RESUMEN
The effects of dobutamine ([+/-]-4-[2-[[3-(p-hydroxyphenyl)-1-methyl propyl] amino] ethyl] pyrocatechol hydrochloride), a new synthetic cardioactive sympathomimetic amine, were examined on direct and continuous measurements of left ventricular (LV) diameter (D), pressures (P), velocity of shortening (V), dP/dt, dP/dt/P, arterial pressure, cardiac output, and regional blood flows in the left circumflex coronary, mesenteric, renal, and iliac beds in healthy, conscious dogs. At the highest dose of dobutamine examined, 40 mug/kg/min, the drug increased dP/dt/P from 65+/-3 to 128+/-4 s(-1) and isolength velocity from 72+/-4 to 120+/-7 mm/s without affecting LV end diastolic D significantly. Mean arterial P rose from 92+/-2 to 104+/-3 mm Hg and heart rate from 78+/-3 to 111+/-7 beats/min, while LV end systolic D fell from 24.1+/-1.4 to 19.9+/-1.8 mm, reflecting a rise in stroke volume from 30+/-4 to 42+/-3 ml. Cardiac output rose from 2.41+/-0.23 to 4.35+/-0.28 liter/min, while calculated total peripheral resistance declined from 0.042+/-0.005 to 0.028+/-0.003 mm Hg/ml/min. The greatest increases in flow and decreases in calculated resistance occurred in the iliac and coronary beds, and the least occurred in the renal bed. Propranolol blocked the inotropic and beta(2) dilator responses while vasoconstricting effects mediated by alpha adrenergic stimulation remained in each of the beds studied. When dobutamine was infused after a combination of practolol and phentolamine, dilatation occurred in each of the beds studied. These observations indicate that dobutamine is a potent positive inotropic agent with relatively slight effects on preload, afterload, or heart rate, and thus may be a potentially useful clinical agent. The one property of this drug which is not ideal is its tendency to cause a redistribution of cardiac output favoring the muscular beds at the expense of the kidney and visceral beds.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Catecolaminas/farmacología , Circulación Coronaria/efectos de los fármacos , Corazón/efectos de los fármacos , Animales , Perros , Dopamina/farmacología , Epinefrina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Isoproterenol/farmacología , Riñón/irrigación sanguínea , Norepinefrina/farmacología , Fenetilaminas/farmacología , Fenoles/farmacología , Fentolamina/farmacología , Propranolol/farmacología , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
The effects of isoproterenol, norepinephrine, dobutamine, exercise, and nitroglycerin on left ventricular diameter, pressure, velocity of shortening, dP/dt, dP/dt/P, arterial pressure, left circumflex coronary blood flow, and coronary vascular resistance were examined in healthy conscious dogs with normal coronary perfusion and in the same animals after moderate global ischemia had been induced by partial occlusion of the left main coronary artery. In the normal nonischemic heart, all interventions improved left ventricular performance, as evidenced by increases in dP/dt/P and velocity at the same or lower left ventricular end-diastolic diameter. Interventions, which in the normal heart caused large increases in heart rate and myocardial contractility, e.g. isoproterenol and exercise, or which decreased coronary perfusion pressure, e.g. nitroglycerin or isoproterenol, elicited paradoxical responses in moderate global ischemia, i.e., left ventricular enddiastolic diameter and pressure rose, and dP/dt/P and velocity fell substantially. On the other hand, norepinephrine, which increased coronary perfusion pressure along with myocardial contractility but did not increase heart rate, improved left ventricular function. Dobutamine, which did not alter heart rate or arterial pressure substantially while improving myocardial contractility, produced an intermediate response between that of norepinephrine and isoproterenol in the presence of moderate global myocardial ischemia. Thus, interventions that increase myocardial O(2) requirements, by increasing heart rate and myocardial contractility without augmenting coronary perfusion pressure, can produce a paradoxical depression of ventricular function in the presence of global myocardial ischemia.
