The effect of fenoldopam on the blood pressure of the rat.

1. Fenoldopam mesylate, a benzazepine derivative, is a D1 receptor agonist that lowers blood pressure through vasodilation of renal, mesenteric, coronary and cerebral vascular beds. 2. Experiments were performed in rats, and mean carotid blood pressure and heart rate were registered. Two series of experiments were performed: (1) fenoldopam as control group and (2) fenoldopam after pretreatment with one of the following drugs: the D1 antagonist SCH 23390, the D2 antagonist sulpiride, the selective beta1-adrenergic antagonist atenolol, the selective beta2-adrenergic antagonist ICI 118.551, the nonselective beta-adrenergic antagonist propranolol and the neurotoxin that destroys catecholaminergic nerve terminals 6-hydroxydopamine (6-OH-DA). 3. Fenoldopam produced a dose-dependent hypotensive effect that was not modified by pretreatment of the rat with atenolol or propranolol; however, ICI 118.551 produced a significant reduction of the hypotensive response induced by fenoldopam. 4. Pretreatment of the animals with SCH 23390 produced a significant dose-related reversal of the rat blood pressure reduction induced by low doses of fenoldopam. Sulpiride produced a result similar to that induced by pretreatment with SCH 23390. 5. The pretreatment of the animals with 6-OH-DA surprisingly attenuated the response induced by fenoldopam and produced only a significant reversal of the reduction of mean blood pressure induced with the lower dose of fenoldopam. 6. The findings obtained in the present work do not provide further evidence of direct participation of beta2-adrenergic receptors on the mechanism of action of fenoldopam. Its action seems to be mainly due to activation of D1 cardiovascular receptors.

[Oral vasodilators in the treatment of congestive heart failure]. / Vasodilatadores orales en la insuficiencia cardíaca.

Oral vasodilators have proved to be valuable drugs in the management of systolic or diastolic congestive heart failure. They produce a clinical and hemodynamic relief of preload, afterload or both during the resting state or exercise. Although left ventricular hypertrophy is an adaptative response to myocardial stress, in the long run it becomes an independent risk factor leading to diastolic dysfunction. At present, pharmacological regression of ventricular hypertrophy has a prognostic importance. Of the large number of available vasodilators, angiotensin converting enzyme inhibitors have proved to be the most successful drugs. They behave as afterload relievers, counteracting both the renin-angiotensin and adrenergic systems, but also are powerful inhibitors of cardiomyocite enlargement and interstitial connective tissue proliferation. This last structural change may revert the compromised diastolic function of the heart.

Congestive heart failure due to hypertensive ventricular diastolic dysfunction.

Left ventricular (LV) diastolic dysfunction is the first discernible manifestation of heart disease in hypertensive patients. Arterial hypertension with LV hypertrophy leads to reduced preload followed by impaired cardiac output (systolic dysfunction stemming from primary diastolic dysfunction). Diastolic dysfunction leads more often than systolic dysfunction to hypertensive heart failure and is in many cases clearly distinguishable from heart failure with low ejection fraction (EF). Mortality due to heart failure from impaired inotropism is higher than mortality due to diastolic dysfunction, but morbidity is lower. Hypertensive cardiomyopathies can be divided into 4 ascending categories, according to the pathophysiologic and clinical impact of hypertension on the heart: Degree I: LV diastolic dysfunction with no associated LV hypertrophy Degree II: LV diastolic dysfunction with echocardiographic LV hypertrophy Degree IIA: Normal exercise capacity in terms of maximal oxygen consumption Degree IIB: Impaired exercise capacity in terms of maximal oxygen consumption Degree III: Congestive heart failure (severe dyspnea and radiographically determined pulmonary edema with normal (> or = 50%) EF Degree IIIA: LV mass/volume ratio > 1.8 with little or no myocardial ischemia Degree IIIB: LV mass/volume ratio < 1.8 with significant myocardial ischemia Degree IV: Profile of dilated cardiomyopathy; LV hypertrophy and impaired EF (< 50%).

[Treatment for prevention of complications. The case of hypertension]. / Tratar para prevenir complicaciones. El caso de la hipertensión.

