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BACKGROUND: Several experiences of Bed Management have been published, most of them focusing on Emergency Department organization. Aosta Hospital is 70 km away from the nearest Hospital, so that ambulance diversion is not feasible and patients' admissions from ED need to be managed at the local level solely. Aim of this study was to test efficacy of an innovative Bed Management model. SETTING AND METHODS: Bed Management procedure consisted of an algorithm of both rational outward allocation of patients and support to "difficult" discharges. Hospital indicators of the pre-intervention period (years 2008-2011) were compared with those of the post-intervention period (years 2012-2015), splitting data into ten medical wards mostly admitting patients form ED and seven surgery wards mostly admitting "planned" patients. RESULTS: In the before-after analysis, mean length of stay decreases from 7.84 to 7.41 days (p= 0.000), and bed occupancy from 81% to 77%. Outlier days fell from 6.3% to 5.4% (p= 0.000), and the same did long stay patients (from 5.8% to 5%, p = 0.000). By contrast, ED admissions increased from 16.5% to 17.8%, as very short stays (23.9 to 25.3%, p= 0.000) and the 30 days unplanned readmissions (9.9% to 11.9%, p =0.000). The observed variations were more significant in the medical wards. Finally, waiting times in ED significantly decreased during the study period in the medical wards. CONCLUSIONS: We propose a comprehensive BM model, including governance of difficult discharges within a general hospital perspective. Further organization research on Bed Management is needed, also to propose BM standards, to be adopted in any Hospital.
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Ocupación de Camas , Servicio de Urgencia en Hospital/organización & administración , Administración Hospitalaria , Hospitalización , Modelos Organizacionales , Algoritmos , Estudios de Seguimiento , Humanos , Italia , Persona de Mediana Edad , Factores de TiempoRESUMEN
PURPOSE: Few real-world data are available on the frequency and management of pain in Internal Medicine (IM). Aims of our study were to assess the prevalence of pain in IM, and to evaluate the effects on pain management of a standardised educational programme. MATERIALS AND METHODS: The study was performed in 26 IM Units in Italy, with two cross-sectional surveys (PRE phase and POST phase) interspersed with an educational programme. In PRE phase each Centre reviewed the hospital charts of the last 100 consecutive patients hospitalised for any cause. An educational programme was conducted in each Centre by means of the 'outreach visit', a face-to-face meeting between health personnel and a trained external expert. Six months after, each Centre repeated the data collection (POST phase), specular to the PRE. RESULTS: A total of 5200 medical charts were analysed. Pain was documented in 37.5% of the patients. After the educational intervention, the intensity of pain was appropriately assessed in a higher percentage of patients (77.4% vs. 47.8%, p = 0.0001), and it was more frequently monitored during hospitalisation. Qualitative definition of pain (pathogenesis, duration, etc.) increased in POST phase (75.4% vs. 62.7%, p = 0.0001). A 73.3% increase in the use of strong opioids was detected following educational programme. CONCLUSIONS: Pain affects 4 out of 10 patients hospitalised in IM. According to our large real-world study, to implement a standardised one-shot educational programme may persistently improve the attitude of health personnel towards the characterisation and management of pain.
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Educación/métodos , Conocimientos, Actitudes y Práctica en Salud , Medicina Interna/métodos , Manejo del Dolor/métodos , Manejo del Dolor/normas , Estudios Transversales , Femenino , Educación en Salud , Humanos , Italia , MasculinoRESUMEN
Many patients with heart failure have underlying renal dysfunction, and similarly, patients with kidney failure are prone to cardiac failure. This has led to the concept of cardio-renal syndromes, which can be an acute or chronic cardio-renal syndrome, when cardiac failure causes deterioration in renal function, or acute and/or chronic Reno-Cardiac syndrome, when renal dysfunction leads to cardiac failure. Patients who develop these syndromes have increased risk of hospital admission and mortality. Although there are clinical guidelines for managing both heart failure and chronic kidney disease, there are no agreed guidelines for managing patients with cardio-renal and/or Reno-Cardiac syndromes, as these patients have typically been excluded from clinical trials. We have therefore reviewed the currently available published literature to outline a consensus of current best clinical practice for these patients.
