Schmidt U, Schwinger R H, Böhm M
Klinik III für Innere Medizin, Universität zu Köln, Germany.
Anesthesiology. 1995 Jun;82(6):1456-62. doi: 10.1097/00000542-199506000-00017.
The terminally failing human myocardium exerts a negative force-frequency relationship (FFR), whereas a positive FFR occurs in nonfailing myocardium. To study the possibility of pharmacologically influencing this defect of the failing human heart, the effect of halothane on the basal FFR and the FFR in the presence of isoproterenol and ouabain was investigated.
Experiments were performed on isolated, electrically driven (0.5-2 Hz, 37 degrees C, Ca2+ 1.8 mmol/l) ventricular preparations. Myocardium from human failing and nonfailing hearts was obtained at cardiac surgery. To further characterize the studied myocardium, the positive inotropic effect of isoproterenol and the density of beta-adrenoceptors were measured using the radioligand 125I-CYP.
Halothane produced a negative inotropic effect. The anesthetic (0.38 mmol/l) reversed the negative FFR in failing myocardium, antagonized the effect of isoproterenol (0.1 mumol/l) on FFR, and restored the FFR in the presence of ouabain.
Halothane restores the FFR in human failing myocardium possibly by influencing the intracellular Ca2+ homeostasis. These findings provide evidence that pharmacologic interventions, e.g., during anesthesia, may influence contractility also as a result of a depressed or enhanced FFR.
终末期衰竭的人类心肌呈现负性力-频率关系（FFR），而在非衰竭心肌中则出现正性FFR。为研究药物影响衰竭人类心脏这一缺陷的可能性，研究了氟烷对基础FFR以及在异丙肾上腺素和哇巴因存在时FFR的影响。
在离体的、电驱动（0.5 - 2 Hz，37℃，Ca2+ 1.8 mmol/L）的心室标本上进行实验。在心脏手术中获取人类衰竭和非衰竭心脏的心肌。为进一步表征所研究的心肌，使用放射性配体125I - CYP测量异丙肾上腺素的正性肌力作用和β - 肾上腺素能受体的密度。
氟烷产生负性肌力作用。该麻醉药（0.38 mmol/L）逆转了衰竭心肌中的负性FFR，拮抗了异丙肾上腺素（0.1 μmol/L）对FFR的作用，并在哇巴因存在时恢复了FFR。
氟烷可能通过影响细胞内Ca2+稳态来恢复人类衰竭心肌中的FFR。这些发现提供了证据，表明药物干预，例如在麻醉期间，也可能由于FFR降低或增强而影响收缩性。
