Background Apoptosis contributes to cell loss after ischemia/reperfusion injury in the heart. This study describes the time course and level of apoptosis in different cell types in the intact heart during ischemia/reperfusion injury. Methods and Results Isolated Langendorff-perfused rat hearts were subjected to perfusion alone (control) or to 35 minutes of regional ischemia, either alone or followed by 5, 60, or 120 minutes of reperfusion. Sections were stained by terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL) and propidium iodide and with anti-von Willebrand factor, anti-desmin, or anti-active caspase 3 antibodies; they were then visualized by confocal microscopy. Sections were also examined by electron microscopy. No TUNEL-positive cells were seen in control hearts or hearts exposed to ischemia alone. Early in reperfusion, TUNEL staining was colocalized with endothelial cells from small coronary vessels. Endothelial apoptosis peaked at 1 hour of reperfusion and, at this time, there was clear perivascular localization of apoptotic cardiac myocytes, whose number was inversely proportional to their distance from a positive vessel. After 2 hours of reperfusion, apoptotic cardiac myocytes assumed a more homogeneous distribution. Active caspase 3 labeling was seen independent of DNA fragmentation during ischemia alone, but it colocalized with TUNEL staining over the 3 time points of reperfusion. Immunocytochemical findings were confirmed by electron microscopy and Western blotting. Conclusions In the very early stages of reperfusion, apoptosis is first seen in the endothelial cells from small coronary vessels. The radial spread of apoptosis to surrounding cardiac myocytes suggests that reperfusion induces the release of soluble pro-apoptotic mediators from endothelial cells that promote myocyte apoptosis.

Background —Cytokine activation and endothelial dysfunction are typical phenomena of congestive heart failure (CHF). We tested the hypothesis that incubating human umbilical vein endothelial cells with serum from patients with CHF will downregulate endothelial constitutive nitric oxide synthase (eNOS) and induce apoptosis. Methods and Results —We studied 21 patients with severe CHF. Levels of tumor necrosis factor-α (TNF-α) and several neuroendocrine parameters were assessed. eNOS was measured by Western Blot analysis and apoptosis by optical microscopy and flow cytometry. We observed (1) eNOS downregulation (difference versus healthy subjects at 24 hours [ P <0.05] and 48 hours [ P <0.001]), (2) nuclear morphological changes typical of apoptosis; and (3) a high apoptotic rate with propidium iodide (increasing from 2.1±0.4% to 11.3±1.2% at 48 hours; P <0.001 versus healthy subjects) and annexin V. An anti-human TNF-α antibody did not completely counteract these effects. A strong correlation existed between eNOS downregulation and apoptosis ( r =−0.89; P <0.001). Conclusions —Serum from patients with severe CHF downregulates eNOS expression and increases apoptosis. High levels of TNF-α likely play a role, but they cannot be the only factor responsible.

Apoptosis contributes, with necrosis, to the cardiac cell loss after ischemia/reperfusion injury. The apoptotic cascade is initiated either by mitochondrial damage and activation of caspase-9 or by death receptor ligation and activation of caspase-8. In the present study, performed in the isolated rat heart exposed either to ischemia alone or ischemia followed by reperfusion, cleavage of caspase-9 was observed primarily in endothelial cells. Conversely, caspase-8 cleavage was only found in cardiomyocytes, where it progressively increased throughout reperfusion. Addition of a specific caspase-9 inhibitor to the perfusate before ischemia prevented endothelial apoptosis, whereas preischemic infusion of a specific caspase-8 inhibitor affected only myocyte apoptosis. Additionally, caspase-8–mediated BID processing was observed only during reperfusion. Production of tBID then sustains mitochondrial injury and perpetuates caspase-9 activation.

Within telehealth there are a number of domains relevant to pulmonary care: telemonitoring, teleassistance, telerehabilitation, teleconsultation and second opinion calls. In the last decade, several studies focusing on the effects of various telemanagement programs for patients with chronic obstructive pulmonary disease (COPD) have been published but with contradictory findings. From the literature, the best telemonitoring outcomes come from programs dedicated to aged and very sick patients, frequent exacerbators with multimorbidity and limited community support; programs using third-generation telemonitoring systems providing constant analytical and decisionmaking support (24 h/day, 7 days/week); countries where strong community links are not available; and zones where telemonitoring and rehabilitation can be delivered directly to the patient’s location. In the near future, it is expected that telemedicine will produce changes in work practices, cultural attitudes and organization, which will affect all professional figures involved in the provision of care. The key to optimizing the use of telemonitoring is to correctly identify who the ideal candidates are, at what time they need it, and for how long. The time course of disease progression varies from patient to patient; hence identifying for each patient a ‘correct window’ for initiating telemonitoring could be the correct solution. In conclusion, as clinicians, we need to identify the specific challenges we face in delivering care, and implement flexible systems that can be customized to individual patients’ requirements and adapted to our diverse healthcare contexts.