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A study was conducted with 82 men and 113 women for a period of 18 months, to understand the prevalence of pulmonary hypertension in adults with sickle cell disease. The developmental mechanism and prognostic significance using Doppler echocardiography therapeutic trials are highlighted along with the results.

We evaluated the direct effect of hyperglycemia on apoptosis of adult rat ventricular myocytes (ARVM) in vitro. Hyperglycemia (16.5 mM) for 24 h increased apoptosis by greater than threefold (48.2 [+ or -] 4.4%, by the TdT-mediated dUTP nick-end labeling method) compared with baseline (14.7 [+ or -] 2.5%). Hyperosmolarity with mannitol (11.0 mM) in the presence of 5.5 mM glucose also increased apoptosis by approximately twofold of baseline. Both glucose and mannitol treatment resulted in the membrane translocation of protein kinase C (PKC)-[delta], and the activation of PKC-[delta] was confirmed by immune complex kinase assay. PKC-[delta]-specific translocation inhibitor peptide ([delta]V1-1) attenuated only apoptosis induced by hyperglycemia but not by mannitol. A PKC-[epsilon]-specific translocation inhibitor peptide ([epsilon]V1-1) affected neither type of apoptosis. Moderate overexpression of PKC-[delta] by adenovirus gene transfer prevented the antiapoptotic effect of [delta]V1-1. Furthermore, [delta]V1-1 attenuated the production of reactive oxygen species (ROS) by glucose. Taken together, our results indicate that increased ROS production regulated by PKC-[delta] is in part responsible for the induction of apoptosis by hyperglycemia and that apoptosis by hyperglycemia is mechanistically different from that by hyperosmolarity. reactive oxygen species; glucose; mannitol; antioxidant; adenovirus

Protein kinase C-[zeta] modulates thromboxane [A.sub.2]-mediated apoptosis in adult ventricular myocytes via Akt. Am J Physiol Heart Circ Physiol 282: H320-H327, 2002.--We hypothesized that thromboxane [A.sub.2] (Tx[A.sub.2]) receptor stimulation directly induces apoptosis in adult cardiac myocytes. To investigate this, we exposed cultured adult rat ventricular myocytes (ARVM) to a Tx[A.sub.2] mimetic [1S-[1[alpha],2[alpha](Z),3[beta](1E,3[S.sup.*]), 4[alpha]]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl] -7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (I-BOP) for 24 h. Stimulation with I-BOP induced apoptosis in a dose-dependent manner and was completely prevented by a Tx[A.sub.2] receptor antagonist, SQ-29548. We further investigated the role of protein kinase C (PKC) in this process. Tx[A.sub.2] stimulation resulted in membrane translocation of PKC-[zeta] but not PKC-[alpha], -[beta]II, -[delta], and -[member of] at 3 min and 1 h. The activation of PKC-[zeta] by I-BOP was confirmed using an immune complex kinase assay. Treatment of ARVM with a cell-permeable PKC-[zeta] pseudosubstrate peptide ([zeta]-PS) significantly attenuated apoptosis by I-BOP. In addition, I-BOP treatment decreased baseline Akt activity and its decrease was reversed by treatment with [zeta]-PS. The inhibition of phosphatidylinositol 3-kinase upstream of Akt by wortmannin or LY-294002 abolished the antiapoptotic effect of [zeta]-PS. Therefore, our results suggest that the activation of PKC-[zeta] modulates Tx[A.sub.2] receptor-mediated apoptosis at least, in part, through Akt activity in adult cardiac myocytes. atypical protein kinase C; eicosanoids; Akt/protein kinase B; mitogen activated protein kinases

Abstract Background Heart transplant (HT) recipients demonstrate limited exercise capacity compared to normal patients, very likely for multiple reasons. In this study we hypothesized that left atrial volume (LAV), which is known to predict exercise capacity in patients with various cardiac pathologies including heart failure and hypertrophic cardiomyopathy is associated with limited exercise capacity of HT recipients. Methods We analyzed 50 patients [age 57 ±2 (SEM), 12 females] who had a post-HT echocardiography and cardiopulmonary exercise test (CPX) within 9 weeks time at clinic follow up. The change in LAV (ΔLAV) was also computed as the difference in LAV from the preceding one-year to the study echocardiogram. Correlations among the measured parameters were assessed with a Pearson's correlation analysis. Results LAV (n = 50) and ΔLAV (n = 40) indexed to body surface area were 40.6 ± 11.5 ml·m-2 and 1.9 ± 8.5 ml·m-2·year-1, data are mean ± SD, respectively. Indexed LAV and ΔLAV were both significantly correlated with the ventilatory efficiency, assessed by the VE/VCO2 slope (r = 0.300, p = 0.038; r = 0.484, p = 0.002, respectively). LAV showed a significant correlation with peak oxygen consumption (r = -0.328, p = 0.020). Conclusions Although our study is limited by a retrospective study design and relatively small number of patients, our findings suggest that enlarged LAV and increasing change in LAV is associated with the diminished exercise capacity in HT recipients and warrants further investigation to better elucidate this relationship.

Abstract We report a case of a 26-year-old female, who presented at 34 weeks of an uncomplicated pregnancy with an acute ST elevation anterior wall myocardial infarction. Cardiac catheterization suggested a left main coronary artery dissection with pseudoaneurysm formation. The patient's course was complicated by congestive heart failure. She was initially managed conservatively by a multidisciplinary team including heart failure specialists, obstetricians, and cardiovascular surgeons. 4 days after admission, her LMC was imaged by dual-source 64 slice Cardiac computed tomography, coronary dissection was identified extending to the lumen, and the presence of pseudoaneurysm was confirmed. She underwent subsequently a staged procedure, which included placement of an intra-aortic balloon pump, cesarean section, and coronary artery bypass grafting. This case illustrates the utility of coronary artery CT imaging to assess the complexity and stability of coronary artery dissections, thereby helping to determine the need for, and timing of revascularization procedures.