RESUMEN
BACKGROUND: Knowledge about the effect of bystander cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OHCA) of non-cardiac origin is lacking. We aimed to investigate the association between bystander CPR and survival in OHCA of presumed non-cardiac origin. METHODS: From the Danish Cardiac Arrest Registry and through linkage with national Danish healthcare registries we identified all patients with OHCA of presumed non-cardiac origin in Denmark (2001-2014). These were categorized further into OHCA of medical and non-medical cause. We analyzed temporal trends in bystander CPR and 30-day survival during the study period. Multiple logistic regression was used to examine the association between bystander CPR and 30-day survival and reported as standardized 30-day survival chances with versus without bystander CPR standardized to the prehospital OHCA-factors and patient characteristics of all patients in the study population. RESULTS: We identified 10,761 OHCAs of presumed non-cardiac origin. Bystander CPR was associated with a significantly higher 30-day survival chance of 3.4% (95% confidence interval [CI]: 2.9-3.9) versus 1.8% (95% CI: 1.4-2.2) without bystander CPR. A similar association was found in subgroups of both medical and non-medical OHCA. During the study period, the overall bystander CPR rates increased from 13.6% (95% CI: 11.2-16.5) to 62.7% (95% CI: 60.2-65.2). 30-day survival increased overall from 1.3% (95% CI: 0.7-2.6) to 4.0% (95% CI: 3.1-5.2). CONCLUSION: Bystander CPR was associated with a higher chance of 30-day survival among OHCA of presumed non-cardiac origin regardless of the underlying cause (medical/non-medical). Rates of bystander CPR and 30-day survival improved during the study period.
Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Anciano , Anciano de 80 o más Años , Asfixia/complicaciones , Trastornos Cerebrovasculares/complicaciones , Dinamarca/epidemiología , Ahogamiento , Sobredosis de Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Paro Cardíaco Extrahospitalario/etiología , Sistema de Registros , Enfermedades Respiratorias/complicaciones , Heridas y Lesiones/complicacionesRESUMEN
Local cutaneous injuries induced by ionizing radiation (IR) are difficult to treat. Many have reported local injection of adipose-derived stromal vascular fraction (SVF), often with additional therapies, as an effective treatment of IR-induced injury even after other local therapies have failed. The authors report a case of a locally recurrent, IR-induced wound that was treated with autologous, non-cultured SVF without other concurrent therapy. A nondestructive testing technician was exposed to 130 kVp x rays to his non-dominant right thumb on 5 October 2011. The wound healed 4 mo after initial conservative therapy with oral/topical α-tocopherol, oral pentoxifylline, naproxen sodium, low-dose oral steroids, topical steroids, hyperbaric oxygen therapy (HBOT), oral antihistamines, and topical aloe vera. Remission lasted approximately 17 mo with one minor relapse in July 2012 after minimal trauma and subsequent healing. Aggressive wound breakdown during June 2013 required additional therapy with HBOT. An erythematous, annular papule developed over the following 12 mo (during which time the patient was not undergoing prescribed treatment). Electron paramagnetic resonance (EPR) done more than 2 mo after exposure to IR revealed dose estimates of 14 ± 3 Gy and 19 ± 6 Gy from two centers using different EPR techniques. The patient underwent debridement of the 0.5 cm papular area, followed by SVF injection into and around the wound bed and throughout the thumb without complication. Eleven months post SVF injection, the patient has been essentially asymptomatic with an intact integument. These results raise the possibility of prolonged benefit from SVF therapy without the use of cytokines. Since there is currently no consensus on the use of isolated SVF therapy in chronic, local IR-induced injury, assessment of this approach in an appropriately powered, controlled trial in experimental animals with local radiation injury appears to be indicated.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas/métodos , Enfermedades Profesionales/terapia , Traumatismos por Radiación/etiología , Traumatismos por Radiación/terapia , Enfermedades de la Piel/etiología , Enfermedades de la Piel/terapia , Accidentes de Trabajo , Humanos , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/etiología , Traumatismos por Radiación/diagnóstico , Liberación de Radiactividad Peligrosa , Enfermedades de la Piel/diagnóstico , Pulgar/lesiones , Pulgar/efectos de la radiación , Trasplante Autólogo/métodos , Resultado del Tratamiento , Rayos X/efectos adversosRESUMEN
Response to a large-scale radiological incident could require timely medical interventions to minimize radiation casualties. Proper medical care requires knowing the victim's radiation dose. When physical dosimetry is absent, radiation-specific chromosome aberration analysis can serve to estimate the absorbed dose in order to assist physicians in the medical management of radiation injuries. A mock exercise scenario was presented to six participating biodosimetry laboratories as one individual acutely exposed to Co under conditions suggesting whole-body exposure. The individual was not wearing a dosimeter and within 2-3 h of the incident began vomiting. The individual also had other medical symptoms indicating likelihood of a significant dose. Physicians managing the patient requested a dose estimate in order to develop a treatment plan. Participating laboratories in North and South America, Europe, and Asia were asked to evaluate more than 800 electronic images of metaphase cells from the patient to determine the dicentric yield and calculate a dose estimate with 95% confidence limits. All participants were blind to the physical dose until after submitting their estimates based on the dicentric chromosome assay (DCA). The exercise was successful since the mean biological dose estimate was 1.89 Gy whereas the actual physical dose was 2 Gy. This is well within the requirements for guidance of medical management. The exercise demonstrated that the most labor-intensive step in the entire process (visual evaluation of images) can be accelerated by taking advantage of world-wide expertise available on the Internet.
