RESUMO
We assessed the effect of alcohol, before and after autonomic blockade, on left ventricular (LV) performance in conscious dogs. 10 animals were instrumented to determine LV volume from ultrasonic LV internal dimensions and measure LV pressure with a micromanometer. The animals were studied in the conscious state after full recovery from the operation. Blood alcohol was undetectable before and 67 +/- 14 mg/dl (mean +/- SD) at 20 min after alcohol administration. In response to alcohol, the LV systolic pressure was reduced slightly, the left ventricular end-diastolic pressure increased slightly. The maximum time derivative of LV pressure (dP/dtmax) and stroke volume were decreased. The end-systolic volume (VES), as well as effective arterial elastance, were significantly increased. There was no significant change in heart rate. Variably loaded pressure-volume loops were generated by acute caval occlusion before, immediately, and 20 min after the intravenous infusion of alcohol (0.2 g/kg). Three measures of LV performance were derived from these variably loaded pressure-volume loops: the end-systolic pressure-volume relation; the stroke work-end-diastolic volume relation; and maximum dP/dt-VED relation. The slopes of all three relations were significantly decreased in response to alcohol, and all three relations were shifted toward the right, indicating a depression of LV contractile performance. Similar, but greater depressions of LV performance with alcohol were observed following autonomic blockade. LV performance was restored by infusing dobutamine. We conclude that mildly intoxicating levels of alcohol (blood concentration less than 100 mg/dl) are capable of producing LV contractile depression in conscious animals, which is more marked after autonomic blockade. This suggests that patients with impaired LV function should avoid even small amounts of alcohol.
Assuntos
Etanol/farmacologia , Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Dobutamina/farmacologia , Cães , Hemodinâmica/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Fatores de TempoRESUMO
Because catecholamines and digitalis have different effects on the time course of myocardial intracellular calcium concentration, their effects on the time course of left ventricular contraction and relaxation may also be different. To study this question, dogs were instrumented to measure left ventricular pressure and determine left ventricular volume from three ultrasonic dimensions. After full recovery from the instrumentation, the effects of dobutamine (2-10 micrograms/kg), ouabain (0.5 mg i.v.) alone, and ouabain given after propranolol (2 mg/kg i.v.), or phentolamine (5 mg i.v.) and incremental doses of ouabain (0.25-0.75 mg i.v.) were assessed on different days. Left ventricular pressure and volume were varied by caval occlusions. Dobutamine significantly increased the slope of the left ventricular end-systolic pressure-volume relation (Emax) and the slope of the dP/dtmax-end-diastolic volume relation (dE/dtmax), while significantly decreasing the time from end-diastole to end-systole (tmax) and the time constant (T) of the isovolumic fall in left ventricular pressure. Ouabain also increased Emax and dE/dtmax but did not alter tmax or T. Dobutamine produced a greater increase in dE/dtmax than in Emax, whereas ouabain produced similar increases in both. These effects of ouabain were not altered by pretreatment with propranolol or phentolamine. We conclude that although dobutamine and ouabain are both positive inotropes that increase Emax, dobutamine speeds the rate of left ventricular contraction (tmax) and relaxation (T), whereas ouabain does not. These effects of ouabain and dobutamine on global parameters of left ventricular chamber performance mirror their influence on intracellular calcium availability. Furthermore, these observations are consistent with the predictions of the time-varying elastance model of the left ventricle and support its usefulness as a conceptual framework to understand and link events occurring during isovolumic contraction, end-systole, and isovolumic relaxation.
Assuntos
Dobutamina/farmacologia , Contração Miocárdica/efeitos dos fármacos , Ouabaína/farmacologia , Animais , Cães , Ventrículos do CoraçãoRESUMO
BACKGROUND: Superoxide (O(2)(-)) generated by enhanced xanthine oxidase (XO) activity may contribute to the increased myocardial oxidative stress in heart failure (CHF). Because blocking XO with allopurinol augments myofilament Ca(2+) sensitivity in reperfusion injury and CHF, we hypothesized that it may improve adrenergic inotropic responsiveness in CHF. METHODS AND RESULTS: We studied the effect of allopurinol on the contractile response to dobutamine and exercise in 7 chronically instrumented conscious dogs before and after producing CHF by rapid pacing. Left ventricular (LV) contractile performance was measured by the slopes of the LV end-systolic pressure-volume relation (E(ES)) and stroke work-end-diastolic volume relation (M(SW)). Before CHF, allopurinol produced no change in LV contractile performance and did not alter the response to dobutamine or exercise. After CHF, allopurinol produced significant (P:<0.05) increases in E(ES) (5.0+/-0.6 versus 3.3+/-0.6 mm Hg/mL) and M(SW). Dobutamine and allopurinol produced greater increases in E(ES) (5.4+/-0.6 versus 7.4+/-0.6 mm Hg/mL) and M(SW) (60.1+/-7.4 versus 73.7+/-4.4 mm Hg) than did dobutamine alone. After allopurinol, dP/dt(max), stroke volume, and M(SW) were higher during CHF exercise. LV diastolic pressures were lower during CHF exercise after allopurinol. CONCLUSIONS: Allopurinol has no discernable effects on LV contractile function or adrenergic responsiveness in normal, conscious animals. In pacing-induced CHF, however, allopurinol improves LV systolic function at rest and during adrenergic stimulation and exercise.