Nowadays treatment of risk factors seem to be most successful than treating illness itself or its complications. The importance of prospective international surveys in reducing complications has been underlined. From an epidemiological point of view, therapeutic strategies have proved to be more eficacious when applied to the whole hypertensive population than to selective high risk groups. Historically, tendency was aimed to lower diastolic blood pressure, classically a marker of essential hypertension. At present, trends seem to indicate that prognosis is more influenced by systolic hypertension, mainly in the aged. As aging progresses, diastolic pressure tends to decrease, arteries become rigid, cardiac output diminished and pulse wave velocity increases enhancing quick blood return to the heart at the end of systole. All these changes heighten blood pressure, overload the heart and diminish coronary flow. It has been recently reported that lowering diastolic blood pressure under 85-80 mmHg leads to coronary insufficiency or death. HOT study is under way in order to achieve the right criteria on this point. In our view, a key figure is not going to be the answer for everyone.

The beta 2 receptor plays a role in the hypotensive effect of L-dopa.

Levodopa is a dopamine precursor exerting its cardiovascular effects by conversion to dopamine and by other mechanisms not elucidated yet. Since beta receptors are involved in levodopa Central Nervous System actions, we tried to find out whether adrenergic receptors are involved in the hypotensive effect of levodopa at peripheral level. Experiments were performed on urethane anesthetized (1 ml/100 g i.p.) and heparinized (300 U.I./kg i.v.) rats. Heart rate and mean carotid blood pressure were registered through a polygraph. Pulmonary ventilation was facilitated by a tracheal cannula. Drugs were infused into the femoral vein through a polyethylene catheter. Two series of the following drugs were assayed: a) Dopamine (3.12 to 25.0 micrograms/100 g i.v.) and levodopa (12.5 to 100 micrograms/100 g i.v.) as control groups. b) The aforementioned drugs and dosages were assayed 20 minutes after intravenous propranolol (50 micrograms/100 g), atenolol (100 micrograms/100 g) and ICI 118.55 (25 micrograms/100 g). Dopamine produced a dose-related hypotensive effect (p < 0.02) which was not modified by propranolol, atenolol or ICI 118.55. Levodopa produced a dose-related blood pressure fall which was not changed by atenolol pre-treatment. Contrariwise, propranolol and ICI 118.55 evoked a blood pressure raise with levodopa. Since propranolol and ICI 118.55 have in common the beta 2 receptor blockade, it is suggested that such receptor has a key role in the hypotensive response induced by levodopa.

The beta 2 receptor plays a role in the hypotensive effect of L-dopa.

Levodopa is a dopamine precursor exerting its cardiovascular effects by conversion to dopamine and by other mechanisms not elucidated yet. Since beta receptors are involved in levodopa Central Nervous System actions, we tried to find out whether adrenergic receptors are involved in the hypotensive effect of levodopa at peripheral level. Experiments were performed on urethane anesthetized (1 ml/100 g i.p.) and heparinized (300 U.I./kg i.v.) rats. Heart rate and mean carotid blood pressure were registered through a polygraph. Pulmonary ventilation was facilitated by a tracheal cannula. Drugs were infused into the femoral vein through a polyethylene catheter. Two series of the following drugs were assayed: a) Dopamine (3.12 to 25.0 micrograms/100 g i.v.) and levodopa (12.5 to 100 micrograms/100 g i.v.) as control groups. b) The aforementioned drugs and dosages were assayed 20 minutes after intravenous propranolol (50 micrograms/100 g), atenolol (100 micrograms/100 g) and ICI 118.55 (25 micrograms/100 g). Dopamine produced a dose-related hypotensive effect (p < 0.02) which was not modified by propranolol, atenolol or ICI 118.55. Levodopa produced a dose-related blood pressure fall which was not changed by atenolol pre-treatment. Contrariwise, propranolol and ICI 118.55 evoked a blood pressure raise with levodopa. Since propranolol and ICI 118.55 have in common the beta 2 receptor blockade, it is suggested that such receptor has a key role in the hypotensive response induced by levodopa.