Asunto(s)
Bioensayo/métodos , Aberraciones Cromosómicas/efectos de la radiación , Cromosomas Humanos/efectos de la radiación , Internet/estadística & datos numéricos , Laboratorios/normas , Incidentes con Víctimas en Masa/prevención & control , Traumatismos por Radiación/diagnóstico , Células Cultivadas , Cromosomas Humanos/genética , Radioisótopos de Cobalto/efectos adversos , Relación Dosis-Respuesta en la Radiación , Humanos , Procesamiento de Imagen Asistido por Computador , Linfocitos/efectos de la radiación , Metafase/efectos de la radiación , Traumatismos por Radiación/genética , Traumatismos por Radiación/prevención & control , Liberación de Radiactividad Peligrosa/prevención & control , RadiometríaRESUMEN
The NCRP Wound Model, which describes the retention of selected radionuclides at the site of a contaminated wound and their uptake into the transfer compartment, has been combined with the ICRP element-specific systemic models for those radionuclides to derive dose coefficients for intakes via contaminated wounds. These coefficients can be used to generate derived regulatory guidance (i.e., the activity in a wound that would result in an effective dose of 20 or 50 mSv, or in some cases, a organ-equivalent dose of 500 mSv) and clinical decision guidance (i.e., activity levels that would indicate the need for consideration of medical intervention to remove activity from the wound site, administration of decorporation therapy or both). Data are provided for 38 radionuclides commonly encountered in various activities such as nuclear weapons, fuel fabrication or recycling, waste disposal, medicine, research, and nuclear power. These include 3H, 14C, 32P, 35S, 59Fe, 57,58,60Co, 85,89,90Sr, 99mTc, 106Ru, 125,129,131I, 134,137Cs, 192Ir, 201Tl, 210Po, 226,228Ra, 228,230,232Th, 234,235,238U, 237Np, 238,239,240,241Pu, 241Am, 242,244Cm, and 252Cf.
Asunto(s)
Dosis de Radiación , Radioisótopos/farmacocinética , Heridas y Lesiones/metabolismo , Humanos , Radio (Elemento)/farmacocinética , Tecnecio/farmacocinética , Torio/farmacocinéticaRESUMEN
The international radiation biodosimetry community has recently been engaged in activities focused on establishing cooperative networks for biodosimetric triage for radiation emergency scenarios involving mass casualties. To this end, there have been several recent publications in the literature regarding the potential for shared scoring in such an accident or incident. We present details from a medical irradiation case where two independently validated laboratories found very different yields of dicentric chromosome aberrations. The potential reasons for this disparity are discussed, and the actual reason is identified as being the partial-body nature of the radiation exposure combined with differing criteria for metaphase selection. In the context of the recent networking activity, this report is intended to highlight the fact that shared scoring may produce inconsistencies and that further validation of the scoring protocols and experimental techniques may be required before the networks are prepared to deal satisfactorily with a radiological or nuclear emergency. Also, the findings presented here clearly demonstrate the limitations of the dicentric assay for estimating radiation doses after partial-body exposures and bring into question the usefulness of rapid "triage mode" scoring in such exposure scenarios.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos , Rayos X , Humanos , Dosis de RadiaciónRESUMEN
The current approach to medical management of irradiated patients begins with early diagnosis of radiation injury. Medical assessment of radiation dose is based on event history, symptomatology and laboratory results, with emphasis on time to emesis and lymphocyte depletion kinetics. Dose assessment provides a basis for early use of haematopoietic growth factors that can shorten the period of neutropaenia for patients with acute radiation syndrome. Assessments of haematopoietic, gastrointestinal and cutaneous syndromes have improved in recent years, but treatment options remain limited. Selected examples of current developments are presented.
