Assuntos
Denervação Autônoma , Sistema Nervoso Autônomo/fisiopatologia , Tolerância ao Exercício , Exercício Físico , Transplante de Coração , Coração/inervação , Músculo Esquelético/fisiopatologia , Animais , Débito Cardíaco , Coração/fisiopatologia , Frequência Cardíaca , Humanos , Contração Muscular , Músculo Esquelético/metabolismo , Regeneração Nervosa , Consumo de Oxigênio , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the results and the feasibility of the technique of percutaneous closing of patent foramen oval (PFO) with Atrial Septal Aneurysm (ASA) among young patients having presented a cryptogenic cerebral ischemia. PATIENTS AND METHODS: Eighteen patients: 14 cryptogenic stroke and 4 TIA with a broad PFO (rank III) and an important ASA (excursion higher than 15 mm) at transesophageal echocardiography (TEE). The average age is 48.2 years: man 61%, women 39%. The patients have little cardiovascular risk factor (0.83/patient) and 38% presented recurrent thromboembolic events. Percutaneous closing is carried out under general anaesthesia with TEE and Amplatzer devices implantation. A control TEE is carried out 6 months after closing. RESULTS: No complication occurred at the time of the procedures. After 72 hours, one patient presented a major complication: one arteriovenous fistula requiring a surgery. Five patients presented a minor complication: two non complicated femoral hematoma, two atrial arrhytmias and one asymptomatic secondary displacement of the device without need for surgery. Seven-teen patients had TEE at six months: the shunt disappeared for 95% from the patients, no thrombus was found. No recurrent thromboembolic event appeared for the 18 patients (median follow-up 19.2 months). CONCLUSION: The installation of a technique of percutaneous closing of the PFO+ASA is safe and effective.
Assuntos
Septo Interatrial , Forame Oval Patente/terapia , Aneurisma Cardíaco/terapia , Próteses e Implantes , Adulto , Idoso , Estudos de Viabilidade , Feminino , Forame Oval Patente/complicações , França , Aneurisma Cardíaco/complicações , Hospitais Gerais , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Chronic heart failure (CHF), the new epidemic in cardiology, is characterized by energetic failure of both cardiac and skeletal muscles. The failing heart wastes energy due to anatomical changes that include cavity enlargement, altered geometry, tachycardia, mitral insufficiency and abnormal loading, while skeletal muscle undergoes atrophy. Cardiac and skeletal muscles also have altered high-energy phosphate production and handling in CHF. Nevertheless, there are differences in the phenotype of myocardial and skeletal muscle myopathy in CHF: cardiomyocytes have a lower mitochondrial oxidative capacity, abnormal substrate utilisation and intracellular signalling but a maintained oxidative profile; in skeletal muscle, by contrast, mitochondrial failure is less clear, and there is altered microvascular reactivity, fibre type shifts and abnormalities in the enzymatic systems involved in energy distribution. Underlying these phenotypic abnormalities are changes in gene regulation in both cardiac and skeletal muscle cells. Here, we review the latest advances in cardiac and skeletal muscle energetic research and argue that energetic failure could be taken as a unifying mechanism leading to contractile failure, ultimately resulting in skeletal muscle energetic failure, exertional fatigue and death.
Assuntos
Metabolismo Energético/fisiologia , Insuficiência Cardíaca/fisiopatologia , Coração/fisiopatologia , Músculo Esquelético/fisiopatologia , Animais , Doença Crônica , Insuficiência Cardíaca/metabolismo , Humanos , Células Musculares/metabolismo , Células Musculares/fisiologia , Músculo Esquelético/metabolismoRESUMO
The purpose of the study was to determine the potential beneficial effect of six weeks oral L-arginine supplementation (LAS) on endurance exercise, an important determinant of daily-life activity in patients with chronic stable heart failure (CHF). After an initial incremental maximal exercise test, CHF patients performed an identical thirty-minute interval endurance exercise test before and after six weeks with (L-arginine group; ARG) or without LAS (control group; CTL). Hemodynamic, respiratory, and metabolic parameters were determined at rest, during exercise, and during recovery. Mean heart rate decreased throughout exercise and recovery after LAS (- 8.2 +/- 1.4 b x min(-1); p = 0.003 and - 6.7 +/- 1.6 b x min(-1); p < 0.001, respectively), systemic blood pressure and respiratory parameters remaining unchanged. Resting L-argininaemia increased from 102 +/- 11 to 181 +/- 37 micromol x l(-1) (p < 0.004) and exercise-induced peak increase in plasma lactate was blunted after LAS (4.13 +/- 0.75 vs. 3.13 +/- 0.39 mmol x l(-1); p = 0.02). No significant change was observed in the control group. In heart failure patients, six weeks oral LAS enhances endurance exercise tolerance, reducing both heart rate and circulating lactates. This suggests that chronic LAS might be useful as a therapeutic adjuvant in order to improve the patient's physical fitness.
