic Research Unit In

Cardiology–Cardiology Department, Coimbra University

Hospital And Medical School, Coimbra, Portugal

Introduction: Diabetics have higher incidence of ischemic

heart failure (HF), with worse prognosis. This may be

improved by statins, like atorvastatin (ATV). Is this true and,

if so, which are the mechanisms?

Aim: To evaluate, in an animal model of diabetes, submitted

to ischemia–reperfusion (IR), if the chronic therapy with ATV

improves cardiac mitochondrial function.

Material and methods: Goto-Kakizaki (GK) diabetic rats

(12 weeks old) were divided in 4 groups (n = 6/group): A—GK

control (no medication/no IR); B—ATV control (ATV 10 mg/

kg/day during 4 weeks/no IR); C—GK IR (no medication/

submitted to IR); D—ATV IR (ATV 10 mg/kg/day during 4

weeks and then IR). At 16 weeks of age, hearts were removed

and submitted to 165min perfusion (control) or 10min perfusion

+35 min ischemia +120 min reperfusion (IR). Mitochondrial

parameters assessed were: oxidative stress (colorimetric tiobar-

bituric acid colourimetry test-TBARS), mitochondrial swelling

and calcium uptake (by fluorimetry).

Results: ATV-treated rats had significantly lower oxidative

stress levels, both in control (0.63 T 0.03 versus 0.7 T 0.03 nmol

TBARS/mg protein;P < 0.05) and in IR (0.9 T 0.02 versus 0.97 T0.05 nmol TBARS/mg protein; P < 0.05). ATV-treated animals

also showed a significant decrease in mitochondrial swelling in

IR (45.1 T 1.3 versus 51.3 T 3.3 arbitrary units–AU; P < 0.05),

but not in control (24.7 T 3.6UAversus 25.2 T 5.3UA; P = n.s.).

ATV therapy showed a significant improvement in calcium

uptake in IR (75.1 T 2.9 versus 72.3 T 1.9 nmol/mg protein; P <

0.05)—Fig. 1.

Conclusion: In ischemic HF subjects with diabetes, ATV

improves cardiac mitochondrial function, due to less oxidative

stress and better ischemia tolerance (higher calcium uptake and

lower mitochondrial swelling).

doi:10.1016/j.yjmcc.2006.03.161

147. Delayed myocardial protection following coronary

microembolization is mediated by TNF-A

Andreas Skyschally, Petra Gres, Simone Hoffmann, Patrick

van Caster, Rainer Schulz, Gerd Heusch. Institute of

Pathophysiology, University of EssenMedical School, Germany

In patients with unstable angina, plaque rupture and

coronary microembolization (ME) can precede complete

coronary artery occlusion and impending infarction. ME

induces an inflammatory reaction with increased expression

of TNF-a, resulting in progressive contractile dysfunction.

TNF-a is not only a negative inotrope but can also protect the

myocardium against ischemia/reperfusion.

We have now studied whether ME at a time when TNF-a

expression is increased, i.e. after 6 h, can establish protection

against infarction. In anesthetized pigs, the LAD was

cannulated and perfused from an extracorporeal circuit.

Placebo controls received saline (PLA; n = 8). ME was

induced by infusion of microspheres (42 Am; 3.000 per ml/

min inflow) into the LAD (ME; n = 7). A third group

received TNF-a antibodies (25 mg/kg body weight) 30 min

before ME (ME + AB; n = 5). Six hours after ME or placebo,

respectively, sustained ischemia was induced by 85% inflow

reduction for 90 min. Infarct size was determined after 2

h reperfusion by TTC-staining.

Reperfusion 15 min 30 min

Control 54.3 T 6.6 – –

2-Cl-IBMECA 29.0 T 3.0* 21.9 T 4.12* 30.0 T 6.9*

2-Cl-IBMECA + U0126 66 T 12.0** 50 T 5.4** 51.3 T 7**

I/R=mean infarct/risk%; *= P <0.05 vs. control; **= P <0.05 vs. 2-

Cl-IBMECA AT R, 15 and 30 min.

ABSTRACTS / Journal of Molecular and Cellular Cardiology 40 (2006) 920–1015974