Assuntos
Alopurinol/farmacologia , Dobutamina/farmacologia , Cardiopatias/fisiopatologia , Contração Miocárdica/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Estimulação Cardíaca Artificial/efeitos adversos , Cardiotônicos/farmacologia , Cães , Interações Medicamentosas , Sequestradores de Radicais Livres/farmacologia , Cardiopatias/etiologia , Frequência Cardíaca/efeitos dos fármacos , Condicionamento Físico Animal/fisiologiaRESUMO
BACKGROUND: Some patients referred for pharmacological stress testing with transthoracic echocardiography (TTE) are unable to undergo testing owing to poor acoustic windows. Fast cine MRI can be used to assess left ventricular contraction, but its utility for detection of myocardial ischemia in patients poorly suited for echocardiography is unknown. METHODS AND RESULTS: One hundred fifty-three patients (86 men and 67 women aged 30 to 88 years) with poor acoustic windows that prevented adequate second harmonic TTE imaging were consecutively referred for MRI to diagnose inducible myocardial ischemia during intravenous dobutamine and atropine. Diagnostic studies were completed in an average of 53 minutes. No patients experienced myocardial infarction, ventricular fibrillation, exacerbation of congestive heart failure, or death. In patients who underwent computer-assisted quantitative coronary angiography, the sensitivity and specificity for detecting a >50% luminal diameter narrowing were 83% and 83%, respectively. In the 103 patients with a negative MRI examination, the cardiovascular occurrence-free survival rate was 97%. CONCLUSIONS: Fast cine cardiac MRI provides a mechanism to assess left ventricular contraction and diagnose inducible myocardial ischemia in patients not well suited for stress echocardiography.
Assuntos
Ecocardiografia , Teste de Esforço/efeitos adversos , Imageamento por Ressonância Magnética , Isquemia Miocárdica/diagnóstico , Agonistas Adrenérgicos beta/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Atropina/administração & dosagem , Angiografia Coronária , Intervalo Livre de Doença , Dobutamina/administração & dosagem , Ecocardiografia/efeitos dos fármacos , Eletrocardiografia , Teste de Esforço/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Imageamento por Ressonância Magnética/efeitos adversos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/fisiopatologia , Seleção de PacientesRESUMO
The slope of the left ventricular end-systolic pressure-volume relation has been proposed as a sensitive index of left ventricular function since it increases in response to positive inotropic agents and decreases with global depression of contractility. The effect of a segmental depression of left ventricular contractile function produced by circumflex coronary artery occlusion on the left ventricular end-systolic pressure-volume relation was evaluated in seven chronically instrumented dogs. Left ventricular volume was calculated from three ultrasonically measured, orthogonal left ventricular endocardial dimensions. Left ventricular pressure was measured with a micromanometer. The left ventricular end-systolic pressure-volume relation was generated by occlusion of the inferior vena cava, before and after inducing regional ischemia, in the presence of autonomic blockade with propranolol and atropine. The end-systolic data in each dog, before and after coronary occlusion, were fit to the equation, P = E(V - V0), with r greater than or equal to 0.95 in all cases. Coronary occlusion shifted the left ventricular end-systolic pressure-volume relation to the right in each animal. During regional ischemia, the volume intercept (V0) increased from 10.1 +/- 7.8 to 20.4 +/- 9.8 ml (mean +/- SD) (p less than 0.005). The slope (E) of the left ventricular end-systolic pressure-volume relation was relatively unchanged. It is concluded that in intact dogs, regional left ventricular ischemia resulting from coronary occlusion produces a rightward shift of the left ventricular end-systolic pressure-volume relation.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Arteriopatias Oclusivas/fisiopatologia , Pressão Sanguínea , Débito Cardíaco , Doença das Coronárias/fisiopatologia , Volume Sistólico , Animais , Cateterismo Cardíaco/métodos , Doença Crônica , Cães , Ventrículos do Coração/fisiopatologia , Hemodinâmica , SístoleRESUMO