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Insuficiencia Cardíaca/terapia , Insuficiencia Renal/terapia , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/etiología , Humanos , Guías de Práctica Clínica como Asunto , Diálisis Renal , Insuficiencia Renal/complicaciones , Insuficiencia Renal/etiología , SíndromeRESUMEN
BACKGROUND: In congestive heart failure (CHF), skeletal muscle shows increased expression of fast myosin heavy chains (MHC) and fibers, muscle atrophy, increased fatigability, and decreased endurance. Atrophy is secondary to myocyte apoptosis, which is probably triggered by tumor necrosis factor-alpha (TNFalpha). Angiotensin II receptors are thought to play a role in controlling apoptosis. We tested the hypothesis that angiotensin II receptor blockade could prevent skeletal muscle apoptosis in rats with CHF. METHODS AND RESULTS: CHF was induced by injecting 36 rats with 30 mg/kg monocrotaline. Ten additional animals were injected with saline and acted as controls. After 2 weeks, 18 of the 36 rats with CHF were treated with 7 mg. kg(-1). d(-1) irbesartan through osmotic minipumps, and 10 of the 36 rats were treated with 2 mg. kg(-1). d(-1) nifedipine in drinking water. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, MHC composition, myocyte apoptosis, Bcl-2, pro-caspase 3, and activated caspases 3 and 9 were determined, as were plasma levels of TNFalpha and angiotensin II. Myocyte apoptosis and muscle atrophy were significantly decreased with irbesartan compared with untreated CHF rats. Irbesartan-treated rats had fewer cells labeled positively with terminal deoxynucleotidal transferase-mediated dUTP nick-end labeling and fewer caspases; however, they also had increased Bcl-2 levels and muscle fiber cross-sectional areas. The MHC pattern in irbesartan-treated animals was similar to that in controls. Nifedipine animals behaved like the untreated CHF animals. Angiotensin II was increased 3- to 4-fold in all CHF rats (treated and untreated). TNFalpha levels were decreased in irbesartan-treated rats but not in nifedipine-treated rats. CONCLUSIONS: Angiotensin II receptor blockade can protect from the development of apoptosis-dependent atrophy and from changes in MHCS: The reduction of TNFalpha may play a role in this process.
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Compuestos de Bifenilo/farmacología , Músculo Esquelético/efectos de los fármacos , Receptor de Angiotensina Tipo 1/efectos de los fármacos , Tetrazoles/farmacología , Angiotensina II/biosíntesis , Angiotensina II/genética , Animales , Apoptosis/efectos de los fármacos , Compuestos de Bifenilo/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/complicaciones , Hipertrofia Ventricular Derecha/etiología , Bombas de Infusión Implantables , Irbesartán , Masculino , Monocrotalina/toxicidad , Fibras Musculares de Contracción Rápida/efectos de los fármacos , Fibras Musculares de Contracción Rápida/patología , Fibras Musculares de Contracción Lenta/efectos de los fármacos , Fibras Musculares de Contracción Lenta/patología , Proteínas Musculares/biosíntesis , Proteínas Musculares/genética , Músculo Esquelético/química , Músculo Esquelético/patología , Atrofia Muscular/prevención & control , Nifedipino/uso terapéutico , Ratas , Ratas Sprague-Dawley , Receptor de Angiotensina Tipo 1/fisiología , Tetrazoles/uso terapéutico , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND: In congestive heart failure (CHF) the skeletal muscle of the lower limbs develops a myopathy characterised by atrophy and shift from the slow to the fast type fibres. The mechanisms responsible for these changes are not clear yet. OBJECTIVES: We investigated the influence of blood flow and degree of muscle atrophy on the myosin heavy chains (MHC) composition of the soleus and extensor digitorum longus (EDL) of rats with right ventricle hypertrophy and failure. METHODS: CHF was induced in 16 rats by injecting 30 mg/kg monocrotaline. Eight animals had the same dose of monocrotaline but resulting in compensated right ventricle hypertrophy. Two age- and diet-matched groups of control animals (nine and five respectively) were also studied. The relative percentage of MHC1 (slow isoform), MHC2a (fast oxidative) and MHC2b (fast glycolytic) was determined by densitometric scan after electrophoretic separation. The relative weights of soleus and EDL (muscle weight/body weight) were taken as an index of muscle atrophy. Skeletal muscle blood flow was measured by injecting fluorescent micropheres. RESULTS: CHF and Control (Con) rats showed similar degree of atrophy both in soleus (0.40 +/- 0.06 vs. 0.44 +/- 0.06 p = NS), and EDL (0.47 +/- 0.04 vs. 0.45 +/- 0.02, p = 0.09). In