Alteration of intracellular Ca2(+)-handling and receptor regulation in hypertensive cardiac hypertrophy: insights from Ren2-transgenic rats.

Abnormal intracellular Ca2(+)-handling appears to be a major cause of systolic and diastolic dysfunction in animals and humans with cardiac hypertrophy due to pressure overload and heart failure. However, the precise mechanisms which cause alteration of Ca2(+)-handling remain unclear. Several lines of evidence suggest that activation of neurohormonal systems may play a central role.

[Safeguarding the quality of health care in relation to cost effectiveness analysis].

A meeting organized by Nederlands Tijdschrift voor Geneeskunde discussed the various interfaces of the quality of care, cost-effectiveness and health care. Cost-effectiveness analyses can contribute greatly to the quality of health care, but such research is methodologically complicated. Also, the effectiveness of particular interventions or therapies should be taken into account, if possible evidence-based, in the introduction of standards or guidelines for health-care workers.

Elevated serum concentrations of cardiac troponin T in acute allograft rejection after human heart transplantation.

Objectives: This study evaluates the concept and diagnostic efficacy of using serum troponin T for the detection of cardiac graft rejection.

Background: Cardiac troponin T is a cardiospecific myofibrillar protein, which is only detectable in the circulation after cardiac myocyte damage. It might be expected to be released during acute heart allograft rejection, allowing noninvasive rejection diagnosis.

Functional coupling of overexpressed beta 1-adrenoceptors in the myocardium of transgenic mice.

To assess functional and cellular effects of myocardial beta 1-adrenoceptor overexpression, alterations of the beta-adrenergic signal transduction pathway and contractile function in transgenic mice with atrial overexpression of the human beta 1-adrenoceptor were investigated. Radioligand binding experiments confirmed a 5- to 6-fold increase in beta-adrenoceptor density and a 2.7-fold increase in high-affinity binding sites in atria of transgenic mice.

Stroke from internal carotid artery occlusion during mumps infection.

During the terminal incubation period of severe mumps infection, a 40-year-old patient suffered from large infarction in the right middle cerebral artery territory. The proximal right internal carotid artery (ICA) was occluded on angiography. Computed tomography of the neck detected a hemorrhage located ventromedial to the right common carotid artery.

['Public Health Status Forecasting 1997': the sum of the parts].

The 1997 edition of Public Health Status and Forecasts, a comprehensive epidemiological overview of the health of the Dutch nation, suggests some important new strategies for the development of a more 'evidence-based health policy'. The growing gap between life expectancy in general and healthy life expectancy demands a stronger effort in the prevention of unhealthy lifestyles, especially smoking. Many indicators of health show the first signs of decline for the coming 10-20 years.

Activation of a phospholipase Cbeta2 deletion mutant by limited proteolysis.

All phosphoinositide-specific phospholipases C (PLC) identified until today exhibit a high degree of similarity within two regions of 170 and 260 residues, respectively, which are designated regions X and Y. The PLCbeta family, including four members designated PLCbeta1, PLCbeta2, PLCbeta3 and PLCbeta4, is regulated by heterotrimeric G proteins. In order to investigate structure-function relationships of PLCbeta2, we expressed PLCbeta2Delta, a deletion mutant of PLCbeta2 which lacks most of the sequence downstream of region Y, in the baculovirus/insect cell system.

Effects of quinapril, losartan and hydralazine on cardiac hypertrophy and beta-adrenergic neuroeffector mechanisms in transgenic (mREN2)27 rats.

1. Desensitization of the myocardial beta-adrenergic signal transduction pathway is an important mechanism which is involved in the progression of hypertensive heart disease. The aim of the present study was to evaluate the differential effects of chronic pharmacotherapy with an angiotensin converting enzyme (ACE)-inhibitor, an AT1-receptor antagonist and a direct vasodilator on blood pressure, cardiac hypertrophy and the beta-adrenergic signal transduction.