The beta-2 receptor plays a role in the hypotensive effect of L-Dopa

La levodopa ejerce efectos cardiovasculares tanto por conversasión a dopamina como por mecanismos no bien dilucidados. Los receptores beta adrenérgicos intervienen en los efectos de levodopa sobre el Sistema Nervioso Central. La participación de los receptores ß adrenérgicos en el efecto hipotensor periférico de la levodopa motiva el presente trabajo. En ratas anestesiadas (uretano 1 ml/100 i.p. y heparinizadas 300 U.I./Kgi.i.v.) se registró en un polígrafo la frecuencia cardíaca y la presión arterial media intracarotídea, una cánula traqueal facilitó la ventilación pulmonar. Los fármacos se inyectaron mediante un catéter de polietileno en la vena femoral. Grupos Experimentales: Grupo Control: a) Se estudió el efecto de Dopamina (3, 12 a 25Ag/100gi.v.) y levodopa (12.5 a 100gi.v.) sobre presión arterial y frecuencia cardíaca. Pretratados con Beta bloqueadores: b) Se estudió la influencia de propranolol (50Ag/100g), atenolol (100Ag/100g) e ICI118.55(25Ag/100g) inyectados 20 min antes sobre el efecto hipotensor de la dopamina y levodopa. La dopamina produjo hipotensión arterial dosis-dependiente (p<0.02) que no se modificó por propranolol, atenolol o ICI118.55. El tratamiento con atenolol no modificó la respuesta hipotensora de levodopa. El propranolol e ICI118.55 aumentaron la presión arterial. Propranolol e ICI118.55 comparten la propiedad de bloquear el receptor ß2. Se sugiere que ese receptor juega un rol fundamental en la hipotensión producida por levodopa (AU)

The beta-2 receptor plays a role in the hypotensive effect of L-Dopa

La levodopa ejerce efectos cardiovasculares tanto por conversasión a dopamina como por mecanismos no bien dilucidados. Los receptores beta adrenérgicos intervienen en los efectos de levodopa sobre el Sistema Nervioso Central. La participación de los receptores ß adrenérgicos en el efecto hipotensor periférico de la levodopa motiva el presente trabajo. En ratas anestesiadas (uretano 1 ml/100 i.p. y heparinizadas 300 U.I./Kgi.i.v.) se registró en un polígrafo la frecuencia cardíaca y la presión arterial media intracarotídea, una cánula traqueal facilitó la ventilación pulmonar. Los fármacos se inyectaron mediante un catéter de polietileno en la vena femoral. Grupos Experimentales: Grupo Control: a) Se estudió el efecto de Dopamina (3, 12 a 25µg/100gi.v.) y levodopa (12.5 a 100gi.v.) sobre presión arterial y frecuencia cardíaca. Pretratados con Beta bloqueadores: b) Se estudió la influencia de propranolol (50µg/100g), atenolol (100µg/100g) e ICI118.55(25µg/100g) inyectados 20 min antes sobre el efecto hipotensor de la dopamina y levodopa. La dopamina produjo hipotensión arterial dosis-dependiente (p<0.02) que no se modificó por propranolol, atenolol o ICI118.55. El tratamiento con atenolol no modificó la respuesta hipotensora de levodopa. El propranolol e ICI118.55 aumentaron la presión arterial. Propranolol e ICI118.55 comparten la propiedad de bloquear el receptor ß2. Se sugiere que ese receptor juega un rol fundamental en la hipotensión producida por levodopa

[The school of Blest and Sazie]. / La Escuela de Blest y Sazie.

The biographies and professional contributions of William Blest, Lorenzo Sazie, José Joaquín Aguirre, Manuel Barros Borgoño and Gregorio Amunátegui are depicted. Dr Blest, arrived to Chile from Great Britain in 1823, helped to dignify the medical profession in Chile, in high disrepute by that times and was the first director of the Medical School, founded in 1833. Dr Sazié, coming from France, was the first dean of the Faculty of Medicine and remained in this position for almost 20 years. He was succeeded by Dr Aguirre a highly skilled surgeon that had three objectives: to bring up more and better physicians and to bring up professors for physicians. He was succeeded by Dr. Borgoño that became head of the University of Chile in 1902. Dr Amunátegui, being the dean of Medicine, also became head of the University in 1923. The works of Dr Armando Larraguibel and Dr Amador Neghme, who completed the cycle of the old Faculty are also outlined.

[Comparison of the frequency of electrocardiographic changes in groups of apparently healthy persons with a positive serology for Chagas' disease, for toxoplasmosis or for both parasitoses]. / Comparación de la frecuencia de alteraciones electrocardiográficas en grupos de personas aparentemente sanas con serología positiva para enfermedad de Chagas, para toxoplasmosis o para ambas parasitosis.

