కార్డియోవాస్కులర్ డిసీజెస్ & డయాగ్నోసిస్

Although the benefits of pre- and post-conditioning have been extensively documented in animal models, the translation from “bench to bedside” has been disappointing and slow. In this article we review the mechanisms of action and potential pharmacological targets of pre and post-conditioning, discuss key findings of clinical trials and provide a summary of ongoing clinical trials. Myocardial protection before planned myocardial ischemia and during reperfusion has the potential to significantly impact clinical outcomes. Industry and government support are critical to validate the findings of small-scale studies to the broader population with cardiovascular disease.

Background: 3D echocardiography derived volumetric data can be used to generate left ventricular volume time curves and has the potential to elucidate aspects of contractility, systolic and diastolic function in normal and disease states. We sought to establish the validity and reproducibility of these volume-time curves and apply novel parameters derived from these curves to a clinical population.

Methods: Consecutive patients, who underwent cardiac MRI and echocardiography within 12 hours, were
used to compare volume-time curves. Inter- and intra observer variability of the 3D echocardiography volume-time curves was assessed. Peak emptying rates, peak filling rates, and peak systolic acceleration were measured in a normal population (normal Ejection Fraction (EF) and no significant valvular disease) and their change with age was evaluated.

Results: 16 patients with an average EF of 55% ± 10% underwent cardiac MRI and 3D echocardiography. Therewas no significant difference between the systolic and diastolic slopes of the volume-time curves derived by the two methods with good correlation for both systole (r=0.62, p < 0.0001) and diastole (r=0.43, p=0.0025). In 50 normal patients aged 19-91, peak emptying rate, peak filling rate, and peak systolic acceleration all decreased with age.

Conclusion: 3D echocardiography volume-time curves correlate well with the gold standard of cardiac MRI. The novel 3D parameters of peak emptying rate, peak filling rate, and peak systolic acceleration may prove to be helpful in the assessment of systolic and diastolic function and provide insight into ventricular performance.

Deregulated or enhanced calcium ion (Ca2+) influx across an unstable sarcolemma has been proposed to directly affect cardiac hypertrophic remodelling, vascular proliferative diseases and degenerative muscle disorders. Aberrant intracellular handling is partly due to a defect in Sarcoplasmic Reticulum (SR) function. Decreased Ca2+ uptake in cardiac, vascular and skeletal myocytes is associated with a decrease in the expression and activity of the fast sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a or SERCA1a isoforms). SERCA2a gene transfer was successfully used in heart failure; this approach holds further therapeutic promises in vascular proliferative diseases and dystrophin-deficient muscular diseases. The growing family of human SERCA isoforms comprises at least 14 mRNA and proteins with different functional characteristics and cell-specific expression. This review focuses on the biological role and therapeutic potential of different isoforms of SERCA in the physiology and pathology of cardiac, vascular and skeletal muscle cells.

This review provides an instructive example of how a botanical and mineral formula known in the tradition of Tibetan medicine as Gabyr-Nirynga (camphor combination), denoted as formula No. 28, has evolved into a contemporary application through scientific research. This developmental pathway has led to a standardized nutraceutical with clinically proven efficacy in alleviation of a form of atherosclerosis-peripheral arterial disease (PAD). The systematic scientific research began in Switzerland in 1970s and resulted in five, double-blind clinical studies conducted in various European countries on cardiovascular use of the formula. The formula’s mechanism of action has been described in Tibetan tradition based on its three groups of botanical and mineral ingredients: (1) main active ingredients, (2) auxiliary ingredients, and (3) components that offset the action of the first two groups and facilitate gastrointestinal absorption of the formula. Based on preclinical and clinical studies, several mechanisms of action relevant to alleviation of the PAD have been discussed, such as an increase in the threshold for platelet aggregation, lower total blood cholesterol and low-density lipoproteins (LDL), and prevention of blood lipid peroxidation. A study in an animal model of CNS inflammation, i.e. Experimental Allergic Encephalomyelitis (EAE), has shown that No. 28 can exert action as a biological response modifier improving response of the organism to chronic inflammation. This latter mechanism may be particularly relevant to the clinical benefits with No. 28 in patients with PAD, in view of cardiovascular disease increasingly considered as an outcome of a chronic inflammatory process. The integration of traditional knowledge of a botanical formula with science-derived pharmacology is referred in this paper as the Interactive Nutrients process.

Background: Gene Expression Profiling (GEP) has been used since 2005 to identify Orthotopic Heart Transplant (OHT) recipients at low risk of allograft rejection. A rise in GEP scores during the first year post OHT has been previously reported. The purpose of this study is to confirm and better characterize this effect of time post-transplant in a larger, unselected cohort.

Methods: All commercially obtained GEP scores (XDx Inc., Brisbane, CA) collected between January 2005 and September 2011 were included. Clinical data were available for patient age, gender and dates of transplantation and tests.

Results: There were 32,043 GEP tests from 9,272 patients at 108 transplant centers (mean age at testing 54.2 ± 14.7 yrs, 25% women). There was a significant effect of time post transplant on GEP, which rose from 24.7 ± 7.8 at 2-6 months to 28.8 ± 5.8 at 7-12 months (p<0.0001) and 29.6 ± 5.0 (p<0.0001) at 13-24 months, after which it remained stable.

Conclusions: A rise in GEP scores is seen during the first year following OHT, which parallels the time frame of decreased corticosteroid dosing. Further study of this test characteristic may better inform clinical use of GEP testing in conjunction with endomyocardial biopsy.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) caused by mutations in polycystic kidney disease 1 or 2 (Pkd1 or Pkd2) gene is the most common inherited renal disease and is characterized by cardiovascular abnormalities like hypertension and aneurysms. Polycystin-1 (PC1) and polycystin-2 (PC2), encoded by Pkd1 and Pkd2 genes, respectively, are detected in the cardiovascular system, indicating that PC1 or PC2 may play an important role in cardiovascular function. In the present review, we summarize current findings of PC1 and PC2 in cardiovascular regulation, such as hypertension and aneurysms associated with ADPKD and embryonic development.