Reacción pulpar frente a fuerzas ortodónticas: evaluación de la primera semana de tratamiento / Pulpal response to orthodontic forces: evaluation of the first week of treatment

Objetivos: Evaluar la correlación entre: (I) los niveles de fuerza aplicados a dientes anteriores en las etapas iniciales del tratamiento ortodóntico; (II) la percepción de dolor y (III) la sensibilidad pulpar. Universo y Muestra: Clínica de Especialización en Ortodoncia y Ortopedia MáxiloFacial de la Universidad San Sebastián en Santiago de Chile durante los años 2012 al 2014. Se obtuvo una muestra no probabilística por conveniencia de 136 dientes en 37 pacientes con brackets y Arcos de (TM)Nitinol termoactivados (35ºC) de 0.014 pulgadas. Material y Método: Estudio observacional prospectivo. Los dientes fueron evaluados con un dinamómetro siendo las fuerzas clasificadas en cuatro categorías: leves, óptimas, altas y extremas. El dolor fue medido con la Escala Visual Análoga al primer, segundo y séptimo día, después del comienzo de la aplicación de la fuerza y al séptimo día también se sometieron los dientes a test térmicos. Resultados: Después de unas horas del comienzo de la aplicación de la fuerza, el dolor comenzó a disminuir. Con el aumento de magnitud de las fuerzas, el dolor no varió en intensidad. El 39.1% de los dientes que recibieron fuerzas "óptimas" y el 22.4% de los que recibieron fuerzas "extremas", mostraron una respuesta aumentada al frío. El 1% de los dientes sometidos a fuerzas "extremas" presentó una respuesta aumentada al calor. Conclusiones: En los primeros siete días, no se observó daño pulpar irreversible independiente de la magnitud de la fuerza aplicada

Objectives: To evaluate the correlation between: (I) force levels applied to anterior teeth in the initial stages of orthodontic treatment; (II) pain perception, and (III) pulp sensitivity. Setting and Sample Population: Orthodontics and Maxillofacial Orthopedics Clinic at San Sebastián University in Santiago, Chile from 2012 to 2014. A non-probabilistic convenience sample was obtained of 136 teeth in 37 patients with braces and 0.014-inch heat-activated (35ºC) Nitinol(TM) arch wires. Material and Method: Prospective observational study. Teeth were evaluated with a dynamometer. Forces were classified into four categories: mild, optimal, high, and extreme. Pain was measured with the Visual Analog Scale (VAS) on the first, second, and seventh day after the force application, and thermal tests were applied on the seventh day. Results: A few hours after the beginning of the force application, the pain began to diminish. The pain did not vary in intensity with increasing force magnitude. 39.1% of the teeth which received "optimal" forces and 22.4% of those which received "extreme" forces exhibited an increased response to cold. 1% of the teeth subjected to "extreme" forces exhibited an increased response to heat. Conclusions: In the first seven days, no irreversible pulpal damage was observed regardless of the magnitude of the applied force

A mixed method evaluation of adult tier 2 lifestyle weight management service provision across a county in Northern England.

Adult obesity in the UK remains a public health priority. Current guidance recommends local areas provide multicomponent interventions to treat adults with overweight and obesity; however, there is currently a dearth of published evidence on the evaluation of these programmes. This study reports on a mixed method evaluation of seven tier 2 weight management programmes funded by a local authority in the North of England through their public health grant (a lifestyle multicomponent weight management programme for the treatment of adults with overweight and obesity, but not severe obesity, or obesity with severe co-morbidities). Data collected from over 2000 participants demonstrated that the proportion of participants achieving 5% initial body weight loss was comparable to that reported in recent UK weight management trials. Two services exceeded national criteria of 30% of participants achieving 5% initial body weight loss at 12 weeks, although long term data was limited. Greater weight loss was also observed in participants aged 35-44 and those without co-morbidities. This study provides important learning points for improvements in real world weight management services, these include: standardised data collection and management tools; staff training and communication requirements; the importance of programmes that are joined up to wider support services; and the importance of providing ongoing peer and provider support, continuous monitoring and feedback, and physical activities tailored to user needs.

