Heart failure (HF) is a complex condition in which multiple molecular mechanisms interact, resulting in compromised cardiac function and often death. Despite the benefits of current therapies including ACE inhibitors and beta-adrenergic blockers, the pathophysiology is still poorly understood and the prognosis remains poor. With the advent of the genetic era, a large number of animal models of cardiac hypertrophy and HF have been created by genetic engineering. These models, combined with sophisticated physiological measurements of cardiac hemodynamics, are expected to yield more and valuable information regarding the molecular mechanisms of HF and aid in the discovery of novel molecular therapeutic targets. This review has summarized various animal models of HF currently available to study mechanisms and to identify new treatment strategy of HF.
Adrenergic beta-Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Animals ; Cardiomegaly ; Genetic Engineering ; Heart ; Heart Failure ; Hemodynamics ; Models, Animal ; Prognosis

BACKGROUND: Clinical and experimental studies have suggested that brain death may cause hemodynamic, electrocardiographic, functional or histopathologic changes of the heart. METHODS: Brain death was induced by increasing intracranial pressure(ICP) abruptly by intermittent bolus injection of saline(model ) or gradually by continuous infusion of saline(model ) to the epidural catheter in 5 mongrel dogs, respectively. Hemodynamic and biochemical changes during the process of brain death and histopathologic changes of the myocardium were analyzed and compared in two brain death models, and the association of apoptosis was also evaluated. RESULTS: 1) Two predominant subsets of acute contraction band lesion were produced in both brain death models : paradiscal and holocystic contraction band lesions. Both contraction band lesions were more prevalent in brain death model . 2) The frequency of both contraction band lesions was lowest in the epicardial layer and highest in the endocardial layer in both models, but no correlation was observed between the degree of contraction band lesions and ICP, LV maximum +dp/dt or catecholamine levels. There was no statistical difference between any of the LV circumferential blocks and either type of contraction band lesion, and transaxial distribution was not also different in both models. 3) There was no remarkable histopathologic changes in the analysis of major epicardial coronary arteries. Apoptotic cells were suggested in the scattered myocytes in the light microscopy and apoptosis was detected by in situ nick end labeling method. Electron microscopy revealed a condensation of nuclear chromatin and convolution of nuclear membrane in those myocytes. CONCLUSIONS: Myocardial changes due to brain were observed frequently, and few apoptotic cells were found in the brain death heart. Studies on the treatment strategy to minimize damages of myocardial structure and function caused by brain death should be followed in the near future.
Animals ; Apoptosis ; Brain Death* ; Brain* ; Catheters ; Chromatin ; Coronary Vessels ; Dogs ; Electrocardiography ; Heart ; Hemodynamics ; In Situ Nick-End Labeling ; Microscopy ; Microscopy, Electron ; Muscle Cells ; Myocardium* ; Nuclear Envelope

Congestive heart failure is the most common ultimate consequence of many primary cardiovascular diseases. Despite significant advances in the understanding of its pathophysiology, and the development of improved medical therapies, it remains a major concern and a growing public health problem. Previously adult hearts were considered incapable of repair, but recently the role of replicating endogenous cardiomyocytes, and the recruitment of other cells (including stem cells), for myocardial regeneration has attracted much attention. There is now growing evidence that stem cells derived from numerous sources, such as embrygnal stem cells, bone marrow-derived (mesenchymal, hematopoietic and endothelial), neural and hepatocyte stem cells, are potential therapeutic options for the treatment of heart failure. It has been shown that stem cells survive and retain the capacity to differentiate into functional endothelial cells, smooth muscle cells and cardiomyocytes when transplanted into the myocardium of various species, including mice, rats, rabbits, and dogs. Stem cells have been introduced by direct intramyocardial injection, intracoronary infusion and systemic intravenous administration. Furthermore, the grafted cells have been reported to support myocardial regeneration following infarction, and improve cardiac function in experimental heart failure models. With recent major advances concerning the biology of adult stem cells (plasticity or transdifferentiation, milieu-dependent differentiation, immunotolerance of stem cells, and possibility of the presence of cardiac stem cells), stem cell transplantation is thus promising for the treatment of end-stage heart failure.
Administration, Intravenous ; Adult ; Adult Stem Cells ; Animals ; Biology ; Cardiovascular Diseases ; Dogs ; Endothelial Cells ; Heart ; Heart Failure ; Hepatocytes ; Humans ; Infarction ; Mice ; Myocardium ; Myocytes, Cardiac ; Myocytes, Smooth Muscle ; Public Health ; Rabbits ; Rats ; Regeneration* ; Stem Cell Transplantation ; Stem Cells* ; Transplants

Hypertension is a major independent risk factor for the development of coronary artery disease, heart failure, stroke, and renal failure. Despite many experimental and clinical trials, no optimal strategy for the treatment of hypertension has been established. This editorial comment presents recent advances in the treatment of hypertension based on randomized clinical trials. This review also introduces the effects of alternative medicine and novel antihypertensives agents and covers some emerging concepts, such as vaccination, gene therapy, and individualized therapy, that will shape the approaches to treatment in the years to come.
Antihypertensive Agents ; Complementary Therapies ; Coronary Artery Disease ; Genetic Therapy ; Heart Failure ; Hypertension ; Renal Insufficiency ; Risk Factors ; Stroke ; Vaccination

