Effects of perhexiline on hemodynamics in anesthetized open-chest dogs

Cardiohemodynamic effects of perhexiline were investigated in anesthetized open-chest dogs, measuring blood flow rates of the pulmonary artery (PAF), superior and inferior venae cavae (SVCF and IVCF), right atrial pressure (RAP), systemic blood pressure (SBP), and heart rate (HR). Sum of SVCF and IVCF was interpreted as venous return (VR). Perhexiline, 0.3-3 mg/Kg, injected intravenously over 2 min caused dose-dependent increases in PAF, VR, and RAP, followed by decreases in PAF and VR at higher doses. SBP and HR were depressed with perhexiline dose-dependently. Verapamil, 0.03-0.3 mg/Kg, also increased PAF, VR, and RAP to the lesser extent than perhexiline. Verapamil decreased these variables except RAP more markedly than perhexiline. Treatment with propranolol (1 mg/Kg) and phentolamine (1 mg/Kg) which completely blocked cardiohemodynamic effect of 1 microgram/Kg of norepinephrine, markedly attenuated the effects of perhexiline on VR and PAF but not completely. It is concluded that the effect of perhexiline to increase VR and PAF is in most part mediated through the cardiovascular reflex control for blood pressure reduction by the drug, though a direct effect on capacitance vessels may be included.