OBJECTIVES: The purpose of this study was to determine the level and functional effects of endogenous bradykinin in congestive heart failure (CHF). BACKGROUND: There is experimental evidence that bradykinin is increased in several cardiac disease states. However, it is unknown whether plasma levels of bradykinin are elevated in CHF. Further, the cardiac and vascular responses to bradykinin in CHF are unclear. METHODS: The circulating levels of bradykinin and the effects of endogenous bradykinin were assessed in eight instrumented, conscious dogs both before and after pacing-induced CHF. RESULTS: Before CHF, the plasma bradykinin level was 53.1 +/- 12.4 pg/ml. Blocking endogenous bradykinin with HOE-140 (0.3 mg/kg), a specific bradykinin B2-receptor antagonist, produced no significant alterations in heart rate, left ventricular (LV) end-systolic pressure (Pes), total systemic resistance (TSR), the time constant of LV relaxation (tau) or the maximal rate of LV filling (dV/dt(max)). However, coronary blood flow was significantly reduced (p < 0.05). LV contractile performance measured by the slopes of pressure-volume relations was unaffected. After induction of CHF, the plasma bradykinin level increased to 234.2 +/- 19.4 pg/ml (p < 0.05). Blocking endogenous bradykinin with HOE-140 reduced coronary blood flow and produced significant increases in Pes and TSR, prolonged tau, decreased dV/dt(max) and elevated minimal LV pressure and mean left atrial pressure. Furthermore, the slopes of pressure-volume relations (p < 0.05) were decreased, indicating depressed contractility with HOE-140 after CHF. CONCLUSIONS: Before CHF, endogenous bradykinin results in coronary dilation but has no effect on systemic arterial vasodilation or cardiac performance. After CHF, endogenous bradykinin is significantly increased and, acting through B2-receptors, produces coronary and arterial vasodilation and improves LV relaxation and contractile performance. Thus, endogenous bradykinin may play an important role in preserving cardiovascular function in CHF.
Assuntos
Bradicinina/fisiologia , Insuficiência Cardíaca/fisiopatologia , Animais , Bradicinina/análogos & derivados , Bradicinina/sangue , Bradicinina/farmacologia , Antagonistas dos Receptores da Bradicinina , Cães , Hemodinâmica/efeitos dos fármacos , Modelos Cardiovasculares , Vasodilatação/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
OBJECTIVES: This study was designed to define and contrast the mechanisms of lumen enlargement from coronary balloon angioplasty and directional coronary atherectomy using intracoronary ultrasound imaging in vivo. BACKGROUND: The mechanisms of lumen enlargement produced by percutaneous transluminal coronary balloon angioplasty and directional coronary atherectomy are not known because the coronary artery wall has not previously been studied both before and after dilation. METHODS: We used intracoronary ultrasound to quantitate coronary lumen, vessel and plaque area both before and immediately after successful coronary angioplasty (n = 30) and directional coronary atherectomy (n = 25) at the site of most severe stenosis. RESULTS: Angioplasty increased lumen area by 2.80 +/- 0.25 mm2 (mean +/- SE, p < 0.0001). Eighty-one percent of this lumen gain resulted from an increase in vessel area and the remaining 19% from a reduction in plaque area. Lumen gain of individual lesions was separated into three groups: 67% had an increase in vessel area (vessel expansion), 13% had a decrease in plaque area and 20% had a combination of both. In contrast, vessel expansion contributed only 22% of the lumen gain with directional coronary atherectomy, with the majority (78%) of increase in lumen size coming from a reduction in plaque area. Directional coronary atherectomy increased lumen area from 2.36 +/- 0.05 to 7.00 +/- 0.28 mm2 (p < 0.0001). Plaque reduction was the sole mechanism in 60% of lesions, vessel expansion was the sole mechanism in 12% and a combination of both mechanisms occurred in 28%. Lumen enlargement of eccentric lesions treated with directional coronary atherectomy was more commonly associated with plaque reduction (p < 0.02), whereas eccentricity did not affect the mechanism of lumen enlargement with coronary angioplasty. CONCLUSIONS: This is the first study to systematically examine the coronary artery wall in vivo at the site of a severe stenosis both before and after catheter-based interventions in humans. Lumen enlargement from coronary angioplasty occurs predominantly from vessel expansion or stretching, although a reduction in plaque area contributes to the lumen gain in many patients and is the sole mechanism in a few. Lumen gain from directional coronary atherectomy is predominantly from reduction in plaque area (probably owing to tissue removal), although vessel stretching (balloon effect) occurs and is the sole mechanism in a small minority of vessels. Plaque reduction is more common in directional coronary atherectomy of eccentric lesions.
