Myocardial ischemia therapy study

No therapy for advanced/decompensated heartfailure studied to date has been shown conclusively to influence mortality. Treatment goals are directed toward restoration of systemic oxygen transport and tissue perfusion, relief of pulmonary edema, and limitation of further cardiac damage. Maximizing oral therapy and using combinations of shortacting intravenous medications with different cardiovascular actions often are needed to optimize cardiac output, relieve pulmonary edema, and limit myocardial ischemia. Invasive hemodynamic monitoring usually is required to provide immediate feedback on treatment efficacy and adverse effects. 

These preclinical studies have led to the initiation of over 20 clinical trials investigating the potential efficacy of angiogenic gene therapy on critical limb and myocardial ischemia (Table 13.1) [5]. These Phase I and Phase II studies have reported reductions in ischemic symptoms, improvements in exercise time, and improvements in quahty of Hfe - subjective measures that have been supported by improvements in objective parameters such as perfusion (SPECT) scaiming and angiography. 

Given the understanding that release of cardiac troponin into the circulation reflects myocardial cell death, it is understandable why, clinically, therapies are oriented toward inhibiting the pathophysiologic processes of thrombosis, fibrinolysis, platelet aggregation, and inflammation leading to ischemia and, ultimately, myocardial cell death. Several markers of ischemia have been proposed [2], and research and development studies are underway to adequately validate their clinical usefulness or lack of evidence. These include the topic of this chapter (ischemia-modified albumin [IMA]), as well as choline, unbound free fatty acids, and nourin. 

Our studies support the hypothesis that cardiac cell membrane lesion sealing with CSIL result in preservation of myocardial viability, as determined by function, histochemistry, and ultra-structural morphology. There is a time response to myocardial preservation with CSIL therapy. Early CSIL intervention after the onset of ischemia resulted in almost complete myocardial recovery (18). Even when the intervention was initiated at 20 min of global ischemia, myocardial preservation was still greater than that seen in hearts with IgG-L or placebo treatment. There is also a dose response to CSIL therapy. Sufficient concentration of CSIL is essential to achieve optimal cell membrane lesion sealing (I9).Therefore, CSIL therapy may find therapeutic applications in preservation of myocardial viability and efficient non-viral gene therapy. 

Studies using embryonic stem cells (ES) have shown cell maturation, successful engraftment, and an improvement of myocardial function. However, there are also certain drawbacks. ES are allogenic and immunosuppressive therapy might be needed, they are susceptible to ischemia and human ES may have the potential to form teratomas when injected into immunocompromized mouse, reviewed by Davani.254... 

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