RESUMO
BACKGROUND: In the heart, the creatine kinase system plays an important role in energy reserves, and myocardial energy production essentially depends upon fatty acid metabolism. PURPOSE: To examine myocardial creatine (CR) concentration and altered cardiac fatty acid metabolism in various forms of heart disease. MATERIAL AND METHODS: Myocardial CR concentration of the septum was measured by gated 1H magnetic resonance spectroscopy (MRS), applying a point-resolved spectroscopy (PRESS) sequence in 34 patients with heart disease. Of these patients, 14 underwent 123I BMIPP (radioactive fatty acid analogue) myocardial scintigraphy to evaluate myocardial fatty acid metabolism. Cardiac 123I BMIPP uptake was calculated as the heart-to-mediastinum count ratio. RESULTS: Myocardial CR concentration correlated positively with the left ventricular ejection fraction (LVEF) by echocardiography (R = 0.61, P<0.001, n = 34), suggesting that the degree of reduced CR is related to the severity of contractile dysfunction. Cardiac 123I BMIPP uptake also correlated positively with LVEF (initial image, R = 0.60, P<0.05; delayed image, R = 0.63, P<0.05; n = 14). There was a significant correlation between myocardial CR and cardiac 123I BMIPP uptake (initial image, R = 0.77, P<0.01; delayed image, R = 0.82, P<0.001; n = 14). CONCLUSION: Our study suggests an association between CR depletion and impaired fatty acid metabolism in various forms of heart diseases.
Assuntos
Cardiomiopatias/metabolismo , Creatina/metabolismo , Ácidos Graxos/metabolismo , Coração/diagnóstico por imagem , Radioisótopos do Iodo , Iodobenzenos , Espectroscopia de Ressonância Magnética , Compostos Radiofarmacêuticos , Adulto , Idoso , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Hipertrófica/metabolismo , Creatina/análise , Ecocardiografia , Ácidos Graxos/análise , Feminino , Septos Cardíacos/química , Septos Cardíacos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Miocárdio/química , Miocárdio/metabolismo , Volume Sistólico/fisiologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
PURPOSE: To investigate whether cardiac parameters obtained by I-123 15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP, a radioactive fatty acid analogue) myocardial scintigraphy are useful as indicators of disease severity and predictors of cardiac events in congestive heart failure (CHF). MATERIAL AND METHODS: Thirty-two CHF patients (functional class: 17 in NYHA II and 15 in NYHA III at the time of this study) were compared with 18 normal control subjects. Myocardial scintigraphy was performed 15 min and 3 hours after I-123 BMIPP injection. The heart-to-mediastinum count ratio of I-123 BMIPP on the initial (H/Mi) and delayed (H/Md) images and the washout rate (WR) were calculated. RESULTS: Both H/Mi and H/Md were lower in CHF than in controls (H/Mi 1.96+/-0.18 vs. 2.30+/-0.29; H/Md 1.72+/-0.15 vs. 1.97+/-0.21; both P<0.001), but WR was higher in CHF than in controls (WR (%) 23.7+/-5.7 vs. 18.2+/-6.0, P<0.01). Both H/Mi (R = 0.42, P<0.05) and H/Md (R = 0.45, P<0.05) correlated positively with the left ventricular (LV) ejection fraction (EF), estimated by echocardiography. The WR correlated positively with the plasma B-type natriuretic peptide (BNP) level (R = 0.47, P<0.01). Kaplan-Meier analysis showed an earlier CHF progression for patients with a lower H/Mi (<1.94). CONCLUSION: Myocardial metabolic abnormality evaluated by I-123 BMIPP scintigraphy is related to the severity of CHF. Furthermore, it may be useful as a predictor for cardiac events.