Assuntos
Angioplastia Coronária com Balão , Aterectomia Coronária , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Vasos Coronários/patologia , Adulto , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia de IntervençãoRESUMO
OBJECTIVES: The aim of the study was to test the hypothesis that angiotensin II (Ang II) blockade would improve exercise tolerance in patients with diastolic dysfunction and a marked increase in systolic blood pressure (SBP) during exercise. BACKGROUND: Diastolic dysfunction may be exacerbated during exercise, especially if there is a marked increase in SBP. Angiotensin II may contribute to the hypertensive response to exercise and impair diastolic performance. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover study of two weeks of losartan (50 mg q.d.) on exercise tolerance and quality of life. The subjects were 20 patients, mean age 64 +/- 10 years with normal left ventricular systolic function (EF >50%), no ischemia on stress echocardiogram, mitral flow velocity E/A <1, normal resting SBP (<150 mm Hg), and a hypertensive response to exercise (SBP >200 mm Hg). Exercise echocardiograms (Modified Bruce Protocol) and the Minnesota Living With Heart Failure questionnaire were administered at baseline, and after each two-week treatment period, separated by a two-week washout period. RESULTS: Resting blood pressure (BP) was unaltered by placebo or losartan. During control, patients were able to exercise for 11.3 +/- 2.5 (mean +/- SD) min, with a peak exercise SBP of 226 +/- 24 mm Hg. After two weeks of losartan, baseline BP was unaltered, but peak SBP during exercise decreased to 193 +/- 27 mm Hg (p < 0.05 vs. baseline and placebo), and exercise time increased to 12.3 +/- 2.6 min (p < 0.05 vs. baseline and placebo). With placebo, there was no improvement in exercise duration (11.0 +/- 2.0 min) or peak exercise SBP (217 +/- 26 mm Hg). Quality of life improved with losartan (18 +/- 22, p < 0.05) compared to placebo (22 +/- 26). CONCLUSIONS: In patients with Doppler evidence of diastolic dysfunction at rest and a hypertensive response to exercise, Ang II receptor blockade blunts the hypertensive response to exercise, increases exercise tolerance and improves quality of life.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Teste de Esforço/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Losartan/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Estudos Cross-Over , Diástole/efeitos dos fármacos , Diástole/fisiologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/fisiopatologia , Losartan/efeitos adversos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
OBJECTIVES: The goal of this study was to determine if cardiac cycle-dependent changes in proximal thoracic aortic area and distensibility are associated with exercise intolerance in elderly patients with diastolic heart failure (DHF). BACKGROUND: Aortic compliance declines substantially with age. We hypothesized that a reduction in cardiac cycle-dependent changes in thoracic aortic area and distensibility (above that which occurs with aging) could be associated with the exercise intolerance that is prominent in elderly diastolic heart failure patients. METHODS: Thirty subjects (20 healthy individuals [10 < 30 years of age and 10 > 60 years of age] and 10 individuals > the age of 60 years with DHF) underwent a magnetic resonance imaging (MRI) study of the heart and proximal thoracic aorta followed within 48 h by maximal exercise ergometry with expired gas analysis. RESULTS: The patients with DHF had higher resting brachial pulse and systolic blood pressure, left ventricular mass, aortic wall thickness and mean aortic flow velocity, and, compared with healthy older subjects, they had a significant reduction in MRI-assessed cardiac cycle-dependent change in aortic area and distensibility (p < 0.0001) that correlated with diminished peak exercise oxygen consumption (r = 0.79). After controlling for age and gender in a multivariate analysis, thoracic aortic distensibility was a significant predictor of peak exercise oxygen consumption (p < 0.04). CONCLUSIONS: Older patients with isolated DHF have reduced cardiac cycle-dependent changes in proximal thoracic aortic area and distensibility (beyond that which occurs with normal aging), and this correlates with and may contribute to their severe exercise intolerance.