Asunto(s)
Traumatismos por Radiación/terapia , Accidentes de Trabajo , Factores Estimulantes de Colonias/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Humanos , Infecciones Oportunistas/terapia , Dosis de Radiación , Traumatismos por Radiación/diagnóstico , Traumatismos por Radiación/etiología , Liberación de Radiactividad PeligrosaRESUMEN
With the continued shortage of available donor organs, the need for a mechanical alternative to support increasing numbers of heart failure patients has become increasingly apparent. This article reviews the ventricular assist devices currently approved by the Food and Drug Administration, and some of the concepts surrounding ventricular assist device therapy. Common postoperative and long-term concerns are addressed, and nursing care of these complicated patients is reviewed.
Asunto(s)
Insuficiencia Cardíaca/terapia , Corazón Auxiliar/estadística & datos numéricos , Cuidados Posoperatorios/enfermería , Diseño de Equipo , Insuficiencia Cardíaca/enfermería , Corazón Auxiliar/tendencias , Humanos , Educación del Paciente como Asunto , Complicaciones Posoperatorias/fisiopatologíaRESUMEN
One of the work practices frequently taught to employees is to estimate the heaviness of load before it is actually handled. If it is 'heavy', then one should ask for help. However, limited information can be found in the ergonomics literature about what a person perceives as a 'heavy load'. This study was conducted on 20 male and 20 female workers in the package delivery industry to estimate the amounts of load that correspond to various levels of load heaviness (e.g. 'somewhat heavy'). Experienced employees were used for this purpose. The distribution of loads within each heaviness level was developed using fuzzy sets theory. The maximum load (i.e. 23 kg) defined by the US National Institute for Occupational Safety and Health represents a 'somewhat heavy' load based on the analysis of load distribution (corresponding to a 1.0 certainty factor). Also, the 40 kg considered in the 1981 NIOSH guidelines may be classified as a 'very heavy' load. A comparative analysis of the results of this study with norms established in prior research indicates that one should be more careful in the interpretation of statistical norms for human perception of load handling. A 'moderate' level of load heaviness (i.e. 14 kg) can be handled by 85% of the worker population.
Asunto(s)
Enfermedades Profesionales/prevención & control , Embalaje de Productos , Percepción del Peso/fisiología , Soporte de Peso , Adolescente , Adulto , Análisis de Varianza , Fenómenos Biomecánicos , Femenino , Lógica Difusa , Guías como Asunto , Humanos , Masculino , Persona de Mediana Edad , National Institute for Occupational Safety and Health, U.S. , Enfermedades Profesionales/etiología , Caracteres Sexuales , Estados UnidosRESUMEN
The effect of the dihydropyridine L-Type Ca chanel agonist Bay K 8644 on post-rest contractions in ferret ventricular muscle and isolated myocytes was investigated. Bay K 8644 was shown to abolish rest potentiation and greatly accelerate rest decay. The post-rest contraction suppressed by Bay K 8644 was accompanied by action potentials of large amplitude and longer duration, but voltage-clamp measurements showed that this suppression was not due to a supra-optimal ICa trigger. Caffeine-induced contractures and rapid cooling contractures demonstrated an accelerated rest-dependent decline in sarcoplasmic reticulum (SR) Ca content in the presence of Bay K 8644, which was present even with Ca-free superfusion during rest. Thus, the Bay K 8644-induced decline of SR Ca during rest was independent of extracellular Ca or ICa. To explore whether the binding of Bay K 8644 to the dihydropyridine receptor could alter the SR Ca release channel/ryanodine receptor in a more direct way, ryanodine binding was measured in the absence and presence of Bay K 8644. Ryanodine binding to isolated ferret ventricular myocytes was increased by Bay K 8644 under conditions where sarcolemmal-SR junctions might be expected to be intact, but not after physical disruption. These results are consistent with a working hypothesis where Bay K 8644 may bind to the dihydropyridine receptor and this may lead to physical changes in the linkage between the dihydropridine receptor and a subset of ryanodine receptors, thereby increasing the opening of the SR Ca release channel during rest (and accelerating resting Ca loss).
