Konstantinos Kallaras

Cardiovascular Effects of Aging Interrelationships of Aortic, Left Ventricular, and Left Atrial Function

Background: Previous studies have shown that elastic properties of the aorta decrease, while left atrial dimensions, the contribution of left atrial systole to left ventricular filling, and left ventricular mass increase with age. In most studies, however, aortic function, and ventricular and atrial parameters were performed in different populations, and thus, the earliest manifestation of aging in the cardiovascular system is not known. The present study was undertaken to define the earliest cardiovascular abnormality(ies) occurring in the cardiovascular system with age. Patients and Method: In 181 normotensive subjects (147 females and 34 males) age 22–64 years, left ventricular mass, volumes, function and work (echocardiography and blood pressure), left atrial volumes and stroke volume (biplane area-length method by echo), pulse wave velocity (PWV) (carotid to femoral artery, Doppler), and left atrial kinetic energy were measured simultaneously: left atrial kinetic energy = 1/2 mV2, where m = left atrial stroke volume × 1.06 (blood specific gravity), v = transmitral A wave velocity. Regression analyses were performed to correlate all measured cardiovascular parameters with age. Results: Pulse wave velocity (r = 0.51), left atrial kinetic energy (r = 0.42), and A wave velocity (r = 0.38) were correlated to age, while left ventricular mass, function and work were not. Multiple regression analysis among ten clinical and echocardiographic parameters demonstrated that only age contributed independently to pulse wave velocity; only age and pulse wave velocity were contributed independently to left atrial kinetic energy; and only age contributed independently to A wave velocity. Conclusions: The data demonstrate that age-related alterations in aortic function and left atrial work (left atrial kinetic energy) can be defined prior to changes in left ventricular structure and systolic function. Simultaneous studies of left atrial, left ventricular, and aortic function are required to better understand the effect of aging on the cardiovascular system.Hintergrund: Frühere Studien haben gezeigt, dass die elastischen Eigenschaften der Aorta mit zunehmendem Alter abnehmen, während die Größe des linken Vorhofs und die linksventrikuläre Muskelmasse steigen. Außerdem nimmt die Vorhoffüllung einen breiteren Raum ein. Die meisten Studien haben jedoch die Funktion der Aorta und der Ventrikel- und Vorhofparameter in den unterschiedlichen Populationen geprüft, so dass nicht bekannt ist, welche Änderungen zuerst auftreten. In der vorliegenden Studie wurde versucht festzustellen, welche kardiovaskulären Veränderungen mit zunehmenden Alter als Erste auftreten. Methoden: Bei 181 normotensiven Menschen (147 Frauen und 34 Männer) im Alter von 22–64 Jahren wurde die linksventrikuläre Masse und Arbeit (Echokardiographie und Blutdruckmessung), die linksatrialen Volumina und Schlagvolumina (biplane Flächen-Längen-Methode im Echokardiogramm), die Pulswellenlaufgeschwindigkeit (Doppler im Bereich der Karotis und Femoralarterie) und die linksatriale kinetische Energie simultan abgestimmt. Die Regressionsanalysen wurden für alle kardiovaskulären Parameter vorgenommen. Ergebnisse: Die Pulswellenlaufgeschwindigkeit (r = 0,51), die linksatriale kinetische Energie (r = 0,42) und die A-Wellen-Geschwindigkeit (r = 0,38) korrelierten mit dem Alter, während die linksventrikuläre Muskelmasse, Funktion und Arbeit nicht korrelierten. Eine multiple Regressionsanalyse unter den zehn klinischen echokardiographischen Parametern zeigte, dass nur das Alter unabhängig zur Pulswellenlaufgeschwindigkeit in Beziehung zu setzen war. Nur Alter und Pulswellenlaufgeschwindigkeit waren unabhängig korreliert zur linksatrialen kinetischen Energie und nur das Alter stand in enger Beziehung zur A-Wellen-Geschwindigkeit. Schlussfolgerung: Die Untersuchungen zeigen, dass altersbezogene Änderungen der Aortenfunktion und der linksatrialen Arbeit Veränderungen aufweisen, noch bevor die linksventrikuläre Struktur und systolische Funktion sich mit zunehmendem Alter ändern. Simultane Untersuchungen in angegebenen Parametern sind notwendig, um einen besseren Überblick über die Auswirkungen des Alterns auf das kardiovaskuläre System zu erhalten.

