Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice

Cardiac pressure-volume loop analysis is the &#8220;gold-standard&#8221; in the assessment of load-dependent and load-independent measures of ventricular ...

Duke University Medical Center

Ambulatory blood pressure is a better predictor of target organ damage and the risk of adverse cardiovascular events than office measurements. Whether this is due to the greater reliability owing to the larger number of measurements that are usually taken using ambulatory monitoring, or the greater validity of these measurements independent of the number, remains controversial.

Superiority of ambulatory to physician blood pressure is not an artifact of differential measurement reliability.

Anger is an independent predictor of coronary heart disease events, although the mechanisms for this relation are unclear. The effects of an anger-provoking interview compared with a neutral interview on endothelium-dependent and -independent vasodilation assessed by brachial artery ultrasound were examined in 14 healthy subjects without coronary heart disease risk factors. The anger provocation condition, but not the neutral condition, caused a significant impairment in endothelium-dependent vasodilation at 90 minutes compared with baseline (p = 0.004) and 30 minutes (p = 0.013). Similarly, endothelium-independent vasodilation was significantly impaired at 90 minutes after the angry interview compared with baseline (p = 0.003) and 30 minutes (p = 0.001). The decreases in endothelium-dependent and -independent vasodilation were greater after the anger-provoking interview than after the neutral interview, especially between 30 and 90 minutes. In conclusion, preliminary results suggest that an episode of anger is associated with a dysregulation in endothelium-dependent and -independent pathways, suggesting that these mechanisms might contribute to the link between anger and coronary heart disease events.

Effect of anger provocation on endothelium-dependent and -independent vasodilation.

Home blood pressure (HBP) monitoring plays an increasingly important role in the diagnosis and treatment of hypertension. We evaluated the independent value of HBP compared with ambulatory blood pressure (ABP) and office blood pressure (OBP) in the prediction of cardiovascular end-organ damage in normotensive subjects and untreated patients with mild hypertension.

Relative utility of home, ambulatory, and office blood pressures in the prediction of end-organ damage.

To examine the association between hostility and platelet reactivity in individuals without a prior history of cardiovascular disease (CVD) events. Hostility is associated with incident CVD events, independent of traditional risk factors. Increased platelet reactivity and thrombus formation over a disrupted coronary plaque are fundamental for CVD event onset.

Hostility and platelet reactivity in individuals without a history of cardiovascular disease events.

Normal cardiac physiology requires highly regulated cytosolic Ca(2+) concentrations and abnormalities in Ca(2+) handling are associated with heart failure. The majority of approaches to identifying the components that regulate intracellular Ca(2+) dynamics rely on cells in culture, mouse models, and human samples. However, a genetically robust system for unbiased screens of mutations that affect Ca(2+) handling remains a challenge.

A method to measure myocardial calcium handling in adult Drosophila.

The Minute syndrome in Drosophila melanogaster is characterized by delayed development, poor fertility, and short slender bristles. Many Minute loci correspond to disruptions of genes for cytoplasmic ribosomal proteins, and therefore the phenotype has been attributed to alterations in translational processes. Although protein translation is crucial for all cells in an organism, it is unclear why Minute mutations cause effects in specific tissues. To determine whether the heart is sensitive to haplo-insufficiency of genes encoding ribosomal proteins, we measured heart function of Minute mutants using optical coherence tomography. We found that cardiomyopathy is associated with the Minute syndrome caused by haplo-insufficiency of genes encoding cytoplasmic ribosomal proteins. While mutations of genes encoding non-Minute cytoplasmic ribosomal proteins are homozygous lethal, heterozygous deficiencies spanning these non-Minute genes did not cause a change in cardiac function. Deficiencies of genes for non-Minute mitochondrial ribosomal proteins also did not show abnormal cardiac function, with the exception of a heterozygous disruption of mRpS33. We demonstrate that cardiomyopathy is a common trait of the Minute syndrome caused by haplo-insufficiency of genes encoding cytoplasmic ribosomal proteins. In contrast, most cases of heterozygous deficiencies of genes encoding non-Minute ribosomal proteins have normal heart function in adult Drosophila.

Cardiomyopathy is associated with ribosomal protein gene haplo-insufficiency in Drosophila melanogaster.

