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Recent Patents on Cardiovascular Drug Discovery
ISSN (Print): 1574-8901
ISSN (Online): 2212-3962
VOLUME: 7
ISSUE: 3
DOI: 10.2174/157489012803832801









Improving RBC K Transport and Hemoglobin-O2 Binding by Amiloride: A Novel Therapeutic Approach for Reversion of Angina and Myocardial Ischemia in Coronary Heart Diseases

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Author(s): Antonio R. Delgado-Almeida, Carlos L. Delgado and Antonio J. Delgado-Leon
Pages 221-235 (15)
Abstract:
Coronary heart disease (CHD) is the leading cause of morbidity and mortality across the entire world, in which reversion of angina or improvement of ECG remains an unrealistic therapeutic option for most patients, suggesting that microvascular dysfunction or impaired oxygen delivery might be critical factors in CHD. This research article, thus presents the rationale basis, clinical and experimental, for the first therapeutic innovation addressing the role of red blood cell (RBC) H/K and O2/CO2 exchanges in CHD. It is followed by a randomized single-blind trial of Amiloride and Optimal Medical Therapy (OMT, n=35 cases) vs OMT alone (n=35 cases) in patients having angina, ST-T alteration and a defective RBC-K transport. All patients had serial clinical evaluation, Ion Transport Studies, ECGs and non-invasive aortic waveform and cardiovascular hemodynamic recordings. Statistical analysis was performed by SAS.

Results: Amiloride rapidly improved RBC-K (93.5 ±4 vs 84.5 ±4 mmol/lc, p= < 0.001), angina (80% of cases, 1.5 ±0.3 weeks, CI:1.72 to 1.45), CCS Class (1.3 ±0.5 vs 3.1 ±0.8, p < 0.001) vs patients with OMT alone CCS Class (3.2 ± 0.4 vs 3.3 ± 0.5, p =0.21). Reversion of angina was sustained through the next 6-months (87% vs 26 % in OMT, RR 2.1, odds ratio 6.31, Pearson 2 34.6,p < 0.0001 at 95% CI) and 1-year (85% vs 37% OMT). At 6-months of amiloride, ECG became normal (29% vs 0%, RR  uncalculated-time, odds ratio , Pearson 2 42.4 at 95% CI, p < 0.0001), improved (55% vs 29%; RR2.1, odds ratio 3.16, 95% CI, p < 0.0001) or unchanged (15% vs 67% OMT). At 1-year, seven patients on amiloride (18%) exhibited evidence of electrical regeneration of the heart, not observed with placebo.

In Conclusion: This therapeutical innovation of amiloride improves RBC H/K and O2/CO2 function, and reverses angina, ST-T alterations while inducing electrical regeneration of the heart, in patients receiving optimal medical treatment for angina. The article has short discussion on the relevant patents to the topic.

Keywords:
Effect of Amiloride on RBC-K and its impact in CHD, Hereditable defect in RBC-K transport in essential hypertension, RBC and myocardial blood flow control, Regulation of H/K and O2/CO2 exchange by RBC, Reversion of angina and ST-T alterations in CHD
Affiliation:
Clinical Research Unit, Instituto Docente de Urologia, 4th Floor, Office 419. Av. Carabobo, Urb. La Viña, Valencia 2001, Venezuela.