Relationship between longitudinal and radial contractility in subclinical diabetic heart disease

Subclinical left ventricular (W) dysfunction may be identified by reduced longitudinal contraction. We sought to define the effects of subclinical LV dysfunction on radial contractility in 53 patients with diabetes mellitus with no LV hypertrophy, normal ejection fraction and no ischaemia as assessed by dobutamine echocardiography, in comparison with age-matched controls. Radial peak myocardial systolic velocity (S-m) and early diastolic velocity (E-m), strain and strain rate were measured in the mid-posterior and mid-anteroseptal walls in parasternal views and each variable was averaged for individual patients (radial contractility). These variables were also measured in the mid-posterior and mid-anteroseptal walls in the apical long-axis view and each variable was averaged for individual patients (longitudinal contractility). Mean radial S-m, strain and strain rate were significantly increased in diabetic patients (2.9+/-0.6 cm/s, 28+/-5% and 1.8+/-0.4 s(-1) respectively) compared with controls (2.4+/-0.7 cm/s, 23+/-4% and 1.6+/-0.3 s(-1) respectively; all P<0.001), but there was no difference in E-m (3.3&PLUSMN;1.2 compared with 3.1&PLUSMN;1.1 cm/s, P=not significant). In contrast, longitudinal S-m, E-m, strain and strain rate were significantly lower in diabetic patients (3.6&PLUSMN;1.1 cm/s, 4.3&PLUSMN;1.6 cm/s, 21&PLUSMN;4% and 1.6&PLUSMN;0.3 s(-1) respectively) than in controls (4.3&PLUSMN;1.0 cm/s, 5.7&PLUSMN;2.3 cm/s, 26&PLUSMN;4% and 1.9&PLUSMN;0.3 s(-1) respectively; all P<0.00 1). Thus radial contractility appears to compensate for reduced longitudinal contractility in subclinical LV dysfunction occurring in the absence of ischaemia or LV hypertrophy.

Echocardiographic parameters in 14 healthy English Bull Terriers

Objective To determine the range of various cardiac parameters using echocardiography in apparently normal, healthy English Bull Terriers. Design Fourteen English Bull Terriers were selected for study. Cardiac auscultation of the parents of these dogs was normal. Echocardiographic examination of one parent of each animal showed: no mitral or aortic valve abnormalities; no myocardial lesions; no two dimensional evidence of fixed or dynamic left ventricular outflow tract obstruction; and no systolic aortic or left ventricular outflow tract turbulence on colour flow Doppler examination. The 14 selected dogs did not have arrhythmias or murmurs, and on echocardiographic examination had similar findings to their parents. Systolic blood pressure was measured in all dogs and they had no clinical evidence of Bull Terrier polycystic kidney disease or Bull Terrier hereditary nephritis. Procedure All dogs were auscultated and subjected to a sequential global echocardiographic assessment of the heart, including two dimensional long and short axis, and colour flow Doppler interrogation of the mitral and aortic valves. Dimensional measurements, including those from the left atrium, aortic annulus and left ventricle, were taken from a right parasternal window, and derived values such as fractional shortening, stroke volume and left atrial to aortic annulus ratio were calculated. Peak systolic aortic velocity was measured from the left parasternal window using two dimensional-guided pulsed wave Doppler with angle correction. Systolic blood pressure was measured using a Doppler monitor. The absence of Bull Terrier polycystic kidney disease was determined using renal ultrasonography, and of Bull Terrier hereditary nephritis using urinary protein to creatinine ratio. Results These 14 dogs had greater left ventricular wall thickness and smaller aortic root diameters than those reported as normal for other breeds of comparable body size. Left atrial dimensions were also larger, however this may have been due to the maximising method of measurement. These apparently normal English Bull Terriers also had higher aortic velocities than those reported for other breeds, possibly due to a smaller aortic root diameter or other anatomic substrate of the left ventricular outflow tract, lower systemic vascular resistance, or breed-specific normal left ventricular hypertrophy. While these dogs were selected to be as close to normal as possible, the breed may have a particular anatomy that produces abnormal left ventricular echocardiographic parameters. Conclusion These echocardiographic parameters may be used to diagnose left ventricular outflow tract obstruction and left ventricular hypertrophy, and inaccurate diagnoses may result if breed-specific values are not used.