Identification of subunits of voltage-gated calcium channels and actions of pregabalin on intrinsic primary afferent neurons in the guinea-pig ileum.

BACKGROUND: The intrinsic primary afferent neurons (IPANs) in the intestine are the first neurons of intrinsic reflexes. Action potential currents of IPANs flow partly through calcium channels, which could feasibly be targeted by pregabalin. The aim was to determine whether pregabalin-sensitive α2δ1 subunits associate with calcium channels of IPANs and whether α2δ1 subunit ligands influence IPAN neuronal properties. METHODS: We used intracellular electrophysiological recording and in situ hybridisation to investigate calcium channel subunit expression in guinea-pig enteric neurons. KEY RESULTS: The α subunits of N (α1B) and R (α1E) type calcium channels, and the auxiliary α2δ1 subunit, were expressed by IPANs. This is the first discovery of the α2δ1 subunit in enteric neurons; we therefore investigated its functional role, by determining effects of the α2δ1 subunit ligand, pregabalin, that inhibits currents carried by channels incorporating this subunit. Pregabalin (10 µmol L(-1)) reduced the action potential duration. The effect was not increased with increase in concentration to 100 µmol L(-1). If N channels were first blocked by ω-conotoxin GVIA (0.5 µmol L(-1)), pregabalin had no effect on the residual inward calcium current. Reduction of the calcium current by pregabalin substantially inhibited the after-hyperpolarising potential (AHP) and increased neuron excitability. CONCLUSION & INFERENCES: Intrinsic primary afferent neurons express functional N (α1B) channel-forming subunits that are associated with α2δ1 modulatory subunits and are inhibited by pregabalin, plus functional R (α1E) channels that are not sensitive to binding of pregabalin to α2δ subunits. The positive effects of pregabalin in irritable bowel syndrome (IBS) patients might be partly mediated by its effect on enteric neurons.

Synaptic responses in cochlear nucleus neurons evoked by activation of the olivocochlear system.

The action of olivocochlear collaterals to the cochlear nucleus is not fully established. Synaptic ultrastructure suggests an excitatory role. Extracellular recordings show spikes evoked by electrical stimulation of olivocochlear axons, but these spikes in the cochlear nucleus may be antidromic (activation of output axons) or orthodromic (synaptic input). We therefore recorded intracellular responses to shocks to olivocochlear axons in anaesthetized guinea pigs. In chopper and primary-like neurons shocks caused either no response or an inhibitory synaptic response (IPSP), but never an excitatory one (EPSP). In contrast, onset neurons never showed IPSPs but showed a variety of other responses; antidromic spikes, EPSPs, orthodromic spikes or no effect. The results agree with earlier extracellular observations in that olivocochlear collaterals provide excitatory input to onset neurons. Because some onset neurons are inhibitory they may be the source of the IPSPs observed in other cochlear nucleus neurons. The data also show that electrical stimulation at the floor of the IVth ventricle results in antidromic spikes as well. However, intracellular recording enabled the orthodromic action to be verified and the presumed olivocochlear action to be better understood. Our data support the hypothesis that olivocochlear collaterals initiate excitatory input onto onset-chopper neurons.

Evidence that TASK1 channels contribute to the background current in AH/type II neurons of the guinea-pig intestine.