Asunto(s)
Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Canales de Calcio/fisiología , Corazón/fisiología , Proteínas Musculares/fisiología , Contracción Miocárdica , Miocardio/metabolismo , Potenciales de Acción/efectos de los fármacos , Animales , Calcio/metabolismo , Calcio/farmacología , Canales de Calcio Tipo L , Células Cultivadas , Hurones , Corazón/efectos de los fármacos , Isradipino/metabolismo , Cinética , Masculino , Contracción Miocárdica/efectos de los fármacos , Ensayo de Unión Radioligante , Rianodina/metabolismo , Canal Liberador de Calcio Receptor de Rianodina , Retículo Sarcoplasmático/efectos de los fármacos , Retículo Sarcoplasmático/metabolismo , Factores de TiempoRESUMEN
In recent years, there has been an increased use of back supports in US industry to reduce the frequency and concomitant costs of lower-back disorders. The obvious question is, 'Can back supports relieve the load on the lumbar spine for employees engaged in industrial operations?'. This paper is directed towards answering this question because there have been mixed conclusions in the literature reporting on the efficacy of back supports. The literature concerning the biomechanical, physiological and psychophysical effects of back supports on the human spine has been reviewed as well as the use of back supports to control injury in the workplace. A critical assessment of the findings reported by various investigators has been made together with a discussion of the mechanisms used by the trunk muscles to provide extrinsic stability to the spine. It is hypothesized that the extrinsic stability of the spine is manifested through more than one mechanism. These mechanisms may act simultaneously or sequentially to stabilize the trunk. Finally, the ergonomics of back supports as a corporate policy are discussed.
Asunto(s)
Vértebras Lumbares/lesiones , Salud Laboral , Equipos de Seguridad , Traumatismos Vertebrales/prevención & control , Humanos , Vértebras Lumbares/fisiología , Soporte de PesoRESUMEN
The hemodynamic and humoral effects of the specific human renin inhibitor R-PEP-27 were studied in six normal human subjects on low and high sodium intake diets. An intravenous infusion of R-PEP-27 (0.5 to 16 micrograms/min/kg body wt) reduced blood pressure in a dose-dependent fashion; the mean arterial blood pressure at the end of the infusion fell from 128 +/- 4/83 +/- 4 to 119 +/- 3/71 +/- 3 mm Hg (mean +/- SEM) (P < .01) during the low sodium intake diet. R-PEP-27 had no effect on blood pressure during the high sodium intake diet. R-PEP-27 significantly reduced plasma angiotensin II and aldosterone concentrations. The temporal response to R-PEP-27 suggests that it is a short-lived although highly potent competitive inhibitor of renin; this peptide is a valuable and specific physiologic probe of the renin-angiotensin system.
Asunto(s)
Angiotensina II/sangre , Presión Sanguínea/efectos de los fármacos , Oligopéptidos/farmacología , Renina/antagonistas & inhibidores , Adulto , Aldosterona/sangre , Femenino , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Oligopéptidos/efectos adversos , Concentración Osmolar , Valores de Referencia , Orina/químicaRESUMEN
The antihypertensive and hemodynamic effects of lisinopril and atenolol were evaluated in 21 patients with mild-to-moderate essential hypertension. Left ventricular systolic and diastolic performances were assessed prior to and following treatment by first-pass radionuclide cineangiography at rest and during peak upright bicycle exercise. Both lisinopril and atenolol treatment significantly reduced the blood pressure. Lisinopril therapy was associated with a reduction in systemic vascular resistance and left ventricular end-diastolic and end-systolic volumes but no change in stroke volume, cardiac output, peak ejection rate, peak filling rate, time to peak ejection rate, or time to peak filling rate. In contrast, atenolol therapy was associated with an increase in end-diastolic volume and stroke volume but no change in cardiac output; the left ventricular peak ejection and peak filling rates were decreased by atenolol treatment. Although both lisinopril and atenolol each significantly reduced the blood pressure, lisinopril had no effect on left ventricular systolic or diastolic performance; in contrast, atenolol decreased both systolic and diastolic parameters of ventricular performance. Left ventricular function may be affected in significantly different ways despite apparent similarities in blood pressure control in patients who respond to angiotensin converting enzyme inhibition or beta-adrenergic receptor blockade. Differences in hemodynamic response to an antihypertensive agent may be important in the selection of a drug for the treatment of subsets of patients with cardiac function abnormalities.