Assuntos
Ácidos Graxos , Insuficiência Cardíaca/diagnóstico por imagem , Radioisótopos do Iodo , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Iodobenzenos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , CintilografiaRESUMO
Despite similar traditional risk factors, morbidity and mortality rates from coronary heart disease in western and non-western cohorts remain substantially different. Careful study of such cohorts may help identify novel risk factors for CHD, and contribute to the formulation of new preventive strategies
Assuntos
Doença das Coronárias/mortalidade , Países Desenvolvidos , Países em Desenvolvimento , Estudos de Coortes , Emigração e Imigração , Humanos , Japão/etnologia , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
1. The roles of ATP-sensitive K+ channels (KATP channels) in ischaemic or pharmacological preconditioning in the rabbit heart remain unclear. Infarct limitation by ischaemic preconditioning was abolished by the KATP channel blocker glibenclamide under ketamine/xylazine anaesthesia, but not under anaesthesia induced by pentobarbital. Infarct limitation by the KATP channel opener pinacidil was detected under ketamine/xylazine anaesthesia, but not under pentobarbital anaesthesia. Thus, these effects appear to be anaesthetic dependent. 2. In the present study, we examined whether nicorandil (a KATP channel opener nitrate) exhibits cardioprotective actions under halothane anaesthesia, another commonly used volatile anaesthetic. Control animals were subjected to 40 min coronary occlusion and 120 min reperfusion. Before 40 min ischaemia, the nicorandil group received nicorandil (100 microg/kg per min, i.v., for 10 min), the 5' preconditioning (PC) group received 5 min ischaemia/20 min reperfusion, the 2.5'PC group received 2.5 min preconditioning ischaemia/20 min reperfusion, the nicorandil +2.5'PC group received both nicorandil and 2.5 min ischaemia/20 min reperfusion, the nicorandil +2.5'PC + 5-hydroxydecanoate (5HD) group received both nicorandil and 2.5 min ischaemia/20 min reperfusion in the presence of 5-hydroxydecanoate (5HD; a KATP blocker) and the 5HD group received 5 mg/kg, i.v., 5HD alone. Myocardial infarct size in control (n = 7), nicorandil (n = 5), 5'PC (n = 8), 2.5'PC (n = 5), nicorandil + 2.5'PC (n = 5), nicorandil + 2.5'PC + 5HD (n = 5) and 5HD (n = 4) groups averaged 44.4 +/- 3.6, 41.7 +/- 5.7, 17.8 +/- 3.2,* 34.1 +/- 4.8, 21.3 +/- 4.2,* 39.1 +/- 5.6 and 38.9 +/- 5.0% of the area at risk, respectively (*P <0.05 vs control). 3. Thus, nicorandil alone did not have an infarct size-limiting effect in halothane-anaesthetized rabbits. However, the results suggest that even when nicorandil alone does not demonstrate a direct cardioprotective effect, it may enhance ischaemic preconditioning via KATP channels. Key words: ATP-sensitive K+ (KATP) channel, ischaemic preconditioning, myocardial infarction, nicorandil, rabbit.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Antiarrítmicos/farmacologia , Halotano/administração & dosagem , Coração/efeitos dos fármacos , Precondicionamento Isquêmico Miocárdico , Infarto do Miocárdio/prevenção & controle , Nicorandil/farmacologia , Canais de Potássio/metabolismo , Vasodilatadores/farmacologia , Transportadores de Cassetes de Ligação de ATP , Anestesia por Inalação/métodos , Animais , Peso Corporal/efeitos dos fármacos , Ácidos Decanoicos/farmacologia , Frequência Cardíaca , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Hidroxiácidos/farmacologia , Canais KATP , Espectroscopia de Ressonância Magnética , Masculino , Infarto do Miocárdio/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização , CoelhosRESUMO
We investigated the cardiovascular profile of nicorandil, an antianginal agent, in humans. Pharmacologically, nicorandil acts as both an adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channel opener and a nitrate. We examined which of these mechanistic components has a predominant vasodilatory effect at clinical doses. Fourteen patients underwent cardiac catheterization. The effects of the continuous intravenous infusion of nicorandil (12 mg/45 min) were examined in angiographically normal coronary arteries. Coronary vascular resistance was calculated from coronary artery diameter and coronary blood flow velocity measured using an intravascular Doppler catheter. We compared the hemodynamic responses to nicorandil with those to the intracoronary injection of nitroglycerin (250 microg) and papaverine (12 mg). The epicardial coronary arteries responded to nicorandil at the lowest plasma concentration examined (dilation of +14.0 +/- 3.3% at approximately 170 ng/ml), whereas dilation of the coronary resistance arteries (i.e., a decrease in coronary vascular resistance) took place only at higher concentrations (>200 ng/ml). Nitroglycerin caused no further changes in coronary artery diameter or coronary vascular resistance. Papaverine caused no further increase in coronary artery diameter, but markedly decreased coronary vascular resistance (1.6 +/- 0.3 to 0.4 +/- 0.1 mm Hg/ml/min; p < 0.05). Nicorandil significantly decreased pulmonary capillary wedge pressure (i.e., reduced cardiac preload) at a plasma level of >200 ng/ml, but did not change either systemic or pulmonary vascular resistance. Thus nicorandil preferentially dilated epicardial coronary arteries rather than coronary resistance arteries, and had a stronger effect on preload than on afterload. These changes in human coronary hemodynamics suggest that the nitrate actions of nicorandil as a coronary vasodilator predominate over those as a K(ATP) opener.