Asunto(s)
Catecolaminas/farmacología , Enfermedad Coronaria/fisiopatología , Corazón/fisiopatología , Nitroglicerina/farmacología , Esfuerzo Físico , Agonistas Adrenérgicos beta/farmacología , Animales , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Volumen Cardíaco , Circulación Coronaria , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/fisiopatología , Perros , Corazón/efectos de los fármacos , Frecuencia Cardíaca , Ventrículos Cardíacos , Isoproterenol/farmacología , Miocardio/metabolismo , Norepinefrina/farmacología , Consumo de Oxígeno , Resistencia VascularRESUMEN
The time relationship for recovery of mechanical function, the intramyocardial electrogram and coronary flow after brief periods of regional myocardial ischemia, was studied in conscious dogs. Total left vemtricular (LV) function was assessed with measurements of LV systolic and diastolic pressures, rate of change of LV pressure (dP/dt), and dP/dt/P. Regional LV function was assessed with measurements of regional segment length and velocity of shortening. An implanted hydraulic occluder on either the left anterior descending or circumflex coronary artery was inflated for 5- and 15-min periods on separate days. A 5-min occlusion depressed overall LV function transiently, but just before release of occlusion overall function had nearly returned to control. At this time regional function in the ischemic zone was still depressed to the point of absent shorteining or paradoxical motion during systole and was associated with marked ST segment elevation (+ 10 +/- 2.2 mV) at the site where function was measured. With release of occlusion and reperfusion the intramyocardial electrogram returned to normal within 1 min, and reactive hyperemia subsided by 5-10 min. In contrast to the rapid return to preocclusion levels for coronary flow and the electrogram, regional mechanical function remained depressed for over 3 h. A 15-min coronary occlusion resulted in an even more prolonged (greater than 6 h) derangement of function in the ischemic zone. Thus, brief periods of coronary occlusion result in prolonged impairement of regional myocardial function which could not have been predicted from the rapid return of the electrogram and coronary flow. These observations indicate that brief interruptions of coronary flow result either in a prolonged period of local ischemia or that alterations of mechanical induced by ischemia far outlast the repayment of the oxygen debt.
Asunto(s)
Vasos Coronarios/fisiología , Corazón/fisiología , Animales , Constricción , Circulación Coronaria , Creatina Quinasa/sangre , Perros , Electrocardiografía , Electrofisiología , Perfusión , Presión , Factores de TiempoRESUMEN
We have assessed resting myocardial contractility and its baroreflex control in normotensive and hypertensive conscious rabbits. Hypertension was induced by bilateral cellophane wrapping of the kidneys with experiments performed 6 weeks later during the established phase of hypertension. The peak rate of change of left ventricular pressure (peak LV dP/dt) was used as the index of myocardial contractility. Baroreflex control of contractility and heart period (HP) was assessed by constructing stimulus response curves relating change in mean arterial pressure (MAP), induced by balloon occluders around the abdominal aorta and inferior vena cava, to change in peak LV dP/dt and HP. These stimulus response curves were obtained in normotensive rabbits with and without cardiac pacing, and in both normotensive and hypertensive animals after cardiac beta sympathetic blockade with propranolol, vagal blockade with methylscopolamine, and combined cardiac autonomic blockade with propranolol and scopolamine, as well as in rabbits with intact autonomic effectors. Resting MAP was significantly higher in the hypertensive rabbits (119 +/- 2 mm Hg) compared to normotensive controls (76 +/- 1 mm Hg). Resting peak LV dP/dt was also greater by 51% in the hypertensive animals (7054 +/- 287 mm Hg sec-1) compared to controls (4690 +/- 223 mm Hg sec-1). There was no significant difference in the resting heart period or resting left ventricular end diastolic pressure. Transient changes in MAP induced by occlusion of the aortic or venous balloons produced significant alterations in peak LV dP/dt in normotensive animals with and without pacing and in hypertensive control animals. In animals with cardiac sympathetic block, the range and slope or sensitivity of the stimulus response curves were not significantly changed but in animals with vagal blockade the sensitivity was reduced by 90% and the range at 30 mm Hg by 88%. After propranolol and methylscopolamine were administered together, the stimulus no longer evoked a response. These experiments demonstrate that myocardial contractility is under baroreflex control and suggest that this is mediated principally via parasympathetic nerves to the heart. There was no significant difference between the sensitivity of baroreflex control of myocardial contractility in the normotensive (-84 +/- 14 mm Hg sec-1 per mm Hg) and the hypertensive (-110 +/- 14 mm Hg sec-1 per mm Hg) rabbits, unlike the baroreflex control of heart period where sensitivity was markedly impaired in the hypertensive (sensitivity 3.8 +/- 0.8 msec/mm Hg) compared to the normotensive (6.9 +/- 1.0 msec/mm Hg) animals.