Assuntos
Arginina/uso terapêutico , Tolerância ao Exercício/efeitos dos fármacos , Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Administração Oral , Análise de Variância , Arginina/administração & dosagem , Teste de Esforço , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Lactatos/sangue , Pessoa de Meia-Idade , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: As cardiac metabolic flexibility is crucial, this study examined whether acute ischaemia can induce specific qualitative alterations of the mitochondrial metabolic pathways as well as energy transfer systems. METHODS: Left descending coronary artery ligation was performed after sternotomy in eight pigs and the heart was excised after 45 min of ischaemia. Maximal O2 uptake (V(max), micromol O2 min(-1) g(-1) dry weight) of saponin-skinned myofibres were measured from ischaemic and non-ischaemic area of ventricular myocardium. RESULTS: V(max) decreased by approximately 20% in ischaemic myocardium with both glutamate-malate (18.1 +/- 1.3 vs. 22.1 +/- 1.7 in control, P < 0.05) and pyruvate substrates (19.3 +/- 1.0 vs. 23.3 +/- 2.0 in control, P < 0.05) whereas no difference was observed with palmitoyl carnitine (15.6 +/- 1.8 vs. 16.6 +/- 0.9 in control). The K(m) of mitochondrial respiration for ADP decreased in ischaemic heart by 24% (679 +/- 79 vs. 899 +/- 84 microm of ADP in control, P < 0.05). Moreover, the mitochondrial creatine kinase efficacy (K(m) without creatine/K(m) with creatine), representative of the coupling of oxidative phosphorylation process with the mitochondrial creatine kinase, was reduced in ischaemic heart (11.6 +/- 2.5 in ischaemic vs. 18.0 +/- 2.2 in control, P < 0.05). CONCLUSIONS: These findings argue for specific mitochondrial impairments at the level of pyruvate oxidation and creatine kinase channelling system after an acute period of in vivo ischaemia, whereas the lipid mitochondrial oxidation pathway seems to be preserved. Such a loss of metabolic flexibility following acute ischaemia could become an early feature of metabolic dysregulation of the heart.
Assuntos
Mitocôndrias Cardíacas/fisiologia , Isquemia Miocárdica/fisiopatologia , Difosfato de Adenosina/farmacologia , Animais , Respiração Celular , Creatina Quinase/metabolismo , Relação Dose-Resposta a Droga , Ventrículos do Coração/fisiopatologia , Fibras Musculares Esqueléticas/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Oxirredução , Consumo de Oxigênio/efeitos dos fármacos , Especificidade por Substrato , SuínosRESUMO
As energetic metabolism is crucial for muscles, they develop different adaptations to respond to fluctuating demand among muscle types. Whereas quantitative characteristics are known, no study described simultaneously quantitative and qualitative differences among muscle types in terms of substrates utilization patterns. This study thus defined the pattern of substrates preferential utilization by mitochondria from glycolytic gastrocnemius (GAS) and oxidative soleus (SOL) skeletal muscles and from heart left ventrical (LV) in rats. We measured in situ, ADP (2 mM)-stimulated, mitochondrial respiration rates from skinned fibers in presence of increasing concentrations of pyruvate (Pyr) + malate (Mal), palmitoyl-carnitine (Palm-C) + Mal, glutamate (Glut) + Mal, glycerol-3-phosphate (G3-P), lactate (Lact) + Mal. Because the fibers oxygen uptake (Vs) followed Michaelis-Menten kinetics in function of substrates level we determined the Vs and Km, representing maximal oxidative capacity and the mitochondrial sensibility for each substrate, respectively. Vs were in the order GAS < SOL < LV for Pyr, Glu, and Palm-C substrates, whereas in the order SOL = LV < GAS with G3-P. Moreover, the relative capacity to oxidize Palm-C is extremely higher in LV than in SOL. Vs was not stimulated by the Lact substrate. The Km was equal for Pyr among muscles, but much lower for G3-P in GAS and lower for Palm-C in LV. These results demonstrate qualitative mitochondrial tissue specificity for metabolic pathways. Mitochondria of glycolytic muscle fibers are well adapted to play a central role for maintaining a satisfactory cytosolic redox state in these fibers, whereas mitochondria of LV developed important capacities to use fatty acids.
