Vascular intracardiac catheterization technique for multiphasic evaluation of rat heart in vivo

Extensive in vivo classification of the latent or acute cardiotoxic manifestations associated with exposure to chemicals has been limited in the past to larger laboratory animals. To facilitate the conduct of similar studies in smaller experimental animals, a cardiologic model with the rat is introduced that permits determination of in vivo cardiac contractility (e.g., left intraventricular pressure, dP/dt) and excitability (e.g., atrioventricular node conductivity, His-Purkinje system conduction time) with subsequent biochemical analysis of the same heart. To evaluate the influence of possible surgically induced artifacts on the metabolic parameters measured, three surgical protocols were compared: invasive intracardiac catheterization, sham surgery, and nonsurgical control. Male Sprague-Dawley rats were weighed and anesthetized with sodium pentobarbital. Venous blood hematocrit and serum osmolalities were determined in rats subjected to sham and intracardiac catheterization procedures. Surface limb-lead ECG recordings were obtained from rats in these two groups throughout the surgical and catheter manipulation procedures. In rats subjected to the intracardiac catheterization procedure, an electrode was inserted into the right jugular vein and advanced into the right atrium for recording the His bundle electrogram. An ultraminiature solid-state cathetertip pressure transducer was inserted into the right carotid artery and advanced into the left ventricle for recording left ventricular contractility characteristics. Upon completion of the electrode and catheter manipulations, myocardial contractility and excitability indices were assessed for time-dependent changes during a 20-min stabilization period. Subsequently, heart perchloric acid extracts were prepared from hearts frozen in liquid N2, and metabolite (e.g., ATP, ADP, AMP, IMP, phosphocreatine, inorganic phosphate) concentrations were analyzed. Cardiac contractility and excitability characteristics, including peak left intraventricular and isovolumic pressures, peak dP/dt, time to peak dP/dt, heart conduction intervals, and heart rate, stabilized within 10 min after surgery. Thereafter, no surgically induced physiologic or metabolic changes were detected relative to either sham-treated or nonsurgical controls. These findings demonstrate the feasibility and integrity of this method and suggest its potential utility for investigating the in vivo cardiotoxicity of various chemical agents using the rat as the animal model.