Asunto(s)
Hipertensión Renovascular/fisiopatología , Contracción Miocárdica , Sistema Nervioso Parasimpático/fisiología , Presorreceptores/fisiología , Animales , Presión Sanguínea , Estimulación Cardíaca Artificial , Femenino , Corazón/inervación , Frecuencia Cardíaca , Hipertensión Renovascular/etiología , Masculino , Sistema Nervioso Parasimpático/anatomía & histología , Presorreceptores/efectos de los fármacos , Propranolol/farmacología , Conejos , Reflejo/fisiología , Escopolamina/farmacología , Estimulación QuímicaRESUMEN
OBJECTIVE: To examine the effects of hypertension on systemic and regional haemodynamic responses to endothelin-1. DESIGN: Comparison of responses between age-matched control and hypertensive rabbits (two-kidney, two wrapped), and between spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats. METHODS: Arterial pressure, heart rate and blood flow responses to 0.2 nmol/kg intravenous endothelin-1 were measured in conscious animals. Blood flow was measured by pulsed ultrasound Doppler in the ascending aorta, distal abdominal aorta, left renal artery and superior mesenteric artery. RESULTS: Endothelin-1 produced qualitatively similar effects in the hypertensive and control animals. In the systemic circulation, brief initial vasodilation preceded sustained vasoconstriction. In the hindlimb, marked vasodilation preceded relatively minor vasoconstriction, and profound vasoconstriction occurred in the renal and mesenteric vascular beds. In the rats but not the rabbits, fleeting vasodilation preceded the renal and mesenteric vasoconstriction. Significant differences between hypertensive and control animals were: accentuation of the pressor effect and heart rate responses in hypertensive animals of both species, and accentuation of hindlimb vasodilation in hypertensive rabbits but not SHR; and attenuation of the depressor effect in SHR but not hypertensive rabbits, attenuation of the mesenteric vasoconstriction in both hypertensive rabbits and rats, and attenuation of renal vasoconstriction in SHR. CONCLUSIONS: The increased responses to endothelin-1 of some variables in the hypertensive animals may involve structural changes in the resistance vessels. However, the reduced responses in the mesenteric vasculature of both species and the renal vasculature of the SHR are due to some mechanism other than structural change.
Asunto(s)
Endotelinas/farmacología , Hemodinámica/efectos de los fármacos , Hipertensión/fisiopatología , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Endotelinas/sangre , Miembro Posterior/irrigación sanguínea , Hipertensión/diagnóstico por imagen , Riñón/irrigación sanguínea , Riñón/diagnóstico por imagen , Masculino , Arterias Mesentéricas/diagnóstico por imagen , Arterias Mesentéricas/efectos de los fármacos , Conejos , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Ultrasonografía Doppler de Pulso , Resistencia Vascular/efectos de los fármacosRESUMEN
Electrolytic lesions of the ventrolateral medulla, coinciding with the A1 catecholamine cells of the conscious rabbit (A1 lesions) cause acute hypertension and bradycardia and in some animals, pulmonary oedema. We have assessed the change in cardiac performance after an A1 lesion, the role of cardiac autonomic effectors in this change; and the mechanism of the pulmonary oedema. Following A1 lesions there was a profound (over 100%) rise in total peripheral resistance and a fall in cardiac output which was mainly due to a fall in stroke volume since it occurred even in animals in which the heart rate was held constant by atrial pacing. This reduced stroke volume occurred despite a 40% increase in myocardial contractility (peak LV dP/dt) and elevation of left ventricular end diastolic pressure. beta-Adrenoceptor blockade with propranolol abolished the rise in peak LV dP/dt, while vagal blockade with methylscopolamine abolished the bradycardia and combined blockade with propranolol and methylscopolamine abolished the rise in peak LV dP/dt and reduced the bradycardia. In rabbits which developed pulmonary oedema, left ventricular end diastolic pressure rose to 35 +/- 3.5 compared to 16 +/- 2.7 mmHg in those which did not, suggesting that the pulmonary oedema was due to raised left ventricular filling pressure.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Corazón/fisiopatología , Hipertensión/fisiopatología , Bulbo Raquídeo/fisiología , Animales , Hemodinámica/efectos de los fármacos , Masculino , Contracción Miocárdica/efectos de los fármacos , Miocardio/metabolismo , N-Metilescopolamina , Norepinefrina/metabolismo , Tamaño de los Órganos , Propranolol/farmacología , Edema Pulmonar/fisiopatología , Conejos , Derivados de Escopolamina/farmacologíaRESUMEN