Left ventricular mass in patients with type 2 diabetes is independently associated with central but not peripheral pulse pressure

An increase in left ventricular mass (LVM) occurs in the presence of type 2 diabetes, apparently independent of hypertension (1), but the determinants of this process are unknown. Brachial blood pressure is not representative of that at the ascending aorta (2) because the pressure wave is amplified from central to peripheral arteries. Central blood pressure is probably more clinically important since local pulsatile pressure determines adverse arterial and myocardial remodeling (3,4). Thus, an inaccurate assessment of the contribution of arterial blood pressure to LVM may occur if only brachial blood pressure is taken into consideration. In this study we sought the contribution of central blood pressure (and other interactive factors known to affect wave reflection, e.g., glycemic control and total arterial compliance) to LVM in patients with type 2 diabetes.

Increased calcium influx mediates increased cardiac stiffness in hyperthyroid rats

Cardiac remodeling (hypertrophy and fibrosis) and an increased left ventricular diastolic stiffness characterize models of hypertension such as the SHR and DOCA-salt hypertensive rats. By contrast, hyperthyroidism induces hypertrophy and hypertension, yet collagen expression and deposition is unchanged or decreased, whereas diastolic stiffness is increased. We determined the possible role of increased calcium influx in the development of increased diastolic stiffness in hyperthyroidism by administering verapamil (15 mg/[kg(.)d] orally) to rats given triiodothyronine (T-3) (0.5 mg/[kg.d] subcutaneously for 14 d). Administration of T3 significantly increased body temperature (control: 36.7 +/- 0.2 degrees C; T-3: 39.6 +/- 0.2 degrees C), left ventricular wet weight (control: 2.09 +/- 0.02 mg/kg; T-3 3.07 +/- 0.07 mg/kg), systolic blood pressure (control: 128 +/- 5 mmHg; T-3: 156 +/- 4 mmHg), and left ventricular diastolic stiffness (control: 20.6 +/- 2.0; T-3: 28.8 +/- 1.4). Collagen content of the left ventricle was unchanged. Contractile response to noradrenaline in thoracic aortic rings was reduced. Relaxation in response to acetylcholine (ACh) was also reduced in T-3-treated rats, whereas sodium nitroprusside response was unchanged. Verapamil treatment of hyperthyroid rats completely prevented the increased diastolic stiffness and systolic blood pressure while attenuating the increased body temperature and left ventricular weight; collagen content remained unchanged. ACh response in thoracic aortic rings was restored by verapamil. Thus, in hyperthyroid rats, an increased calcium influx is a potential mediator of the increased diastolic stiffness independent of changes in collagen.

Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A(2) in young spontaneously hypertensive rats

The development of fibrosis in the chronically hypertensive heart is associated with infiltration of inflammatory cells and cardiac hypertrophy. In this study, an inhibitor of the proinflammatory enzyme, group IIA human secretory phospholipase A(2) (sPLA(2)-IIA), has been found to prevent collagen deposition as an important component of cardiovascular remodeling in a rat model of developing chronic hypertension. Daily treatment of young male spontaneously hypertensive rats (SHR) with an sPLA2-IIA inhibitor (KH064, 5-(4-benzyloxyphenyl)-4S-(phenyl-heptanoylamino)-pentanoic acid, 5 mg/kg/day p.o.) prevented increases in the content of perivascular,(SHR 20.6 +/- 0.9%, n = 5; SHR+KH064 14.0 +/- 1.2%, n = 5) and interstitial (SHR 7.9 +/- 0.3%, n = 6; SHR+KH064 5.4 +/- 0.7%, n = 6) collagen in the left ventricle of rat hearts, but did not affect numbers of infiltrating monocytes/macrophages, left ventricular hypertrophy (SHR 2.88 +/- 0.08, n = 12; SHR+KH064 3.09 +/- 0.08 mg/g body weight, n = 9), increased systolic blood pressure, or thoracic aortic responses. This selective antifibrotic activity suggests that sPLA2-IIA may have an important but specific role in cardiac fibrosis, and that its inhibitors could be useful in dissecting molecular pathways leading to fibrotic conditions.