Assuntos
Circulação Coronária/efeitos dos fármacos , Nicorandil/farmacologia , Vasodilatadores/farmacologia , Adulto , Idoso , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiologia , Relação Dose-Resposta a Droga , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Nicorandil/sangue , Pressão Propulsora Pulmonar/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacosRESUMO
OBJECTIVES: This study examined the changes in myocardial energy metabolism during myocardial ischemia after "remote preconditioning" and investigated the involvement of adenosine receptors in the mechanisms of this effect. BACKGROUND: Recent studies have indicated that a brief period of ischemia and reperfusion (ischemic preconditioning, PC) in a remote organ reduces myocardial infarct size (IS) protecting against subsequent sustained myocardial ischemia. However, the mechanisms of "remote PC" remain unclear. We assessed myocardial energy metabolism during sustained myocardial ischemia and reperfusion after renal PC (RPC), in comparison with that after myocardial PC (MPC) in open-chest rabbits. It has been established that adenosine receptors are involved in the mechanisms of MPC. METHODS: Rabbits that had been anesthetized with halothane were divided into six groups. The control (CNT) group underwent 40-min coronary occlusion followed by 120 min reperfusion. Before the procedure, the MPC group underwent an additional protocol of 5 min coronary artery occlusion and 20 min reperfusion, and the RPC group received a 10 min episode of renal artery occlusion and 20 min reperfusion. In additional experimental groups, 8 sulfophenyl-theophylline (SPT, 10 mg/kg), an adenosine receptor inhibitor, was intravenously injected before the 40 min myocardial ischemia (SPT, MPC + SPT and RPC + SPT groups, respectively). Myocardial levels of phosphocreatine (PCr), ATP and intracellular pH (pHi) were measured by 31P-NMR spectroscopy. RESULTS: RPC and MPC delayed the decreases in ATP levels, preserved pHi during 40-min myocardial ischemia and resulted in better recovery of ATP and PCr during 120 min reperfusion compared with the controls. SPT abolished the improvement in myocardial energy metabolism and the reduction in myocardial IS caused by MPC or RPC. Myocardial IS in the CNT (n = 8), MPC (n = 9), RPC (n = 9), SPT (n = 6), MPC + SPT (n = 8) and RPC + SPT (n = 8) groups averaged 42.8+/-3.5%, 18.2+/-1.8%*, 19.6+/-1.3%*, 44.9+/-5.0%, 35.6+/-2.7% and 34.8+/-3.6% of the area at risk (*p < 0.05 vs. CNT), respectively. CONCLUSIONS: PC in a remote organ, similar to MPC, improved myocardial energy metabolism during ischemia and reperfusion and reduced IS in vivo by an adenosine-dependent mechanism in rabbits.
Assuntos
Metabolismo Energético , Isquemia , Precondicionamento Isquêmico Miocárdico , Rim/irrigação sanguínea , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Receptores Purinérgicos P1/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Concentração de Íons de Hidrogênio , Infusões Intravenosas , Líquido Intracelular/metabolismo , Precondicionamento Isquêmico Miocárdico/métodos , Espectroscopia de Ressonância Magnética , Masculino , Isquemia Miocárdica/diagnóstico , Miocárdio/patologia , Fosfocreatina/análogos & derivados , Fosfocreatina/metabolismo , Projetos Piloto , Antagonistas de Receptores Purinérgicos P1 , Coelhos , Teofilina/análogos & derivados , Teofilina/farmacologiaRESUMO
Although exercise electrocardiography (ECG) is a useful noninvasive screening test for coronary artery disease (CAD), one prerequisite for ECG screening is that patient be able to exercise enough to evoke myocardial ischemia. Thus, exercise ECG may not be suitable for, some elderly people with CAD who cannot exercise enough. We compared electron beam Computed Tomography (EBCT) with exercise ECG for detecting CAD in 196 patients (mean age, 58.4 +/- 12.5 [standard deviation]) who had undergone coronary angiography. Using the angiographic findings as the "gold standard", we found that the sensitivity, specificity, positive predictive value, and negative predictive value were 88%, 77%, 89%, and 77%, respectively, for EBCT, and 66%, 72%, 83%, and 52%, respectively, for exercise ECG. Although the results were similar when the subjects were divided into different age groups, the negative predictive value for exercise ECG, among older patients was very low. These findings suggest that EBCT is superior to exercise ECG in detecting CAD in the elderly.