Assuntos
Metabolismo Energético/fisiologia , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Difosfato de Adenosina/metabolismo , Difosfato de Adenosina/farmacologia , Animais , Carnitina/metabolismo , Respiração Celular/efeitos dos fármacos , Respiração Celular/fisiologia , Ácidos Graxos/metabolismo , Ácido Glutâmico/metabolismo , Glicerofosfatos/metabolismo , Glicólise/fisiologia , Cinética , Ácido Láctico/metabolismo , Malatos/metabolismo , Masculino , Oxirredução/efeitos dos fármacos , Fosforilação Oxidativa , Ácido Pirúvico/metabolismo , Ratos , Ratos WistarRESUMO
To investigate the effect of L-arginine supplementation (L-ARG) on physiological and metabolic changes during exercise, we determined in a double-blind study the cardiorespiratory (heart rate, oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) and the metabolic (lactate and ammonia) responses to maximal exercise after either an intravenous L-ARG hydrochloride salt or placebo load in 8 healthy subjects. Exercise-induced increases in heart rate, VO(2) and VCO(2) were not significantly different after L-ARG or placebo. By contrast, peak plasma ammonia and lactate were significantly decreased after L-ARG load (60.6 +/- 8.2 vs. 73.1 +/- 9.1 micro mol x l(-1), p < 0.01 and 7.1 +/- 0.7 vs. 8.2 +/- 1.1 mmol x l(-1), p < 0.01, for ammonia and lactate, respectively). Plasma L-citrulline increased significantly during exercise only after L-ARG load, despite a concomitant decrease in plasma L-ARG. Furthermore, a significant inverse relationship was observed between changes in lactate and L-citrulline concentrations after L-ARG load (r = -0.84, p = 0.009). These results demonstrate that intravenous L-ARG reduces significantly exercise-induced increase in plasma lactate and ammonia. Taken together, the specific L-citrulline increase and the inverse relationship observed between L-citrulline and plasma lactate after L-ARG might support that L-ARG supplementation enhances the L-arginine-nitric oxide (NO) pathway during exercise.
Assuntos
Amônia/sangue , Arginina/farmacologia , Exercício Físico/fisiologia , Lactatos/sangue , Adulto , Arginina/sangue , Citrulina/sangue , Método Duplo-Cego , Humanos , Masculino , Músculo Esquelético/metabolismo , Óxido Nítrico/metabolismo , Ornitina/sangueRESUMO
This study explores the importance of creatine kinase (CK) in the regulation of muscle mitochondrial respiration in human subjects depending on their level of physical activity. Volunteers were classified as sedentary, active or athletic according to the total activity index as determined by the Baecke questionnaire in combination with maximal oxygen uptake values (peak V(O2), expressed in ml min(-1) kg(-1)). All volunteers underwent a cyclo-ergometric incremental exercise test to estimate their peak V(O2) and V(O2) at the ventilatory threshold (VT). Muscle biopsy samples were taken from the vastus lateralis and mitochondrial respiration was evaluated in an oxygraph cell on saponin permeabilised muscle fibres in the absence (V(0)) or in the presence (V(max)) of saturating [ADP]. While V(0) was similar, V(max) differed among groups (sedentary, 3.7 +/- 0.3, active, 5.9 +/- 0.9 and athletic, 7.9 +/- 0.5 micromol O2 min(-1) (g dry weight)(-1)). V(max) was correlated with peak V(O2) (P < 0.01, r = 0.63) and with V(T) (P < 0.01, r = 0.57). There was a significantly greater degree of coupling between oxidation and phosphorylation (V(max)/V(0)) in the athletic individuals. The mitochondrial K(m) for ADP was significantly higher in athletic subjects (P < 0.01). Mitochondrial CK (mi-CK) activation by addition of creatine induced a marked decrease in K(m) in athletic individuals only, indicative of an efficient coupling of mi-CK to ADP rephosphorylation in the athletic subjects only. It is suggested that increasing aerobic performance requires an enhancement of both muscle oxidative capacity and mechanisms of respiratory control, attesting to the importance of temporal co-ordination of energy fluxes by CK for higher efficacy.