Asunto(s)
Antihipertensivos/farmacología , Atenolol/farmacología , Dipéptidos/farmacología , Hemodinámica/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Dipéptidos/uso terapéutico , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/fisiopatología , Lisinopril , Masculino , Persona de Mediana Edad , Resistencia Vascular/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Abnormalities of left ventricular (LV) systolic performance develop during exercise in patients with coronary artery disease (CAD) as a result of ischemia-induced regional wall motion abnormalities. Like patients with hypertension and those with hypertrophic cardiomyopathy, patients with CAD display abnormalities of LV diastolic performance under basal conditions in the absence of ischemia. The purpose of these studies was to compare the effects of bepridil versus those of propranolol or diltiazem in patients with exertional angina pectoris. LV systolic and diastolic performance were assessed at rest and during peak upright bicycle exercise by first-pass radionuclide ventriculography. Compared with propranolol, bepridil increased exercise capacity, cardiac output, and stroke volume and decreased systemic vascular resistance. Compared with diltiazem, bepridil increased exercise capacity, peak filling rate, and early diastolic filling fraction and decreased systemic vascular resistance, heart rate, time to peak filling rate, and atrial filling volume. Bepridil therapy is associated with improved exercise capacity and decreased anginal frequency and nitroglycerin consumption. In addition, its use is accompanied by favorable changes in LV systolic and diastolic function at rest and during exercise. These changes are consistent with benefits resulting from resolution of myocardial ischemia as well as from positive lusitropic effects of bepridil on the ventricular myocardium.
Asunto(s)
Angina de Pecho/tratamiento farmacológico , Bepridil/farmacología , Diltiazem/farmacología , Propranolol/farmacología , Función Ventricular Izquierda/efectos de los fármacos , Angina de Pecho/fisiopatología , Diástole/efectos de los fármacos , Prueba de Esfuerzo/efectos de los fármacos , Humanos , Sístole/efectos de los fármacos , Resistencia Vascular/efectos de los fármacosRESUMEN
Numerous pharmacologic agents are capable of lowering the blood pressure of hypertensive patients; however, each drug has a characteristic side effect profile and effect on cardiac performance. In this study, the hemodynamic effects of the angiotensin converting enzyme inhibitor fosinopril were assessed at rest and at peak upright bicycle exercise by first-pass radionuclide cineangiography in 12 patients with essential hypertension. Fosinopril reduced blood pressure at rest in the seated position from 152/101 to 131/85 mm Hg (P less than .01) and at peak exercise from 206/103 to 184/91 mm Hg (P less than .01). Fosinopril therapy was associated with an increase in stroke volume and cardiac output and a decrease in systemic vascular resistance at rest and during peak exercise. Both peak ejection rate and peak filling rate increased significantly at rest during fosinopril therapy. The unique cardiotropic response to fosinopril may reflect its effects on the myocardial renin-angiotensin system, and suggests that this agent may offer a therapeutic advantage compared with other angiotensin converting enzyme inhibitors.
Asunto(s)
Antihipertensivos/farmacología , Corazón/fisiología , Hipertensión/diagnóstico por imagen , Hipertensión/fisiopatología , Prolina/análogos & derivados , Adolescente , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Diástole/efectos de los fármacos , Diástole/fisiología , Método Doble Ciego , Femenino , Fosinopril , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prolina/farmacología , Prolina/uso terapéutico , Angiografía por Radionúclidos , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , Sístole/efectos de los fármacos , Sístole/fisiología , Función Ventricular Izquierda/efectos de los fármacos , Función Ventricular Izquierda/fisiologíaRESUMEN
The effects of the nifedipine gastrointestinal therapeutic system (GITS) on blood pressure (BP), systemic vascular resistance (SVR), and left ventricular (LV) performance were determined in eight patients with essential hypertension. LV systolic and diastolic performance were assessed by first-pass radionuclide cineangiography at rest and during upright bicycle exercise after initial and long-term BP reduction. After initial treatment, end-diastolic volume (LVEDV) increased in association with an increase in stroke volume (SV), cardiac output (CO), and peak ejection rate. After long-term treatment, LVEDV decreased, SV and CO returned to pretreatment values, early diastolic filling fraction increased, and time to peak filling rate decreased. These hemodynamic changes are consistent with an initial predominant effect of vasodilation on LV function. With long-term treatment, the effects on LV diastolic performance are consistent with a positive lusitropic effect of nifedipine GITS. Nifedipine GITS is an effective agent for control of hypertension; its hemodynamic effects are consistent with both an effect on SVR due to decreased vascular smooth muscle contraction and a direct lusitropic effect on myocardial function.