This study tested the hypothesis that a sphygmomanometer cuff bladder long enough to encircle the arm in most adults ('obese cuff') would provide a more accurate and precise estimate of intra-arterial pressure than the usual 'standard' cuff bladder. In 53 patients undergoing diagnostic coronary angiography (35 males, 18 females, aged 36-79 years), indirect blood pressure, measured in the left arm with a random-zero sphygmomanometer, was compared with simultaneously measured femoral intra-arterial pressure. Duplicate indirect measurements were made with each of two cuffs containing bladders measuring 39 x 15 cm ('obese') and 23 x 12 cm ('standard'). The obese cuff bladder encircled 80% or more of the arm circumference in all subjects, whereas the standard cuff bladder met this requirement in only 19% of the subjects. For both systolic and diastolic pressure there was marked interindividual variability in the differences between indirect and direct measurements with both cuffs. With the obese cuff there was no systematic error in the diastolic blood pressure measurement. The standard cuff consistently overestimated diastolic pressure by 7.7 +/- 8.3 mmHg (mean +/- s.d.). For both cuffs, the difference between indirect and direct diastolic pressure increased with arm size (P less than 0.05). Both cuffs underestimated systolic blood pressure, the obese cuff by 15.5 +/- 11.7 mmHg and the standard cuff by 7.6 +/- 12.1 mmHg. These systolic blood pressure underestimates were greater at higher blood pressures (P less than 0.01) and with smaller arms (P less than 0.05). Age was not related to measurement error with either cuff.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Determinación de la Presión Sanguínea/instrumentación , Adulto , Anciano , Brazo/anatomía & histología , Arterias , Diseño de Equipo , Estudios de Evaluación como Asunto , Femenino , Humanos , Hipertensión/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
The baroreflex control of myocardial contractility has been assessed in the conscious normotensive and hypertensive rabbit. Stimulus response curves relating graded changes in mean arterial pressure (MAP) to induced changes in peak rate of change of left ventricular pressure (peak LV dP/dt) were compared during constant heart rate controlled by atrial pacing and when heart rate was uncontrolled. The experiments were repeated after beta-block, cholinergic block and during combined block in both A rise in MAP produced a fall in peak LV dP/dt which was due to two components. There was a reflex negative inotropic effect which was independent of heart rate and a reduction in peak LV dP/dt due to reflex bradycardia. The sympathetic nerves were primarily responsible for the direct negative inotropic effect and the vagus for the indirect effect, secondary to the bradycardia. The slope of the stimulus response curves relating the baroreflex fall in peak LV dP/dt to rises in MAP were similar in normotensive and hypertensive animals, in contrast to the sensitivity of the baroreflex heart rate response which is impaired in animals with chronic hypertension.
Asunto(s)
Estimulación Cardíaca Artificial , Contracción Miocárdica , Presorreceptores/fisiología , Sistema Nervioso Simpático/fisiología , Nervio Vago/fisiología , Vigilia/fisiología , Animales , Presión Sanguínea/efectos de los fármacos , Hipertensión/fisiopatología , Contracción Miocárdica/efectos de los fármacos , N-Metilescopolamina , Presorreceptores/efectos de los fármacos , Propranolol/farmacología , Conejos , Reflejo/efectos de los fármacos , Reflejo/fisiología , Derivados de Escopolamina/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Nervio Vago/efectos de los fármacos , Vigilia/efectos de los fármacosAsunto(s)
Arritmias Cardíacas/fisiopatología , Circulación Sanguínea , Gasto Cardíaco , Frecuencia Cardíaca , Animales , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Peso Corporal , Circulación Coronaria , Perros , Ventrículos Cardíacos/fisiopatología , Miembro Posterior/irrigación sanguínea , Arteria Ilíaca , Riñón/irrigación sanguínea , Arterias Mesentéricas , Flujo Sanguíneo Regional , Arteria Renal , Reología , Taquicardia/fisiopatología , Resistencia VascularRESUMEN
To determine the role of the arterial baroreceptor reflex in mediating the cardiovascular response to a cardiac glycoside, we examined the effects of ouabain (G-strophanthin), 17.5 mug/kg, iv, on direct and continuous measurements of left ventricular diameters, pressures, velocity of shortening, (dP/dt)/P, arterial pressure, cardiac output, and total peripheral resistance. These studies were conducted on healthy conscious dogs before and after total arterial baroreceptor denervation (TABD). Maximal pressor effects were observed in the first 3-5 minutes; mean arterial pressure increased by 11 +/- 1 mm Hg in normal dogs compared to 33 +/- 4 mm Hg in denervated dogs. In intact dogs at this time heart rate decreased by 18 +/- 2 beats/min and cardiac output fell by 18 +/- 3%; these values gradually returned toward control over 15-30 minutes. When heart rate was kept constant, cardiac output did not fall after injection of ouabain. In contrast, heart rate and cardiac output did not change significantly after ouabain in dogs with TABD. The maximal effects on the contractile state of the heart occurred between 15-30 minutes and were similar in both groups. Arterial baroreceptor reflexes appear to be responsible for the reduction in heart rate and cardiac output caused by administration of ouabain to the intact dog. They exert an important buffering action on the vasopressor effect but a less important action on the inotropic response.