Local geometric changes in left ventricular remodeling post-infarction can lead to apparent reduction in scar thickness

Serial reduction in scar thickness has been shown in animal models. We sought whether this reduction in scar thickness may be a result of dilatation of the left ventricle (LV) with stretching and thinning of the wall. Contrast enhanced magnetic resonance imaging (CMRI) was performed to delineate radial scar thickness in 25 patients (age 63±10, 21 men) after myocardial infarction. The LV was divided into 16 segts and the absolute radial scar thickness (ST) and percentage scar to total wall thickness (%ST) were measured. Regional end diastolic (EDV) and end systolic volumes (ESV) of corresponding segments were measured on CMRI. All patients underwent revascularization and serial changes in ST, %ST, and regional volumes were assessed with a mean follow up of 15±5 months. CMRI identified a total of 93 scar segments. An increase in EDV or ESV was associated with a serial reduction inST(versusEDV, r =−0.3, p = 0.01; versusESV, r =−0.3, p = 0.005) and%ST(versusEDV, r =−0.2, p = 0.04; versus ESV, r =−0.3, p = 0.001). For segts associated with a positive increase in EDV (group I) or ESV (group II) there was a significant decrease in ST and %ST, but in those segts with stable EDV (group III) or ESV (group IV) there were no significant changes in ST and %ST (Table).

A naturally shaped silicone ventricle evaluated in a mock circulation loop: a preliminary study

Mock circulation loops are used to evaluate the performance of cardiac assist devices prior to animal and clinical testing. A compressible, translucent silicone ventricle chamber that mimics the exact size, shape and motion of a failing heart is desired to assist in flow visualization studies around inflow cannulae during VAD support. The aim of this study was therefore to design and construct a naturally shaped flexible left ventricle and evaluate its performance in a mock circulation loop. The ventricle shape was constructed by the use of CT images taken from a patient experiencing cardiomyopathic heart failure and used to create a 3D image and subsequent mould to produce a silicone ventricle. Different cardiac conditions were successfully simulated to validate the ventricle performance, including rest, left heart failure and VAD support.

NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure

Markers of increased oxidative stress are known to be elevated following acute myocardial infarction and in the context of chronic left ventricular hypertrophy or heart failure, and their levels may correlate with the degree of contractile dysfunction or cardiac deficit. An obvious pathological mechanism that may account for this correlation is the potential deleterious effects of increased oxidative stress through the induction of cellular dysfunction, energetic deficit or cell death. However, reactive oxygen species have several much more subtle effects in the remodelling or failing heart that involve specific redox-regulated modulation of signalling pathways and gene expression. Such redox-sensitive regulation appears to play important roles in the development of several components of the phenotype of the failing heart, for example cardiomyocyte hypertrophy, interstitial fibrosis and chamber remodelling. In this article, we review the evidence supporting the involvement of reactive oxygen species and redox signalling pathways in the development of cardiac hypertrophy and heart failure, with a particular focus on the NADPH oxidase family of superoxide-generating enzymes which appear to be especially important in redox signalling.

