These results are consistent with the hypothesis that during initial reperfusion NCX activity results in net reverse mode operation contributing to Ca(2+) overload, hypercontracture and cell death, and that NCX inhibition during this phase is beneficial. Beyond this phase, NCX inhibition may impair forward mode-dependent Ca(2+) extrusion and be detrimental. These findings may help in the design of therapeutic strategies against lethal reperfusion injury, with NCX as the target.

Objective: To assess the structural and functional characteristics of pulmonary arteries by intravascular ultrasound (IVUS) in the setting of primary pulmonary hypertension, and to correlate the ultrasound findings with haemodynamic variables and mortality at follow up. Design: Prospective observational study. Setting: University hospital (tertiary referral centre). Patients: 20 consecutive patients with primary pulmonary hypertension (16 female; mean (SD) age, 39 (14) years). Methods: Cardiac catheterisation and simultaneous IVUS of pulmonary artery branches at baseline and after infusion of epoprostenol. Results: 33 pulmonary arteries with a mean diameter of 3.91 (0.80) mm were imaged, and wall thickening was observed in all cases, 64% being eccentric. Mean wall thickness was 0.37 (0.13) mm, percentage wall area 31.0 (9.3)%, pulsatility 14.6 (4.8)%, and pulmonary/elastic strain index 449 (174) mm Hg. No correlation was observed between IVUS findings and haemodynamic variables. Epoprostenol infusion increased pulsatility by 53% and decreased the pulmonary/elastic strain index by 41% (p = 0.0001), irrespective of haemodynamic changes. At 18 (12) months follow up, nine patients had died. A reduced pulsatility and an increased pulmonary/elastic strain index were associated with increased mortality at follow up ( Conclusions: IVUS demonstrated pulmonary artery wall abnormalities in all patients with primary pulmonary hypertension, mostly eccentric. The severity of the changes did not correlate with haemodynamic variables, and epoprostenol improved pulmonary vessel stiffness. There was an association between impaired pulmonary artery functional state as determined by IVUS and mortality at follow up. P rimary pulmonary hypertension is a life threatening disease characterised by a progressive increase in pulmonary blood pressure that often leads to right ventricular failure and death.1 Median survival is 2.8 years from the time of diagnosis, and mortality reaches 65% at three years of follow up.2 Calcium channel blockers, warfarin, and prostacyclin have improved the prognosis, but the three year mortality has remained as high as 50%. The diagnosis of primary pulmonary hypertension is based on clinical and haemodynamic data, and prognosis is determined by the alterations in haemodynamic variables (mean pulmonary artery pressure, cardiac output, mean right atrial pressure).The assessment of pulmonary artery morphology in primary pulmonary hypertension has been limited to pulmonary angiography and to the histological study of lung samples obtained at biopsy. Pulmonary angiography, which is not free of complications in these cases, only shows the vessel lumen and provides no information about vessel wall abnormalities. Histological evaluation of lung biopsies provides a valuable quantitative and qualitative description of the pulmonary wall changes, but remains a static in vitro examination without functional assessment and requires a thoracotomy. Intravascular ultrasound (IVUS) has been validated as a reliable method for...

Platelets (Plt) accumulate in reperfused myocardium but their effect on myocardial necrosis has not been established. We tested the hypothesis that the effect of Plt depends on their activation status. Pig Plt were obtained before 48 min of coronary occlusion (pre-CO-Plt), 10 min after reperfusion (R-Plt), or after a 60-min sham operation (sham-Plt). Plt were infused into isolated rat hearts (n = 124) and subsequently submitted to 60 min of ischemia and 60 min of reperfusion. P-selectin expression was higher (P = 0.02) in R-Plt than in pre-CO-Plt or sham-Plt. Lactate dehydrogenase (LDH) release during reperfusion was similar in hearts receiving pre-CO-Plt, sham-Plt, or no Plt, but R-Plt increased LDH release by 60% (P = 0.004). Activation of pre-CO-Plt with thrombin increased P-selectin expression and LDH release (P < 0.001), and these results were unaffected by tirofiban. There was a close correlation between P-selectin expression and LDH release (r = 0.84; P < 0.001), and myocardial Plt accumulation (r = 0.85; P < 0.001). We conclude that the deleterious effect of Plt on reperfused myocardium depends on their activation status as represented by P-selectin expression, which is enhanced by ischemia-reperfusion.

The results suggest that selectin-dependent adhesion is a prominent mechanism of platelet deposition in reperfused cardiac microvessels and highlight its potential as a therapeutic target in patients with acute myocardial infarction.

The end-effectors of ischemic preconditioning (IPC) are not well known. It has been recently shown that transgenic mice underexpressing the gap junction protein connexin43 (Cx43) cannot be preconditioned. Because gap junctions allow spreading of cell death during ischemia-reperfusion in different tissues, including myocardium, we hypothesized that the protection afforded by IPC is mediated by effects on gap junction-mediated intercellular communication. To test this hypothesis, we analyzed the effect of IPC (5 min ischemia-5 min reperfusion x 2) on the changes in electrical impedance (four electrode probe) and impulse propagation velocity (transmembrane action potential) induced by ischemia (60 min) and reperfusion (60 min) in isolated rat hearts. IPC (n = 8) reduced reperfusion-induced lactate dehydrogenase release by 65.8% with respect to control hearts (n = 9) (P = 0.04) but had no effect on the time of onset of rigor contracture (increase in diastolic tension), electrical uncoupling (sharp changes in tissue resistivity and phase angle in impedance recordings), or block of impulse propagation during ischemia. Normalization of electrical impedance during reperfusion was also unaffected by IPC. The lack of effect of IPC on ischemic rigor contracture and on changes in tissue impedance during ischemia-reperfusion were validated under in vivo conditions in pigs submitted to 48 min of coronary occlusion and 120 min of reperfusion. IPC (n = 12) reduced infarct size (triphenyltetrazolium) by 64.9% (P = 0.01) with respect to controls (n = 17). We conclude that the protection afforded by IPC is not mediated by effects on electrical coupling. This result is consistent with recent findings suggesting that Cx43 could have effects on cell survival independent on changes in cell-to-cell communication.