Assuntos
Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Esforço Físico/fisiologia , Adulto , Respiração Celular/fisiologia , Creatina Quinase/metabolismo , Citosol/enzimologia , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cadeias Pesadas de Miosina/metabolismo , Consumo de Oxigênio/fisiologiaRESUMO
We previously described a strong concordance between nocturnal oscillations in plasma renin activity (PRA) and the rapid eye movement (REM) and non-REM (NREM) sleep cycles, but the mechanisms inducing PRA oscillations remain to be identified. This study was designed to examine whether they are linked to sleep stage-related changes in arterial blood pressure (ABP). Analysis of sleep electroencephalographic (EEG) activity in the delta frequency band, intra-arterial pressure, and PRA measured every 10 min was performed in eight healthy subjects. Simultaneously, the ratio of low frequency power to low frequency power + high frequency power [LF/(LF + HF)] was calculated using spectral analysis of R--R intervals. The cascade of physiological events that led to increased renin release during NREM sleep could be characterized. First, the LF/(LF + HF) ratio significantly (P < 10(-4) decreased, indicating a reduction in sympathetic tone, concomitantly to a significant (P < 10(- 3) decrease in mean arterial pressure (MAP). Delta wave activity increased (P < 10(-4) 10-20 min later and was associated with a lag of 0-10 min with a significant rise in PRA (P < 10(-4) . Rapid eye movement sleep was characterized by a significant increase (P < 10(-4) in the LF/(LF + HF) ratio and a decrease (P < 10(-4) in delta wave activity and PRA, whereas MAP levels were highly variable. Overnight cross-correlation analysis revealed that MAP was inversely correlated with delta wave activity and with PRA (P < 0.01 in all subjects but one). These results suggest that pressure-dependent mechanisms elicit the nocturnal PRA oscillations rather than common central processes controlling both the generation of slow waves and the release of renin from the kidney.
Assuntos
Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Renina/sangue , Sono REM/fisiologia , Adulto , Sistema Nervoso Autônomo/metabolismo , Eletroencefalografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , MasculinoAssuntos
Transplante de Coração/fisiologia , Transplante de Rim/fisiologia , Transplante de Pâncreas/fisiologia , Adulto , Cardiomiopatia Dilatada/cirurgia , Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/cirurgia , Seguimentos , Insuficiência Cardíaca , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoAssuntos
Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/fisiologia , Coração/fisiologia , Hemodinâmica/fisiologia , Consumo de Oxigênio , Função Ventricular Esquerda/fisiologia , Adulto , Anaerobiose , Teste de Esforço , Coração/fisiopatologia , Frequência Cardíaca , Humanos , Cinética , Pessoa de Meia-Idade , Valores de Referência , Fatores de TempoRESUMO
OBJECTIVES: We investigated the in situ properties of muscle mitochondria using the skinned fiber technique in patients with chronic heart failure (CHF) and sedentary (SED) and more active (ACT) controls to determine: 1) whether respiration of muscle tissue in the SED and ACT groups correlates with peak oxygen consumption (pVO(2)), 2) whether it is altered in CHF, and 3) whether this results from deconditioning or CHF-specific myopathy. BACKGROUND: Skeletal muscle oxidative capacity is thought to partly determine the exercise capacity in humans and its decrease to participate in exercise limitation in CHF. METHODS: M. Vastus lateralis biopsies were obtained from 11 SED group members, 10 ACT group members and 15 patients with CHF at the time of transplantation, saponine-skinned and placed in an oxygraphic chamber to measure basal and maximal adenosine diphosphate (ADP)-stimulated (V(max)) respiration rates and to assess mitochondrial regulation by ADP. All patients received angiotensin-converting enzyme (ACE) inhibitors. RESULTS: The pVO(2) differed in the order CHF < SED < ACT. Compared with SED, muscle alterations in CHF appeared as decreased citrate synthase, creatine kinase and lactate dehydrogenase, whereas the myosin heavy chain profile remained unchanged. However, muscle oxidative capacity (V(max), CHF: 3.53 +/- 0.38; SED: 3.17 +/- 0.48; ACT: 7.47 +/- 0.73, micromol O(2).min(-1).g(-1)dw, p < 0.001 vs. CHF and SED) and regulation were identical in patients in the CHF and SED groups, differing in the ACT group only. In patients with CHF, the correlation between pVO(2) and muscle oxidative capacity observed in controls was displaced toward lower pVO(2) values. CONCLUSIONS: In these patients, the disease-specific muscle metabolic impairments derive mostly from extramitochondrial mechanisms that disrupt the normal symmorphosis relations. The possible roles of ACE inhibitors and level of activity are discussed.