New statin use and left ventricular structure: estimating long-term associations in the Multi-Ethnic Study of Atherosclerosis (MESA)

Thesis (Master's)--University of Washington, 2016-08

Left Ventricular Thrombosis in a Young Ulcerative Colitis Patient: Review with a Case Report

Inflammatory bowel disease (IBD) patients are at increased risk of developing thromboembolic complications. We report here a rare case of left ventricle thrombus in a young woman with ulcerative colitis. We discuss the pathophysiology of hypercoagulable state in IBD, and briefly address current prophylactic anticoagulation recommendations.

Associação entre a apresentação fenotípica e os indicadores de prognóstico em gatos com cardiomiopatia hipertrófica

Dissertação de Mestrado Integrado em Medicina Veterinária

Computational fluid dynamics of a centrifugal heart pump as biventricular assist device(BVAD)

The results of a recent study have shown that there is a severe shortage of donor hearts to meet the demand of patients suffering from acute heart failures, and patients who received a left ventricular assist device (LVAD) have extended lives. However, some of them develop right heart failure syndrome, and these patients required a right ventricular assist device (RVAD). Hence, current research focus is in the development of a bi-ventricular assist device (Bi-VAD). Computational Fluid Dynamics (CFD) is useful for estimating blood damage for design of a Bi-VAD centrifugal heart pump to meet the demand of the left and right ventricles of a normal hearts with a flow rate of 5 lit/min and the supply pressure of 100 mmHg for the left ventricle and 20 mmHg for the right ventricle. Numerical studies have been conducted to predict pressure, flow rate, the velocity profiles, and streamlines in a continuous flow Bi-VAD using. Based on the predictions of numerical simulations, only few flow regions in the Bi-VAD exhibited signs of velocity profiles and stagnation points, thereby signifying potentially low levels of thrombogenesis.

Passive control of a bi-ventricular assist device : an experimental and numerical investigation

For the last two decades heart disease has been the highest single cause of death for the human population. With an alarming number of patients requiring heart transplant, and donations not able to satisfy the demand, treatment looks to mechanical alternatives. Rotary Ventricular Assist Devices, VADs, are miniature pumps which can be implanted alongside the heart to assist its pumping function. These constant flow devices are smaller, more efficient and promise a longer operational life than more traditional pulsatile VADs. The development of rotary VADs has focused on single pumps assisting the left ventricle only to supply blood for the body. In many patients however, failure of both ventricles demands that an additional pulsatile device be used to support the failing right ventricle. This condition renders them hospital bound while they wait for an unlikely heart donation. Reported attempts to use two rotary pumps to support both ventricles concurrently have warned of inherent haemodynamic instability. Poor balancing of the pumps’ flow rates quickly leads to vascular congestion increasing the risk of oedema and ventricular ‘suckdown’ occluding the inlet to the pump. This thesis introduces a novel Bi-Ventricular Assist Device (BiVAD) configuration where the pump outputs are passively balanced by vascular pressure. The BiVAD consists of two rotary pumps straddling the mechanical passive controller. Fluctuations in vascular pressure induce small deflections within both pumps adjusting their outputs allowing them to maintain arterial pressure. To optimise the passive controller’s interaction with the circulation, the controller’s dynamic response is optimised with a spring, mass, damper arrangement. This two part study presents a comprehensive assessment of the prototype’s ‘viability’ as a support device. Its ‘viability’ was considered based on its sensitivity to pathogenic haemodynamics and the ability of the passive response to maintain healthy circulation. The first part of the study is an experimental investigation where a prototype device was designed and built, and then tested in a pulsatile mock circulation loop. The BiVAD was subjected to a range of haemodynamic imbalances as well as a dynamic analysis to assess the functionality of the mechanical damper. The second part introduces the development of a numerical program to simulate human circulation supported by the passively controlled BiVAD. Both investigations showed that the prototype was able to mimic the native baroreceptor response. Simulating hypertension, poor flow balancing and subsequent ventricular failure during BiVAD support allowed the passive controller’s response to be assessed. Triggered by the resulting pressure imbalance, the controller responded by passively adjusting the VAD outputs in order to maintain healthy arterial pressures. This baroreceptor-like response demonstrated the inherent stability of the auto regulating BiVAD prototype. Simulating pulmonary hypertension in the more observable numerical model, however, revealed a serious issue with the passive response. The subsequent decrease in venous return into the left heart went unnoticed by the passive controller. Meanwhile the coupled nature of the passive response not only decreased RVAD output to reduce pulmonary arterial pressure, but it also increased LVAD output. Consequently, the LVAD increased fluid evacuation from the left ventricle, LV, and so actually accelerated the onset of LV collapse. It was concluded that despite the inherently stable baroreceptor-like response of the passive controller, its lack of sensitivity to venous return made it unviable in its present configuration. The study revealed a number of other important findings. Perhaps the most significant was that the reduced pulse experienced during constant flow support unbalanced the ratio of effective resistances of both vascular circuits. Even during steady rotary support therefore, the resulting ventricle volume imbalance increased the likelihood of suckdown. Additionally, mechanical damping of the passive controller’s response successfully filtered out pressure fluctuations from residual ventricular function. Finally, the importance of recognising inertial contributions to blood flow in the atria and ventricles in a numerical simulation were highlighted. This thesis documents the first attempt to create a fully auto regulated rotary cardiac assist device. Initial results encourage development of an inlet configuration sensitive to low flow such as collapsible inlet cannulae. Combining this with the existing baroreceptor-like response of the passive controller will render a highly stable passively controlled BiVAD configuration. The prototype controller’s passive interaction with the vasculature is a significant step towards a highly stable new generation of artificial heart.