Assuntos
Aorta Torácica/patologia , Tolerância ao Exercício , Insuficiência Cardíaca/patologia , Disfunção Ventricular Esquerda/patologia , Adulto , Elasticidade , Teste de Esforço , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Consumo de Oxigênio , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
To simplify and clarify the methods of obtaining attenuation-corrected equilibrium radionuclide angiographic estimates of absolute left ventricular volumes, 27 patients who also had biplane contrast cineangiography were evaluated. Background-corrected left ventricular end-diastolic and end-systolic counts were obtained by semiautomated variable and hand-drawn regions of interest and were normalized to cardiac cycles processed, frame rate and blood sample counts. Blood sample counts were acquired on (d degree) and at a distance (d') from the collimator. A simple geometric attenuation correction was performed to obtain absolute left ventricular volume estimates. Using blood sample counts obtained at d degree or d', the attentuation-corrected radionuclide left ventricular end-diastolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-diastolic volumes (r = 0.95 to 0.96). However, both mean radionuclide semiautomated variable left ventricular end-diastolic volumes (179 +/- 100 [+/- 1 standard deviation] and 185 +/- 102 ml, p less than 0.001) were smaller than the average cineangiographic end-diastolic volume (217 +/- 102 ml), and both mean hand-drawn left ventricular end-diastolic volumes (212 +/- 104 and 220 +/- 106 ml) did not differ from the average cineangiographic end-diastolic volume. Using the blood sample counts obtained at d degree or d', the attenuation-corrected radionuclide left ventricular end-systolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-systolic volumes (r = 0.96 to 0.98). Also, using blood sample counts at d degree, the mean radionuclide semiautomated variable left ventricular end-systolic volume (116 +/- 98 ml, p less than 0.05) was less than the average cineangiographic end-systolic volume (128 +/- 98 ml), and the other radionuclide end-systolic volumes did not differ from the average cineangiographic end-systolic volume. Therefore, it is concluded that: 1) a simple geometric attenuation-correction of radionuclide left ventricular end-diastolic and end-systolic count data provides accurate estimates of biplane cineangiographic end-diastolic and end-systolic volumes; and 2) the hand-drawn region of interest selection method, unlike the semiautomated variable method that underestimates end-diastolic and end-systolic volumes, provides more accurate estimates of biplane cineangiographic left ventricular volumes irrespective of the distance blood sample counts are acquired from the collimator.
Assuntos
Volume Cardíaco , Coração/diagnóstico por imagem , Adulto , Idoso , Cineangiografia , Feminino , Coração/fisiopatologia , Cardiopatias/diagnóstico por imagem , Cardiopatias/fisiopatologia , Humanos , Masculino , Matemática , Pessoa de Meia-Idade , CintilografiaRESUMO
The performance of the heart is regulated by the level of myocardial contractility and the cardiac preload and afterload. These factors, previously of interest primarily to basic scientists, are now clinically important for an understanding of both cardiac function and therapeutics. In this brief review, the essence of these concepts is summarized and related to the treatment of cardiac failure.
Assuntos
Insuficiência Cardíaca/fisiopatologia , Coração/fisiologia , Aorta/fisiologia , Fenômenos Biomecânicos , Pressão Sanguínea , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Contração Miocárdica , Resistência VascularRESUMO
OBJECTIVE: To compare the cardiovascular risk of exercise in the morning and afternoon in patients with established heart disease. DESIGN: Retrospective cohort study. PATIENTS: Patients with established heart disease referred for participation in a comprehensive cardiac rehabilitation program. INTERVENTION: Supervised, submaximal exercise (1 hour three times per week) performed either in the morning (7:30 AM) or the afternoon (3 PM). MAIN OUTCOME: Documented cardiac events that occurred while patients were exercising in the rehabilitation programs. RESULTS: There were five cardiac events in 168,111 patient-hours of exercise in the morning, with an incidence of 3.0 +/- 1.3 events per 100,000 patient-hours. There were two events during the 84,491 patient-hours of exercise in the afternoon, for an incidence of 2.4 +/- 1.5 events per 100,000 patient-hours (not significant). The risk ratio of cardiac events during exercise in the morning compared with the afternoon was 1.27 (95% confidence interval, 0.25 to 6.55). CONCLUSION: In patients with coronary artery disease, the incidence of cardiac events is low during regular, submaximal exercise whether performed in the morning or the afternoon.
Assuntos
Ritmo Circadiano/fisiologia , Exercício Físico/fisiologia , Isquemia Miocárdica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/reabilitação , Estudos RetrospectivosRESUMO
OBJECTIVE: Since portions of autonomic nerves and receptors are located superficially on the heart, it is possible that neuromodulatory substances in pericardial fluid may modulate cardiac contractile function by altering autonomic neurotransmission. The aim of the study was to examine this hypothesis in anaesthetised dogs instrumented to measure left ventricular pressure and volume (conductance catheter). METHODS: The effects of electrical stimulation of cardiac sympathetic efferents in the ansa subclavia (n = 6), or parasympathetic efferents in the vagus (n = 6), on left ventricular contractility were evaluated during epicardial superfusion with Tyrode solution, or Tyrode solution containing hexamethonium (1 x 10(-4) M), or procaine (2%). The slope of the end systolic pressure-volume relationship (Ees), a load independent measure of left ventricular contractility, and the position of the relationship (Vmid) were obtained by rapid transient vena caval occlusion. RESULTS: Ansa subclavia stimulation increased Ees from 4.8(SD 1.8) to 8.3(3.0) mm Hg.ml-1 (p < 0.05), and Vmid shifted to the left, from 9(10) to 0(16) ml (p < 0.05). This response was abolished by epicardial superfusion with procaine, but not with hexamethonium. Vagal stimulation decreased Ees from 13.3(7.4) to 6.3(4.2) mm Hg.ml-1 (p < 0.05) and Vmid shifted to the right, from 12(10) to 18(8) ml (p < 0.05). These changes were abolished by both procaine and hexamethonium. Procaine did not affect the positive inotropic response to intravenous noradrenaline nor the cardiac depressor response to intravenous methylcholine, indicating that the myocardial contractile response was intact during epicardial superfusion with procaine. CONCLUSIONS: Neuromodulatory substances in the pericardial space may alter left ventricular contractility by modifying cardiac efferent autonomic neurotransmission on the epicardial surface of the heart.