Assuntos
Envelhecimento/fisiologia , Doença das Coronárias/diagnóstico , Eletrocardiografia , Teste de Esforço , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
To evaluate the prognostic value of the simultaneous assessment of perfusion and left ventricular wall motion, exercise non-gated/rest electrocardiogram (ECG)-gated 99mTc methoxy-isobutyl isonitrile (MIBI) single-photon emission computed tomography (SPECT) was performed in 182 patients suspected of having coronary artery disease. After injection of 250 MBq of 99mTc-MIBI at peak exercise, stress perfusion images were classified into 3 groups: normal, equivocal, and abnormal. Normal subjects completed the 1-day protocol but not the resting study, whereas patients with abnormal or equivocal perfusion images underwent ECG-gated SPECT study with injection of 750 MBq of 99mTc-MIBI 3 h later. Patients with normal perfusion during this protocol had a benign prognosis. Only 4 soft events occurred in the normal group (4.8%). In contrast, patients with both myocardial infarction and abnormal wall motion at rest experienced more cardiac events (7 cardiac events including 1 cardiac death among a total of 45 patients; 15.6%, p<0.05 compared with normal subjects). In addition, ischemic patients also experienced more cardiac events (7 events including 2 cardiac deaths among a total of 25 subjects; 28.0%, p<0.01 compared with normal patients). Our data suggest that the simultaneous assessment of perfusion and wall motion by stress/rest ECG-gated 99mTc-MIBI SPECT is a reliable indicator of prognosis in patients suspected of having coronary artery disease.
Assuntos
Circulação Coronária , Doença das Coronárias/diagnóstico , Eletrocardiografia , Teste de Esforço , Infarto do Miocárdio/epidemiologia , Ventriculografia com Radionuclídeos , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único , Função Ventricular Esquerda , Idoso , Doença das Coronárias/complicações , Morte Súbita Cardíaca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Prognóstico , Estudos Prospectivos , Recidiva , Descanso , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnósticoRESUMO
UNLABELLED: This study assessed the utility of myocardial fatty acid imaging using 123I-labeled 15-(beta-methyl-p-iodophenyl-pentadecanic acid (BMIPP) to evaluate improvement after percutaneous transluminal coronary angioplasty in patients with chronic coronary artery disease. METHODS: Thirty-eight patients (18 old myocardial infarction and 20 angina pectoris patients) with chronic coronary artery stenosis and 8 control subjects were enrolled in this study. All patients underwent successful angioplasty, and BMIPP SPECT was performed before and after angioplasty. SPECT images were divided into 13 segments and scored visually from 0 (normal uptake) to 4 (defect). The defect score was calculated as the summation of the total scores in each patient. The regional washout rate was calculated in both the reperfused areas and normal uptake areas using a bull's-eye map. RESULTS: In nonrestenosis patients, BMIPP defect scores before and after angioplasty did not change on the initial image (9.6 +/- 9.3 compared to 9.0 +/- 9.2, nonsignificant p value), whereas they improved significantly on the delayed image (9.9 +/- 8.8 compared to 8.2 +/- 8.7, p < 0.05). In nonrestenosis patients, BMIPP washout rate in reperfused areas after angioplasty was significantly lower than that before angioplasty and the washout rate in control subjects (22.9% +/- 8.4% compared to 31.5% +/- 10.6% and 29.5% +/- 8.0%, p < 0.01 and p < 0.05, respectively). In restenosis patients, BMIPP washout rate in both reperfused areas and normal uptake areas did not change after angioplasty. CONCLUSION: These data suggest that decreased BMIPP washout rate after angioplasty indicates improved fatty acid utilization in patients with chronic coronary artery disease.
Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/metabolismo , Doença das Coronárias/terapia , Ácidos Graxos/metabolismo , Miocárdio/metabolismo , Adulto , Idoso , Doença das Coronárias/diagnóstico por imagem , Feminino , Humanos , Radioisótopos do Iodo , Iodobenzenos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
To demonstrate the usefulness of in vivo 31P nuclear magnetic resonance spectroscopy (MRS) in the diagnosis of ischemic heart disease, major findings from three clinical cardiac MRS investigations performed at our institute are summarized. The first study investigated whether 31P MRS with handgrip exercise testing could detect myocardial ischemia demonstrated by exercise 201Tl scintigraphy. Contrary to findings in normal subjects or patients with fixed thallium defects, the ratio of phosphocreatine (PCr) to ATP decreased significantly during exercise in patients with reversible thallium defects. In the second study, PCr and ATP content was measured by 31P MRS and compared in human myocardium with reversible ischemia or scar diagnosed by exercise thallium scintigraphy. Although the PCr content decreased in patients with either reversible or fixed thallium defects, the ATP content decreased only in the latter group. In the third study, postischemic myocardium with chronic mechanical dysfunction that exhibits recovery after revascularization in left ventriculography was metabolically characterized using quantitative cardiac 31P MRS. Postischemic myocardium with reversible mechanical dysfunction demonstrated reduced PCr but normal ATP content. These results suggest that 31P MRS is a clinically important method both for the detection of myocardial ischemia and in the evaluation of myocardial viability.
Assuntos
Espectroscopia de Ressonância Magnética , Isquemia Miocárdica/diagnóstico , Sobrevivência de Tecidos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Isótopos de FósforoRESUMO
Reversible thallium-201 (201Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise 201Tl and rest 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise 201Tl in 19/28 patients with HCM. 123I-BMIPP uptake was decreased compared with delayed 201Tl in 106/364 (29%) of the total myocardial segments (p<0.01, McNemar symmetry test). Such disparity between 123I-BMIPP and 201Tl was observed more often in the 49/75 (65%) segments with reversible exercise 201Tl defects (p<0.001). Our results indicate that exercise-induced myocardial ischemia exists in HCM, resulting in metabolic abnormalities. The combination of 123I BMIPP and 201Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM.
Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/metabolismo , Metabolismo Energético , Ácidos Graxos/metabolismo , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/metabolismo , Idoso , Cardiomiopatia Hipertrófica/fisiopatologia , Teste de Esforço , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , CintilografiaRESUMO
Although both aging and hypertrophy are extremely important factors for cardiac performance, their influence on cardiac metabolism, especially that of high-energy phosphates, has not been fully elucidated as yet. Quantitative measurements of high-energy phosphates were attempted by comparing myocardial 31P NMR spectra with an external reference using depth-resolved surface-coil spectroscopy. The voxel size of the region of interest (ROI) was disk-shaped with 15-cm diameter and 25-mm thickness, but the left ventricular weight actually involved in the ROI was estimated to be between 22 and 66 g using MRI. Myocardial phosphocreatine (PCr) content and adenosine triphosphate (ATP) content for the 30 normal volunteers showed significant age dependence since both decreased in relation to increasing age. Myocardial PCr content and ATP content in patients with hypertension did not differ significantly from the age-matched control group. PCr content (6.1 +/- 2.2 micromol/g wet tissue, n = 10) and ATP content (4.1 +/- 1.3 micromol/g wet tissue) in patients with hypertrophic cardiomyopathy were less than the age-matched control group (n = 15; PCr: 9.7 +/- 2.5 micromol/g wet tissue, P < 0.01; ATP: 6.4 +/- 1.8 micromol/g wet tissue, P < 0.05), respectively. These results indicate that quantitative 31P MRS may be valuable in the assessment of changes in high-energy phosphate metabolism caused by aging or hypertrophy.