Neurons that have AH (designation of neurons with a prominent and prolonged after hyperpolarizing potential that follows the action potential) electrophysiological characteristics and type II morphology (AH/type II neurons) are the first neurons in reflex circuits in the small intestine. Thus, the state of excitation of these neurons strongly influences the properties of enteric reflexes. The resting outward current in the type II neurons is reduced, causing depolarization and increased excitability, when protein kinase C (PKC) or synaptic inputs are activated, suggesting that regulation of background channels is an important determinant of the state of excitability of these neurons. However, the channels that carry the background current are not yet identified. We used intracellular microelectrodes to record from myenteric AH/type II neurons of the guinea-pig ileum, immunohistochemistry to localize channels and reverse transcriptase-polymerase chain reaction (RT-PCR) to characterize channel transcripts. The blockers of TASK1 channels, bupivacaine (1 mM) and methanandamide (10 muM), depolarized AH/type II neurons by 11.6 mV and 7.9 mV, respectively, and increased resting input resistance by about 30%. The reversal potential determined for the effect of bupivacaine was -92 mV, indicating that bupivacaine acts at K(+) channels, without significant action on other channel types that are open at rest. The membrane potential of type II neurons was depolarized by acidification to pH 6.4, but this depolarization was associated with decreased input resistance and was not reduced by bupivacaine. Thus an unidentified current that is activated by reduced pH masks effects on TASK channels. Slow excitatory post-synaptic potentials in the neurons were reduced in amplitude by methanandamide, suggesting that they are generated in part by closure of TASK1 channels. TASK1 immunoreactivity occurred in all type II neurons (determined by double labeling for IB4 and NeuN), but no type II neurons were immunoreactive for TASK2 or TASK3. These latter channels were localized to non-type II neurons. Transcripts for TASK1, TASK2, TASK3 and other two-pore-domain potassium channels were found in ganglion extracts. It is concluded that TASK1 channels contribute to the resting outward current in AH/type II neurons, and that neurotransmitters that evoke slow depolarizations in these neurons do so through the closure of resting K(+) channels that include TASK1 channels.

Effects of experience in a dynamic environment on postural control.

BACKGROUND: Surfing is a balance-reliant, open skill performed in a dynamic environment rich in visual, somatosensory and vestibular information. OBJECTIVE: To evaluate adaptations to the postural control system by surfing experience. METHODS: Postural control was assessed in an upright bipedal stance in 60 male volunteers (21 elite surfers, 20 intermediate level surfers, and 19 controls) using various closed-stance positions. Six tasks were performed with two trials including a cognitive task, in the following order: eyes open, head in a neutral position (EO1); eyes closed, head in a neutral position (EC); eyes closed, head back (ECHB); eyes open, head in a neutral position, cognitive task 1 (EOC1); eyes open head in a neutral position, cognitive task 2 (EOC2); eyes open head in a neutral position (EO2). Dependent variables were area of 95th centile ellipse (AoE) and sway path length (SPL). RESULTS: All participants showed systematic increases in SPL and AoE in EC and ECHB trials. Expert surfers displayed significantly (p<0.05) increased SPL but not AoE when sharing attention with both concurrent mental tasks compared with controls. Controls showed a slight, non-significant change in postural control (reduced SPL and AoE) when attending to concurrent mental tasks. CONCLUSIONS: The findings indicate that standard postural sway indices are not able to elucidate whether expertise in surfing facilitates adaptations to the postural control system. However, concurrent mental task findings illustrate that systematic differences in balance abilities between expert surfers and controls may exist.

Olivocochlear collaterals evoke excitatory effects in onset neurones of the rat cochlear nucleus.

Axons of medial olivocochlear neurones in the superior olivary complex terminate on the outer hair cells of the cochlea and also give off collaterals that terminate in the cochlear nucleus. Previous work in our laboratory, using extracellular recordings in the cochlear nucleus, has indicated that stimulation of the olivocochlear axons may have an excitatory effect on specific cell populations of the cochlear nucleus, such as onset-choppers, in contrast to the peripheral suppressive action of the same axons. We have investigated whether this excitation is produced by action of the olivocochlear collaterals in the cochlear nucleus or whether it is mediated via the peripheral suppression, by measuring intracellular responses in the rat cochlear nucleus to electrical stimulation of the olivocochlear axons in silence. The results demonstrate that single shocks applied to the olivocochlear axons can evoke excitatory postsynaptic potentials in onset neurones. We observed an inhibitory effect in one chopper only. In the same animals in all other neurones investigated (i.e. three primary-like neurones and eight choppers) the same stimulation was without any effect on cell membrane potential. We conclude that the excitatory effects in onset neurones are not caused by suppression in the auditory peripheral organ, but by activation of olivocochlear collaterals in the cochlear nucleus.