Asunto(s)
Hipertensión/tratamiento farmacológico , Nifedipino/farmacología , Función Ventricular Izquierda/efectos de los fármacos , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/fisiopatología , Bombas de Infusión , Masculino , Persona de Mediana Edad , Nifedipino/administración & dosificación , Nifedipino/uso terapéuticoRESUMEN
Rapid cooling contractures were used to assess changes in sarcoplasmic reticulum (SR) Ca content in isolated rabbit and rat ventricular muscle during rest, with altered transsarcolemmal [Na] and [Ca] gradients and in the presence and absence of 100 nM ryanodine. In rabbit there is normally a rest-duration dependent decline in SR Ca content (rest decay), whereas in rat there is a short-term increase in SR Ca content (rest potentiation) and little evidence of rest decay. Ryanodine greatly accelerates the rate of rest decay in rabbit, depleting the SR of Ca in approximately 1 s, whereas in rat, ryanodine does not appear to drain the SR even after a 10 min rest. Elevation of intracellular Na activity in rabbit (by Na-pump inhibition) to a level similar to that measured in control rat during rest (Shattock and Bers, Am. F. Physiol., 256: C813-C822, 1989) makes rest-dependent changes of SR Ca content in these two tissues similar. The rest decay in rabbit in the presence of ryanodine is also markedly slowed after Na-pump inhibition. In rat, reduction of [Ca]0 allows rest decay to occur (+/- ryanodine), but this rest decay can be largely prevented by simultaneous reduction of [Na]o (to maintain [Na]3/[ Ca] constant) which serves to keep the thermodynamic driving force on a 3:1 Na/Ca exchange constant. We conclude that the process of rest decay and rest potentiation in both rabbit and rat ventricle depends on the sarcolemmal Na/Ca exchange. Furthermore, these species can be functionally interconverted by manipulation of the [Na] and [Ca] gradients. The ability of ryanodine to deplete the SR of Ca also depends critically on other transport systems (particularly Na/Ca exchange) to remove Ca from the cytoplasm.
Asunto(s)
Calcio/metabolismo , Ventrículos Cardíacos/efectos de los fármacos , Descanso/fisiología , Rianodina/farmacología , Sodio/metabolismo , Animales , Ventrículos Cardíacos/metabolismo , Contracción Miocárdica/fisiología , Conejos , Ratas , Función VentricularRESUMEN
The effects of nifedipine and propranolol on cardiac function both at rest and at peak exercise were compared in 22 hypertensive patients whose diastolic blood pressures remained in excess of 95 mm Hg despite diuretic therapy. In this double-blind, placebo-controlled study, left ventricular systolic and diastolic function at rest and at peak exercise during bicycle ergometry was assessed by first-pass radionuclide angiography using the Baird Scinticor before and after treatment with either nifedipine or propranolol. Both agents effectively reduced blood pressure in the supine and upright positions and at peak exercise. Nifedipine was associated with a significant increase in cardiac output and stroke volume at rest and at peak exercise, while propranolol decreased cardiac output at rest and at peak exercise. Systemic vascular resistance decreased with nifedipine treatment at rest and at peak exercise, but increased significantly with propranolol. Nifedipine increased ejection fraction in patients at rest and also increased maximal oxygen consumption at peak exercise, while propranolol decreased maximal oxygen consumption at peak exercise. At rest and at peak exercise, nifedipine increased peak filling rate, but time to peak filling rate was not affected by either drug. The fraction of total diastolic filling at the midpoint of diastole was significantly increased by nifedipine therapy at rest but was not affected by propranolol therapy. Nifedipine significantly decreased atrial filling volume while propranolol had no effect. Propranolol therapy did not result in any improvement in left ventricular function. In contrast, nifedipine improved left ventricular systolic and diastolic function at rest and peak exercise. Future selection of an antihypertensive agent should include consideration of the impact of therapy on left ventricular function.
