Restenosis is a reparative process in response to injury induced by angioplasty. This process can be temporarily classified into three phases:
Phase 1 – Recoil, which tends to occur within the first 24 hours.
Phase 2 – Mural thrombus are thrombi adherent to the vessel wall. (Mural thrombus formation with subsequent organization by connective tissue, which occurs within the first 2-3 weeks.) Blood clot is the final product of blood coagulation. It is achieved via the aggregation of platelets that form a platelet plug.
Phase 3 – Smooth muscle cell activation, migration, and proliferation along with increased synthesis of the extracellular matrix which occurs within the first 3 months.
Modern medicine is a discipline founded on the premise that humans can alleviate their suffering from disease by intervention (that, after the cause and the course of the disease). Over many years, humans developed diverse ways to interfere with diseases by using chemical, physical, mental, and most recently EBOO SAFE technology (Extra-corporeal Blood Oxygenation and Ozonation, Simple Access Fluid Extraction) aimed at improving the quality and duration of life.
However, in the course of proactive interventions in diseases processes, undesired consequences are often produced while prompting to gain benefits. This experience led practitioners to be cautious to avoid harm prior to considering intervention. In today’s medicine, new interventions are required to establish a clinically acceptable “therapeutic Index” (meaning that benefit clearly must surpass any liabilities or harmful consequences to the patient).
Ultimately, the whole enterprise of medical Science
and pharmacology is about safety and efficacy. Historians of private professional regulation have shown that professional men and women built institutions to research test, certify and monitor drug purity and efficacy even before the FDA existed, (Ref: Burrow 1970, Dowling 1970, Sonnedecker 1970) (described the era prior to Federal government interventions) “Having relied on voluntary and democratic decision making for the creation of the pharmacopoeia, organized medicine and later organized pharmacy also relied on voluntary compliance. It thus seemed a characteristic American Venture of free and independent professions”.
Thereupon, PPPOM (Pertubuhan Pengamal Perubatan Ozon Malaysia or The Organization of Malaysian Ozone Practitioners) is set up to inspect the quality and safety of the seller’s product. PPPOM shall grant certification mark or seal of approval and therefore it shall underwrite the charters of modern regulatory agencies, which seek safety and efficacy as the basis of drug and device approval for medical use.
With this in mind, EBOO SAFE reflects the reality of medical interventional cardiology – mitigating the consequence of an old disease, atherosclerosis, while at the same time, eliciting a new pathology, restenosis. The need to relieve obstruction to blood flow in essential blood vessels such as the coronary arteries has led to novel and powerful intervention that produce rapid relief from life threatening events such as abrupt vessel obstruction. PTCA, stents, EBOO SAFE and other interventions have proven to be of a great benefit to patients in danger of death from myocardial infarction. In particular, the use of PTCA and stents is currently a common practice in many medical centers with a success ratio of 96%, and minimal hospitalization, timely morbidity and mortality. The only real shadow cast over their modern success in conquering coronary (and other vessel) obstructions and heart attacks is the phenomenon of restenosis, or is simply re-occlusion of vessels that have been successfully opened by direct mechanical intervention.
Restenosis is a new disease, one of the many that medicine has encountered en route to introducing physical (e.g. radiation) or chemical (drugs) agents for therapeutic use.
Restenosis, however, was not a predicted liability (un-like consequences to chemotherapy or radiation) because the pathology underlying restenosis differs substantially from the pathology of the disease leading to obstruction of the blood vessel in the first place, namely, atherosclerosis and thrombosis. Restenosis is a significant medical problem because it occurs in a large proportion of patients (30-50%) undergoing PTCA or stent placements, which may result in morbidity and mortality, and adds significant burden on medical costs.
Why does restenosis occur? A definitive answer to this question has not been delivered, but significant strides have been made in understanding major components in the evolution of restenosis. (This article to you and to your doctor is designed to provide a state-of-the-art review of three aspects of the problem). This area is of particular importance since no drug has received regulatory agency approval for treatment of restenosis, in spite of enormous basic research, animal experimentation, and costly clinical trials. Better understanding of the role of animal models in pharmacological studies of restenosis is necessary, and careful analyses of the benefit as well as limitations of animal models of restenosis are essential for effective progression of pharmacological agents into clinical practice.
Thus this article provides the updated and comprehensive review of the pharmacology of restenosis.
First, it highlights the key conceptual support of research on restenosis with emphasis on the mechanism of “non-intima formation” (a key event to Restenosis) and elaborates on the phenomenon of vascular remodeling, a fundamental process that shapes the overall capacity of blood vessels to respond to physiological and pathological condition. In this aspect, you will therefore understand the succinct review of the molecular and cellular events that shape the vessel walls in response to injuries introduced by mechanical intervention (PTCA. Stents)
Second, the role of thrombosis in restenosis is of great interest and importance, since blood cells and blood borne factors play a key role in initiation and propagation of many of the processes in neo-intima formation and vascular remodeling in response to injury. There are several books that address the issue of thrombosis in restenosis, where the role of platelets and coagulation factors are reviewed, and strategies for intervention in various aspects of the coagulation cascade and platelet aggregation are evaluated. The importance of thrombosis in acute occlusion of vessels subjected to intervention has recently been demonstrated by clinical trials with anti-thrombotic agents (an antibody that blocks the platelet fibrinogen factor, GP11b/111a) which have shown significant efficacy in reducing morbidity and mortality in patients undergoing PTCA. However, it is still unclear whether anti-thrombotic agents are capable of combating the restenosis process per se.
Third, this article to you addresses the potential of EBOO SAFE therapy in restenosis. EBOO SAFE is an emerging concept and technology, in which extensive research is being conducted for cardiovascular disease. A simple and straightforward description of the technologies are available for EBOO SAFE Therapy. The pros and cons of various delivery systems can be explained and examples of success, (proof of hypothesis) in vivo human models are available. While this form of restenosis therapy may not be available for some time, it is important for researchers and clinicians to become familiar with this technology.
Lastly, we hope that this unique and stimulating approach to the problem of restenosis will help basic scientist to readily identify research direction and novel targets for therapeutics and help clinicians to better design and execute productive clinical trials. It is our hope that graduate students in various biology disciplines as well as physicians in training who seek rapid introduction to the multiple dimensions of this new medical condition – restenosis, take it upon themselves to review and use this innovative technology in their quest for a better option than what is available at present.