CHF rats these two muscles showed a statistically significant MHCs redistribution toward the fast type isozymes. In fact in EDL of CHF rats MHC2a was 30.5 +/- 6.1% vs. 35.8 +/- 8.6% of the Con (p < 0.05). MHC2b was however higher (68.5 +/- 6.6% vs. 61.0 +/- 9.6%, p = 0.017). In the soleus of CHF rats MHC1 was decreased (87.6 +/- 3.4% vs. 91.9 +/- 5.2%, p = 0.02), while MHC2a was increased (12.04 +/- 3.5% vs. 7.9 +/- 5.2%; p = 0.028). Similar changes were not found in the muscles of the compensated hypertrophy animals. No correlation was found between MHC pattern and the relative muscle weight in the CHF animals. Soleus blood flow in CHF rats was significantly lower than that of Con (0.11 +/- 0.03 ml/min/g vs. 0.22 +/- 0.03 p < 0.05), while no differences were found in EDL (0.06 +/- 0.02 ml/min/g vs. 0.08 +/- 0.02, p = NS). CONCLUSIONS: In rats with CHF a skeletal muscle myopathy characterised by a shift of the MHCs toward the fast type isoforms occurs. The magnitude of the shift correlates neither with the degree of atrophy, nor with the skeletal muscle blood flow, suggesting that these two factors do not play a pivotal role in the pathogenesis of the myopathy.
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Cardiomiopatía Dilatada/metabolismo , Monocrotalina , Músculo Esquelético/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Animales , Peso Corporal , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/fisiopatología , Electroforesis en Gel de Poliacrilamida , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/patología , Cadenas Pesadas de Miosina/análisis , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo RegionalRESUMEN
The changes in ventricular isomyosin composition and Ca2+-activated ATPase activity occurring with regression of both hypertension and cardiac hypertrophy were investigated by using polyacrylamide gel electrophoresis under nondenaturing conditions, heavy chain peptide mapping, and an enzymatic assay. Eight control male Wistar rats and 14 two-kidney, one clip (Goldblatt II) hypertensive rats were studied from the fifth week of age. At 10 weeks of age, five Goldblatt II rats and four normotensive controls were killed. Five other Goldblatt II rats underwent nephrectomy of the ischemic kidney, which resulted in subsequent normalization of blood pressure. The remaining four control, four Goldblatt II rats, and five nephrectomized rats were killed at 15 weeks of age. Both the 10- and 15-week-old hypertensive rats had a significantly higher (p less than 0.001) biventricular weight to body weight ratio than the age-matched controls (3.84 +/- 0.76 X 10(-2) vs 2.75 +/- 0.25 X 10(-2); 5.93 +/- 2.26 X 10(-2) vs 2.65 +/- 0.17 X 10(-2]. The 15-week-old nephrectomized rats had a biventricular weight to body weight ratio (2.90 +/- 0.25 X 10(-2] close to that of age-matched controls and significantly lower (p less than 0.05) than that of age-matched hypertensive rats. In both the 10- and 15-week-old hypertensive rats left ventricular myosin Ca2+-activated ATPase activity was significantly lower (p less than 0.001) than in the age-matched controls (0.44 +/- 0.03 vs 0.59 +/- 0.06; 0.24 +/- 0.05 vs 0.48 +/- 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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ATPasas Transportadoras de Calcio/metabolismo , Cardiomegalia/metabolismo , Hipertensión Renovascular/metabolismo , Miosinas/metabolismo , Animales , Cardiomegalia/etiología , Hipertensión Renovascular/complicaciones , Masculino , Miocardio/metabolismo , Ratas , Ratas EndogámicasRESUMEN
In the myocardium, myosin and creatine kinase isoforms possess different capacities for using O2 and energy-rich phosphates. We studied electrophoretically the distribution of these isoforms in 19 hypertensive rats (two-kidney, one clip model of hypertension) and in age-matched controls. After 6 weeks of hypertension, seven rats were treated with captopril (2 mg/kg daily) for 4 weeks, six were left hypertensive for another 4 weeks, and the remaining rats were killed under ether anesthesia. In the latter, ventricular mass was significantly higher than in controls; V3 isomyosin was 32.3 +/- 6.8% versus 0%, and both creatine kinase-MB and -BB were increased at the expense of creatine kinase-MM (creatine kinase-MB = 29 +/- 2.8% vs. 14.7 +/- 1.8%, p less than 0.001; creatine kinase-BB = 3.1 +/- 0.6% vs. 1.7 +/- 0.8%, p less than 0.001). After 10 weeks of hypertension, ventricular mass, V3 isomyosin, and both creatine kinase-MB and -BB isoforms were found to be persistently higher than in controls. At the same time, captopril-treated rats showed reduced but not normalized blood pressure levels, normalized ventricular mass, and prevalence of the V1 isomyosin (56.9 +/- 22% vs. 47.9 +/- 23.8% in normotensive controls, p = NS). However, higher levels of creatine kinase-MB and -BB were still found in these rats in comparison with the normotensive controls (creatine kinase-MB = 22.4 +/- 5.4% vs. 15.8 +/- 2.8%, p less than 0.025; creatine kinase-BB = 2.3 +/- 0.1% vs. 1.8 +/- 0.3%, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Captopril/farmacología , Creatina Quinasa/metabolismo , Hipertensión Renovascular/enzimología , Miocardio/enzimología , Miosinas/metabolismo , Animales , Electroforesis en Gel de Poliacrilamida , Ventrículos Cardíacos , Isoenzimas/metabolismo , Ratas , Ratas EndogámicasRESUMEN