BACKGROUND: Herpes simplex virus thymidine kinase (HSVtk) phosphorylates the prodrug ganciclovir to a nucleoside analog that inhibits DNA synthesis, causing cell death. Neighbouring nontransfected cells may be affected through a 'bystander effect', thereby amplifying the antiproliferative actions. This study was carried out to determine whether retrovirus-mediated HSVtk gene therapy could reduce intimal hyperplasia and prevent stenosis following balloon injury of the rat carotid artery. METHODS: A replication-defective recombinant retroviral vector containing HSVtk cDNA (LtkSN) was constructed. Cultured primary rat smooth muscle cells (SMCs) infected with this vector (SMC/LtkSN) were transplanted to the balloon injured rat right carotid artery. One week after transplantation, HSVtk gene therapy group was administered a 2-week treatment of ganciclovir (30 mg/kg/d). Three weeks after balloon injury and SMC/LtkSN transplantation, carotid arteriography was performed and carotid arteries were perfusion-fixed for histologic examination. RESULTS: Carotid arteriographic evaluation comparing with the uninjured left carotid artery showed that the mean luminal diameter of HSVtk gene therapy group (n=5, 85+/-3%) was significantly larger than that of balloon injury only group (n=5, 65+/-5%). The neointimal mass of HSVtk gene therapy group was less than that of balloon injury only group. SMC/LtkSN transplantation without ganciclovir treatment group (n=3) showed asymmetric intimal proliferation probably because of gravitational pooling of seeding. There were inflammatory cell infiltrations at the gravity dependent portion of HSVtk gene therapy group. CONCLUSION: Retrovirus-mediated HSVtk gene therapy following balloon injury of the rat carotid artery reduced neointimal expansion and arteriographic stenosis.
Angiography ; Animals ; Carotid Arteries* ; Carotid Artery Injuries* ; Cell Death ; Constriction, Pathologic* ; DNA ; DNA, Complementary ; Ganciclovir ; Genetic Therapy* ; Gravitation ; Herpes Simplex* ; Hyperplasia ; Myocytes, Smooth Muscle ; Phenobarbital ; Phosphotransferases* ; Rats* ; Simplexvirus* ; Thymidine Kinase ; Zidovudine

Recent global hypertension guidelines recommend an early, strict and 24-hour blood pressure (BP) control for the prevention of target organ damage and cardiovascular events. Out-of-office BP measurement such as ambulatory BP monitoring and home BP monitoring is now widely utilized to rule out white-coat hypertension, to detect masked hypertension, to evaluate the effects of antihypertensive medication, to analyze diurnal BP variation, and to increase drug adherence. Nocturnal hypertension has been neglected in the management of hypertension despite of its clinical significance. Nighttime BP and non-dipping patterns of BP are stronger risk predictors for the future cardiovascular mortality and morbidity than clinic or daytime BP. In addition to ambulatory or home daytime BP and 24-hour mean BP, nocturnal BP should be a new therapeutic target for the optimal treatment of hypertension to improve prognosis in hypertensive patients. This review will provide an overview of epidemiology, characteristics, and pathophysiology of nocturnal hypertension and clinical significance, therapeutic implication and future perspectives of nocturnal hypertension will be discussed.
Blood Pressure ; Chronotherapy ; Epidemiology ; Humans ; Hypertension ; Masked Hypertension ; Mortality ; Prognosis

Leaving behind substantial reflections or skepticisms on the shortage of evidences about blood pressure (BP) thresholds for antihypertensive drug therapy and target BPs, major hypertensive guidelines including Korean hypertension guidelines were recently updated for earlier and more intensive control of BP. Because hypertension is one of the major risk factors for death, stroke, cardiovascular (CV) disease, heart failure, and cognitive impairment, substantial improvement of hypertension management is necessary to reduce disease and socioeconomic burdens and to promote CV health. Theoretically, earlier intervention in terms of age and BP level and thorough control of BP into within normal range would prevent or delay major adverse CV events. Revised hypertension guidelines were developed by the American College of Cardiology/American Heart Association, Korean Society of Hypertension, European Society of Cardiology/European Society of Hypertension, and Japanese Society of Hypertension in order. In this article, recent updates and clinical significances of the Korean hypertension guidelines will be discussed with comparison of foreign hypertension guidelines and considerable changes in the management of hypertension will be introduced for cardiologists and general practitioners.