Asunto(s)
Hipertensión/tratamiento farmacológico , Contracción Miocárdica/efectos de los fármacos , Nifedipino/uso terapéutico , Propranolol/uso terapéutico , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angiografía por RadionúclidosRESUMEN
Developed twitch tension and action potentials were recorded in rabbit ventricular muscle in physiological saline at 30 degrees C stimulated at 0.5 Hz. Addition of 5 microM nifedipine to block Ca entry via Ca channels almost abolished twitches (to 2.5 +/- 0.7%, S.E.M., n = 10 of control). This suggests that under normal conditions Ca entry via Na-Ca exchange is insufficient to activate contractions. However, when muscles are first exposed to 4 microM acetylstrophanthidin to elevate [Na]i the same exposure to nifedipine only partially suppresses twitches (to 59 +/- 12% of the original control). This suggests that when [Na]i is elevated, Ca entry via the Na-Ca exchange may be adequate to partially activate contraction. From this result it is not clear whether Ca entry via Na-Ca exchange is sufficient to activate contraction directly or whether sarcoplasmic reticulum (SR) Ca release is required. When these experiments were carried out in the presence of 5 to 10 mM caffeine or 100 nM ryanodine similar results were obtained. That is, nifedipine still abolished contractions in the presence of caffeine or ryanodine (to 3.8 +/- 0.3% and 1.3 +/- 0.4%, respectively), but only partially inhibited contractions in the presence of caffeine + acetylstrophanthidin (to 21 +/- 5%) or ryanodine + acetylstrophanthidin (10 +/- 2%). Thus, it appears that even in the absence of a functional SR and with Ca current blocked, Na-Ca exchange might bring sufficient Ca into the cell to activate appreciable contractions, but only when [Na]i is elevated. Action potential duration is decreased by nifedipine and acetylstrophanthidin and is further decreased when nifedipine is added on top of acetylstrophanthidin. If this Ca entry is by an electrogenic 3 Na: 1 Ca exchange, Ca entry will be favored at more positive membrane potentials. If the action potential were not so abbreviated with these drugs, Na-Ca exchange might bring in more Ca and activate additional tension.
Asunto(s)
Calcio/fisiología , Proteínas Portadoras/fisiología , Contracción Miocárdica , Potenciales de Acción/efectos de los fármacos , Animales , Cafeína/farmacología , Ventrículos Cardíacos/efectos de los fármacos , Técnicas In Vitro , Contracción Miocárdica/efectos de los fármacos , Nifedipino/farmacología , Conejos , Rianodina/farmacología , Intercambiador de Sodio-Calcio , Estrofantidina/análogos & derivados , Estrofantidina/farmacología , Función VentricularRESUMEN
The efficacy of bepridil (400 mg once a day) was assessed in 15 patients with exertional angina pectoris. All 15 patients reported substantial clinical improvement during bepridil treatment compared with placebo treatment. Episodes of angina were 11.8 +/- 4.1 (mean +/- standard error of the mean)/week with placebo and 3.8 +/- 1.6 with bepridil (p less than 0.05); nitroglycerin use was 9.1 +/- 3.3 tablets/week with placebo and 3.5 +/- 1.7 with bepridil (p less than 0.05). Five of 15 patients receiving bepridil did not experience angina during treadmill exercise; in the remaining 10 patients, time to onset of angina during exercise was 5.7 +/- 0.9 minutes with bepridil as opposed to 4.5 +/- 0.8 minutes with placebo (p less than 0.05). Left ventricular (LV) performance at peak exercise as measured by first-pass radionuclide angiography revealed the ejection fraction to be 38 +/- 3% during placebo therapy and 47 +/- 4% during bepridil therapy (p less than 0.0025). End-diastolic LV volume was unchanged, but end-systolic volume was 136 +/- 11 and 117 +/- 13 ml (p less than 0.05) and stroke volume was 82 +/- 6 and 97 +/- 9 ml (p less than 0.05) during placebo and bepridil therapy, respectively. Heart rate at peak exercise was 136 +/- 3 beats/min with placebo and 128 +/- 3 beats/min with bepridil; however, blood pressure was unchanged. These studies demonstrate that bepridil results in significant clinical improvement and enhanced LV performance in patients with angina pectoris.