In hypertension, the heart of small mammals can express different isoenzymic forms of proteins under the influence of overload and other modulating factors. The increase in ventricular mass is generally paralleled by progressive changes in the isoforms of at least two proteins that are involved in the contraction process, namely, myosin and creatine-kinase. This review summarizes the biochemical and molecular changes occurring during progression and with regression of cardiac hypertrophy in rats, humans, and other animals, and focuses on the role played by antihypertensive drugs in modulation of ventricular isomyosins. The implications of these observations for humans remain to be fully determined.
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Cardiomegalia/enzimología , Creatina Quinasa/metabolismo , Hipertensión/complicaciones , Miosinas/metabolismo , Animales , Cardiomegalia/fisiopatología , Humanos , Isoenzimas , Miocardio/enzimología , Ratas , Especificidad de la EspecieRESUMEN
Eight patients with end-stage dilated cardiomyopathy were studied. Right ventricular endomyocardial biopsy morphometric findings were correlated with those of full-thickness samples of the right ventricle and interventricular septum obtained from the hearts of the same patients at cardiac transplant. The percentage area of myocytes and fibrosis was measured on histologic sections by means of a quantitative method. The results showed a close correlation between fibrosis and myocytes of biopsies and those of subendocardial, subepicardial, and midwall layers of the right ventricle free wall. No correlation was found with the subendocardial layers or with the midwall of the interventricular septum. These data suggest that histologic features of biopsies taken from the right ventricle from patients with dilated cardiomyopathy resemble those of the right ventricle free wall only.
RESUMEN
Myocytes were isolated from the right or left ventricles of failing and non-failing human hearts. Contractile responses to increasing concentrations of Ca2+, isoprenaline, forskolin and dibutyryl cyclic AMP (a lipophilic analogue of cyclic AMP) were determined. Responses were correlated with the age of the patient, and the severity of failure as defined by New York Heart Association class of symptoms (NYHA), left ventricular ejection fraction (LVEF), left ventricular end diastolic pressure (LVEDP) and dose of diuretics prescribed (diuretic class). The maximum contraction amplitude in high Ca2+ did not change with either age or severity of failure (n = 31-40 patients). Responses to isoprenaline (relative to Ca2+ in the same cell, isoprenaline/calcium ratio) decreased with increasing age (P < 0.001, n = 38), and increasing severity of disease (NYHA, P < 0.001, n = 38; LVEF, P < 0.001, n = 34; LVEDP, P < 0.001, n = 30; diuretic class, P < 0.01, n = 36). The decrease in forskolin/calcium ratio also correlated with age (n = 17, P < 0.005) and increasing severity (NYHA, P < 0.002, n = 17; LVEF, P < 0.05, n = 15; LVEDP, P < 0.02, n = 14; diuretic class, P < 0.05, n = 15). Multiple regression indicated that the contribution of age was greater than that of disease severity for both isoprenaline and forskolin responses. The dibutyryl cyclic AMP/calcium ratio did not change significantly with the age of the patient (P > 0.1, n = 13), or severity as defined by LVEDP (P = 0.05-0.1, n = 12) but did decrease with increasing NYHA class (P < 0.01, n = 13) or diuretics (P < 0.02, n = 12) or with low LVEF (P < 0.002, n = 12). Overall, neither forskolin nor dibutyryl cyclic AMP produced maximum responses greater than isoprenaline in myocytes from failing hearts. Where the response to isoprenaline was not limited by the appearance of arrhythmias, forskolin or dibutyryl cyclic AMP could give a significant (but small) increase in contraction over that with isoprenaline alone. These results provide evidence for a post-receptor defect in addition to beta-adrenoceptor desensitisation in myocytes from failing human heart.
