Perinatal cardiopulmonary adaptation to the thin air of the Alto Andino by a native Altiplano dweller, the llama.

Most mammals have a poor tolerance to hypoxia, and prolonged O2 restriction can lead to organ injury, particularly during fetal and early postnatal life. Nevertheless, the llama (Lama Glama) has evolved efficient mechanisms to adapt to acute and chronic perinatal hypoxia. One striking adaptation is the marked peripheral vasoconstriction measured in the llama fetus in response to acute hypoxia, which allows efficient redistribution of cardiac output toward the fetal heart and adrenal glands. This strong peripheral vasoconstrictor tone is triggered by a carotid body reflex and critically depends on α-adrenergic signaling. A second adaptation is the ability of the llama fetus to protect its brain against hypoxic damage. During hypoxia, in the llama fetus there is no significant increase in brain blood flow. Instead, there is a fall in brain O2 consumption and temperature, together with a decrease of Na+-K+-ATPase activity and Na+ channels expression, protecting against seizures and neuronal death. Finally, the newborn llama does not develop pulmonary hypertension in response to chronic hypoxia. In addition to maintaining basal pulmonary arterial pressure at normal levels the pulmonary arterial pressor response to acute hypoxia is lower in highland than in lowland llamas. The protection against hypoxic pulmonary arterial hypertension and pulmonary contractile hyperreactivity is partly due to increased hemoxygenase-carbon monoxide signaling and decreased Ca2+ sensitization in the newborn llama pulmonary vasculature. These three striking physiological adaptations of the llama allow this species to live and thrive under the chronic influence of the hypobaric hypoxia of life at high altitude.

Pharmacological approaches in either intermittent or permanent hypoxia: A tale of two exposures.

Hypoxia induces several responses at cardiovascular, pulmonary and reproductive levels, which may lead to chronic diseases. This is relevant in human populations exposed to high altitude (HA), in either chronic continuous (permanent inhabitants) or intermittent fashion (HA workers, tourists and mountaineers). In Chile, it is estimated that 1.000.000 people live at highlands and more than 55.000 work in HA shifts. Initial responses to hypoxia are compensatory and induce activation of cardioprotective mechanisms, such as those seen under intermittent hypobaric (IH) hypoxia, events that could mediate preconditioning. However, whenever hypoxia is prolonged, the chronic activation of cellular responses induces long-lasting modifications that may result in acclimatization or produce maladaptive changes with increase in cardiovascular risk. HA exposure during pregnancy induces hypoxia and oxidative stress, which in turn may promote cellular responses and epigenetic modifications resulting in severe impairment in growth and development. Sadly, this condition is accompanied with an increased fetal and neonatal morbi-mortality. Further, developmental hypoxia may program cardio-pulmonary circulations later in postnatal life, ending in vascular structural and functional alterations with augmented risk on pulmonary and cardiovascular failure. Additionally, permanent HA inhabitants have augmented risk and prevalence of chronic hypoxic pulmonary hypertension, right ventricular hypertrophy and cardiopulmonary remodeling. Similar responses are seen in adults that are intermittently exposed to chronic hypoxia (CH) such as shift workers in HA areas. The mechanisms involved determining the immediate, short and long-lasting effects are still unclear. For several years, the study of the responses to hypoxic insults and pharmacological targets has been the motivation of our group. This review describes some of the mechanisms underlying hypoxic responses and potential therapeutic approaches with antioxidants such as melatonin, ascorbate, omega 3 (Ω3) or compounds that increase the nitric oxide (NO) bioavailability.

Fetal and postnatal pulmonary circulation in the Alto Andino.

Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the llama fetus compared to the sheep fetus. Altogether these data show that the fetal llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the llama. The llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.

Caracterización y control metabólico de los pacientes con diabetes mellitus tipo 2 insulino-requirentes en control; en el hospital Dr. Gustavo Fricke / Characterization and metabolic control in patients with diabetes mellitus type 2 requiring insulin under therapy at Dr. Gustavo Fricke Hospital

La diabetes mellitus (DM) es una de las patologías que genera mayor discapacidad y mortalidad en el mundo. Muchos estudios han comprobado que un óptimo control de la enfermedad con acciones fundamentadas en el control metabólico, constituye una herramienta clave para disminuir la magnitud de sus complicaciones agudas y crónicas. En este contexto se desarrolla el presente estudio, con el objetivo de describir la situación de los pacientes diabéticos tipo 2 insulino requirentes en control en el Policlínico de Endocrinología del Hospital Dr. Gustavo Fricke de Viña del Mar. Este se realizó de forma transversal descriptivo, a partir de las 939 cartolas de control y seguimiento de estos pacientes, de las cuales 474 cumplieron los criterios de inclusión. Se estudiaron las variables relacionadas con la caracterización de los pacientes, el nivel de control metabólico y la presencia de complicaciones y factores de riesgo concomitantes. El promedio de controles, durante el período de estudio de 18 meses (Enero 2006-Junio 2007), fue de 2,8. El 19,4 por ciento presentaba un buen control metabólico según glicemias de ayunas. La hipertensión arterial, dislipidemia y obesidad se presentaron asociadas en un 65 por ciento, 55 por ciento y 31 por ciento respectivamente. Un 31 por ciento presenta algún grado de nefropatía, 23 por ciento neuropatía periférica y 7 por ciento pie diabético. Del 30 por ciento que registra al menos un examen de fondo de ojo realizado, el 64 por ciento era patológico. No se encontraron diferencias en el control metabólico de los pacientes dependiendo si disponían o no de equipos de automonitoreo. Se concluye que la población de pacientes DM2IR controlados en el HGF ha aumentado, su control metabólico es deficiente y el número de complicaciones crónicas, así como la asociación con otros factores de riesgo, es elevado. La "tarjeta de control y seguimiento", representa una buena herramienta, que debiera ser mejor utilizada.

Diabetes mellitus (DM) is one of the diseases that causes more incapacity and mortality in the world. Many studies have verified that an optimal control of the disease, with actions based on metabolic control, constitutes a key tool to diminish the magnitude of the acute and chronic complications. Against this background, the present study was developed with the aim of describing the situation of diabetic type 2 patients with insulin therapy under follow up in the Endocrinology Clinic at Hospital Dr. Gustavo Fricke, in Viña del Mar. Using a descriptive cross-sectional form, of the 939 patient follow up control cards, 474 fulfilled the inclusion criteria. The characterization variables were the level of metabolic control and the presence of complications and concomitant risk factors. Control average during the period of study of 18 months (January 2006-June 2007), was 2,8 times; 19.4 percent displayed good metabolic control according to fasting blood sugar. Arterial hypertension, hyperlipidemia and obesity were associated in 65 percent, 55 percent and 31 percent respectively. Thirty one percent of the cases presented some degree of nephropathy, 23 percent peripheral neuropathy and 7 percent diabetic foot. Of the 30 percent that registers at least a basic ophthalmoscopy, 64 percent were pathological. No differences were detected in the metabolic control of the patients depending if they had or not auto monitoring devices. Conclusions of the study are that DM2IR patients under control at our hospital have increased, their metabolic control is deficient, they have an elevated number of chronic complications as well as an association with other factors of risk. The "control and pursuit card" represents a good tool that should be better used.