Ca2+ handling in excitation-contraction coupling requires considerable O2 consumption (Vo 2) in cardiac contraction. We have developed an integrative method to quantify total Ca2+ handling in normal hearts. However, its direct application to failing hearts, where futile Ca2+ cycling via the Ca2+-leaky sarcoplasmic reticulum (SR) required an increased Ca2+handling Vo 2, was not legitimate. To quantify total Ca2+ handling even in such failing hearts, we combined futile Ca2+ cycling with Ca2+ handling Vo 2 and the internal Ca2+ recirculation fraction via the SR. We applied this method to the canine heart mechanoenergetics before and after intracoronary ryanodine at nanomolar concentrations. We found that total Ca2+ handling per beat was halved after the ryanodine treatment from ∼60 μmol/kg left ventricle before ryanodine. We also found that futile Ca2+ cycling via the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine. These results support the applicability of the present method to the failing hearts with futile Ca2+ cycling via the SR.

We studied whether intracoronary Ca administration after beta-blockade would increase the internal Ca recirculation fraction (RF) analogously to the Ca administration before beta-blockade. This was performed in excised cross-circulated canine hearts. We analyzed the exponential decay component of the postextrasystolic potentiation (PESP) following a spontaneous extrasystole. All the PESPs decayed in alternans with atrial pacing at a constant rate. We obtained the time constant (tau(e)) of the monoexponential decay component of the alternans PESP. An increment of intracoronary Ca by 1.5 mmol/l enhanced the left ventricular contractility index Emax (end-systolic maximum elastance) by 2.5 times before and after beta-blockade with propranolol. The intracoronary Ca after beta-blockade slightly but significantly increased tau(e), and hence increased RF calculated from tau(e) by RF = exp(-1/tau(e)). This was analogous to the slightly increased tau(e) and RF with Ca before beta-blockade. We speculate that the myocardial cyclic AMP-dependent phosphorylation level would not significantly alter the effect of intracoronarily administered Ca on myocardial Ca handling, in terms of tau(e) and RF.

Neiguan ) is a traditional acupoint in the bilateral forearms, overlying the median nerve trunk. Acupuncture at some acupoints including Neiguan, has been believed to affect cardiovascular function and is used in traditional Chinese medicine to improve or treat a wide range of heart diseases [1-6]. However, physiological mechanisms of these circulatory effects remain to be established scientifically.Clinical evidence indicates that acupuncture at Neiguan acupoints has therapeutic effects on some types of hypertension, arrhythmias, angina pectoris, and myocardial infarction [1][2][3][4]. Studies in anesthetized animals (rabbit, cat, and dog) have also demonstrated beneficial effects of acupuncture and electroacupuncture at Neiguan acupoints (Neiguan EA) on myocardial ischemia, arrhythmias, hypertension, and hypotension [5]. However, no experiments have been done to assess the effects of Neiguan EA on hemodynamics and cardiac contractility under physiological conditions.The purpose of this study was to obtain basic physiological evidence of the effects of Neiguan EA on hemodynamics and cardiac contractility in anesthetized open-chest dogs. We successfully observed that Neiguan EA significantly improved hemodynamics and cardiac contractility. Key words: Chinese medicine, Neiguan acupoint, cardiac performance, ventricular contractility. METHODS Surgical preparation. Ten adult mongrel dogsAbstract: Neiguan (PC-6) is a traditional acupoint in the bilateral forearms, overlying the median nerve trunk. Neiguan electroacupuncture (EA) has been believed to affect cardiovascular function and used in traditional Chinese medicine to improve or treat a wide range of health conditions and diseases, including angina pectoris, myocardial infarction, hypertension, and hypotension. However, few physiological studies have assessed the beneficial effects of Neiguan EA on the cardiovascular function. In the present study, we investigated its effects on the cardiovascular function in normal open-chest dogs under pentobarbital and fentanyl anesthesia. We also obtained left ventricular (LV) pressure-volume (P-V) data with a micromanometer catheter and a volumetric conductance catheter. Mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, and end-systolic pressure gradually decreased by 5 to 10% over 1.5 h without Neiguan EA. Neiguan EA at 40 Hz, however, increased these cardiovascular variables by 10 to 15%, especially end-systolic elastance (Ees) by 40% (pϽ0.05) over 15 to 60 min. After Neiguan EA was stopped at 1 h, these facilitated cardiovascular variables decreased below the pre-EA level. This beneficial effect of electroacupuncture may contribute to the effectiveness of the acupuncture in Chinese medicine.

Recently we have shown that the left ventricular end-systolic pressure-volume relation (ESPVR) of in situ rat hearts is an upward convex curve in contrast to the linear left ventricular ESPVR in dog and human hearts. Within the smaller left ventricular volume range, the left ventricular end-systolic pressure rose steeply with increases in left ventricular volume, but it gradually reached a plateau at the larger left ventricular volumes. In adult rat hearts, the myosin isozyme is V1, unlike V3 in dog and human hearts. To investigate whether myosin isozyme affects the curvilinearity of the left ventricular ESPVR, we evaluated the left ventricular ESPVR in hypothyroid rats in which the left ventricular myosin isozyme had been shifted to V3. In the hypothyroid rats, the left ventricular contractility was depressed and the ESPVR became closer to linear. However, after dobutamine administration the ESPVR returned to curvilinear. In nor-mal rats the curvilinearity of the left ventricular ESPVR was decreased by negative inotropic agents such as adrenergic blockers. These results indicate that the depressed left ventricular contractility in the hypothyroidism make ESPVR linear and that the enhanced left ventricular contractility from dobutamine make it curvilinear. We concluded that the curvilinearity of the rat left ventricular ESPVR is not determined by myosin isozyme per se, but by the left ventricular contractility.

We investigated the effects of intracoronary Ca2+ and epinephrine on the intracellular Ca2+ recirculation fraction (RF) and total Ca2+ handling in the left ventricle (LV) of the excised cross-circulated canine heart preparation. We analyzed LV postextrasystolic potentiation (PESP) following a spontaneous extrasystole that occurred sporadically under constant atrial pacing. All PESPs decayed in alternans and none decayed monotonically. We extracted an exponential decay component from the alternans PESP, determined its beat constant (taue), and calculated RF = exp(-1/taue). Increased intracoronary Ca2+ slightly increased taue and RF, but epinephrine did not change them, although both agents enhanced LV contractility 2-3 times. Neither Ca2+ nor epinephrine affected the sinusoidal decay of the alternans PESP. These results indicate that RF via the sarcoplasmic reticulum was slightly augmented by Ca2+, but not by epinephrine. We combined these RF data with LV Ca2+ handling O2 consumption data and obtained 40-110 micromol/kg as the total amount of Ca2+ handled in one cardiac cycle in the control and enhanced contractile states. These results indicate that this new LV-level approach seems to better the understanding of the Ca2+ mass dynamics responsible for the mechanoenergetics enhanced by inotropic interventions.