Effect of Ramipril Alone Compared to Ramipril with Eplerenone on Diabetic Nephropathy in Streptozocin-Induced Diabetic Rats

Background/Aims: We studied the effect of the combined treatment with an angiotensin-converting enzyme (ACE) inhibitor (ramipril) and eplerenone compared with ramipril alone in streptozocin-induced diabetic rats. Methods: Wistar rats were divided into 4 groups: nondiabetic controls, streptozocin-treated diabetic rats (50 mg/kg), diabetic rats receiving ramipril (1 mg/kg) and diabetic rats treated with the combination of ramipril (1 mg/kg) and eplerenone (100 mg/kg) for 8 weeks. Our model produced early-stage diabetic nephropathy. Results: The diabetic rats developed polyuria, proteinuria, hyperfiltration (assessed by creatinine clearance) and histopathological evidence of renal injury including glomerular hypertrophy and mesangial expansion. Ramipril reduced proteinuria but its combination with eplerenone did not produce any greater benefit. Both treatment approaches prevented glomerular hypertrophy. Addition of eplerenone to ramipril prevented glomerular hyperfiltration. Conclusion: Whether eplerenone should be used in addition to an ACE inhibitor or an angiotensin receptor blocker at an early stage of diabetic nephropathy remains questionable.

Atrial natriuretic peptide decreases aorta stiffness in cholesterol-fed anesthetized rabbits

Aortas from Watanabe heritable hyperlipidemic rabbits show in vitro impaired vasodilatory response to atrial natriuretic peptide (ANP) during atherosclerosis progression. To test a similar reaction in vivo, the effect of ANP administration on pulse wave velocity (PWV, index of aorta stiffness) was investigated in 10 normal and 10 cholesterol-fed (2% cholesterol-loaded feeding for 4 weeks) anesthetized male New Zealand White (NZW) rabbits. Invasively taken carotid and femoral blood pressures (BP) were recorded, simultaneously with ECG, and blood samples for ANP measurement (by RIA) were taken at 0 min and 20, 40, 60 min following an intravenous 20-min administration of either 0.2 microg kg(-1)min(-1) hANP in 5 ml normal saline or only 5 ml saline. Mild to moderate atherosclerosis was found in ascending aorta. BP decreased by ANP only at 20 min in both groups, whereas only in cholesterol-fed rabbits the borderline (p=0.09) increased at 0 min PWV was lowered (p=0.008) in all recording times. With any degree of increase of systolic BP (SBP) PWV increased less in ANP receivers. Atherosclerosis and SBP were the most important determinants of PWV and the effect of ANP was independent of confounding factors. It is concluded that short-term ANP administration in doses to achieve levels approximately threefold the pretreatment ones in normal and mildly to moderately atherosclerotic anesthetized NZW rabbits, causes an improvement of aorta stiffness only in atherosclerotic rabbits.

A semi-automated approach towards generating three-dimensional mesh of the heart using a hybrid MRI/histology database.

Both the forward and inverse problems of electrocardiography rely on the precise modelling of the anatomic and electrical properties of the thoracic tissues. This, in turn, requires good knowledge of the electrical anisotropy as well as conductivity inhomogeneity of the heart, lungs and the rest of the thorax. Cardiac electrical anisotropy is related to its microstructure (fibre length, density and orientation). We hereby present detailed three-dimensional (3D) meshes of the thorax and heart, using image data from contiguous 2D magnetic resonance (MR) imaging slices as well as a realistic 3D cardiac fibre orientation model that derives its data from high-resolution ex vivo human heart MR images and from histology specimens of heart tissue. Using specific software, we integrated the 3D thorax and heart meshes in one that addresses the related modelling requirements for the solution of the forward and inverse problems of electrocardiography.

A fiber orientation model of the human heart using classical histological methods, magnetic resonance imaging and interpolation techniques

We present a cardiac model of post-mortem heart that can be applied to quantitative analysis of electrocardiologic problems. Two adult postmortem hearts in the systolic state were photographed and then were subjected to MRI scanning. Hence, anatomical slicing was performed using an automatic cutter that created 3 mm thick sections. The first one dissected vertical to its longitudinal axis, and the second one at the sagittal plane. Each section was further diced into smaller specimens for further histological process. All the microscopic slides were digitized in order to be used for histological sections reconstructing. The need to define the fiber orientation led us to create a specific drawing package in MATLABreg called FiberCad. For each point of the extracted model, information of the electrical characteristics and the prevalent fiberspsila orientation can be accurately modeled.

Neurotransmitter release and histological changes following perinatal asphyxia in rats and the neuroprotective action of lamotrigine

Background Perinatal asphyxia remains a frequent cause of a variety of brain disorders including cerebral palsy, epilepsy, mental retardation, learning disability and attention deficit disorders. Excessive amounts of glutamate, aspartate and other neurotransmitters are released into the extracellular space during perinatal asphyxia and may contribute to neuronal loss and brain injury in several regions of the developing brain, especially in the hippocampus. Lamotrigine, a novel antiepileptic drug, is believed to act by reducing excitatory amino acids release due to an inhibition of Na+ channels. The purpose of our study was to investigate the acute effects of lamotrigine administration on the release of glutamate, aspartate, glutamine and GABA. Its potentional cerebroprotective action on the rats hippocampus after perinatal asphyxia was also studied.