Atsushi Mikuniya

Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency

Nitric oxide (NO) affects myocardial contractility and myocardial oxygen consumption (MVO2) in vitro. In alpha-chloralose-anesthetized dogs instrumented for the measurements of left ventricular (LV) pressure, LV volume using a conductance catheter, coronary blood flow, and coronary venous oxygen saturation (ScvO2) using a fiber-optic catheter, LV end-systolic pressure-volume relationships (ESPVR) and the relationship between MVO2 and LV pressure-volume area (PVA) were analyzed before and after intravenous infusions of the NO synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA; 5 mg/kg, 8 dogs) and the NO substrate L-arginine (600 mg/kg, 7 dogs). L-NMMA increased the slope of the ESPVR (Emax) (P < 0.05) without changing contractile efficiency indicated by the inverse of the slope of the MVO2-PVA line. L-NMMA also increased unloaded MVO2, indicated by the y-axis intercept of the MVO2-PVA line (P < 0.05). In contrast, L-arginine decreased Emax (P < 0.05) while decreasing MVO2 (P < 0.05), and without changing contractile efficiency. The basal oxygen metabolism was not affected by L-NMMA and L-arginine. These data imply that endogenous NO spares MVO2 by reducing oxygen use in excitation-contraction coupling and attenuates cardiac contractility without changing contractile efficiency.

A study on the effects of endogenous nitric oxide on coronary blood flow, myocardial oxygen extraction and cardiac contractility.

Abstract— The purpose of the present study was to clarify how endogenous nitric oxide (NO) affects cardiac contractility and myocardial oxygen consumption (MVO2) in vivo. α‐Chloralose‐anesthetized dogs (n = 18) were instrumented to perform continuous and simultaneous measurements of coronary blood flow (CBF), anterior interventricular vein oxygen saturation (with the use of a fiberoptic catheter), aortic pressure, left ventricular pressure, and left ventricular volume. CBF, myocardial oxygen extraction (O2‐extract), MVO2, the relationship between CBF and O2‐extract during direct vasodilation induced by intracoronary papaverine (0.1, 0.2, 0.4 mg/kg), and cardiac contractility (Emax) were examined at control, after intracoronary infusion of NG‐monomethyl‐L‐arginine (L‐NMMA, 2 mg/kg) and after antagonization of NO by L‐arginine (20 mg/kg). L‐NMMA decreased CBF from 62.0 ± 1.7 to 59.7 ± 2.4 (mL/min/100 g, P < 0.05) and increased O2‐extract from 68.2 ± 1.7 to 79.0 ± 1.7% (P < 0.05). Emax was increased after L‐NMMA from 3.2 ± 0.2 to 3.7 ± 0.1 (mmHg/mL/100 g, P < 0.05). These effects of L‐NMMA were antagonized by L‐arginine (P < 0.05 vs. after L‐NMMA, P = NS vs. before L‐NMMA). L‐NMMA shifted CBF and O2‐extract relationship determined by papaverine injection upward and L‐arginine antagonized it to its baseline level. Endogenous NO reduces cardiac contractility and decreases MVO2, while increasing CBF.

Effect of Inferior Vena Cava Occlusion on Left Ventricular End-Systolic Pressure-Volume Relations in Intact Canine Hearts

The effect of inferior vena cava occlusion (IVCO) on end-systolic pressure-volume relations (ESPVR) of the left ventricle was studied in intact canine hearts. In 12 anesthetized open-chest dogs, left ventricular (LV) pressure and volume were measured simultaneously using a microtip catheter and a conductance catheter, respectively. ESPVR was constructed from LV pressure-volume loops during IVCO (10 sec) and subsequent IVCO release under 5 conditions: control, after righ or left cardiac sympathetic nerve (CSN) stimulation, bilateral vagotomy (VAT), and both VAT and bilateral CSN resection. Emax in IVCO release was significantly greater than that in IVCO in the control state. Following right or left CSN stimulation, Emax was increased increased in both IVCO and IVCO release, with the same hysteretic change in Emax. With VAT, however, no hysteretic change was observed because Emax was the same in IVCO and IVCO release. After VAT and CSN resection, Emax was decreased in both IVCO and IVCO release, and again no hysteretic change was observed. These data imply that a sudden decrease in venous return into the heart induces a decrease in afferent vagal nerve activity, and thus increases efferent CSN activity, resulting in enhanced myocardial contractility.

A Conscious Animal Model for Studies of Coronary Collateral Blood Flow Dynamics

We describe a new animal model and protocols for measurements of the rate of development of coronary collateral perfusion stimulated by repetitive episodes of regional, reversible myocardial ischemia in conscious dogs and for measurements of the integrated effects of interventions on collateral perfusion after development of collaterals. Examples of the results are illustrated and potential sources of errors are identified. We propose this model to complement the other in vitro and in vivo models for studies of coronary collateral dynamics in conscious animals.

Coronary Hemodynamic Characteristics in Small Vessel Disorder: Impaired Endothelium-Dependent Vasodilation

The endothelium plays a crucial role in the control of vascular tone through the production of endothelium-derived relaxing and contracting factors. To define coronary hemodynamic characteristics in small vessel disorder that is not detected by coronary angiography, we examined endothelium-independent vasodilation with papaverine (PAP), and endothelium-dependent vasodilation with acetylcholine (ACh) in patients with syndrome X. Responses of the large coronary artery in syndrome X to papaverine and acetylcholine were similar to those in control patients. However, changes in coronary venous oxygen saturation (CSO2-Sat) in response to acetylcholine were significantly lower in syndrome X compared with control patients, while response of CSO2-Sat to papaverine was preserved. These results imply that small vessel disorder involves impaired endothelium-dependent relaxation at the prearteriolar levels, resulting in the development of myocardial ischemia during exercise through the coronary steal phenomenon.