Asunto(s)
Gasto Cardíaco/efectos de los fármacos , Ouabaína/farmacología , Presorreceptores/fisiología , Animales , Aorta Torácica/inervación , Presión Sanguínea/efectos de los fármacos , Volumen Cardíaco/efectos de los fármacos , Seno Carotídeo/inervación , Desnervación , Perros , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacosRESUMEN
Effects of intravenous and intra-arterial norepinephrine (NE) and angiotensin II (AN) were compared in 18 conscious dogs instrumented with Doppler or electromagnetic flow probes on the iliac, mesenteric, and renal arteries, and catheters in the aorta and iliac arteries. NE and AN administered intravenously constricted the mesenteric and renal beds, and constricted the iliac bed when administered directly into the iliac artery. In contrast, intravenous NE and AN caused striking reflex increases in iliac flow and reductions in iliac resistance, respectively, in 12 of 18 dogs studied. The reflex iliac dilatation was not prevented by beta blockade with propranolol, cholinergic blockade with atropine, or prostaglandin synthetase inhibition with indomethacin. However, the responses were abolished by either phentolamine, 1 mg/kv iv, or after local blockade of the limb with either phentolamine, 0.5 mg/kg, or with tripelennamine, 2 mg/kg. The dilatation was not prevented by either bilateral carotid sinus and aortic nerve section or by bilateral vagotomy alone, but was prevented by a combination of these procedures. Thus, intravenous NE and AN cause striking reflex iliac dilatation in the limb in the conscious dog; the afferent arc of this reflex involves both arterial baroreceptor and vagal pathways, while the efferent mechanism involves an interaction of alpha-adrenergic and histaminergic receptors.
Asunto(s)
Angiotensina II/farmacología , Arteria Ilíaca/efectos de los fármacos , Arterias Mesentéricas/efectos de los fármacos , Norepinefrina/farmacología , Arteria Renal/efectos de los fármacos , Angiotensina II/administración & dosificación , Animales , Atropina/farmacología , Velocidad del Flujo Sanguíneo , Perros , Indometacina/farmacología , Inyecciones Intraarteriales , Inyecciones Intravenosas , Norepinefrina/administración & dosificación , Fentolamina/farmacología , Propranolol/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Tripelenamina/farmacología , Vasoconstrictores , Vasodilatadores , Sistema Vasomotor/efectos de los fármacosRESUMEN
The interaction of chemoreflex and pulmonary inflation reflex control of the coronary circulation was examined in conscious dogs by comparing the responses to chemoreflex stimulation (intracarotid injection of nicotine) when ventilation was allowed to increase with those when ventilation was controlled. The responses were also compared with those elicited by both forced mechanical and spontaneous hyperinflation. When the heart rate was constant, intracarotidly administered nicotine induced an increase in the depth of respiration followed closely by an increase in late diastolic coronary flow from 48 +/- 2 to 106 +/- 8 ml/min and a reduction in late diastolic coronary resistance from 1.62 +/- 0.08 to 0.78 +/- 0.06 mm Hg/ml min-1. After beta-receptor and cholinergic blockade, a similar coronary dilation in response to nicotine occurred only when ventilation was allowed to increase. However, when ventilation was controlled, intracarotidly administered nicotine increased coronary resistance after combined beta-receptor and cholinergic blockade. The reflex coronary dilation was not observed after carotid sinus nerve section or after alpha-receptor blockade. Thus, nicotine stimulation of the carotid chemoreflex results in a striking coronary dilation that has two components. The minor component involves a chemoreflex with its efferent pathway in tthe vagi. The major component of coronary dilation follows an increase in the depth of respiration, and its efferent component appears to involve withdrawal of alpha-adrenergic constrictor tone. An almost identical period of reflex coronary dilation followed either forced mechanical or spontaneous hyperinflation in the conscious dog.