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Bucladesina/farmacología , Colforsina/farmacología , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Adulto , Envejecimiento/fisiología , Calcio/farmacología , Diuréticos/farmacología , Femenino , Ventrículos Cardíacos/citología , Humanos , Técnicas In Vitro , Isoproterenol/farmacología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: In congestive heart failure (CHF) the skeletal muscle of the lower limbs develops a myopathy with atrophy and shift from the slow type to the fast type fibres. The aim was to test the hypothesis that this myopathy is specific and not simply related to detraining, by comparing patients with different degrees of CHF with patients with severe muscle atrophy due to disuse. DESIGN: Case-control study involving 50-150 micrograms needle biopsies of the gastrocnemius muscle. By an electrophoretic micromethod, the three isoforms of myosin heavy chains (MHC) were separated. PATIENTS: Five patients restricted to bed for more than one year because of stroke with disuse atrophy and normal ventricular function, and 19 with CHF were studied. There were seven age matched controls. MAIN OUTCOME MEASURES: The percentage of MHC1 (slow isoform), MHC2a (fast oxidative), and MHC2b (fast glycolytic) was determined by densitometric scan and correlated with indices of severity of cardiac failure. RESULTS: Ejection fraction was 42.5 (SD 15.2)% in CHF, 59.5 (1.0)% in disuse atrophy and 60.3 (1.4)% in controls (P < 0.001 v both). The degree of muscle atrophy as calculated by the body mass index/gastrocnemius cross sectional area, showed a profound degree of atrophy in patients with muscle disuse [0.94 (0.39)]. This was worse than in the controls [4.27 (0.16), P < 0.0005] and the CHF patients [2.60 (1.10), P < 0.005]. Atrophy in CHF patients was also greater than in controls (P < 0.005). MHC1 was lower in CHF than in disuse atrophy [51.83 (15.04) v 84.5 (17.04), P < 0.01] while MHC2b was higher [23.5 (7.4) v 7.25 (7.92), P < 0.001]. There was a similar trend for MHC2a [24.83 (15.01) v 8.25 (9.12), P < 0.05]. Within the CHF group there was a positive correlation between NYHA class and MHC2a (r = 0.47, P < 0.05) and MHC2b (r = 0.55, P < 0.01) and a negative correlation between NYHA class and MHC1 (r = -0.74, P < 0.001). Similarly, significant correlations were found for ejection fraction, diuretic consumption score, exercise test tolerance, and degree of muscle atrophy. CONCLUSIONS: The CHF myopathy appears to be specific and not related to detraining. The magnitude of MCH redistribution correlates with the severity of the disease. The electrophoretic micromethod used is very sensitive and reproducible. Biopsies are so well tolerated that can be repeated frequently, allowing thorough follow up.