Assuntos
Exercício Físico/fisiologia , Insuficiência Cardíaca/metabolismo , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Consumo de Oxigênio , Citrato (si)-Sintase/metabolismo , Creatina Quinase/metabolismo , Feminino , Humanos , L-Lactato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Cadeias Pesadas de Miosina/metabolismoRESUMO
One of the greatest challenges in exercise physiology is to develop a valid, reliable, non-invasive and affordable measurement of cardiac output (CO). The purpose of this study was to evaluate the reproducibility and accuracy of a new impedance cardiograph device, the Physio Flow, during a 1-min step incremental exercise test from rest to maximal peak effort. A group of 12 subjects was evaluated to determine the reproducibility of the method as follows: (1) each subject performed two comparable tests while their CO was measured by impedance cardiography using the new device (COImp1, COImp2), and (2) in a subgroup of 7 subjects CO was also determined by the direct Fick method (COFick) during the second test. The mean difference between the values obtained by impedance (i.e. COImp1-COImp2) was -0.009 l.min-1 (95% confidence interval: -4.2 l.min-1, 4.2 l.min-1), and CO ranged from 3.55 l.min-1 to 26.75 l.min-1 (n = 146). When expressed as a percentage, the difference (COImp1-COImp2) did not vary with increasing CO. The correlation coefficient between the values of COImp and COFick obtained during the second exercise test was r = 0.94 (P < 0.01, n = 50). The mean difference expressed as percentage was -2.78% (95% confidence interval: -27.44%, 21.78%). We conclude that COImp provides a clinically acceptable evaluation of CO in healthy subjects during an incremental exercise.
Assuntos
Débito Cardíaco/fisiologia , Cardiografia de Impedância/instrumentação , Teste de Esforço/instrumentação , Adulto , Cardiografia de Impedância/normas , Teste de Esforço/normas , Humanos , Oxigênio/sangue , Consumo de Oxigênio/fisiologia , Reprodutibilidade dos TestesRESUMO
Although cyclosporin (CsA) is considered to be the best immunosuppressive molecule in transplantation, it has been suspected to alter mitochondrial respiration of various tissues. We evaluated the acute effect of CsA and its vehicle on maximal oxidative capacity (V(max)) of cardiac, soleus and gastrocnemius muscles of rats by an oxygraphic method in saponin skinned muscle fibres. The effects of Sandimmun (a formulation of CsA), vehicle of Sandimmun (cremophor and ethanol (EtOH)), CsA in EtOH and EtOH alone were tested. Increasing concentrations (5 - 20 - 50 - 100 microM) of CsA (or vehicles) were used. Sandimmun profoundly altered the V(max) of all muscles. For example, at 20 microM, inhibition reached 18+/-3, 23+/-5, 45+/-5%, for heart, soleus and gastrocnemius respectively. There were only minor effects of CsA diluted in EtOH and EtOH alone on V(max) of cardiac muscle. Because the effects of vehicle on V(max) were similar or higher than those of Sandimmun, the inhibition of oxidative capacity could be entirely attributed to the vehicle for all muscles. Next, we investigated the potential sites of action of the vehicle on the different complexes of the mitochondrial respiratory chain by using specific substrates and inhibitors. The vehicle affected mitochondrial respiration mainly at the level of complex I ( approximately -85% in skeletal muscles, and -32% in heart), but also at complex IV ( approximately -26% for all muscles). The mechanism of action of the vehicle on the mitochondrial membrane and the implications for the clinical use of immunosuppressive drugs are discussed.