Asunto(s)
Circulación Coronaria , Pulmón/fisiología , Reflejo/efectos de los fármacos , Antagonistas Adrenérgicos alfa/farmacología , Antagonistas Adrenérgicos beta/farmacología , Animales , Bloqueo Nervioso Autónomo , Presión Sanguínea/efectos de los fármacos , Seno Carotídeo/inervación , Células Quimiorreceptoras/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Dilatación Patológica/fisiopatología , Perros , Hiperventilación/fisiopatología , Inyecciones Intraarteriales , Neuronas Aferentes/fisiopatología , Nicotina/administración & dosificación , Nicotina/farmacología , Parasimpatolíticos/farmacología , Presión , Respiración/efectos de los fármacos , Estimulación Química , Vagotomía , Resistencia Vascular/efectos de los fármacos , Sistema Vasomotor/efectos de los fármacosRESUMEN
Both clonidine and labetalol when given by bolus intravenous injection into conscious rabbits produce an initial rise in left ventricular pressure associated with a decrease in myocardial contractility as assessed by left ventricular dP/dt. While clonidine also produces a marked bradycardiac effect, labetalol causes no change in heart rate. Acute beta-adrenoceptor blockade with propranolol, 1 mg/kg, i.v., does not significantly modify the response produced by either clonidine or labetalol. Following cardiac cholinergic blockade with scopolamine methylbromide, 50 microgram/kg, the negative inotropic effect produced by clonidine is abolished and is replaced by a positive inotropic effect, while the negative inotropic response produced by labetalol is attenuated. Following cardiac autonomic blockade with propranolol and scopolamine methyl-bromide, both clonidine and labetalol produce a positive inotropic response. These positive inotropic responses may be due to the partial alpha-adrenoceptor-agonist properties which both drugs possess and which could be unmasked by cardiac autonomic blockade.
Asunto(s)
Clonidina/farmacología , Etanolaminas/farmacología , Labetalol/farmacología , Contracción Miocárdica/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Propranolol/farmacología , Conejos , Receptores Adrenérgicos alfa/efectos de los fármacos , Receptores Adrenérgicos beta/efectos de los fármacos , Escopolamina/farmacología , Estimulación QuímicaRESUMEN
The role of different central nervous regions in the reflex apnea, bradycardia, and mesenteric vasoconstriction evoked by nasopharyngeal stimulation with cigarette smoke was examined in unanesthetized shamoperated, thalamic, and pontine rabbits with intact and sectioned carotid sinus and aortic nerves (CS and AN). Apnea occurred in all preparations. In pontine animals with intact CS and AN, the heart rate response was reduced but not the mesenteric vasoconstriction. The role of suprabulbar and bulbospinal regions became more apparent when individual components of the input profile were examined in animals with controlled ventilation. The bradycardia and mesenteric vasoconstriction evoked by apnea without smoke, but not by smoke without apnea, were reduced in pontine animals. Prior section of the CS and AN attenuated the response in all neural preparations but to the least extent when cerebral hemispheres were intact. The data indicate that the respiratory reflex is predominantly integrated at bulbospinal sites, but the cardiovascular reflex is integrated at both bulbospinal and suprabulbar sites, or is integrated at bulbospinal and modulated from suprabulbar sites.