A comparative study of prothrombinase and thrombin inhibitors in a novel rabbit model of non-occlusive deep vein thrombosis.

A quantitative and non-occlusive deep vein thrombosis model was developed in rabbits. We used this model to test the antithrombotic activity of the prothrombinase complex inhibitors factor rXai and its chemical analog glutamyl-glycyl-arginyl chloromethyl ketone inactivated human factor Xa (EGR-Xai), along with the thrombin inhibitors D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK) and heparin. Dose dependent effects of the inhibitors during constant infusion were monitored. Measurements included thrombus weights, hemostatic parameters and both cuticle and ear bleeding times. In this model, factor rXai and EGR-Xai had comparable in-vivo efficacy, and showed 80%-93% inhibition at plasma levels of 6.5 nM (rXai) and 8 nM (EGR-Xai). Effects on ex-vivo clotting times varied among the inhibitors. At 80-100% thrombus inhibition, factor rXai and EGR-Xai had no statistically significant effect, while PPACK extended thrombin clotting time (TCT) times 2.3-fold, and heparin prolonged both activated partial thromboplastin time (APTT), prothrombin time (PT) and TCT ex-vivo clotting times 6.9-, 1.2-, and 7-fold respectively. At these dosages, cuticle and ear bleeding times were prolonged for all inhibitors and showed increases of 177%-389% (cuticle) and 45%-129% (ear). Our results demonstrate that direct inhibition of prothrombinase complex assembly is effective in arresting venous thrombosis.

Effect of combined nitroglycerin and dobutamine infusion in left ventricular dysfunction.

The immediate therapy of severe left ventricular (LV) failure after acute myocardial infarction (AMI) frequently requires simultaneous preload reduction, pump output augmentation, and maintenance of systemic blood pressure. Therefore the effects of intravenous nitroglycerin (NG) and dobutamine (DB) were evaluated in 12 patients with severe LV failure following AMI. Nitroglycerin achieved salutary lowering of abnormally elevated LV filling pressure (23 to 14 mm Hg, p less than 0.001) while DB markedly augmented LV pump function (cardiac index rose from 1.7 to 2.5 L/min/m2, p less than 0.005). Notably, the combined infusion of NG + DB simultaneously decreased preload (LV filling pressure 23 to 14 mm Hg, p less than 0.001) and markedly enhanced LV pump performance (cardiac index increased from 1.7 to 2.4 L/min/m2, p less than 0.001). Minor decline in mean systemic blood pressure with NG (72 to 66 mm Hg, p less than 0.05) was rapidly reversed by DB addition (69 mm Hg, p greater than 0.05). Both agents were well tolerated without clinical or ECG evidence of myocardial ischemia or dysrhythmias. Thus the principally venodilator effects of NG minimize systemic hypotension while salutary augmentation of cardiac function in AMI with LV failure is achieved by NG + DB.

Complementary combined captopril and terbutaline therapy in severe chronic congestive heart failure.

