Perindopril and indapamide reverse coronary microvascular remodelling and improve flow in arterial hypertension.

OBJECTIVES: Patients and animal models of arterial hypertension are characterized by structural and functional abnormalities of the coronary microcirculation. Using a translational approach, we ascertained whether antihypertensive treatment can reverse microvascular remodelling and improve myocardial perfusion. METHODS: In 20 hypertensive patients with left ventricular hypertrophy, blood pressure, left ventricular mass index and myocardial blood flow were measured at baseline and after 6 months of treatment with perindopril + indapamide. In spontaneously hypertensive rats, blood pressure, coronary flow and histomorphometry of intramural coronary arterioles were measured after 8 weeks of treatment with placebo or perindopril + indapamide. RESULTS: In patients, treatment decreased blood pressure (161 ± 10/96 ± 5 to 136 ± 12/81 ± 6 mmHg; P < 0.0001) and left ventricular mass index (93 ± 16 to 85 ± 17 g/m; P < 0.01) while increasing baseline (0.69 ± 0.13 to 0.88 ± 0.36 ml/min per g; P < 0.05) and hyperaemic myocardial blood flow (1.42 ± 0.32 to 1.94 ± 0.99 ml/min per g; P < 0.05). In rats treated with perindopril + indapamide (n = 11), blood pressure was 93 ± 18/55 ± 18 mmHg compared to 215 ± 18/161 ± 17 mmHg in placebo (n = 6; P < 0.001), baseline flow was unchanged whilst hyperaemic coronary flow was 19.89 ± 3.50 vs. 12.15 ± 0.99 ml/min per g, respectively (P < 0.01). The medial area of intramural arterioles was 1613 ± 409 with perindopril + indapamide and 8118 ± 901 µm with placebo (P < 0.001). CONCLUSION: In patients with arterial hypertension and left ventricular hypertrophy, perindopril + indapamide reduced blood pressure and left ventricular mass index and improved resting and hyperaemic myocardial blood flow. Data in rats provide evidence that the improvement in coronary flow observed after treatment is due to reverse remodelling of intramural coronary arterioles and improved microvascular function.

Adverse effects of cigarette smoke and induction of oxidative stress in cardiomyocytes and vascular endothelium.

Active and passive exposure to cigarette smoke (CS) increases the risk of, and has deleterious effects in, ischaemic heart disease. Exposure to CS increases infarct size in experimental models of coronary occlusion and reperfusion. Among many possible mechanisms for these deleterious effects in intact animals and humans three have more substantial evidence: 1) functional alterations of endothelial cells, neutrophils and platelets; 2) impaired mitochondrial function and energy metabolism caused by toxins in CS, including oxidative free radicals; 3) increased arterial stiffness and vulnerability of the atherosclerotic plaque. In addition to the various pro-mitogenic, carcinogenic and apoptotic pathways thought to be affected and upregulated by CS, a direct necrotic action on cardiomyocytes is also believed to exist. Many, if not all, of these alterations are caused by oxidative stress, either as a direct consequence of inhalation of free radicals, or by induction from the vast range of chemicals present in both the gas and solid phase of tobacco smoke. Here, some of the proposed mechanisms will be reviewed and their impact on the cardiomyocytes and peripheral vasculature discussed.

Children with chronic complex medical illnesses: Is inpatient care family-centered?

BACKGROUND: Families of children with complex chronic medical illnesses (CCMI) benefit from coordinated, family-centered healthcare. OBJECTIVE: Compare parental perceptions of inpatient family-centered care for children with CCMI in structured clinical programs (SCPs) with those who are not in SCPs. DESIGN/METHODS: Cross-sectional mail survey of parents of children with CCMIs using the 56-item Measure of Processes of Care (MPOC) to rate perceptions of family-centered healthcare. We compared responses of SCP to non-SCP children. RESULTS: 215 (36.6%) of 588 surveys were returned. Response rates were 40.0% for SCP and 33.8% for non-SCP children. The proportion of favorable (6-7) ratings was higher for the SCP group than for the non-SCP group (52.4% vs. 48.3%, p < 0.035). The proportion of unfavorable ratings was also different (5.4% vs. 12.3%, p =< 0.001). SCP families felt care was directed at the whole child and consistent. Non-SCP families reported more unmet needs and less recognition of their role. CONCLUSIONS: Parents of children with CCMI perceive inpatient care as more family-centered when provided in conjunction with a SCP. Children receiving non-SCP care may benefit from inclusion in SCPs dedicated to their needs. Further studies to determine the best way to provide this care are needed.