Asunto(s)
Encéfalo/fisiología , Fenómenos Fisiológicos Cardiovasculares , Nasofaringe/inervación , Reflejo , Fenómenos Fisiológicos Respiratorios , Animales , Aorta/inervación , Apnea , Bradicardia , Seno Carotídeo/fisiología , Constricción , Frecuencia Cardíaca , Bulbo Raquídeo/fisiología , Arterias Mesentéricas/fisiología , Puente/fisiología , Conejos , Humo , Tálamo/fisiología , Resistencia Vascular , Sistema Vasomotor/fisiologíaRESUMEN
1. We studied the effects of an intravenous bolus of endothelin-1 on arterial pressure and myocardial contractility in the conscious rabbit. 2. Endothelin produced an initial fall in arterial pressure accompanied by an increase in heart rate. This was followed by a dose-dependent increase in arterial pressure, peaking about 7 min after injection, accompanied by a reciprocal fall in heart rate. 3. Left ventricular rate of change of pressure (LV dP dt) increased with endothelin except at higher doses (0.8 and 1.6 nmol/kg), where in some animals it decreased.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Endotelinas/farmacología , Contracción Miocárdica/efectos de los fármacos , Animales , Arterias/efectos de los fármacos , Arterias/fisiología , Endotelinas/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intravenosas , Masculino , Conejos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
1. Changes in arterial pressure, heart rate and left ventricular contractility induced by intravenous injections of neuropeptide Y (NPY; 1-30 micrograms/kg) were studied in the conscious rabbit. 2. NPY has a brief pressor effect associated with a bradycardia, an increase in left ventricular end diastolic pressure, and a prolonged fall in peak left ventricular dP/dt (LVdP/dt). 3. The haemodynamic changes increase substantially with increasing doses up to 10 micrograms/kg. Beyond 10 micrograms/kg there are only slight effects on heart rate or peak LV dP/dt.
Asunto(s)
Neuropéptido Y/farmacología , Función Ventricular , Animales , Presión Sanguínea , Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca , Masculino , Contracción Miocárdica/efectos de los fármacos , ConejosRESUMEN
The effects of intravenous boluses of amiodarone (5 mg/kg), racemic sotalol (enantiomeric ratio d/l-sotalol 1:1;1.5 mg/kg), and d-sotalol (0.75 mg/kg) on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), left ventricular end-diastolic pressure (LVEDP), and peak rate of change of left ventricular pressure (LV dp/dt) were assessed in conscious rabbits. Amiodarone and sotalol had a modest negative inotropic effect: amiodarone reduced peak LV dp/dt by 8 +/ 2% (mean +/- SEM) (p < 0.05) and sotalol by 6 +/- 2% (p < 0.05). These two drugs had quite different effects on CO as a result of differences in their actions on peripheral blood vessels: amiodarone caused a 13 +/- 3% (p < 0.05) increase in CO associated with a substantial vasodilatory effect (TPR reduced 25 +/- 3%; p < 0.01); sotalol did not produce any substantial change in either CO or TPR. Bolus intravenous injection of amiodarone was associated with a significant increase in HR (12 +/- 3%; p < 0.01), whereas sotalol reduced HR by 7 +/- 1% (p < 0.05). In contrast, administration of the dextro-rotatory optical isomer, d-sotalol, produced no significant change in peak LV dp/dt, LVEDP, CO, TPR, or HR. These results confirm that amiodarone and racemic sotalol have a comparatively weak cardiodepressant action. The experiments also show that the reduction in cardiac performance associated with racemic sotalol is mediated predominantly through the beta-adrenoreceptor blocking action of the levo-rotatory isomer (l-sotalol) rather than any substantial cardiodepressant effect of the dextro-rotatory isomer.
Asunto(s)
Amiodarona/farmacología , Hemodinámica/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Sotalol/farmacología , Amiodarona/farmacocinética , Animales , Depresión Química , Masculino , Conejos , Sotalol/farmacocinética , EstereoisomerismoRESUMEN
1. The effects of intravenous (i.v.) neuropeptide Y (NPY, 10 micrograms/kg bolus) on the stimulus-response curves relating changes in heart period (HP) and in peak left ventricular (LV) dP/dt to acute changes in mean arterial pressure (MAP) were determined in conscious, normotensive rabbits. 2. The relationship between increases and decreases in MAP and the subsequent changes in HP were represented by a sigmoid-shaped curve described by a logistic function. Following NPY administration there was a baroreflex-dependent increase in the maximum slope (sensitivity) at the midpoint of this MAP-HP curve from 7.0 +/- 0.5 to 10.6 +/- 1.3 ms/mmHg (P less than 0.05). NPY caused an upward shift in the whole curve which reflected the NPY-induced bradycardia and was independent of baroreflexes. 3. The relationship between increases in MAP and decreases in peak LV dP/dt was determined during fixed-rate atrial pacing to prevent the effects of the accompanying bradycardia. Increases in MAP and the corresponding reductions in peak LV dP/dt were represented by an exponential function. The slope of the curve, measured at its origin 5-15 min after NPY administration, was reduced from -0.9 +/- 0.2 to -0.4 +/- 0.1 units (P less than 0.05). 4. The effects of NPY are consistent with an action on efferent connections of the arterial baroreceptor reflex, mediated through a reduction in cardiac beta-adrenergic tone. They would also be explained through actions on the afferent or central neural connections of the baroreflex.