Effects of angiotensin II type 1 receptor blockade and angiotensin-converting enzyme inhibition on cardiac beta-adrenergic signal transduction.

Inhibition of the renin-angiotensin system has been shown to improve symptoms and prognosis in heart failure. We compared the effects of inhibition of angiotensin-converting enzyme or blockade of angiotensin II type 1 (AT1) receptors in a model with renin-induced hypertension that is known to exhibit similar changes in sympathetic activation and beta-adrenergic desensitization, as observed in heart failure. Treatment with captopril (100 mg/kg of feed) or the AT1-antagonist Bay 10-6734 (100 mg/kg of feed) was performed in transgenic rats harboring the mouse renin 2d gene [TG(mREN2)27].

Beta-adrenergic signal transduction in the failing and hypertrophied myocardium.

A strong sympathetic activation has been observed in heart failure and is the cause of beta-adrenergic desensitization in this condition. On the receptor level there is downregulation of beta1-adrenergic receptors and uncoupling of beta2-adrenoceptors. The latter mechanism has been related to an increased activity and gene expression of beta-adrenoceptor kinase in failing myocardium, leading to phosphorylation and uncoupling of receptors.

Alpha-adrenergic signal transduction in renin transgenic rats.

The alpha1-adrenoceptor-G protein-phosphoinositide-specific phospholipase C (PLC) signal transduction pathway is assumed to play an important role in the regulation of contractile force and in the pathophysiology of myocardial hypertrophy. In the present study, the components of this pathway were investigated in left ventricles of hearts from hypertensive transgenic rats overexpressing the mouse renin gene [TG(mREN2)27] in comparison to age- and weight-matched Sprague-Dawley control rats. Contractile force was assessed in isolated electrically driven left ventricular papillary muscle strips.

G protein-independent stimulation of human myocardial phospholipase C by mastoparan.

1 Phosphoinositide-specific phospholipase C (PLC) is involved in the regulation of many cellular functions. In the myocardium, PLC-generated second messengers play a role in the regulation of contractile function and in the pathophysiology of myocardial hypertrophy. 2 In the present study, the effect of mastoparan, a tetradecapeptide which is capable of activating heterotrimeric G proteins by mimicking the action of an activated receptor, on membrane-bound human myocardial PLC, was investigated in a cell-free assay with exogenous phospholipids as a substrate.

Cardiac angiotensin II receptors: studies on functional coupling in Sprague-Dawley rats and TGR(alphaMHC-hAT1) transgenic rats.

The renin-angiotensin system plays an important role in the pathogenesis of cardiac hypertrophy and chronic heart failure as angiotensin II has been shown to induce cardiac hypertrophy and fibrosis. Besides these structural alterations, functional effects on cardiomyocytes have been reported in different mammalian species. Angiotensin II is known to produce a positive inotropic effect in some species, and differences in atrial and ventricular myocardium have been described.

Down-regulation of aortic and cardiac AT1 receptor gene expression in transgenic (mRen-2) 27 rats.

1. Transgenic(TG) (mRen-2) rats overexpressing the mouse renin gene develop fulminant hypertension and cardiac hypertrophy. Since the activation of AT1 receptor by angiotensin II is involved in blood pressure regulation, cardiac performance and myocardial growth, we investigated the biological effects of angiotensin II and the regulation of the AT1 receptor in the heart and aorta of TGR (mRen-2)27 rats in comparison to control animals.

Surface plasmon resonance analysis of topoisomerase I-DNA binding: effect of Mg2+ and DNA sequence.

Surface plasmon resonance detection was used to characterize interactions of human topoisomerase I and DNA. The disassociation of topoisomerase I and DNA is characterized by two rate constants. This suggests two parallel but independent pathways of release.

Transferral of extrathoracic donor neoplasm by the cardiac allograft.

