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Changes in calcium transient and left ventricular function during positive inotropic stimulation and myocardial
1First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Insights
This study measured intracellular calcium (Ca2+) and heart function in guinea-pig hearts. Results show how Ca2+ levels and heart contractility change during drug treatments and ischemia.
Area of Science:
- Cardiovascular Physiology
- Cardiac Excitation-Contraction Coupling
- Myocardial Ischemia Research
Background:
- Understanding excitation-contraction coupling and myocardial ischemia requires measuring intracellular free Ca2+ and heart mechanical function.
- Simultaneous measurement of Ca2+ and mechanical function in perfused hearts is crucial for physiological and pharmacological studies.
Purpose of the Study:
- To investigate changes in Ca2+ transient and left ventricular (LV) function during inotropic stimulation and myocardial ischemia.
- To evaluate the utility of a technique for simultaneously measuring Ca2+-dependent indo-1 fluorescence and LV pressure in Langendorff-perfused guinea-pig hearts.
Main Methods:
- Simultaneous beat-to-beat measurement of Ca2+-dependent indo-1 fluorescence and LV pressure in Langendorff guinea-pig hearts.
- Manipulation of perfusate Ca2+ concentration, administration of inotropic agents (digoxin, milrinone), and induction of myocardial ischemia by reducing coronary perfusion pressure.
Main Results:
- Increased perfusate [Ca2+] correlated with increased Ca2+ transient and LV developed pressure.
- Inotropic stimulation with digoxin and milrinone increased LV contractility and Ca2+ transient, with milrinone showing a greater relative increase in Ca2+ transient.
- Myocardial ischemia induced by reduced coronary perfusion pressure decreased LV contractility and increased the indo-1 fluorescence ratio.
Conclusions:
- Ca2+ responsiveness of the contractile apparatus declines during inotropic stimulation with milrinone and during myocardial ischemia.
- The experimental technique is effective for investigating the relationship between Ca2+ regulation and LV function under various physiological and pharmacological conditions.
Abstract:
To elucidate the issues such as excitation-contraction coupling and myocardial ischemia, it is necessary to measure intracellular free Ca2+ concentration and mechanical function of hearts perfused via the normal arterial circulation. For this purpose, we simultaneously measured Ca(2+)-dependent indo-1 fluorescence and left ventricular (LV) pressure on a beat-to-beat basis in Langendorff guinea-pig hearts, and investigated the changes in Ca2+ transient and LV function during inotropic stimulation and myocardial ischemia. The indo-1 fluoresence ratio and LV developed pressure increased the perfusate [Ca2+] increased from 1.6 to 3.2 mmol/L, and there was a good correlation between Ca2+ transient and LV contractility. Digoxin (10(-6) mol/L) and milrinone (10(-5) mol/L) increased LV contractility with a concomitant increase in Ca2+ transient, and the relative increase of Ca2+ transient produced by milrinone was much more than that by digoxin. The reduction of coronary perfusion pressure from 80 to 40 mm Hg decreased LV contractility with an increase in indo-1 fluorescence ratio. These results suggest that Ca2+ responsiveness of contractile apparatus declines during inotropic stimulation by milrinone and during myocardial ischemia. Thus, this experimental technique is useful to investigate the interrelation of Ca2- regulation and LV function during a variety of pharmacological and physiologic perturbations.