Preventable harm occurring to critically ill children.

OBJECTIVE: To develop a trigger tool for identifying adverse events occurring in critically ill pediatric patients; to identify and characterize adverse events and preventable adverse events experienced by critically ill pediatric patients; and to characterize the patients who experience preventable adverse events. DESIGN: Retrospective chart review using a trigger tool. SETTING: Pediatric intensive care unit of a tertiary, university-affiliated pediatric hospital. PATIENTS: A systematic sample of 259 pediatric intensive care unit patients from a 1-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured frequency of occurrence (0.19 preventable adverse events per patient-day), severity of harm (78% minor, 19% moderate, 3% serious, no deaths), and type of event (sedation, 22%; skin, 16%; medical device complication, 14%; pulmonary, 13%; and cardiovascular, 11%). Patients who experienced preventable adverse events were younger, had longer lengths of stay, and had higher illness burdens. Preventable adverse events occurred more frequently among surgical patients than medical patients. CONCLUSIONS: Preventable adverse events occurred fairly frequently in the pediatric intensive care unit, but serious harm was rare. Conditions that increased the likelihood of a preventable adverse event were a) need for sedation or pain control; b) relative immobility; and c) need for vascular devices, feeding tubes, or ventilators. Adverse event prevention strategies that focus on improving patient monitoring under increased-risk conditions and improving early detection and treatment of potential harm will likely be more effective than strategies aimed at general error prevention.

Harvesting of males delays female breeding in a socially monogamous mammal; the beaver.

Human exploitation may skew adult sex ratios in vertebrate populations to the extent that males become limiting for normal reproduction. In polygynous ungulates, females delay breeding in heavily harvested populations, but effects are often fairly small. We would expect a stronger effect of male harvesting in species with a monogamous mating system, but no such study has been performed. We analysed the effect of harvesting males on the timing of reproduction in the obligate monogamous beaver (Castor fiber). We found a negative impact of harvesting of adult males on the timing of parturition in female beavers. The proportion of normal breeders sank from over 80%, when no males had been shot in the territories of pregnant females, to under 20%, when three males had been shot. Harvesting of males in monogamous mammals can apparently affect their normal reproductive cycle.

Standard drug concentrations and smart-pump technology reduce continuous-medication-infusion errors in pediatric patients.

OBJECTIVE: To determine if combining standard drug concentrations with "smart-pump" technology reduces reported medication-infusion errors. DESIGN: Preintervention and postintervention comparison of reported medication errors related to infusion therapies during the calendar years 2002 and 2003. SETTING: A 242-bed university-affiliated tertiary pediatric hospital. INTERVENTION: Change in continuous-medication-infusion process, comprising the adoption of (1) standard drug concentrations, (2) "smart" syringe pumps, and (3) human-engineered medication labels. MAIN OUTCOME MEASURES: Comparison of reported continuous-medication-infusion errors before and after the intervention. RESULTS: The number of reported errors dropped by 73% for an absolute risk reduction of 3.1 to 0.8 per 1000 doses. Preparation errors that occurred in the pharmacy decreased from 0.66 to 0.16 per 1000 doses; the number of 10-fold errors in dosage decreased from 0.41 to 0.08 per 1000 doses. CONCLUSIONS: The use of standard drug concentrations, smart syringe pumps, and user-friendly labels reduces reported errors associated with continuous medication infusions. Standard drug concentrations can be chosen to allow most neonates to receive needed medications without concerns related to excess fluid administration.