The hemodynamic effects of captopril (CPT) alone and in combination with the beta-adrenergic receptor agonist terbutaline (TBT) were evaluated in 10 patients with severe chronic congestive heart failure (CHF). The heart rate remained unchanged, while CPT lowered mean systemic blood pressure from 86 to 64 mm Hg (p less than 0.001) and decreased left ventricular filling pressure markedly from 27 to 19 mm Hg (p less than 0.001). The addition of TBT produced no further change in these variables (p greater than 0.05). Simultaneously, CPT augmented cardiac index (CI) from 2.1 to 2.9 L/min/m2 (p less than 0.001) and stroke index (SI) from 27 to 37 ml/beat/m2 (p less than 0.001). Concomitant CPT-TBT further raised CI to 3.2 L/min/m2 and SI to 40 ml/beat/m2 (both less than 0.001). Further, the CPT-effected decline in total systemic vascular resistance from 1577 to 841 dynes . sec . cm-5 (p less than 0.001) was not reduced additionally by CPT-TBT combination (p greater than 0.05). These results indicate than both CPT and TBT markedly augment cardiac function in CHF. Moreover, the salutary effects of the systemic vasodilator appear additive to the beneficial actions of the beta-adrenergic receptor agonist, thereby providing substantial augmentation of the function of the failing heart.

Long-term hemodynamic and clinical efficacy of captopril therapy in ambulatory management of severe chronic congestive heart failure.

The 6-month extended vasodilator efficacy of the oral angiotensin converting enzyme (ACE) inhibitor, captopril (CPT), was evaluated by sequential cardiac catheterization, nuclear scintigraphy, echocardiography, treadmill exercise, and symptomatology in nine patients with severe chronic left ventricular (LV) failure (CHF). CPT lowered LV filling pressure (from 23 to 14 mm Hg acutely (p less than 0.001) and to 14 mm Hg (p less than 0.01) with continuous 6-month therapy; concomitantly CPT raised cardiac index from 2.03 to 2.46 L/min/m2 initially (p less than 0.02) and to 2.33 L/min/m2 (p less than 0.02) at 6 months. Simultaneously CPT raised LV ejection fraction from 0.21 to 0.25 acutely (p less than 0.01) and to 0.30 (p less than 0.001) and to 60 mm (p less than 0.001) at 6 months. These beneficial actions of CPT on LV pump function raised treadmill exercise duration (from 339 to 426 seconds initially (p less than 0.05) and to 499 seconds (p less than 0.05) at 6 months, while considerably reducing CHF symptomatology (p less than 0.001). Thus ACE inhibition by CPT provides markedly beneficial sustained hemodynamic and clinical improvement in advanced LV failure without fluid accumulation or late vasodilator drug tolerance.

Importance of neuroendocrine regulators of vascular tone and integral adrenoreceptor interaction during oral vasodilator therapy of severe congestive heart failure with prazosin.

The cardiocirculatory actions of the oral vasodilator prazosin were evaluated by cardiac catheterization, forearm plethysmography, echocardiography, treadmill exercise, and symptoms in patients with advanced long-standing congestive heart failure. The administration of oral prazosin (2-7mg) reduced forearm venous tone and forearm vascular resistance. Concomitantly, mean systemic arterial pressure and left ventricular filling pressure decreased, and the cardiac index increased. These effects of a single dose of prazosin on left ventricular function were rapid in onset, maximal at 1 h, and sustained for the entire 6-h period of observation. After 2 weeks of outpatient therapy with 2-7 mg of prazosin four times daily, echographic end-diastolic dimension decreased, whereas the duration of treadmill exercise increased. Symptoms (dyspnea, fatigue, angina) were diminished throughout the course of prazosin therapy, and there was an improvement in the New York Heart Association functional class from 3.7 to 2.2. Thus, prazosin possesses sustained nitroprusside-like balanced dilator actions on the systemic arterial and venous beds, which are effectively translated into the beneficial hemodynamic effects of augmenting cardiac output and relieving excessive left ventricular end-diastolic pressure. The delayed vasodilator tolerance that occurs in 30% of the patients is prevented by the prior use of aldosterone antagonists, and is easily treated when present. Subacute hemodynamic suppression of beneficial prazosin vasodilator actions is transient and does not preclude successful sustained prazosin therapy of severe heart failure.

The hemodynamic actions of prenalterol in left ventricular failure.