In order to compare the frequency of electrocardiographical abnormalities among apparently healthy persons with Trypanosoma cruzi and Toxoplasma gondii infections, electrocardiogram (EKG) and the corresponding indirect hemagglutination tests (IHAT) were performed to 13,444 randomly selected rural and suburban inhabitants from the seven first regions of Chile which are located in the geographic area of distribution of Chagas' disease in the country. The IHAT for each parasitosis resulted positive (titers > or = 1:16) for Chagas' disease alone in 1,289 (9.6%), for toxoplasmosis alone in 3,519 (26.2%) and for the two infections in 994 (7.4%). EKG abnormalities of all type (AAT) and suggestive of a chagasic etiology (ASChE) were found in 18.5 and 8.3% respectively of the T. cruzi infected group, in 10.9 and 3.2% of the T. gondii infected group, in 18.9 and 4.8% of the group simultaneously infected by the two parasites, whereas AAT and ASChE were found in 7.9 and 1.8% of the IHAT negative group. All the corresponding percentage differences between abnormal EKG had a statistical significance (p < 0.05). Besides the increasing of the IHAT positivity, for each infection parallels to the age grouping of the studied persons, a similar situation was observed in the frequence of the AAT and ASChE mainly among people aged > or = 50 years. As T. cruzi and T. gondii infections sometimes isoletely adopt a high virulence and overlap in a proportion higher than 43.0% in Chagas' disease endemic areas, it is advisable to consider these etiologic possibilities in the presence of patients with a myocardiopathy of dubious interpretation, particularly when AIDS is involved.

[Frequency of electrocardiographic alterations in apparently healthy persons with indirect hemagglutination reaction positive for toxoplasmosis]. / Frecuencia de alteraciones electrocardiográficas en personas aparentemente sanas con reacción de hemaglutinación indirecta positiva para toxoplasmosis.

An indirect hemagglutination test (IHAT) for toxoplasmosis and electrocardiogram (EKG) were performed to 11,161 apparently healthy inhabitants with negative IHAT for Chagas' disease, from 259 rural and periurban localities sited in the first seven regions of Chile (geographic area of distribution of Chagas' disease in the country). The age of the 11,161 examined people ranged between 5 and 94 years, being 4,518 males and 6,643 females. The IHAT for toxoplasmosis was considered positive with titers > or = 1:16. This test resulted positive in 3,519 (31.1%) persons (30.8% in males and 32.0% in females). Positivity of the IHAT increased from 21.2%, in the youngest group (< 10 years) up to 46.9% in the oldest group (> or = 60 years). Different types of EKG alterations were observed in 10.9% of the IHAT positive individuals and in 7.9% of the IHAT negative ones. In both groups the percentages of altered EKG increased parallel with age. The overall difference of percentages of altered EKG in IHAT positive and IHAT negative persons has a statistical significance with p < 0.001. This study suggest the convenience to consider toxoplasmosis as a cause of chronic myocardiopathy in epidemiological studies on Chagas' disease, because a possible Toxoplasma gondii infection may contribute to overincrease the magnitude of the impact of Trypanosoma cruzi in the generation of the quoted myocardiopathy.

[Electrocardiographic alterations in persons with a positive serology for toxoplasmosis]. / Alteraciones electrocardiográficas en personas con serología positiva para toxoplasmosis.

To each of 11,161 randomly taken people from urban and peri-urban localities of the first seven regions of Chile (geographic area of distribution of Chagas' disease in the country), with negative serology for Chagas' disease, an indirect hemagglutination test (IHAT) for toxoplasmosis and an EKG were practiced. The IHAT for toxoplasmosis resulted positive in 3,519 individuals (31.5%). The EKG showed alterations in 10.9% of the IHAT positive individuals and in 7.9% of the IHAT negative ones. This difference between the proportion of altered EKG in IHAT positive people and altered EKG in those with negative IHAT is statistically significative with p < 0.001. These results suggest the convenience of considering toxoplasmosis as a cause of chronic myocardiopathy in epidemiological studies on Chagas' disease, since not discard the presence of Toxoplasma gondii infection should overvaluete the magnitude of the impact of Trypanosoma cruzi in the genesis of such a myocardiopathy.

[Etiopathogenic factors of arterial hypertension]. / Factores en la etiopatogenia de la hipertensión arterial.

High blood pressure of unknown etiology has been related to many pathogenetic factors, mainly dietary salt intake, mental stress, alcohol consumption, sedentary living and aging. Hypertension is more common in condition such as obesity and diabetes mellitus. Sustained elevation of arterial pressure is mediated by vasoconstriction in response to catecholamine release and activation of the renin-angiotensin-aldosterone system. In obese and diabetic subjects, insulin resistance and hyperinsulinemia have been found to be related to development of hypertension. The hypertension phenotype may correspond to many different genotypes codifying various alterations of hormone and receptor function, as well as inherited diseases linked to hypertension. An outstanding epidemiologic example of how hypertension may appear in a community is found in Easter Island. Hypertension among native adults increased from 3 to 30% in a 10 year period, in relation to influx of tourism and changes in salt intake and diet.