Assuntos
Ciclosporina/farmacologia , Imunossupressores/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Musculares/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Animais , Antimicina A/farmacologia , Ácido Ascórbico/farmacologia , Carbonil Cianeto p-Trifluormetoxifenil Hidrazona/farmacologia , Relação Dose-Resposta a Droga , Transporte de Elétrons/efeitos dos fármacos , Técnicas In Vitro , Masculino , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Wistar , Tetrametilfenilenodiamina/farmacologia , Desacopladores/farmacologiaRESUMO
PURPOSE: The mechanisms of the training-induced improvements in left ventricular assist (LVAD) patients are unknown. METHODS: We measured the hemodynamic, gas exchange, and metabolic and hormonal effects of 6-wk exercise training in a cardiogenic shock patient who was assisted by an LVAD. RESULTS: After training, the peak power and VO2 increased by 166% and 56%, respectively (80 W and 16.1 mL x min(-1) x kg(-1)), whereas the ventilatory drive decreased. Although the LVAD output increased little with exercise, the systemic cardiac output rose (adequately for the VO2) from 5.91 and 4.90 L x min(-1) at rest to 9.75 and 9.47 L x min(-1) at peak work rate, before and after training, respectively. Thus, the left ventricle ejected again through the aortic valve. Unloading and/or retraining resulted in a left ventricular filling pressure decrease. Although the right ventricular ejection fraction increased with exercise, it decreased again at the maximal load after training. For a given work rate the arterial lactate, the norepinephrine (NE) and epinephrine (E) concentrations fell after training, but the enhanced maximal work rate elicited higher NE and E concentrations (4396 and 1848 pg x mL(-1), respectively). The lack of right ventricular unloading might have kept the atrial natriuretic peptide higher after training, but the blood cyclic GMP and endothelin were lower after training. CONCLUSION: In an LVAD patient, retraining returns the exercise capacity to the class III level by peripheral and left ventricular hemodynamic improvements, but the safety of maximal exercise remains to be proven in terms of right ventricular function and orthosympathetic drive.
Assuntos
Cardiomiopatias/terapia , Exercício Físico/fisiologia , Coração Auxiliar , Hemodinâmica/fisiologia , Hormônios/fisiologia , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Hormônios/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Adrenomedullin (ADM) is a newly discovered potent vasorelaxing and natriuretic peptide that recently has been shown to be increased after heart transplantation. To investigate the hemodynamic factors modulating its release and the eventual role of ADM in blood pressure regulation after heart transplantation, seven matched heart-transplant recipients (Htx) and seven normal subjects performed a maximal bicycle exercise test while monitoring for heart rate, blood pressure, and circulating ADM. Baseline heart rate and systemic blood pressure were higher in Htx; left ventricular mass index and ADM tended to be higher after heart transplantation and correlated positively in Htx (r = 0.79, P = 0.03). As expected, exercise-induced increase in heart rate was lower in Htx than in controls (60 +/- 11 % vs. 121 +/- 14 %, respectively) and blood pressure increase was similar in both groups. Maximal exercise increased significantly plasma ADM in both groups (from 25.3 +/- 3.1 to 30.7 +/- 3.5 pmol/L, P < 0.05 and from 15.2 +/- 1.4 to 29.1 +/- 4.4 pmol/L, P = 0.02 in Htx and controls, respectively), the hypotensive peptide level remaining elevated until the 30th min of recovery. A significant inverse relationship was observed between peak mean blood pressure and circulating ADM in Htx (r = -0.86, P < 0.02). Besides showing that circulating ADM is increased after heart transplantation, the present study demonstrates a positive relationship between baseline ADM and left ventricular mass index. Furthermore, maximal exercise-induced increase in ADM is inversely related to mean blood pressure in Htx, suggesting that ADM might participate in blood pressure regulation during exercise after heart transplantation.