The hemodynamic effects of prenalterol, a parenteral cardioselective beta 1-receptor agonist, were evaluated by cardiac catheterization in patients with refractory severe congestive heart failure (CHF). Prenalterol (PN) (4 mg i.v.) did not alter (p greater than 0.05) heart rate (HR), mean blood pressure (MBP) or left ventricular filling pressure (LVFP). Concomitantly PN markedly augmented cardiac index (CI) from 1.9 to 2.6 l/min/m2 (p less than 0.01) and substantially elevated stroke index (SI) from 24 to 30 ml/beta/m2 (p less than 0.001). In addition PN raised stroke work index (SWI) from 21 to 26 g . m/m2 (p less than 0.005) and decreased total systemic vascular resistance (TSVR) from 1702 to 1260 dyn . s. cm-5 (p less than 0.001). An important finding was that the heart rate x systolic blood pressure product was unchanged (p greater than 0.05) and precipitation of cardiac dysrhythmias or myocardial ischemia were not observed. Further PN 1 mg, 4 mg and 8 mg i.v. was sequentially injected and peak hemodynamic effects were determined 10 min after drug administration. PN 1 mg raised CI from 2.1 to 2.5 1/min/m2 (p less than 0.01), elevated SI from 24 to 29 ml/beat/m2 (p less than 0.01), and augmented SWI from 21 to 25 g . m/m2 (p less than 0.01), however, TSVR declined from 1702 to 1392 dyn . s. cm-5. Subsequent incremental PN doses of 4 and 8 mg did not provide (p greater than 0.05) additional enhancement of cardiac function. Thus, prenalterol produced markedly beneficial enhancement of cardiocirculatory function without untoward effects and may be useful in the management of patients with severe congestive heart failure. Moreover, dose-response analysis indicates these salutary improvements can be maximally produced by the small dose of 1 mg obviating the need for larger doses.

Cardiocirculatory and myocardial energetic effects of prostaglandin E1 in severe left ventricular failure due to chronic coronary heart disease.

The cardiocirculatory actions of brief (69 +/- 5 minutes) infusions of prostaglandin E1 were evaluated in nine chronic coronary heart disease patients with severe left ventricular (LV) failure caused by previous myocardial infarction. Prostaglandin E1 infusion did not alter heart rate (HR) and produced modest declines in mean systemic blood pressure (BP) (85 +/- 6 to 76 +/- 5 mm Hg, P less than 0.025) and LV filling pressure (19 +/- 3 to 15 +/- 2 mm Hg, P less than 0.01). Simultaneously, prostaglandin E1 augmented LV pump function raising cardiac index from 1.9 +/- 0.2 to 2.5 +/- 0.1 L/min/m2 (p less than 0.005), elevating stroke index from 28 +/- 2.4 to 35 +/- 2.9 ml/beat/m2 (p less than 0.01), and increasing stroke work index from 26 +/- 4.3 to 30 +/- 4.4 gm . m/m2 (p less than 0.02). Additionally, total systemic vascular resistance decreased from 1862 +/- 192 to 1282 +/- 100 dynes-sec-cm-5 (p less than 0.02) and double product LV aerobic index of HR . systolic BP diminished from 9492 +/- 666 to 8278 +/- 492 (p less than 0.02). Concomitantly, in the forearm, vascular resistance fell, blood flow rose, and venous tone remained unchanged. These results indicate that prostaglandin E1 is a potent systemic arteriolar dilator with markedly beneficial effects on cardiac function in chronic coronary patients having severe ischemic LV failure refractory to conventional therapy.

Management of refractory congestive heart failure with prazosin.