Assuntos
Anti-Hipertensivos/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Hexametônio/farmacologia , Pericárdio/efeitos dos fármacos , Procaína/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Cães , Estimulação Elétrica , Contração Miocárdica/efeitos dos fármacos , PerfusãoRESUMO
To assess the influence of captopril on left ventricular mass in 24 normal Sprague-Dawley rats, 12 were given high sodium (group 1) and 12 low sodium (group 2) diets. Half the rats given each diet were treated with 30 mg.kg-1/day captopril by gavage, the others were given placebo. Mean(SEM) arterial pressure was significantly reduced in group 2 treated rats (102.3(2.0) vs 123.4(1.5) mmHg, p less than 0.0002) but not in group 1 treated rats (113.8(2.5) vs 123.7(2.9)mmHg, NS). Blood pressure response to a 200 ng.kg-1 iv dose of angiotensin I was blocked in both group 2 (8.3(2.1) increase vs 29.7(3.6) mmHg increase for controls) and group 1 treated rats (7.8(2.8) increase vs 36.5(4.0) mmHg increase for controls). In group 2 treated rats the left ventricular to body weight ratio (X 10(-3)) was reduced compared with control (2.1(0.05) vs 2.4(0.08), p = 0.026), whereas in group 1 rats this ratio was not significantly different in the treated and control groups (2.3(0.06) vs 2.5(0.18), NS), suggesting that the reduction in left ventricular mass resulted from the influence of captopril on blood pressure. It is concluded that captopril causes a reduction in left ventricular mass in normal rats as a result of a reduction in blood pressure, independent of the effects of angiotensin I converting enzyme. This supports the concept that left ventricular mass is determined primarily by wall stress and is capable of both upward and downward regulation.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Coração/efeitos dos fármacos , Animais , Coração/anatomia & histologia , Ventrículos do Coração/anatomia & histologia , Ventrículos do Coração/efeitos dos fármacos , Tamanho do Órgão , Ratos , Ratos Endogâmicos , Sistema Renina-Angiotensina , Sódio/administração & dosagemRESUMO
STUDY OBJECTIVE: The aim was to determine whether depressed myocardial contractility is responsible for the decline in stroke volume that occurs with cardiac tamponade. DESIGN: Left ventricular contractile performance was assessed before and after beta adrenergic blockade using the end systolic pressure-volume relation, the left ventricular dP/dtmax-end diastolic volume relation, and the left ventricular stroke work-end diastolic volume relation during acute cardiac tamponade in dogs. EXPERIMENTAL MATERIAL: In eight pentobarbitone anaesthetised dogs (15.7-24.8 kg), transducer tipped and volume impedance catheters were positioned in the left ventricle. Through a median sternotomy incision, a pericardial catheter was inserted to produce varying stages of cardiac tamponade. By the use of transient bicaval occlusions, variably loaded pressure-volume loops were recorded. MEASUREMENTS AND RESULTS: Incremental tamponade reduced mean arterial pressure from 105(SEM 3) to 89(2) mm Hg (mild tamponade), 75(2) mm Hg (moderate tamponade), and 59(10) mm Hg (severe tamponade). The slope of the end systolic pressure-volume relation was 6.3(1.2) mm Hg.ml-1 at baseline and increased slightly to 7.7(1.8), 8.5(1.3), and 9.2(1.5) mm Hg.ml-1 with the progressive levels of tamponade (NS). The role of autonomic reflexes was assessed by repeating the tamponade sequence after beta adrenergic blockade with 10 mg of metoprolol intravenously. The slope of the end systolic pressure-volume relation was reduced by metoprolol, at 4.9(1.0) mm Hg.ml-1 (p less than 0.01), but was not significantly altered by the sequence of tamponade following beta blockade [5.6(0.9), 6.0(1.0), and 5.5(7.0) mm Hg.ml-1, respectively (NS)]. Neither were changes found indicative of depressed contractile function with progressive tamponade in the slopes of the left ventricular dP/dtmax-end diastolic volume and stroke work-end diastolic volume relations. CONCLUSIONS: Left ventricular contractility was not altered during acute cardiac tamponade in an anaesthetised, closed chest canine model. Depressed left ventricular contractile function was not responsible for the observed haemodynamic deterioration.