Asunto(s)
Frecuencia Cardíaca/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Neuropéptido Y/farmacología , Presorreceptores/efectos de los fármacos , Reflejo/efectos de los fármacos , Animales , Masculino , Conejos , Estimulación QuímicaRESUMEN
We studied the effects of an intravenous (i.v.) bolus of endothelin-1 (ET-1, 0.2 nmol/kg) in conscious rabbits, measuring arterial blood pressure (BP), heart rate (HR), myocardial contractility, and cardiac output and evaluating direct and indirect effects of ET-1 with pacing and pharmacologic antagonists. ET-1 caused a brief initial decrease in BP of 18 +/- 1 mm Hg, followed by a sustained increase of 26 +/- 3 mm Hg (n = 16, p < 0.001). HR increased initially by 60 +/- 11 beats/min and then decreased by 68 +/- 6 beats/min (n = 16, p < 0.001). Left ventricular (LV) dP/dt increased by 2,120 +/- 380 mm Hg/s (n = 5, p < 0.01). LV end-diastolic pressure (LVEDP) increased by 4 +/- 1 mm Hg (n = 5, p < 0.05). Cardiac output (CO) increased initially by 34 +/- 4% and then decreased by 28 +/- 3% (n = 16, p < 0.001). Total peripheral resistance (TPR) decreased initially by 34 +/- 3% and then increased by 72 +/- 13% (n = 16, p < 0.001). Pacing did not alter the effect of ET-1 on arterial BP, LVdP/dt, or LVEDP. The combination of propranolol and scopolamine significantly reduced the increase and decrease in HR and the increase in LVdP/dt. None of the antagonists significantly altered the effect of ET-1 on TPR. ET-1 causes brief initial vasodilation and increased myocardial contractility, followed by sustained vasoconstriction. The vascular effects appear to be of greater significance than the cardiac effects at the dose used.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Endotelinas/farmacología , Contracción Miocárdica/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Estimulación Cardíaca Artificial , Sistema Cardiovascular/metabolismo , Cateterismo Periférico , Endotelinas/antagonistas & inhibidores , Frecuencia Cardíaca/efectos de los fármacos , Conejos , Resistencia Vascular/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaRESUMEN
The direct and reflex-mediated components of the cardiovascular response to administration of neuro-peptide Y (NPY) in intact conscious rabbits were determined by studies with cardiac beta adrenoceptor and vagal blockade, and during total autonomic blockade. Cardiac pacing was used to prevent bradycardia, and sinoaortic denervation (SAD) was used to remove afferent baroreflex input. In control animals, NPY (10 micrograms/kg bolus i.v.) caused arterial pressure to increase from 77.4 +/- 1.5 mm Hg (mean +/- SEM) to a maximum of 91.4 +/- 1.6 mm Hg (p less than 0.05). This pressor response was independent of autonomic effectors but was buffered by arterial baroreflexes. The fall in heart rate (HR) from 281 +/- 14 to 252 +/- 18 beats/min (p less than 0.05) was mediated in part through baroreceptor-dependent changes in cardiac autonomic efferent activity, but was in part independent of autonomic neural mechanisms. Peak left ventricular (LV)dP/dt fell from 5,551 +/- 342 to 4,182 +/- 394 mm Hg/s (p less than 0.05) following NPY in control rabbits. This reduction was maintained during pacing and following SAD, and was caused partly by a withdrawal of cardiac beta-adrenergic tone and partly through a non-beta-mediated myocardial depression. Small changes in cardiac output (CO) and in LV end-diastolic pressure (LVEDP) after NPY were secondary to bradycardia. Total autonomic blockade did not impair the NPY-induced rise in total peripheral resistance (TPR), suggesting a direct vasoconstrictor action that was independent of neural mechanisms.