Assuntos
Trifosfato de Adenosina/metabolismo , Envelhecimento/metabolismo , Cardiomiopatia Hipertrófica/metabolismo , Espectroscopia de Ressonância Magnética , Miocárdio/metabolismo , Fosfocreatina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Eletrocardiografia , Teste de Esforço , Feminino , Humanos , Hipertensão/metabolismo , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
S-Nitrosocaptopril (S-NO-Cap), a nitrate and an angiotensin-converting enzyme (ACE) inhibitor, may be produced after coadministration of nitroglycerin (NTG) and captopril (CAP). We synthesized S-NO-Cap and investigated its in vivo tolerance. In open-chest dogs, S-NO-Cap [300 microg; intracoronary (i.c.)] and NTG (50 microg, i.c.) increased coronary blood flow (CBF) similarly (8.0 vs. 9.0 ml/min; p = NS; n = 5). After a 2-h i.c. NTG infusion at high dose (1.32 micromol/min), NTG (50 microg, i.c.) had no significant effect on CBF, whereas S-NO-Cap (300 microg, i.c.) still produced an attenuated increase in CBF (4.9 ml/min; p < 0.05 vs. control). On the other hand, after a 2-h i.c. infusion of S-NO-Cap (1.32 micromol/min), the CBF response to S-NO-Cap (300 microg) showed no attenuation, whereas that to NTG (50 microg) was potentiated (8.8 vs. 12.6 ml/min; p < 0.05; n = 6). Under basal conditions, S-NO-Cap (30-300 microg, i.c.) increased CBF dose dependently, whereas CAP (30-300 microg, i.c.) had no effect on CBF, suggesting that S-NO-Cap dilates coronary vessels by a nitrate action but not by an ACE-inhibitory action. In nonsurgical dogs, 2-h intravenous (i.v.) infusion of S-NO-Cap (1.32 micromol/min) had a stable hypotensive effect, whereas that of NTG (1.32 micromol/min) gradually attenuated the effect. Plasma NO3-, an oxidative product of nitric oxide (NO), increased after both infusions, suggesting that S-NO-Cap may act partially as an NO donor, similarly to NTG. Plasma ACE activity was reduced after an S-NO-Cap infusion (5.84 vs. 4.10 IU/L; p < 0.01; n = 5), and plasma aldosterone was markedly increased after NTG infusion relative to that after S-NO-Cap infusion (243.0 vs. 38.6 pg/ml; p < 0.05). Plasma norepinephrine increased after both infusions (393.6 vs. 289.0 pg/ml; p = NS). As judged by the increase in CBF, whereas S-NO-Cap showed partial tolerance with NTG, no tolerance was found with S-NO-Cap itself. The in vivo coronary vascular response to S-NO-Cap may, therefore, be partially reduced by activation of the adrenergic or renin-angiotensin-aldosterone systems or both induced by NTG, because S-NO-Cap showed no cross-tolerance with NTG in our earlier in vitro study.
Assuntos
Captopril/análogos & derivados , Circulação Coronária/efeitos dos fármacos , Nitroglicerina/farmacologia , Vasodilatadores/farmacologia , Aldosterona/sangue , Animais , Captopril/farmacologia , GMP Cíclico/sangue , Cães , Relação Dose-Resposta a Droga , Interações Medicamentosas , Tolerância a Medicamentos , Feminino , Hemodinâmica/efeitos dos fármacos , Infusões Intra-Arteriais , Infusões Intravenosas , Masculino , Nitratos/sangue , Óxido Nítrico/metabolismo , Norepinefrina/sangue , Peptidil Dipeptidase A/sangue , Renina/sangueRESUMO
Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients with essential hypertension. Ten patients (four men and six women) with essential hypertension received candesartan cilexetil 2-8 mg/day orally for 8-12 weeks. After drug administration, systolic blood pressure (BP) decreased from 178.9 +/- 17.2 mmHg (mean +/- SD) to 150.2 +/- 14.3 mmHg (P < 0.0001) and diastolic BP from 101.4 +/- 6.5 mmHg to 87.8 +/- 11.9 mmHg (P = 0.0021). Both MRI and echocardiography revealed a significant decrease in LV mass index (LVMI) after candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 +/- 31.3 g/m2 to 102.6 +/- 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from 123.9 +/- 31.1 g/m2 to 115.8 +/- 31.4 g/m2 (P = 0.0316). Total systemic vascular resistance decreased significantly during treatment with candesartan cilexetil in both MRI and echocardiography assessment, from 1847.2 +/- 636.3 dynes.s.cm-5 to 1540.4 +/- 432.0 dynes.s.cm-5 (P = 0.0034) on MRI and from 1820.4 +/- 318.8 dynes.s.cm-5 to 1659.0 +/- 317.7 dynes.s.cm-5 (P = 0.0060) on echocardiography. These findings suggest that candesartan cilexetil 2-8 mg/day orally for 8-12 weeks is beneficial in the regression of cardiac hypertrophy in patients with essential hypertension.