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Insuficiencia Cardíaca/metabolismo , Músculo Esquelético/química , Atrofia Muscular/metabolismo , Cadenas Pesadas de Miosina/análisis , Anciano , Anciano de 80 o más Años , Diuréticos/uso terapéutico , Electrocardiografía , Electroforesis , Tolerancia al Ejercicio , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Both the reproducibility of the surface measurements of aortic atherosclerosis and the agreement between gross inspective and histologic changes were evaluated. Aortas from male broad breasted white turkeys were chosen because of the high incidence of spontaneous and typical atherosclerotic lesions in this animal strain. Ten male turkeys were killed at 33 weeks of age. The aortas were removed including the iliac bifurcation and stained with Sudan III. Each aorta was processed blindly by four pathologists and a computerized planimeter to determine normal areas, sudanophilic areas and areas covered by plaques. The analysis of variance showed significant differences among the four pathologists' measurements of sudanophilic areas (P less than 0.01) and areas covered by plaques (P less than 0.001). The coefficients of variation among the four determinations made by one pathologist on the same aorta were 3.6% for total aortic area; 10.08% for sudanophilic area; 47.6% for the area covered by plaques. On each aorta histology was performed at the level where all the four pathologists recorded the same findings at inspection, namely a normal area, a sudanophilic area, and an area covered by plaques. Important discrepancies occurred between findings at inspection and those of histologic examination: the ten areas classified as "normal" by all the four pathologists at inspection were shown at histologic examination to be normal in only two cases. In one case a musculo-elastic layer and in seven cases a fibro-elastic layer were found. The ten areas classified as "sudanophilic" by all the observers showed a fibro-elastic layer in five cases, a musculo-elastic layer in two cases and normal findings in three cases. The ten areas classified as "covered by plaques" displayed a typical atherosclerotic plaque in all cases but one. In conclusion, our data indicate that the reproducibility of gross inspective methods is low. Important discrepancies exist between findings at inspection and histologic examinations. The relevance of these findings remains to be established as far as the assessment of human atherosclerosis is concerned.
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Enfermedades de la Aorta/patología , Arteriosclerosis/patología , Animales , Aorta/patología , Tejido Elástico/patología , Displasia Fibromuscular/patología , Masculino , Músculo Liso Vascular/patología , PavosRESUMEN
This paper deals with some changes at the cardiac and aortic levels observed in normotensive rats and in hypertensive rats and turkeys by using two different beta-blockers, namely propranolol and oxprenolol. Chronic treatment with propranolol induced in the heart of normotensive rats a shift in the ventricular myosin pattern toward the "slow" V2 and V3 isoforms which are characterized by a reduced oxygen consumption. Oxprenolol treatment did not modify the blood pressure levels in the renal hypertensive rats nor in the spontaneously hypertensive turkeys. Nevertheless, in both experimental models a substantial modification of the media and intima, respectively, took place. In untreated hypertensive and normal rats the thickness of the aortic media was significantly higher than that of the treated ones, therefore suggesting a direct effect of oxprenolol on the smooth muscle cells of the aortic media. In the spontaneously hypertensive turkeys the atherosclerotic plaques appeared to be more frequent and thicker than those found in the oxprenolol-treated animals. These two experiments demonstrate that beta-blockers can prevent the development of hypertrophy of the media and decrease both the incidence and severity of intimal proliferations independently of blood pressure control. It therefore appears that the well-known myocardial protective effect played by beta-blockers, which mainly consists of a reduced myocardial oxygen consumption, is certainly obtained by reducing blood pressure and heart rate but also by changing the contractile protein pattern. In addition, an indirect myocardial protective effect could be exerted by beta-blockers at the vascular level by preventing medial hypertrophy and the development of atherosclerosis.
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Antagonistas Adrenérgicos beta/uso terapéutico , Hipertensión/tratamiento farmacológico , Animales , Aorta/efectos de los fármacos , Aorta/fisiopatología , Presión Sanguínea/efectos de los fármacos , ATPasas Transportadoras de Calcio/metabolismo , Cardiomegalia/prevención & control , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/fisiopatología , Corazón/efectos de los fármacos , Corazón/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/fisiopatología , Masculino , Miocardio/enzimología , Tamaño de los Órganos/efectos de los fármacos , Oxprenolol/uso terapéutico , Propranolol/uso terapéutico , Ratas , Ratas Endogámicas , PavosRESUMEN
The interest evoked by the Broad Breasted White Turkey (BBWT) as an animal model for studying the cardiovascular damages produced by hypertension and catecholamines is mainly due to the fact that hypertension is spontaneous and tissue and circulating catecholamines, especially norepinephrine, are extremely high. In this paper we focused our attention on three characteristic pathophysiological features displayed by these animals which are strictly related, as well as in humans, to the elevated blood pressure values and to catecholamine action. We also described the possibility of modifying the development of some of these lesions with pharmacological interventions liable to antagonize the peripheral effects of norepinephrine and epinephrine. The dissecting aneurysm of the aorta accounts for 5-10% of sudden deaths in this animal strain. It can be prevented by lowering blood pressure, especially with beta-blockers, and facilitated by MAO-inhibitors. The degree of cardiac hypertrophy is remarkably high and unexpectedly characterized by the synthesis of a "fast" V1-like isomyosin with high Ca++ activated ATPase activity, oxygen consumption and speed of muscle shortening. Neither the reduction of the degree of cardiac hypertrophy, nor treatment with labetalol alone were able to modify this peculiar pattern. In spite of having very high levels of high-density-lipoproteins, which are known to be protective against atherosclerosis, this animal develops a severe atheromatous disease especially in the abdominal aorta, where the cellular growth has also been proven to be in vitro more pronounced than in the thoracic tract. Treatment with beta-blockers reduced the severity and extent of the lesion even in absence of a significant reduction in blood pressure.