The cardiocirculatory actions of prazosin (PZN) orally were evaluated by cardiac catheterization, forearm plethysmography, echocardiography, treadmill exercise, and symptoms in patients with advanced long-standing congestive heart failure (CHF). PZN orally (2 to 7 mg) reduced forearm venous tone and decreased forearm vascular resistance. Concomitantly mean systemic arterial pressure declined, left ventricular filling pressure (LVFP) decreased, and cardiac index (CI) was raised. These effects of a single dose of PZN on LV function were rapid in onset, maximal at 1 hour, and sustained for the entire 6 hours of observation. After 2 weeks of outpatient therapy with 2 to 7 mg PZN four times daily, echographic LV end-diastolic dimension decreased and the duration of treadmill exercise increased. Symptoms (dyspnea, fatigue, angina) were diminished throughout the course of PZN therapy, and New York Heart Association functional class improved for III to II. Thus PZN possesses sustained nitroprusside-like balanced dilator actions on the systemic arterial and venous beds, which are effectively translated into beneficial hemodynamics of augmenting lowered cardiac output and relieving excessive LVFP. Delayed vasodilator tolerance, occurring in 30% of patients, is prevented by prior use of aldosterone antagonists and is easily treated. Subacute hemodynamic suppression of beneficial PZN vasodilator actions is transient and does not preclude successful sustained PZN therapy of severe chronic CHF.

Therapeutic application of prazosin in chronic refractory congestive heart failure. Tolerance and "tachyphylaxis" in perspective.

The cardiocirculatory actions on the oral vasodilator prazosin were evaluated by cardiac catheterization, forearm plethysmography, echocardiography, treadmill exercise and symptoms in patients with advanced long-standing congestive heart failure. The administration of oral prazosin (2 to 7 mg) reduced forearm venous tone and forearm vascular resistance. Concomitantly, mean systemic arterial pressure and left ventricular filling pressure decreased, and the cardiac index increased. These effects of a single dose of prazosin on left ventricular function were rapid in onset, maximal at 1 hour and sustained for the entire 6-hour period of observation. After two weeks of outpatient therapy with 2 to 7 mg of prazosin four times daily, echographic end-diastolic dimension decreased, whereas the duration of treadmill exercise increased. Symptoms (dyspnea, fatigue, angina) were diminished throughout the course of prazosin therapy, and there was an improvement in the New York Heart Association functional class from 3.7 to 2.2. Thus, prazosin possesses sustained nitroprusside-like balanced dilator actions of the systemic arterial and venous beds, which are effectively translated into the beneficial hemodynamic effects of augmenting cardiac output and relieving excessive left ventricular end-diastolic pressure. The delayed vasodilator tolerance that occurs in 30 percent of the patients is prevented by the prior use of aldosterone antagonists and is easily treated when present. Subacute hemodynamic suppression of beneficial prazosin vasodilator actions is transient and does not preclude successful sustained prazosin therapy of severe heart failure.

Hemodynamic actions of prenalterol in severe congestive heart failure due to chronic coronary disease.

To provide improved inotropic agents for enhanced therapy of severe congestive heart failure (CHF), the hemodynamic efficacy of prenalterol (PN), a recently developed cardioselective beta-1 receptor agonist, was evaluated by cardiac catheterization in nine patients with refractory CHF due to chronic coronary disease. PN (4.8 mg intravenously) markedly augmented the cardiac index from 1.9 to 2.6 L/min/m2 (p less than 0.01) and substantially elevated stroke index from 24 to 30 ml/beat/m2 (p less than 0.001). Additionally, PN raised stroke work index 21 to 26 gm.m/m2 (p less than 0.005) and decreased total systemic vascular resistance from 1,702 to 1,260 dynes-sec cm(-5) (p less than 0.001). Concomitantly, heart rate, mean blood pressure, and left ventricular filling pressure were unaltered ( p greater than 0.05). Importantly, the heart rate-systolic blood pressure product was unchanged (p less than 0.05), and precipitation of cardiac dysrhythmias or myocardial ischemia was not observed. Thus PN produced considerable improvement of depressed cardiocirculatory performance without untoward effects and thereby appears a valuable new cardiotonic in the clinical management of severe low output ventricular dysfunction.