Recent global hypertension guidelines recommend an early, strict and 24-hour blood pressure (BP) control for the prevention of target organ damage and cardiovascular events. Out-of-office BP measurement such as ambulatory BP monitoring and home BP monitoring is now widely utilized to rule out white-coat hypertension, to detect masked hypertension, to evaluate the effects of antihypertensive medication, to analyze diurnal BP variation, and to increase drug adherence. Nocturnal hypertension has been neglected in the management of hypertension despite of its clinical significance. Nighttime BP and non-dipping patterns of BP are stronger risk predictors for the future cardiovascular mortality and morbidity than clinic or daytime BP. In addition to ambulatory or home daytime BP and 24-hour mean BP, nocturnal BP should be a new therapeutic target for the optimal treatment of hypertension to improve prognosis in hypertensive patients. This review will provide an overview of epidemiology, characteristics, and pathophysiology of nocturnal hypertension and clinical significance, therapeutic implication and future perspectives of nocturnal hypertension will be discussed.

Percuaneous mitral valvuloplasty(PMV) is an alternative to surgical mitral commissurotomy for patients with mitral stenosis. To assess the immediate and follow-up results of PMV and to identify factors in fluencing the outcome and coplications of PMV, we analyzed the clinical, echocardiographic and hemodynamic data of 108 patients who underwent PMV. 1) Good hemodynamic results were obtained in 86 patients(79.6%). The factors predicting immediate outcome of PMV were mitral valve mobility, total echoscore, and EBDA/BSA. 2) Predictors of the increase in mitral valve area by PMV were age, sex, rhythm, and NYHA functional class before PMV. The independant predictors were rhythm(p=0.008) and functional class(p=0.002). 3) The degree of mitral regurgitation increased in 26 patients(24%), did not changed in 79 patients(73%) and decreased in 3 patients(3%). The increase of MR could not predicted from any features of the clinical, echocardiographic or hemodynamic daa. The severity of MR decreased by one grade in 15% of patients and did not change in 66% of patients during follow-up. 4) Left-to-right shunt was detected in 19 patients(18%). The predictors were valve mobility, pulmonary artery pressure and pulmonary vascular resistance. 5) Follow-up catheterization(mean 14 months) identified restenosis in six of 16 patients. The predictors of restenosis were sex, total echosecore, and left atrial volume. 6) The hemodynamic data at follow-up were good compared with prePMV data(p<0.01), but follow-up miral valve area decreased than that of postPMV(p<0.05). Immediate decrease in pulmonary vascular resistance followed by progressive improvement during follow-up. 7) Immediate complications of PMV were peripheral arterial embolism in one patient(1%), pericardial effusion in two(2%), transient arrhythmia in four(4%), left-to-right shunt in nineteen(18%) and increase in the grade of MR in twenty-six(24%). This study suggests, that PMV produces excellent immediate and follow-up results and is a safe and effective procedure in the nonsurgical treatment of mitral stenosis.
Arrhythmias, Cardiac ; Echocardiography ; Embolism ; Follow-Up Studies* ; Hemodynamics ; Humans ; Mitral Valve ; Mitral Valve Insufficiency ; Mitral Valve Stenosis* ; Pericardial Effusion ; Pulmonary Artery ; Vascular Resistance

Percuaneous mitral valvuloplasty(PMV) is an alternative to surgical mitral commissurotomy for patients with mitral stenosis. To assess the immediate and follow-up results of PMV and to identify factors in fluencing the outcome and coplications of PMV, we analyzed the clinical, echocardiographic and hemodynamic data of 108 patients who underwent PMV. 1) Good hemodynamic results were obtained in 86 patients(79.6%). The factors predicting immediate outcome of PMV were mitral valve mobility, total echoscore, and EBDA/BSA. 2) Predictors of the increase in mitral valve area by PMV were age, sex, rhythm, and NYHA functional class before PMV. The independant predictors were rhythm(p=0.008) and functional class(p=0.002). 3) The degree of mitral regurgitation increased in 26 patients(24%), did not changed in 79 patients(73%) and decreased in 3 patients(3%). The increase of MR could not predicted from any features of the clinical, echocardiographic or hemodynamic daa. The severity of MR decreased by one grade in 15% of patients and did not change in 66% of patients during follow-up. 4) Left-to-right shunt was detected in 19 patients(18%). The predictors were valve mobility, pulmonary artery pressure and pulmonary vascular resistance. 5) Follow-up catheterization(mean 14 months) identified restenosis in six of 16 patients. The predictors of restenosis were sex, total echosecore, and left atrial volume. 6) The hemodynamic data at follow-up were good compared with prePMV data(p<0.01), but follow-up miral valve area decreased than that of postPMV(p<0.05). Immediate decrease in pulmonary vascular resistance followed by progressive improvement during follow-up. 7) Immediate complications of PMV were peripheral arterial embolism in one patient(1%), pericardial effusion in two(2%), transient arrhythmia in four(4%), left-to-right shunt in nineteen(18%) and increase in the grade of MR in twenty-six(24%). This study suggests, that PMV produces excellent immediate and follow-up results and is a safe and effective procedure in the nonsurgical treatment of mitral stenosis.
Arrhythmias, Cardiac ; Echocardiography ; Embolism ; Follow-Up Studies* ; Hemodynamics ; Humans ; Mitral Valve ; Mitral Valve Insufficiency ; Mitral Valve Stenosis* ; Pericardial Effusion ; Pulmonary Artery ; Vascular Resistance