Improving red blood cell K-uptake and its impact on O(2)/CO(2) exchange, and NO-generation in microvascular CHD: a
1The Clinical Research Unit, Ion Transport Laboratory, University of Carabobo Medical School, Docent Institute of Urology and Nephrology, La Viña Valencia, Venezuela. delgado_almeida@hypertensresearch.org
Insights
Coronary heart disease (CHD) management is evolving. New research explores improving red blood cell (RBC) function to potentially reverse angina and ECG changes in patients with coronary artery disease.
Area of Science:
- Cardiology
- Vascular Biology
- Biochemistry
Background:
- Coronary heart disease (CHD) is a global health crisis, with limited therapeutic options for angina and ECG changes.
- Research has historically focused on atherosclerosis, neglecting cases with normal coronary arteries.
- There's a need for comparative therapeutic research in CHD management.
Purpose of the Study:
- To review the pathophysiology and management of CHD.
- To highlight neglected findings and recent patents in CHD research.
- To present novel approaches for reversing angina and ECG alterations.
Main Methods:
- Review of physiological principles of myocardial oxygen delivery.
- Emphasis on red blood cell (RBC) oxygen sensing and delivery in ischemia.
- Analysis of recent therapeutic advances and patents.
Main Results:
- Discussion of RBC sensing of O(2) demand and delivery in myocardial ischemia.
- Presentation of approaches to reverse angina and ECG alterations.
- Introduction of a New Drug Application targeting RBC K uptake for improved tissue exchange and NO-generation.
Conclusions:
- Improved RBC K uptake may reverse angina and ST-T alterations in CHD.
- This approach influences tissue H/K and O(2)/CO(2) exchanges and NO-generation.
- Novel therapeutic strategies are emerging for CHD patients with normal coronary arteries.
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.
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