Endovascular Therapy of Critical Upper Limb Ischaemia, Performed Two Months after Thromb-Embolic Occlusion of Axillary to Brachial Artery

A 68 years old female patient, hypertensive, non-diabetic, under medical treatment for clinically diagnosed Ischaemic Heart disease, had sudden onset acute pain in the right arm with development of pallor of the arm and absence of radial pulse detected by her husband. On hospitalization (district level), previously undiagnosed atrial fibrillation was detected on ECG, and no pulse was available distal to the axillary artery. Arterial Doppler examination confirmed thrombotic occlusion of the axillary artery at the level of neck of humerus. 

Clinical diagnosis was thrombo-embolic occlusion of right axillary artery following development of atrial fibrillation of unknown duration. As per the discharge report from the district hospital, she was treated in intensive care unit with Morphine, Heparin (low molecular0, Clopidogrel and Aspirin. The next morning an angiogram was performed from right femoral artery, confirming the clinical diagnosis in addition to a highly tortuous double U-turn subclsvian artery. She was continued on medical management only and discharged after 7 days under Warfarin, reporting significantly improved condition of the arm. Read more....................

Cell Therapy for Cardiovascular Diseases

Ischemia/reperfusion (IR) initiates various cellular and molecular changes often resulting in myocardial infarction and cardiac dysfunction. Inhibition of enzymes that are involved in cell pathology could be potential therapeutic targets especially phosphodiesterases. Pharmacological preconditioning (PC) with tadalafil, a PDE5A inhibitor enhances protein kinaseG-1 (PKG-I) activity resulting in stem cell survival and cardioprotection. PC protection has two different phases, an early (2 h) and late (24 h).

However, the mechanism of protection during these phases remained grossly unknown. Mesenchymal stem cells (MSC) from adult male Fischer-344 rats were pre-treated with tadalafil (100 μM) for an hour and subjected to 2 h of hypoxia (1% O2) followed by reoxygenation (HR: in vitro model mimicking ischemia/reperfusion). 

We observed increased MSC survival with reduced cell cytotoxicity as revealed by low LDH release and trypan blue staining respectively in tadalafil treated cells upon HR; decrease in TUNEL positivity as well as caspases activity ; an increase in pAKT/AKT, iNOS, eNOS and pGSK3β/GSK3β during early protection phase of PC. This protection seemed to be a spontaneous adaptive response of MSCs against HR and was independent of tadalafil whereas an increase in Bcl2/Bax was tadalafil dependent;  during late phase, we observed phosphorylation of STAT3 at serine727 leading to its entry inside the nucleus and binding onto the promoter of PKG-I by 3 fold (P<0.05).