Decrease in internal H+ and positive inotropic effect of heptaminol hydrochloride: a 31P n.m.r. spectroscopy study in...

Area of Science:

• Cardiology
• Biochemistry
• Pharmacology

Background:

• The cardiotonic effects of heptaminol hydrochloride require further investigation.
• Intracellular pH regulation is crucial for cardiac function, especially during ischemic conditions.

Purpose of the Study:

• To investigate the cardiotonic effect of heptaminol hydrochloride.
• To determine if intracellular realkalinization mediates heptaminol's effect.
• To explore the role of Na-H exchange in heptaminol's action during ischemia.

Main Methods:

• Isolated rat hearts were perfused using the Langendorff method.
• Left ventricular pressure (LVP) and mechanical activity were measured.
• 31P-nuclear magnetic resonance (n.m.r.) spectroscopy was used to monitor intracellular pH (pHi), adenosine triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi).
• Experiments were conducted under normoxic, moderately ischemic, and severely ischemic conditions, with and without Na-H exchange inhibitors (amiloride, guanidinium chloride).

Main Results:

• In normoxia, heptaminol increased LVP and Pi but did not significantly alter pHi.
• During moderate ischemia, heptaminol restored both pHi and LVP, which were reduced by ischemia.
• In severe ischemia, heptaminol lost its ability to restore pHi and LVP.
• Na-H exchange inhibitors worsened pHi and LVP during moderate ischemia, and heptaminol could not reverse these effects when co-administered.

Conclusions:

• Heptaminol hydrochloride exhibits a positive inotropic effect during moderate ischemia.
• This effect appears to be mediated by the restoration of intracellular pH.
• The findings suggest that heptaminol's action during moderate ischemia involves stimulation of the Na-H exchange mechanism.