[Lorenzo Sazie. His 2nd and 3rd deanships]. / Lorenzo Sazie. Segunda y tercera etapas de su decanato.

This is the continuation of previous articles on Lorenzo Sazie, MD. It deals with advances in Medicine during his second period as a Dean (1855-1865) and the political and cultural atmosphere at the time. Dr Sazie was re-elected as a Dean of the Faculty of Medicine and died from typhoid fever which he acquired while taking care of patients during the 1865 epidemics in Santiago.

[Lorenzo Sazié]. / Don Lorenzo Sazié.

The first Dean of the University of Chile School of Medicine was Dr Lorenzo Sazié a young and bright French academician, endowed with superb skills in Surgery and Obstetrics. His nomination as Dean (1843) extended until December 1st, 1865 when he died, just a few days after the passing away of Andrés Bello, the Rector of the University of Chile. Sazié's fulfillment as physician, Professor, Dean, Member of the University Council and President of Protomedicatus Court, was outstanding. He organized medical curricula according to French medical scopes, to local resources and to Chilean prevalent diseases. He enabled scientific development by means of a close connection between the School of Medicine and the School of Physical and Mathematical Sciences. Works of both Schools were supposed to be related with matters of public interest and were published in "Revista de Santiago". He also provided subscriptions to the principal European scientific journals. As President of Protomedicatus he applied severe measures to regulate medical and paramedical performances. In addition, as President of the "Junta de Beneficencia de Santiago" he supervised and updated hospital care management and founded several health institutions such as the Madhouse, the Orphan House and the School of Midwifery. As a physician Sazié was a frugal, generous and dedicated man who, regardless of social or economic positions, served everyone with the same devotion. He died from typhoid fever while taking care of his patients during an epidemic outbreak which took place in Santiago in those days.

[Unexpected news, the origin of general anesthesia in Chile]. / Una noticia inesperada, los origenes de la anestesia general en Chile.

This article contains material from a manuscript titled "Anesthesiology in Chile. The first years" by Ernesto Sazie a historian who was the great grand child of Lorenzo Sazie, the first Dean of the Faculty of Medicine. According to this publications Dr Sazie introduced general anesthesia with nitrous oxide in Chile and in the world.

[Protomedicato in Chile]. / El protomedicato en Chile.

In 1566 Alonso de Villadiego was nominated by the Chilean Cabildo as "Adviser and Examiner in Surgery". By means of this edict, the Spanish Crown paralleled its classical health organization, inspired in rules coming from XIIIth century. The Hospital del Socorro was the focal point of these activities. It turned to be prosperous under the administration of "San Juan de Dios" monks (1617), who rebaptized the Hospital with their name. During the administration of the "Universidad de San Felipe" (1738-1839), the Protomedicato followed the standards imposed by the Cahir of Prima Medicina. Domingo Nevin, Frenchman, and José Antonio Ríos, Chilean, were the first and the last doctors in charge of this task. Ríos conducted the antivariolic campaign, supervised the "Midwifery Law" and controlled the medical and paramedical practice. Afterwards, the Institution plunged into a profound crisis to reflourish in 1833 when it was incorporated within the structure of the School of Medicine. Blest, Cox, Bustillos and Moran were the architects of its splendour. With the foundation of the Universidad de Chile in 1842, its Faculty of Medicine took over the Protomedicato functions. The Institution came to an end in 1892.

[The protomedicate in Spain]. / El protomedicato en España.

Protomedicate, a Royal Medical Court devoted to preserve higher academic proficiency and moral standards in the medical profession, was first conceived by the law-oriented monarch Alphonse X, the Wise one (XIII A C) and fully applied in the Iberian Peninsula and its American Colonies about mid XVIth century. Candidates were required to prove their knowledge and manual skills in the presence of the Protomedical and three examiners appointed by the King. According to legal regulations, surgery candidates had to accomplish a four year practice under the supervision of an experienced surgeon. Protomedicate was a unique, peculiar institution developed in Spanish speaking lands. Whereas in England, France or Italy medical teaching was delivered through scientific Academies, Royal Colleges and rarely in Universities, in Spain it was almost exclusively performed by the Protomedicate.