2. Academic Validation
  3. Cyclocreatine Phosphate: A Novel Bioenergetic/Anti-Inflammatory Drug That Resuscitates Poorly Functioning Hearts and Protects against Development of Heart Failure

Cyclocreatine Phosphate: A Novel Bioenergetic/Anti-Inflammatory Drug That Resuscitates Poorly Functioning Hearts and Protects against Development of Heart Failure

  • Pharmaceuticals (Basel). 2023 Mar 16;16(3):453. doi: 10.3390/ph16030453.
Salwa A Elgebaly 1 2,  Charles Van Buren 3,  Robert Todd 4,  Robert Poston 1,  Reem K Arafa 5,  Nashwa El-Khazragy 6,  Donald Kreutzer 2 7,  Mostafa A Rabie 8,  Ahmed F Mohamed 8,  Lamiaa A Ahmed 8,  Nesrine S El Sayed 8
Affiliations

Affiliations

  • 1 Research & Development, Nour Heart, Inc., Vienna, VA 22180, USA.
  • 2 Department of Surgery, School of Medicine, UConn Health, Farmington, CT 06030, USA.
  • 3 Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
  • 4 Chemistry Department, ProChem Intl., LLC, Sheboygan, WI 53081, USA.
  • 5 Biomedical Sciences Program & Drug Design and Discovery Lab, Zewail City of Science and Technology, Cairo 12578, Egypt.
  • 6 Department of Clinical Pathology-Hematology, Ain Shams Medical Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt.
  • 7 Cell & Molecular Tissue Engineering, LLC, Farmington, CT 06030, USA.
  • 8 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
PMID: 36986552 DOI: 10.3390/ph16030453
Abstract

Irreversible myocardial injury causes the exhaustion of cellular adenosine triphosphate (ATP) contributing to heart failure (HF). Cyclocreatine phosphate (CCrP) was shown to preserve myocardial ATP during ischemia and maintain cardiac function in various animal models of ischemia/reperfusion. We tested whether CCrP administered prophylactically/therapeutically prevents HF secondary to ischemic injury in an isoproterenol (ISO) rat model. Thirty-nine rats were allocated into five groups: control/saline, control/CCrP, ISO/saline (85 and 170 mg/kg/day s.c. for 2 consecutive days), and ISO/CCrP (0.8 g/kg/day i.p.) either administrated 24 h or 1 h before ISO administration (prophylactic regimen) or 1 h after the last ISO injection (therapeutic regimen) and then daily for 2 weeks. CCrP protected against ISO-induced CK-MB elevation and ECG/ST changes when administered prophylactically or therapeutically. CCrP administered prophylactically decreased heart weight, hs-TnI, TNF-α, TGF-β, and Caspase-3, as well as increased EF%, eNOS, and connexin-43, and maintained physical activity. Histology indicated a marked decrease in cardiac remodeling (fibrin and Collagen deposition) in the ISO/CCrP rats. Similarly, therapeutically administered CCrP showed normal EF% and physical activity, as well as normal serum levels of hs-TnI and BNP. In conclusion, the bioenergetic/anti-inflammatory CCrP is a promising safe drug against myocardial ischemic sequelae, including HF, promoting its clinical application to salvage poorly functioning hearts.

Keywords

adenosine triphosphate; anti-inflammatory; bioenergetic; cyclocreatine phosphate; heart failure; myocardial ischemia.

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