Improving red blood cell K-uptake and its impact on O(2)/CO(2) exchange, and NO-generation in microvascular CHD: a novel therapeutic approach.

Abstract

Coronary heart disease (CHD) is the leading cause of morbidity and mortality across the entire world. In effect, reversion of angina or improvement of ECG remains an unrealistic therapeutic option for most patients. Unfortunately, most research clinical trials in these patients have focused on coronary atherosclerosis, even decades after the first observation that angina, and myocardial infarction may occur in the presence of normal coronary arteries. Further, there has been little attention from academic and pharmaceutical institutions on comparative therapeutic research as it has been recently addressed by the Institute of Medicine of the National Academies in USA, and by a similar statement from the World Medical Association in the year 2000. This review, thus, has tried to present the best of our knowledge on the pathophysiology and management of CHD, along with other striking relevant but neglected findings with some recent patents. Four sections were included from the physiological principles of myocardial oxygen delivery, with emphasis on RBC sensing O(2) demand and delivery in myocardial ischemia, up to the recent advances on approaches intended to reverse angina and the ECG alteration in coronary heart disease. Finally, this review presents the principles, design and results of the first New Drug Application to address improvement in RBC K uptake, and consequently the chain of simultaneous tissue H/K and O(2)/CO(2) exchanges, and NO-generation, along with their promising therapeutic effect on reversion of angina, and ST-T alterations in coronary artery disease patients.