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Arteriosclerosis/complicaciones , Enfermedades Cardiovasculares/fisiopatología , Catecolaminas/fisiología , Hipertensión/complicaciones , Pavos , Animales , Enfermedades Cardiovasculares/complicaciones , Modelos Animales de EnfermedadRESUMEN
Creatinephosphokinase (CPK) and myoglobin (Mb) were measured in 15 patients admitted to the Coronary Care Unit for acute myocardial infarction (AMI). Blood samples were collected from the right atrium every six hours for 48 hours starting from the time of arrival in the Unit and were tested for CPK by a spectrophotometric technique and for Mb by an RIA method. Mb usually started to increase earlier than CPK and reached the peak plasma level more quickly. In five cases Mb but not CPK subsequently showed further increases during the course of the study. The suggestion is made that Mb measurements might be more reliable than CPK for the early detection and the initial followup of AMI.
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Creatina Quinasa/sangre , Infarto del Miocardio/sangre , Mioglobina/sangre , Adulto , Anciano , Creatina Quinasa/biosíntesis , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/patología , Mioglobina/biosíntesis , NecrosisRESUMEN
Hyperthyroidism, and alternatively hypothyroidism, were induced in spontaneously hypertensive broad-breasted white turkeys (BBWT) to see if these conditions influenced the pattern of Ca++-activated ATPase activity and isomyosin synthesis in the cardiac muscle. Nine animals were given thyroxine 500 micrograms p.o., 9 animals propylthiouracil 150 mg p.o., 6 animals placebo p.o. All animals were treated daily from the 27th to the 33rd week of age. The ventricular myosin Ca++-activated ATPase activity was assayed in all the animals; aortic smooth-muscle myosin light chains were analysed by mono- and two-dimensional gel electrophoresis, and myosin heavy chains by proteolytic mapping. No significant difference was found between the three groups in the ventricular myosin Ca++-activated ATPase activity. As for aortic myosin, a similar peptide map of heavy chains but a different phosphorylative level of the LC1 light chain was found in the three groups of animals. It is concluded that a thyroid-hormone modulation of contractile proteins in vascular smooth muscle, but not in cardiac muscle, exists in the broad-breasted white turkey.
Asunto(s)
Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Miocardio/metabolismo , Miosinas/metabolismo , Adenosina Trifosfatasas/metabolismo , Animales , Aorta/metabolismo , ATPasas Transportadoras de Calcio/metabolismo , Ventrículos Cardíacos/metabolismo , Masculino , Músculo Liso Vascular/metabolismo , Miosinas/aislamiento & purificación , PavosRESUMEN
In spontaneously hypertensive turkeys, both high blood pressure and high catecholamine levels play a role in the development of vascular hypertrophy. We studied the effect of labetalol, an alpha- and beta-blocking drug, on the aortic media. Seventeen turkeys were given increasing doses of the drug (20-35 mg/kg daily) from the 2nd to the 35th week of age; 13 control birds were given a daily placebo. The actively treated turkeys showed significantly lower values of blood pressure and a lower heart rate compared with the controls throughout the study period. After the turkeys had been killed, seriate histological sections taken from the abdominal aorta near the bifurcation were used for a three-dimensional assessment of the aortic media by computerized morphometry. The volume of aortic media was significantly lower in the labetalol-treated birds than in the controls. This was also observed in the non-responder turkeys. This finding indirectly supports the view that catecholamines may play a major but independent role in the development of vascular hypertrophy.