Assuntos
Antagonistas de Receptores de Angiotensina , Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Tetrazóis , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Ecocardiografia , Feminino , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pulso ArterialRESUMO
The main purpose of this study was to investigate whether in vivo 31P three-dimensional chemical shift imaging(3D-CSI) of the human heart could serve as a useful tool for evaluating myocardial metabolism. We performed slice-selective 3D-CSI employing nuclear magnetic resonance(NMR) imaging with slice selection in one dimension and phase encoding in two dimensions. 31P NMR images of phosphocreatine (PCr) and ATP were superimposed on a corresponding 1H image of the heart. Our study revealed that while accurate in vivo 31P 3D-CSI measurement of the human heart is difficult to achieve it is not impossible, although various additional techniques for improving signal to noise ratio are indicated.
Assuntos
Aumento da Imagem/métodos , Espectroscopia de Ressonância Magnética , Miocárdio/metabolismo , Trifosfato de Adenosina/metabolismo , Humanos , Fosfocreatina/metabolismo , FósforoRESUMO
UNLABELLED: Septal hypoperfusion is often observed in patients with complete left bundle branch block (LBBB) in myocardial perfusion imaging. Abnormal wall motion in the septal region may potentially cause artifactual perfusion abnormalities. To assess the effect of abnormal wall thickening on myocardial perfusion images, ECG-gated sestamibi SPECT was performed on 12 patients with LBBB and 10 normal subjects used as controls. METHODS: After administration of 740 MBq 99mTc-sestamibi injection at rest, ECG-gated SPECT was obtained 60 min later with division of the cardiac cycle into eight frames. RESULTS: Septal hypoperfusion was noted in 10 patients on nongated images and 11 patients on end-systolic (ES) images, whereas only two patients showed abnormalities on end-diastolic (ED) images. The septal to lateral wall count ratio in the LBBB group was lower (0.72 +/- 0.09) than in the control group (0.84 +/- 0.09) (p < 0.01) at nongated images, while it was similar at ED images (0.84 +/- 0.11 versus 0.86 +/- 0.12; ns). In addition, the count increase from ED to ES during a cardiac cycle in the septal region was smaller compared with the lateral region in the LBBB patients (25% +/- 19% in the septal region, versus 48% +/- 14% in the lateral region; p < 0.01), indicating less wall thickening in the septal region. CONCLUSION: Smaller count increase due to reduced wall thickening in the septal region may mimic hypoperfusion in patients with LBBB. This artifact can be eliminated with ECG-gated 99mTc-sestamibi SPECT, particularly with ED images.
Assuntos
Bloqueio de Ramo/diagnóstico por imagem , Coração/diagnóstico por imagem , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Artefatos , Bloqueio de Ramo/fisiopatologia , Circulação Coronária , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The purpose of this study was to clarify any association between clinically detectable silent myocardial ischemia (SMI) and myocardial 123I-metaiodobenzyl-guanidine (MIBG) uptake. Subjects of this study were (1) patients with SMI with diabetes (n = 15), (2) patients with angina pectoris with diabetes (n = 15), (3) patients with SMI without diabetes (n = 8) and (4) normal subjects (n = 23). Subjects underwent planar and single photon-emission-computed tomography (SPECT) imaging 15 min and 3 hours after injection of 123I-MIBG. H/M ratio was significantly lower in diabetic SMI (2.1 +/- 0.3) and non-diabetic SMI (2.3 +/- 0.3) than control subjects (2.6 +/- 0.3). The inferior-to-anterior wall count ratio (I/A) in diabetic SMI group was the lowest among all groups (p < 0.05). A significant difference was observed in relative regional uptake in the inferior segment of the distal left ventricle between SMI and angina group in patients with diabetes mellitus (p < 0.05). The decreased MIBG uptake in the inferior wall may be an important sign of cardiac sympathetic dysfunction, suggesting the abnormalities in cardiac nervous system play an important role in the mechanism of diabetic silent myocardial ischemia.