Pulmonary vascular responses to endothelin (ET-1), a peptide derived from endothelial cells in culture, were investigated in the ovine fetus delivered by cesarean section from chloralose-anesthetized ewes with intact umbilical circulation. Circulation to the lower left lobe of the fetal lung was isolated in situ and perfused at constant flow with blood withdrawn from the inferior vena cava. Injection of graded doses of ET-1 into the left pulmonary artery decreased pulmonary arterial perfusion pressure in a dose-related manner. At doses of 100, 300, and 1,000 ng, pulmonary vascular resistance per kilogram body weight (PVR/kg) was decreased 30, 40, and 42%, respectively. However, when fetuses were ventilated with 100% oxygen, 100- and 300-ng doses of ET-1 decreased PVR/kg by 5 and 9%, respectively. In contrast, injection of 1,000 ng of ET-1 resulted in a reversal of the response, and PVR/kg was increased by 70%. Ventilation of the right lung alone resulted in a similar reversal of the vasodilator response to 1,000 ng of ET-1, and a 138% increase in PVR/kg was recorded. These studies demonstrate for the first time that ET-1 has vasodilator activity in the normally high-tone ovine fetal pulmonary circulation. In addition, these results show that ET-1 has vasoconstrictor activity in the newly ventilated low-tone pulmonary vasculature. The present data indicate the pulmonary vascular responses to ET-1 are tone dependent in the ovine fetal pulmonary circulation.
Our study confirmed a relatively high prevalence of polypharmacy in Slovak elderly patients. Polypharmacy risk rose especially with the increased prevalence of diseases of advancing age (diabetes mellitus, heart failure, arterial hypertension, dementia and cerebrovascular diseases). The increasing numbers of medications in inpatients indicate the need for the careful re-evaluation of pharmacotherapy during the stay in hospital.
Non-steroidal anti-inflammatory drugs (NSAIDs) belong to the most widely prescribed and used pharmacological agents worldwide. Data gathered in the last decade show increased incidence of thrombotic events during NSAID administration. Analysis of NSAID usage and assessment of risk for development of cardiovascular adverse effects is needed for improving patient safety. For limiting the impact of adverse effects on the health of patients, NSAID users should be informed about the possible adverse effects and their symptoms to ensure early detection and treatment discontinuation. In the presented study, we retrospectively analyzed the administration of NSAIDs in a group of patients (n=428) in need of analgesic treatment hospitalized at a department of internal medicine. Factors increasing the risk for cardiovascular adverse effects were also investigated. A separate questionnaire study was conducted to gather information concerning the knowledge of hospitalized NSAID users (n=251) about adverse effects of the medication used. For purpose of comparison, we conducted a similar study in a group of 234 random respondents from a shopping center. Data were evaluated using descriptive statistics, Student′s t-test and chi-squared test. Our results suggest that the majority of patients treated with NSAIDs have factors indicating increased risk of development of adverse effects, most commonly arterial hypertension (58.2% of patients). The results of our questionnaire study show limited knowledge of NSAID users about the risk of the therapy. Nearly half of the respondents were unaware of any adverse effects. We consider as alarming that only a limited number of respondents were informed by their physician or pharmacist about the possible risks of treatment. In conclusion, we found that hospitalized NSAID users often have a history of diseases predisposing to the development of cardiovascular adverse effects of NSAIDs. Despite this, their knowledge about the risk of treatment is insufficient.
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