Clinical disease presentation and ECG characteristics of mutation carriers.

Objective: Mutations in the gene encoding lamins A and C of the nuclear lamina are a frequent cause of cardiomyopathy accounting for 5-8% of familial dilated cardiomyopathy (DCM). Our aim was to study disease onset, presentation and progression among mutation carriers.

Methods: Clinical follow-up data from 27 mutation carriers and 78 patients with idiopathic DCM without an mutation were collected.

Increased ventilatory response to exercise in symptomatic and asymptomatic LMNA mutation carriers: a follow-up study.

Background: LMNA mutations are an important cause of cardiomyopathy often leading to cardiac arrhythmias, heart failure and even heart transplantation. An increasing number of asymptomatic mutation carriers are identified, as family members of the index patients are screened. Our aim was to study the disease progression in asymptomatic LMNA mutation carriers and in patients with symptomatic cardiolaminopathy by repeated spiroergometric testing in a prospective clinical follow-up study.

Effects of angiotensin II blockade on cardiomyocyte regeneration after myocardial infarction in rats.

Introduction: We studied the effects of angiotensin type 1 receptor blockade (ARB) on formation of new cardiomyocytes, neovascularization and ventricular remodelling after myocardial infarction (MI).

Methods: Male Wistar rats with MI or sham-operated controls were treated with either losartan or vehicle. Bromodeoxyuridine (BrdU) was given to identify newly formed cardiac cells.

Characteristics of atrial fibrillation and comorbidities in familial atrial fibrillation.

Introduction: One-third of lone atrial fibrillation (AF) presents as familial disorder. Heterogeneity of both genetic background and clinical manifestations remains largely uncharacterized. We aimed to evaluate the clinical characteristics and especially the triggering factors of familial AF.

Pregnancy and childbirth in carriers of the lamin A/C-gene mutation.

This retrospective case report describes 11 pregnancies in five women. All of the women were carriers of the lamin A/C gene mutation known to cause dilated cardiomyopathy, often together with atrioventricular conduction disturbances. The penetrance of these mutations is age-dependent but almost complete.

Activation of protective and damaging components of the cardiac renin-angiotensin system after myocardial infarction in experimental diabetes.

Introduction: Diabetes is associated with prolonged apoptotic cell death of cardiac myocytes and adverse remodelling after myocardial infarction (MI). Because the renin-angiotensin system (RAS) has a major role in the remodelling, we studied whether diabetes is associated with altered regulation of RAS after MI in rats.

Methods: Male Wistar rats were randomised to receive either streptozotocin (diabetic group) or citrate buffer (control group) intravenously.

Vasopeptidase inhibition has beneficial cardiac effects in spontaneously diabetic Goto-Kakizaki rats.

In this study we examined diabetes- and hypertension-induced changes in cardiac structure and function in an animal model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We hypothesized that treatment with omapatrilat, a vasopeptidase inhibitor, which causes simultaneous inhibition of angiotensin converting enzyme and neutral endopeptidase, provides additional cardioprotective effects, during normal- as well as high sodium intake, compared to treatment with enalapril, a selective inhibitor of angiotensin converting enzyme. Fifty-two GK rats were randomized into 6 groups to receive either normal-sodium (NaCl 0.

Cardioprotective effects of vasopeptidase inhibition vs. angiotensin type 1-receptor blockade in spontaneously hypertensive rats on a high salt diet.

The aim of our study was to compare the cardioprotective effects of vasopeptidase inhibition with those of angiotensin type 1 (AT1)-receptor blockade, a diuretic and the combination of AT1-receptor blockade and a diuretic in an experimental rat model of essential hypertension on a high salt diet. Spontaneously hypertensive rats (SHR) (n =73) were divided into 6 groups to receive the following diet and drug regimens for 8 weeks: 1) low salt controls (NaCl 0.5%); 2) high salt controls (NaCl 6%); 3) omapatrilat (40 mg/kg/d) on a high salt diet; 4) losartan (30 mg/kg/d) on a high salt diet; 5) hydrochlorothiazide (HCTZ; 10 mg/kg/d) on a high salt diet; and 6) losartan+HCTZ (30+10 mg/kg/d) on a high salt diet.

Effect of vasopeptidase inhibitor omapatrilat on cardiomyocyte apoptosis and ventricular remodeling in rat myocardial infarction.

We have shown earlier that cardiomyocyte apoptosis continues at a high level late after myocardial infarction and contributes to adverse cardiac remodeling. Here we studied whether this process can be inhibited by the vasopeptidase inhibitor omapatrilat, a drug which causes simultaneous inhibition of both angiotensin converting enzyme and neutral endopeptidase. Our hypothesis was that omapatrilat-treated rats would have less cardiomyocyte apoptosis, and less adverse cardiac remodeling compared to rats treated with selective inhibitors of angiotensin converting enzyme, neutral endopeptidase or placebo.

Expression of heme oxygenase-1 in response to myocardial infarction in rats.

Heme oxygenase-1 (HO-1) is a heat shock protein catalysing the degradation of heme to yield biliverdin, carbon monoxide and iron. Several recent studies have proposed the stress-inducible HO-1 to participate in cellular protection also in the heart. We, therefore, examined the expression and localization of HO-1 in a rat experimental myocardial infarction model.