Adenosine acts through its receptors (A1, A2A, A2B, and A3) via G-proteins and causes an increase in coronary flow (CF) mostly through A2A AR. However, the role of other ARs in the modulation of CF is not well understood. Using KOs, we investigated the role for each AR in the regulation of CF. Using the isolated heart from A3 KO mice; we reported an increase in A2A-mediated CF.  Similarly, we found an increase in CF in A1 KO mice with A2A agonist (CGS-21680). Also, in A2A KO mice, response to CGS was abolished. On the other hand, A2A KO mice showed a decrease in CF to NECA (non-selective agonist). BAY60-6583 (A2B selective agonist) was without an effect on CF in A2B KO mice; however, it increased CF significantly in A2A KO. CGS also caused a significant increase in CF in A2B KO mice. Also, exogenous adenosine-induced increase in CF in WT, A2A KO, and A2B KO mice were significantly reduced with catalase. BAY-induced increase in CF in WT was significantly inhibited with glibenclamide. Overall, our data support stimulatory roles for A2A and A2B and inhibitory roles for A1 and A3 in the regulation of CF.  These observations provide new evidence for the presence of all four ARs in CF regulation. We propose, that activation of A2A/B may release H2O2 which then activates KATP channels, leading to vasodilation. These studies may lead to better understanding of the role of ARs in coronary disease and may lead to better therapeutic approaches

Introduction: Transcatheter valves manufactured using biological tissue, as the essential structural component, can be induced to: mechanical degradation after crimping and early calcification in pediatric patients. 

Objectives: Manufacture and successful tests of one expandable polyurethane stent valve, may reduce the repeated operations of valve replacement, during the growing children. 

Material / Methods:I-Physical testing.Prostheses were submitted to universal testing in machine EMIC and a computer with Tesc software, able to generate graphs of force versus deformation (stretching) II-Hydrodynamic testing. Prostheses with diameters from 12 to 22 mm, were submitted to pulsatile physiological flow and stress conditions.III-Experimental implants in sheep.Ten sheep was submitted to prosthesis implant, by trans catheter technique in pulmonary position.In Group A: Four sheep w/ <20 kg, the stent was expanded up to 18mm and in Group B: Six sheep w/ > 20 kg, expanded up to 22mm.

Results: Physical and Hydrodynamic testing of Polyurethane strip removal of stent valve, before and after undergoing to 30 minutes crimping, showed preservation of properties of resistance and elasticity elongation. In vitro durability was proven for >15 years. Eight sheep, were submited to 3D echo study, performed in the 6th month of f.-up,  showed:  there was no significant transvalvular gradients and trivial regurgitation in 3 cases. Histologic, radiologic and electron microscopic study of the first prosthesis shows: integrity of structure and free of calcification. Seven survival sheep are well, after 24th months of follow-up.  

Conclusion: Expandable polyurethane stent valve, with special design for implant and expansion in growing children, has experimental satisfactory  hemodynamic performance and durability in vitro and in vivo tests. Calcification and structural changes were not observed. In the next step, clinical studies are be planned. 

Targeted removal of damaged/misfolded proteins in the cell is primarily performed by the ubiquitin-proteasome system (UPS). When escaped from UPS-mediated degradation, misfolded proteins tend to form aberrant aggregates which are no longer accessible by the proteasome and are generally believed to be removed by macroautophagy. Remarkable accumulation of myocardial ubiquitinated proteins and autophagosomes are observed in human heart failure of nearly all causes, indicative of UPS and autophagic dysfunction in the development of cardiac failure. The creation of stable cell lines, adenoviruses, and stable transgenic mice expressing a surrogate UPS substrate, such as green fluorescence protein (GFP) modified by fusion with degron CL1 (known as GFPu or GFPdgn), has made it possible and convenient to monitor dynamic changes in UPS performance in situ or in vivo, and thereby enabled my lab to demonstrate for the first time in intact animals that increases in misfolded proteins and resultant aberrant protein aggregation impair UPS function and cause proteasome functional insufficiency (PFI). Similarly, we and collaborators detected cardiac UPS functional insufficiency in acute ischemia/reperfusion (I/R), chronic pressure overload, and diabetic cardiomyopathy.

Using both gain- and loss-of-function approaches, we were able to demonstrate that PFI is a major factor underlying UPS malfunction and plays an important pathogenic role in heart disease with increased proteotoxic stress such as proteinopathy, I/R injury and diabetic cardiomyopathy in mice.