P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions.

It is known that adenosine 5'-triphosphate (ATP) is a cotransmitter in the heart. Additionally, ATP is released from ischemic and hypoxic myocytes. Therefore, cardiac-derived sources of ATP have the potential to modify cardiac function. ATP activates P2X(1-7) and P2Y(1-14) receptors; however, the presence of P2X and P2Y receptor subtypes in strategic cardiac locations such as the sinoatrial node has not been determined. An understanding of P2X and P2Y receptor localization would facilitate investigation of purine receptor function in the heart. Therefore, we used quantitative PCR and in situ hybridization to measure the expression of mRNA of all known purine receptors in rat left ventricle, right atrium and sinoatrial node (SAN), and human right atrium and SAN. Expression of mRNA for all the cloned P2 receptors was observed in the ventricles, atria, and SAN of the rat. However, their abundance varied in different regions of the heart. P2X(5) was the most abundant of the P2X receptors in all three regions of the rat heart. In rat left ventricle, P2Y(1), P2Y(2), and P2Y(14) mRNA levels were highest for P2Y receptors, while in right atrium and SAN, P2Y(2) and P2Y(14) levels were highest, respectively. We extended these studies to investigate P2X(4) receptor mRNA in heart from rats with coronary artery ligation-induced heart failure. P2X(4) receptor mRNA was upregulated by 93% in SAN (P < 0.05), while a trend towards an increase was also observed in the right atrium and left ventricle (not significant). Thus, P2X(4)-mediated effects might be modulated in heart failure. mRNA for P2X(4-7) and P2Y(1,2,4,6,12-14), but not P2X(2,3) and P2Y(11), was detected in human right atrium and SAN. In addition, mRNA for P2X(1) was detected in human SAN but not human right atrium. In human right atrium and SAN, P2X(4) and P2X(7) mRNA was the highest for P2X receptors. P2Y(1) and P2Y(2) mRNA were the most abundant for P2Y receptors in the right atrium, while P2Y(1), P2Y(2), and P2Y(14) were the most abundant P2Y receptor subtypes in human SAN. This study shows a widespread distribution of P2 receptor mRNA in rat heart tissues but a more restricted presence and distribution of P2 receptor mRNA in human atrium and SAN. This study provides further direction for the elucidation of P2 receptor modulation of heart rate and contractility.