Effects of oral perhexiline on canine myocardial flow distribution

Area of Science:

• Cardiovascular pharmacology
• Myocardial blood flow dynamics

Background:

• Perhexiline maleate is used for angina.
• Its effect on regional coronary flow distribution is not fully understood.

Purpose of the Study:

• To investigate the effect of perhexiline maleate on regional transmural coronary resistance.
• To determine if perhexiline maleate alters coronary flow distribution during normal and reduced flow states, and in myocardial infarction.

Main Methods:

• Administration of perhexiline maleate to normal dogs.
• Measurement of relative regional transmural resistance.
• Induction of acute myocardial infarction.
• Correlation analysis between drug plasma concentration and endo:epi ratio.

Main Results:

• Perhexiline maleate increased the endocardium:epicardium (endo:epi) ratio during reduced coronary flow in normal dogs.
• In acute myocardial infarction, heart rate was lower, and the endo:epi ratio of perfused areas increased under normal coronary flow.
• A linear relationship was found between the endo:epi ratio and plasma concentrations of perhexiline and its metabolite.

Conclusions:

• Perhexiline maleate appears to redistribute coronary blood flow, favoring the endocardium.
• This mechanism may contribute to its anti-anginal effects.
• The drug's action is dose-dependent and related to plasma concentrations.