Furthermore, we have discovered that cGMP-dependent kinase (PKG) positively regulates the proteasome in cardiomyocytes, PKG activation by either genetic or pharmacological means, such as phosphodiesterase 5 (PDE5) inhibition, promotes proteasome-dependent degradation of a surrogate and a bona fide misfolded protein in cardiomyocytes, and PDE5 inhibition by sildenafil reduces misfolded protein abundance and aggregation and slows down disease progression in a well-established mouse model of cardiac proteinopathy. We have also collected strong evidence that the protection of PDE5 inhibition against I/R injury depends largely on improving proteasome function. Muscarinic receptor activation can enhance cardiac proteasomal function in a PKG dependent manner. These findings demonstrate the feasibility to use pharmacological method to enhance UPS-mediated degradation of misfolded proteins and thereby to treat heart disease with elevated misfolded proteins. A good body of evidence has also demonstrated that increasing autophagy is beneficial to the treatment of most heart diseases. Hence, improving cardiac protein quality control through UPS enhancement and increasing autophagic flux has emerged as a promising novel therapeutic strategy warranted for translational studies.   

Myocardial bridging (MB) is congenital anatomic variation in which a band of cardiac muscle covers a part of an epicardial coronary artery. The artery under the cover of myocardium is known as ‘tunnelled segment’.

The clinical implication of myocardial bridging is a debatable subject since early 1960s at the introduction of coronary arteriography. Myocardial bridge is considered benign by many authors but recent literature describes it as associated with various clinical conditions such as  myocardial ischaemia, circulatory problems, angina, myocardial infarction, sudden cardiac death, systolic compression and other cardiac insults that may require surgical intervention. It is also said that myocardial bridges has ‘protective effect’ from atherosclerosis within the coronary artery that is bridged when compared with uncovered vessels of the same heart.

The present study is aimed to analyse the presence of myocardial bridges over coronary arteries and their branches by coronary angiography. 380 coronary angiographs consisting of 292 male and 88 females were analysed retrospectively for the presence of MB on the coronary arteries and their branches in department of Anatomy and cardiology, AIIMS Rishikesh. 20 MBs was observed in 19 cases (2 females and 17males) out of 380 cases of angiographs (88 females and 292 males) constituting 5.26 %. Single MB was observed in 18 cases and two MBs were observed in one case. In 18 cases, MB was observed only on LAD while in one case, both LAD and LCX were covered by MB. Length of MB ranged between 12mm to 30 mm with mean 21.5 ± 2.12. Percentage reduction of diameter and area of coronary artery covered by MB ranged between 22.9- 78.69 and 40.48- 95.5 respectively. In our case all the patients with MB were having coronary artery diseases except one. Thus isolated MB may be benign anomaly but it is definitely a contributing factor in causing various coronary heart diseases. It is great challenge to cardiologist to detect symptomatic patients with MB and to plan better therapeutic and surgical interventions. An optimal use of new non-invasive diagnostic methods in combination with invasive methods will enhance our understanding of this anomaly and help in reducing the mortality.

Background :

Surgical AVR is  the treatment of choice for patients with symptomatic severe degenerative aortic stenosis, as it offers both symptomatic relief and the potential for improved long-term survival .  An increasing number of elderly patients with multiple comorbidities are referred for transcatheter aortic valve implantation (TAVI), partly due to the perceived high risks of surgery. These include in particular patients who have had previous cardiac surgery. The study aim was to compare the outcomes of patients with aortic valve disease ,

METHODS:

All patients aged > 76 years that underwent a procedure for severe aortic stenosis with or without coronary revascularization at the authors' institution were included in the study; thus, 308 patients underwent  previous cardiac surgery was allocated to TAVI TAVI and 192 underwent  previous surgery and subsequently had redo surgery AVR. Patients in the TAVI group were older (mean age 87 ) . Treatment modalities were chosen for individual patients according to their EuroSCORE and had a higher logistic EuroSCORE .

Results:

a total of 500 patients was discussed ,of these patients, 192 underwent TAVI, 308 of whom had undergone previous cardiac surgery Twenty one patients (10%) died during the procedure in the TAVI group, and 32 (13%) died in the AVR group . Predictors for mortality were: age, female gender  and surgical valve replacement  .Gradients across the implanted valves at one to three months postoperatively were lower in the TAVI group  .

Conclusion :

Surgical aortic valve replacement remains the 'gold standard' treatment for aortic valve disease.Improved risk stratification in patients with aortic valve disease and re-do cardiac surgery is required .AVR and TAVI will likely be offered to different groups of patients Transcatheter aortic valve implantation is the treatment of choice for symptomatic aortic stenosis in the unacceptably high-risk or inoperable patients, and is a reasonable option for high-risk patients in general.