Assuntos
Tamponamento Cardíaco/fisiopatologia , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologia , Doença Aguda , Animais , Pressão Sanguínea/fisiologia , Cães , Hemodinâmica/fisiologia , Volume Sistólico/fisiologiaRESUMO
Because of ventricular interdependence, part of the measured left ventricular diastolic pressure can be attributed to the right ventricle. Therefore, we examined the hypothesis that left ventricular diastolic properties are modified by alterations in right ventricular compliance and pressure even without a change in right ventricular volume. To examine this hypothesis, the hearts were removed from six dogs, the coronary arteries perfused with cool cardioplegic solution, and the hearts submerged in cool cardioplegic solution. Balloons were inserted into each ventricle. Left ventricular pressure-volume curves were recorded and approximated by an exponential equation. With no fluid in the right ventricular balloon (control), the exponential coefficient and constant were 0.038 (SD 0.004) ml-1 and 2.38(0.75) mm Hg respectively. With right ventricular pressure held constant at 20 mm Hg, the exponential coefficient and constant were 0.035(0.002) ml-1 and 3.71(1.64) mm Hg (p less than 0.05 v control constant), respectively. With a fixed right ventricular volume, the exponential coefficient and constant were significantly different (p less than 0.05 v control values) at 0.040(0.006) ml-1 and 2.81(0.96) mm Hg, respectively. After decreasing right ventricular free wall compliance by injecting glutaraldehyde into the right coronary artery, the exponential coefficient and constant were significantly different (p less than 0.01 v control values) at 0.058(0.010) ml-1 and 1.86(0.60) mm Hg, respectively. Thus, even with a constant right ventricular pressure or volume, a significant upward shift in the left ventricular pressure-volume relation occurred. Decreasing right ventricular free wall compliance further increased left ventricular pressure. The results of these studies indicate that the diastolic properties of the left ventricle can be modified by changes in right ventricular pressure and compliance even without a change right ventricular volume. Thus indices of left ventricular diastolic properties may be altered by changes in the characteristics of the right ventricle.
Assuntos
Coração/fisiologia , Animais , Complacência (Medida de Distensibilidade) , Diástole , Cães , Técnicas In Vitro , Pressão , Volume Sistólico , Função VentricularRESUMO
OBJECTIVE: The positive inotropic effect of endothelin-1 (ET-1) on normal myocardial contraction may be altered in pathological states. The purpose of this study was to assess the direct effect of ET-1 on cardiomyocyte performance and its cellular mechanism in congestive heart failure (CHF). METHODS: We measured the plasma levels of ET-1 and compared the effects of ET-1 (10(-10)-10(-8) M) on contractile performance and the [Ca2+]i transient in the myocytes of left ventricles (LV) from 15 age-matched normal adult rats and 15 rats with isoproterenol (ISO)-induced CHF. RESULTS: With CHF, the plasma levels of ET-1 (19.7 +/- 6.3 vs. 4.1 +/- 0.5 fmol/ml, p < 0.05) were markedly elevated. In normal myocytes, superfusion of ET-1 caused significant increases in the systolic amplitude (SA, 8-16%) and the peak velocity of shortening (dL/dtmax, 20-35%; p < 0.01) without causing a change in the peak [Ca2+]i transient. In contrast, in myocytes from CHF rats, ET-1 produced significant reductions in SA (9-13%) and in the velocity of relengthening, dR/dtmax (10-14%; p < 0.05). The myocytes' dR/dtmax also decreased by 8-10% (p < 0.05). These changes were associated with a significant decrease in the peak [Ca2+]i transient (20-23%, p < 0.01). These responses to ET-1 were abolished by the incubation of myocytes with an ETA receptor antagonist (BQ123) or a protein kinase C (PKC) inhibitor (H-7 or staurosporine). CONCLUSION: ISO-induced CHF is associated with elevated plasma ET-1 and an altered cardiomyocyte response to ET-1. After CHF, ET-1 produces a direct depression of cardiomyocyte contractile performance that is associated with a significant decrease in the peak [Ca2+]i transient. These effects are likely to be mediated through ETA receptors and involve the PKC pathway.