The transference of neoplasm from the donor to the recipient is a rare but recognized complication of organ transplantation. It has been reported after kidney transplantation from cadaver donors. We report a case in which an extrathoracic tumor was transmitted by the donor heart.

Identification and characterization of G protein-regulated phospholipase C in human myocardium.

The generation of the second messengers inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG) by phosphoinositide-specific phospholipases C (PLCs) is a key mechanism by which many cellular functions such as intracellular calcium handling or growth and differentiation are modulated. In the myocardium, PLC plays a role in the mediation of positive inotropic effects and is possibly involved in the pathogenesis of myocardial hypertrophy. Among the variety of PLC isozymes known, the PLC beta family is regulated by heterotrimeric G proteins.

Cellular edema and alterations in metabolite content in the ischemic and reperfused canine heart following different forms of cardiac arrest.

This study investigates firstly how far cellular edema correlates with parameters of the anaerobic energy turnover independent of the method used for cardiac arrest, and secondly to what extent cellular edema developing during reversible global ischemia is reduced after reperfusion. Canine hearts were arrested 1. by aortic cross clamping (ACC), 2.

Aspergillus endocarditis, myocarditis and pericarditis complicating necrotizing fasciitis. Case report and subject review.

A patient with Aspergillus endocarditis, myocarditis and pericarditis is described. A 55-year-old man developed necrotizing fasciitis of the lower abdominal wall, pelvis and right thigh. Despite aggressive surgical débridement and antibiotic coverage, the patient died of multisystem organ failure.

Heterotrimeric G proteins in heart disease.

Heterotrimeric G proteins couple many types of cell surface receptors to intracellular effectors such as enzymes or ion channels. In the mammalian heart, G protein-mediated signalling pathways are involved in the regulation of contractile force, heart rate, conduction velocity, and relaxation. In the first part of this review we summarize some important structural and functional features of receptors, G proteins, and effectors with special focus on the heart.

Adverse effects of crystalloid cardioplegia and slow cooling for protection of immature rat hearts.

Background: Studies on the benefit of methods for protection of the hypertrophied immature myocardium are rare and controversial.

Methods: We assessed the effects of (1) rapid cooling by topical hypothermia alone, (2) slow prearrest cooling by coronary perfusion hypothermia, and (3) cardioplegic cardiac arrest with St. Thomas' Hospital solution no.

Different effect of inhaled nitric oxide on yucatan micropig with and without congenital ventricular septal defect.

A strain of Yucatan micropigs is known to have heritable ventricular septal defects (VSDs) and thus may develop overflow pulmonary hypertension. Since inhaled nitric oxide (NO) selectively dilates pulmonary vessels, we determined its hemodynamic and co-agulatory effects in this new animal model. Eight Yucatan micropigs were anesthetized with midazolam, piritramide (a synthetic opioid) and vecuronium bromide.

Sarcoplasmic reticulum Ca2+ATPase and phospholamban mRNA and protein levels in end-stage heart failure due to ischemic or dilated cardiomyopathy.

Abnormalities in intracellular Ca2+ handling play a crucial role in the pathogenesis of heart failure. The reduced capacity of failing human myocardium to restore low resting Ca2+ levels during diastole has been explained by the impairment of Ca2+ uptake into the sarcoplasmic reticulum (SR) via the SR Ca2+ATPase. It is unclear whether Ca2+ATPase function, protein levels, and mRNA steady-state levels correspond to one other, and whether the cause of heart failure, namely idiopathic dilated or ischemic cardiomyopathy, produces different changes.

Role of G-proteins in altered beta-adrenergic responsiveness in the failing and hypertrophied myocardium.

In the heart and other tissues, beta-adrenergic desensitization occurs during treatment with catecholamines. In heart failure, a strong sympathetic activation has been observed and is the cause of beta-adrenergic desensitization in this condition. On the receptor level, there is a downregulation of beta 1-adrenergic receptors as well as an uncoupling of beta 2-adrenoceptors.