Asunto(s)
Aorta/patología , Hipertensión/veterinaria , Pavos , Administración Oral , Animales , Evaluación Preclínica de Medicamentos/veterinaria , Hipertensión/complicaciones , Hipertensión/patología , Hipertrofia/etiología , Hipertrofia/patología , Hipertrofia/prevención & control , Hipertrofia/veterinaria , Labetalol/uso terapéutico , MasculinoRESUMEN
We studied the distribution of four isoenzymes of creatine-kinase (MM, MB, BB and the mitochondrial) in 13 renovascular hypertensive rats and five age-matched controls. After 6 weeks of hypertension, seven rats were treated with captopril (2 mg/kg daily) for 4 weeks and the other six were left untreated for 4 weeks. After the rats were killed an adaptive increase in MB and BB was found at the expense of MM in the hypertensive rats compared with the controls. The captopril-treated rats displayed persistently higher levels of both MB and BB than the controls. Therefore, the regression in cardiac hypertrophy that is achieved by captopril is accompanied by persistence of the isoenzymic pattern that leads to better use of energy-rich phosphates.
Asunto(s)
Cardiomegalia/enzimología , Creatina Quinasa/análisis , Hipertensión Renovascular/enzimología , Miocardio/enzimología , Animales , Captopril/uso terapéutico , Cardiomegalia/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Ventrículos Cardíacos/enzimología , Hipertensión Renovascular/tratamiento farmacológico , Isoenzimas , Miocardio/análisis , Ratas , Ratas Endogámicas , Inducción de RemisiónRESUMEN
We investigated the changes in ventricular isomyosin composition and Ca2+-activated ATPase activity during progression and regression of hypertension and cardiac hypertrophy. Eight control male Wistar rats and 14 Goldblatt-II (two-kidney, one clip) hypertensive rats were studied from the 5th week of age. Five of the Goldblatt-II rats underwent nephrectomy of the ischaemic kidney after 5 weeks, with normalization of blood pressure. The hypertensive rats showed a higher biventricular weight to body weight ratio (P less than 0.02), a lower ATPase activity (P less than 0.005), and an increased expression of 'slow' isomyosins in comparison with the age-matched controls. These changes were more pronounced at 15 than at 10 weeks of age. The 15-week-old nephrectomized rats showed the same degree of cardiac hypertrophy, ATPase activity and isomyosin pattern as the age-matched controls. In conclusion, the changes in ventricular myosin observed during the progression of cardiac hypertrophy regressed after normalization of blood pressure and ventricular mass.
Asunto(s)
Cardiomegalia/etiología , Hipertensión Renovascular/metabolismo , Miocardio/metabolismo , Miosinas/metabolismo , Animales , Presión Sanguínea , ATPasas Transportadoras de Calcio/metabolismo , Cardiomegalia/metabolismo , Hipertensión Renovascular/complicaciones , Masculino , Ratas , Ratas EndogámicasRESUMEN
AIM: Glomerular filtration rate (GFR) is commonly calculated using the modification of diet in renal disease (MDRD) and Cockroft-Gault (CG) formulas and recently by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm and not directly measured, so that the real impact of antihypertensive therapy on GFR could not be well defined. In this study, the effect of Aliskiren on the GFR measured by radionuclide clearance of 99mTc-diethylene triamine penta-acetic acid (DTPA) was investigated. METHODS: In 106 hypertensive subjects (53% men) aged 61.9±12.7 years with uncontrolled blood pressure (BP) receiving at least 2 antihypertensive medications, Aliskiren was added once-daily at a dose of 150-300 mg for 12 months. Clinic BP measurements were taken at every follow-up visit (1st, 6th and 12th month), while 24-hours ambulatory BP and GFR (in mL/min/1.73 m2) were evaluated at baseline and at the end of the follow-up. Analysis of variance for repeated measures of BP, GFR and microalbuminuria was provided. RESULTS: With the use of Aliskiren a significant reduction of BP and microalbuminuria was found (P<0.0001). Only in male population, a significant reduction in GFR calculated with CKD-EPI (82.4±15 vs. 78.6±18.2, P<0.01) and CG (81.6±29.5 vs. 74.2±28.4, P<0.0001) formulas was observed. This impairment of GFR was not found either with MDRD formula (70.5±19.6 vs. 68.3±23.4) or by radionuclide clearance (62.4±18.6 vs. 61.4±20.5). CONCLUSION: This study seems to demonstrate that the efficacy on BP control of Aliskiren is not accompanied by an impairment of GFR. In order to evaluate the effect of Aliskiren on GFR scintigraphy technique or MDRD formula resulted to be the most accurate methods.