Pharmacological blockade of the ANG II type 1 receptor (AT1R) is a common therapy for treatment of congestive heart failure and hypertension. Increasing evidence suggests that selective engagement of β-arrestin-mediated AT1R signaling, referred to as biased signaling, promotes cardioprotective signaling. Here, we tested the hypothesis that a β-arrestin-biased AT1R ligand TRV120023 would confer cardioprotection in response to acute cardiac injury compared with the traditional AT1R blocker (ARB), losartan. TRV120023 promotes cardiac contractility, assessed by pressure-volume loop analyses, while blocking the effects of endogenous ANG II. Compared with losartan, TRV120023 significantly activates MAPK and Akt signaling pathways. These hemodynamic and biochemical effects were lost in β-arrestin-2 knockout (KO) mice. In response to cardiac injury induced by ischemia reperfusion injury or mechanical stretch, pretreatment with TRV120023 significantly diminishes cell death compared with losartan, which did not appear to be cardioprotective. This cytoprotective effect was lost in β-arrestin-2 KO mice. The β-arrestin-biased AT1R ligand, TRV120023, has cardioprotective and functional properties in vivo, which are distinct from losartan. Our data suggest that this novel class of drugs may provide an advantage over conventional ARBs by supporting cardiac function and reducing cellular injury during acute cardiac injury.

β-Arrestin-biased AT1R stimulation promotes cell survival during acute cardiac injury.

Abnormal sarcoendoplasmic reticulum Calcium ATPase (SERCA) function has been associated with poor cardiac function in humans. While modifiers of SERCA function have been identified and studied using animal models, further investigation has been limited by the absence of a model system that is amenable to large-scale genetic screens. Drosophila melanogaster is an ideal model system for the investigation of SERCA function due to the significant homology to human SERCA and the availability of versatile genetic screening tools. To further the use of Drosophila as a model for examining the role of SERCA in cardiac function, we examined cardiac function in adult flies. Using optical coherence tomography (OCT) imaging in awake, adult Drosophila, we have been able to characterize cardiac chamber dimensions in flies with disrupted in Drosophila SERCA (CaP60A). We found that the best studied CaP60A mutant, the conditional paralytic mutant CaP60A(kum170), develops marked bradycardia and chamber enlargement that is closely linked to the onset of paralysis and dependent on extra cardiac CaP60A. In contrast to prior work, we show that disruption of CaP60A in a cardiac specific manner results in cardiac dilation and dysfunction rather than alteration in heart rate. In addition, the co-expression of a calcium release channel mutation with CaP60A (kum170) is sufficient to rescue the cardiac phenotype but not paralysis. Finally, we show that CaP60A overexpression is able to rescue cardiac function in a model of Drosophila cardiac dysfunction similar to what is observed in mammals. Thus, we present a cardiac phenotype associated with Drosophila SERCA dysfunction that would serve as additional phenotyping for further large-scale genetic screens for novel modifiers of SERCA function.

Disruption of sarcoendoplasmic reticulum calcium ATPase function in Drosophila leads to cardiac dysfunction.

Ischemia–reperfusion injury is strongly associated with increased oxidative stress, mitochondrial dysfunction, and cell death. These processes are diminished in an animal model of ischemia–reperfusion by the genetic loss or pharmacological inhibition of troponin I–interacting kinase.

Inhibition of the cardiomyocyte-specific troponin I-interacting kinase limits oxidative stress, injury, and adverse remodeling due to ischemic heart disease.

Nowadays esthetics plays an important role in dentistry along with function of the prosthesis. Various soft tissue augmentation procedures are available to correct the ridge defects in the anterior region. The newer technique, vascularized interpositional periosteal connective tissue (VIP-CT) flap has been introduced, which has the potential to augment predictable amount of tissue and has many benefits when compared to other techniques.

Vascularized interpositional periosteal connective tissue flap: A modern approach to augment soft tissue.

Whether biomechanical force on the heart can induce exosome secretion to modulate cardiovascular function is not known. We investigated the secretion and activity of exosomes containing a key receptor in cardiovascular function, the angiotensin II type I receptor (AT1R).

Dennis Abraham

Department of Medicine

Duke University Medical Center

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice

Dennis Abraham

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Medicine

Duke University Medical Center

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice

Department of Medicine