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Objectives: Much of the understanding about the cardiac interval-force relationship of the whole heart, including mechanical restitution and postextrasystolic potentiation (PESP), has been inferred from isolated muscle studies. We tested whether results from isolated muscles about intracellular Ca2+([Ca2+]i) transients underlying the interval-force relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+]i transients underlying mechanical restitution and postextrasystolic potentiation. Methods: [Ca2+]i transients were studied in isolated perfused rat hearts by surface fluorometry and Indo-1. Using computer-controlled pacing protocols, we performed restitution curves for left ventricular developed pressure and [Ca2+]i (developed pressure and [Ca2+]i plotted as a function of extrasystolic intervals). To quantify restitution curves, we fitted monoexponential functions to plots and analyzed their shift and slope. Then, we used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. Results: Interval-dependent changes in developed pressure were strongly correlated to interval-dependent changes in the amplitude of [Ca2+]i transients in isolated whole rat hearts. Additionally, nifedipine and low [Ca2+]o led to similar downward shifts but not to a changed slope of restitution curves for [Ca2+]i. On the other hand, PESP increased the slope of restitution curves for [Ca2+]i. Furthermore, the effect of PESP on developed pressure was blunted by high concentrations of Ca2+ antagonists. Conclusions: The results from isolated muscles about [Ca2+]i transients underlying the interval-force relationship could be substantiated in whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o) decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably accelerated Ca2+ release kinetics of the sarcoplasmic reticulum. [ABSTRACT FROM PUBLISHER]

Objective: The aim was to evaluate effects of ethanol on cardiac function and intracellular Ca2+ ([Ca2+]i) in perfused rat hearts. Methods: A Langendorff perfused rat heart preparation was used. Changes in [Ca2+]i were evaluated by surface fluorometry in hearts loaded with Indo 1-AM. Results: Clinically relevant concentrations of ethanol (0.2 or 0.4% vol/vol) had no significant haemodynamic effects. High concentrations of ethanol (1, 2, 3, and 4% vol/vol) showed dose dependent decreases in developed pressure and the systolic peak and overall amplitude of the Indo 1 fluorescence transients (−[Ca2+]i), that were partially antagonised by high extracellular Ca2+ ([Ca2+]O=4 mM). The ethanol concentrations that decreased developed pressure by 50% were 1.4 and 2.6% in the low (1.5 mM) and high [Ca2+]O, respectively. Four per cent ethanol decreased the amplitude of Indo 1 fluorescence transients to 54.5(SD 3.1) and 64.6(7.9)% of control values in the low and high [Ca2+]O, respectively. A relationship between the amplitude of Indo 1 fluorescence and developed pressure was fitted to a single sigmoid curve irrespective of [Ca2+]O. During ethanol washout, there was a dose dependent overshoot of the fluorescence ratio. Conclusions: Only high concentrations of ethanol depressed left ventricular function in a dose dependent manner by decreasing the amplitude of [Ca2+]i transients. High [Ca2+]O partially antagonised acute alcoholic cardiac depression by increasing the amplitude of [Ca2+]i transients. [Ca2+]i is a mediator of the acute cardiac effects of ethanol in perfused intact rat hearts.Cardiovascular Research 1993;27:811-816 [ABSTRACT FROM PUBLISHER]

Objective: The aim was to determine whether left ventricular apical myocardium has mechanisms to compensate for sparse sympathetic innervation. Methods: Contractile and metabolic responses to various adrenergic stimuli and β adrenergic receptor density were compared between left ventricular basal and apical regions in 26 anaesthetised mongrel dogs, weight 12-28 kg. Results: Regional contractile changes in response to graded cardiac sympathetic nerve stimulation were compared among three basal (anterior, middle, and posterior) regions, and between basal middle and apical regions. There were significant differences in contractile changes among the three basal regions with distinct regions of innervation from right and/or left sided sympathetic ganglia, but not between apical and basal regions. Constant infusion of noradrenaline (0.2-0.4 μg·kg−1·min−1) produced a greater response in normalised end systolic length in the apical myocardium than in the basal region, at 9.86(SEM 0.06) mm v 10.14(0.04) mm (n=5, p<0.025), and a greater increase in tissue cyclic AMP: 1.04(0.20) v 0.60(0.08) pmol·mg−1 (n=5, p<0.05). Giving a forskolin derivative (30 μg·kg−1, n=5) produced a greater increase in cyclic AMP in the apical region than in the basal region: 1.26(0.18) v 0.88(0.19) pmol·mg−1 (p<0.02). β Adrenergic receptor density in the apical region was greater than in the basal region: 455(45) v 341(35) fmol·mg−1 protein (n=5, p<0.05). Conclusions: Greater β adrenergic receptor density and/or increased myocardial responsiveness to adenylate stimulation in apical myocardium compensates, at least in part, for its sparse sympathetic innervation.Cardiovascular Research 1993;27:192-198 [ABSTRACT FROM PUBLISHER]

Study objective – The aim was to evaluate the effective and safe dosage for intracoronary administration of nicorandil (2-nicotinamidoethyl nitrate) in dogs.Design – Five ml of saline with or without nicorandil (0.025, 0.25, 1.0 or 2.5 mg) was constantly infused into the left anterior descending coronary artery (LAD) in 1 min without blood flow reduction in group A (normoxic group, n = 5) and with 50% blood flow reduction of the control value in group B (ischaemic group, n = 5).Subjects – 10 mongrel dogs of either sex were used, weight 14.6–20.5 kg.Measurements and main results – The myocardial weight of the perfused area was 33.2(SD 7.9) g. In group A, LAD blood flow increased from 28.4(8.6) to 86.3(25.0) ml·min−1, p<0.05, following intracoronary infusion of 0.25 mg nicorandil. Higher doses caused no further increase. In both groups, high doses (1.0 mg or more) suppressed regional myocardial contraction, expressed as % segment shortening, from 20.0(4.7) to 10.0(9.0)%, p<0.05, in group A, and from 12.7(8.5) to 6.5(5.6)%, p<0.05, in group B. Multiple ventricular premature beats developed in both groups only at the dose of 2.5 mg: 6.8(5.5) beats·min−1 in group A and 4.5(4.2) beats·min−1 in group B. Ventricular fibrillation developed in two dogs in group B. Nicorandil did not affect the local bipolar electrocardiogram of the subendo- and subepicardium in the perfused area in either group.Conclusions – Intracoronary administration of 0.25 mg of nicorandil was effective for coronary vasodilatation without deleterious mechanical or electrical effects. Larger doses of the agent showed adverse effects depending on the dosages. [ABSTRACT FROM PUBLISHER]