Taketoshi Namba

Effects of Intracoronary Fentanyl on Left Ventricular Mechanoenergetics in the Excised Cross-circulated Canine Heart

Background: It is still unclear whether fentanyl directly alters left ventricular (LV) contractility and oxygen consumption. This is because of the difficulty in defining and evaluating contractility and energy use independently of ventricular loading conditions and heart rate in beating whole hearts. Methods: This study was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl in six excised cross‐circulated canine hearts. The authors used the framework of the Emax (a contractility index)‐PVA (systolic pressure‐volume area, a measure of total mechanical energy)‐VO2 (myocardial oxygen consumption per beat) relationship practically independent of ventricular loading conditions. The authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen content difference to calculate Emax, PVA, and VO2. They first obtained the VO2 ‐PVA relationship for varied LV volumes at control Emax. The authors then obtained the VO2 ‐PVA relationship at a constant LV volume, whereas coronary blood fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they obtained the VO2 ‐PVA relationship for varied LV volumes at the final dose of fentanyl. Results: Fentanyl at any concentrations did not significantly change Emax, PVA, and VO2 from the control. The linear end‐systolic pressure‐volume relations and their slopes were virtually the same between the control and fentanyl volume loading in each heart. Further, either the slope (oxygen cost of PVA) or the VO2 intercept (unloaded VO2) of the linear VO2 ‐PVA relationship remained unchanged by fentanyl. Conclusions: These results indicate that intracoronary fentanyl produces virtually no effects on LV mechanoenergetics for a wide range of its blood concentration.

Effects of intracoronary fentanyl on left ventricular mechanoenergetics in the excised cross-circulated canine heart (revised publication).

Background It is still unclear whether fentanyl directly alters left ventricular (LV) contractility and oxygen consumption. This is because of the difficulty in defining and evaluating contractility and energy use independently of ventricular loading conditions and heart rate in beating whole hearts. Methods This study was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl in six excised cross-circulated canine hearts. The authors used the framework of the Emax (a contractility index)-PVA (systolic pressure-volume area, a measure of total mechanical energy)-VO2 (myocardial oxygen consumption per beat) relationship practically independent of ventricular loading conditions. The authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen content difference to calculate Emax, PVA, and VO2. They first obtained the VO2 -PVA relationship for varied LV volumes at control Emax. The authors then obtained the VO2 -PVA relationship at a constant LV volume, whereas coronary blood fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they obtained the VO2 -PVA relationship for varied LV volumes at the final dose of fentanyl. Results Fentanyl at any concentrations did not significantly change Emax, PVA, and VO2 from the control. The linear end-systolic pressure-volume relations and their slopes were virtually the same between the control and fentanyl volume loading in each heart. Further, either the slope (oxygen cost of PVA) or the VO2 intercept (unloaded VO2) of the linear VO2 -PVA relationship remained unchanged by fentanyl. Conclusions These results indicate that intracoronary fentanyl produces virtually no effects on LV mechanoenergetics for a wide range of its blood concentration.

How to measure cardiac energy expenditure

Total energy expenditure of the heart can be directly determined by cardiac oxygen consumption (Vo2) according to the energy equivalence of oxygen in aerobic metabolism (1 ml O2 = 19-21 J). However, Vo2 determination of an in situ heart is invasive and not always possible, particularly in clinical settings. To circumvent this problem, various methods to predict Vo2 have been developed over many years. They include external work, total contractile work, systolic pressure, active tension, tension time integral, Vmax, etc. They have high correlations with directly measured Vo2 under limited conditions. Both myocardial tension and contractility have been generally accepted as the primary determinants of Vo2. However, based on detailed mechanoenergetic studies of canine cardiac contractions, we have recently proposed that the total mechanical energy generated by ventricular contraction can be quantitatively assessed by the ventricular pressure-volume area (PVA) which is a specific area bounded by the end-systolic and end-diastolic pressure-volume relations and the systolic pressure-volume trajectory of the ventricle. Myocardial force-length area (FLA) is a muscle version of PVA. Cardiac Vo2 has been shown to linearly correlate with PVA and FLA. This linear relation ascends or descends in proportion to contractility (Emax). These results have shown that PVA is a physiologically sound and reliable predictor of the energy expenditure of the heart.

Adenosine inhibits efferent function of extrinsic capsaicin-sensitive sensory nerves in the enteric nervous system

Capsaicin (1-3 microM) and electrical stimulation of mesenteric nerves in the presence of hexamethonium and guanethidine antidromically stimulate extrinsic sensory nerve fibers to produce a specific slow depolarizing response of myenteric neurons and a contractile response of muscles in the isolated guinea-pig ileum, mediated by release of substance P and acetylcholine. Adenosine (1-100 microM) inhibited the response to mesenteric nerve stimulation. Adenosine (10-100 microM) suppressed the contractile response to a threshold concentration of capsaicin (1 microM) while leaving the contractile response to a submaximal concentration of substance P (1 nM) and acetylcholine (0.1 microM) intact. Adenosine (1-10 microM) inhibited dose dependently the capsaicin 10 microM)-induced depolarization of myenteric neurons, but did not inhibit the depolarizing response to exogenous substance P. The adenosine P1 receptor antagonist, 8-phenyltheophylline (1-10 microM), antagonized the inhibitory effect of adenosine (1-10 microM) on the mechanical responses. We conclude that adenosine-induced prejunctional inhibition of the mechanical responses is mediated by adenosine P1 receptors.