Assuntos
Cardiotônicos/farmacologia , Endotelina-1/farmacologia , Insuficiência Cardíaca/patologia , Miocárdio/patologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Amilorida/análogos & derivados , Amilorida/farmacologia , Animais , Antiarrítmicos/farmacologia , Cálcio/metabolismo , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , Antagonistas dos Receptores de Endotelina , Endotelina-1/sangue , Inibidores Enzimáticos/farmacologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/metabolismo , Hemodinâmica/efeitos dos fármacos , Isoproterenol , Masculino , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Peptídeos Cíclicos/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/fisiologia , Ratos , Ratos Sprague-Dawley , Receptor de Endotelina A , Receptores de Endotelina/fisiologia , Trocadores de Sódio-Hidrogênio/efeitos dos fármacos , Trocadores de Sódio-Hidrogênio/fisiologia , Estaurosporina/farmacologiaRESUMO
Persistent dyskinesis is universally observed after reperfusion of a severely ischaemic segment. Although inotropic stimulation shows a latent contractile reserve, it is not known whether this reserve can be recruited by increasing end diastolic segment length (local length-tension relation). To investigate this, six anaesthetised open chest dogs were placed on right heart bypass to increase end diastolic segment length independently of mean arterial pressure. Instantaneous left ventricular pressure-segment length relations and fractional systolic shortening were determined by sonomicrometry in the centre of the region perfused by the left anterior descending coronary artery during sequential increases in end diastolic segment length. Measurements were made before occlusion of the left anterior descending coronary artery, during 1 h of occlusion, and after 2 h of reperfusion. Before ischaemia, segmental shortening increased from 11.0(SEM 1.6)% to 23.5(1.5)% (p less than 0.05) as end diastolic segment length increased. Dyskinesis developed during occlusion of the left anterior descending coronary artery [12.1(2.6)% control v -7.2(1.6)% occlusion, p less than 0.05] and was present over the entire range of end diastolic segment lengths. Following reperfusion, segmental dyskinesis [-2.5(2.4)%] persisted at the lower end of the range of end diastolic segment length, but was progressively replaced by active shortening, averaging 7.3(3.2)% (p less than 0.05) as end diastolic segment length was sequentially increased. We conclude that segmental function following reperfusion is sensitive to changes in end diastolic segment length, and that active shortening is recruited from an apparently dyskinetic segment as end diastolic segment length progressively increases.
Assuntos
Doença das Coronárias/fisiopatologia , Contração Miocárdica , Animais , Pressão Sanguínea , Ponte Cardiopulmonar , Doença das Coronárias/etiologia , Vasos Coronários/cirurgia , Cães , Ligadura , Reperfusão Miocárdica , Fatores de TempoRESUMO
To compare the accuracy of attenuated and attenuation-corrected equilibrium radionuclide angiographic (RNA) left ventricular (LV) volume estimates, we studied 23 consecutive patients with biplane contrast cineangiography (CINE). Attenuated RNA end-diastolic (ED) and end-systolic (ES) volumes were calculated from background-corrected ED and ES counts obtained from hand-drawn regions of interest that were normalized to cardiac cycles processed, frame rate, and blood activity. A simple, geometric attenuation correction was performed to obtain attenuation-corrected RNA LV volumes. The attenuated and attenuation-corrected RNA LV EDV estimates correlated with the CINE LV EDVs ; however, the attenuation-corrected RNA LV EDV estimates correlated more closely. Also, the average attenuation-corrected RNA LV EDV did not differ significantly from the mean CINE LV EDV. Attenuated and attenuation-corrected RNA LV ESV estimates also correlated with the CINE LV ESVs , but the attenuation-corrected RNA LV ESV estimates correlated more closely. Also, the average attenuation-corrected RNA LV ESV did not differ significantly from the mean biplane CINE LV ESV.
Assuntos
Volume Cardíaco , Ventrículos do Coração/diagnóstico por imagem , Adulto , Idoso , Cineangiografia/métodos , Diástole , Feminino , Humanos , Masculino , Matemática , Pessoa de Meia-Idade , Cintilografia , Albumina Sérica , Sístole , Tecnécio , Agregado de Albumina Marcado com Tecnécio Tc 99mRESUMO
Serial angiographic studies of patients with myocardial infarction and unstable angina suggest that the culprit plaque underlying a thrombus need not have produced severe luminal obstruction before onset of the event. An atherosclerotic coronary artery lesion can, therefore, have 2 important characteristics. First, it may be obstructive. Second, it may be "vulnerable" in that it has the potential to become thrombogenic if exposed to the appropriate triggering stimulus. A lesion need not be obstructive to become thrombogenic, nor do all obstructive lesions have thrombogenic potential. The cause of an infarction may thus be rupture of a nonobstructive plaque leading to occlusive thrombus formation. Because it may be difficult to predict the site of a subsequent occlusion from a coronary angiogram, coronary bypass surgery or angioplasty directed only at discernible stenotic lesions may not be effective for preventing subsequent myocardial infarctions. Appropriate therapy may need to be directed at the entire coronary tree. Such therapy might include cholesterol lowering, beta blockade and aspirin.