Effects of nontransmural ischemia on inner and outer wall thickening in the canine left ventricle

The effect of ischemic subendocardial dysfunction on contractile function in the normally perfused subepicardium remains controversial. Accordingly, regional wall thickening (WT) was measured directly in the left ventricle of 10 open-chest dogs using epicardial echocardiography. Two silk sutures, used as echocardiographic targets, were inserted beneath the transducer to a depth of 25.0 +/- 0.7% (subepicardium) and 48.0 +/- 2.7% (midmyocardium) of transmural thickness. A hydraulic cuff, placed around the left anterior descending coronary artery (LAD) was then inflated slowly until transmural WT was reduced to 62 +/- 2% of baseline. Myocardial blood flow (MBF) was not significantly altered in the subepicardial third of the wall; however, flow to the midwall and subendocardial thirds decreased by 39% (p p p p p r = 0.88, p < 0.001). Thus the degree of dysfunction produced by nontransmural ischemia increased progressively from the subepicardium to the subendocardium, parallelling the pattern of perfusion. We conclude that perfusion, rather than transmural tethering, largely determines subepicardial function in the setting of nontransmural ischemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29072/1/0000107.pd

"Protective effect of Placenta Growth Factor (PIGF) against hypoxia-reoxgyenation and serum-deprivation induced apoptosis in neonatal rat cardiomyocytes"

Kyle Bohman, Marin Schweizer and Bob Berendt are all Drake University students. Ronald J. Torry is Associate Professor of Pharmacology at Drake University. Donald S. Torry is a faculty member at the Southern Illinois University School of Medicine.Placenta growth factor (PlGF) is known to induce angiogenesis and protect placental trophoblast from apoptosis. We have shown that PlGF mRNA expression is increased in hypoxic human myocardium and in rat neonatal cardiomyocytes. However, little is known regarding the function of PlGF in heart tissue. Others have shown that PlGF or PlGF/VEGF significantly inhibited apoptosis in endothelial cells from PlGF knockout mice and we have shown that PlGF rescues cultured trophoblast from apoptosis induced by serum deprivation. Accordingly, our hypothesis is that PlGF protects cardiomyocytes from ischemia-induced or serum deprivation-induced apoptosis. The role of PlGF will be investigated during cardiomyocyte apoptosis induced by serum-deprivation and hypoxia-reoxygenation (H/R)--physiological conditions relevant to ischemic cardiomyopathy. Hypoxic conditions were established by culturing the cells at 1-2% O2. Caspase-3,7 luminescence assay (Promega) was used to determine the level of activated Caspases 3 and 7. The caspase family of cysteine proteases, especially caspase-3, is central in amplifying the cascade of proteolysis that culminates in cell death. Serum-deprivation and H/R have been found to be consistent methods of creating ischemic stresses and inducing apoptosis in rat cardiomyocytes. Serum-deprivation produced a 1.55 fold increase of apoptosis over normoxic values (n=10). H/R lead to a 1.98 fold increase of apoptosis (n=1). Our preliminary data suggest that a PlGF (25ng/ml) or PlGF/VEGF (25ng/ml each) does not reduce apoptosis induced by serum-deprivation. However, an 8 hour pretreatment of PlGF (25ng/ml) by itself reduced caspase 3 activity by 25.5% (n=1) and 30.7% (n=3) during hypoxia or serum deprivation, respectively. The preliminary data show an 8 hour pretreatment with PlGF/VEGF (25ng/ml each) decreased caspase activity more than PlGF (25ng/ml) alone. Thus, early evidence indicates that pretreatment with PlGF or PlGF/VEGF may protect cardiomyocytes from hypoxia-reoxygenation and/or serum deprivation-induced apoptosis.Drake University, College of Pharmacy and Health Sciences. Department of Pharmaceutical Sciences

"Detection of PIGF protein in neonatal rat cardiomyocytes"

Marin Schweizer, Kyle Bohman, Carrie Mittelstedter and Ben Colton are all Drake University students. Ronald J. Torry is Associate Professor of Pharmacology at Drake University. Donald S. Torry is on the faculty at Southern Illinois University School of Medicine.Angiogenesis, the formation of blood vessels, can provide blood to the heart when its normal arteries are compromised. Angiogenesis is highly dependent on the Vascular Endothelial Growth Factor (VEGF) family. Placental Growth Factor (PlGF) is a member of this family and is crucial for pathological angiogenesis in the adult. PlGF coupled with the more common VEGF could greatly increase angiogenesis in the heart tissue, thus providing oxygen to ischemic heart tissue. Previous research has shown that PlGF mRNA increases with six hours of hypoxia which models ischemia. However, not much is known about PlGF expression on the protein level. We intend to establish that PlGF protein expression will increase in rat cardiomyocytes which have undergone 6, 12 and 24 hours of hypoxia compared to normoxic rat cardiomyocytes. This information will later be used in studies of potential protective treatments using PlGF.Drake University, College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences