Rhodes Samhita S, Ropella Kristina M, Camara Amadou K S, Chen Qun, Riess Matthias L, Pagel Paul S, Stowe David F
Department of Anesthesiology, M4280, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
J Appl Physiol (1985). 2006 Mar;100(3):940-50. doi: 10.1152/japplphysiol.00285.2005. Epub 2005 Nov 10.
Positive inotropic drugs may attenuate or exacerbate the deleterious effects of ischemia and reperfusion (IR) injury on excitation-contraction coupling in hearts. We 1) quantified the phase-space relationship between simultaneously measured myoplasmic Ca2+ concentration ([Ca2+]) and isovolumetric left ventricular pressure (LVP) using indexes of loop area, orientation, and position; and 2) quantified cooperativity by linearly modeling the phase-space relationship between [Ca2+] and rate of LVP development in intact hearts during administration of positive inotropic drugs before and after global IR injury. Unpaced, isolated guinea pig hearts were perfused at a constant pressure with Krebs-Ringer solution (37 degrees C, 1.25 mM CaCl2). [Ca2+] was measured ratiometrically by indo 1 fluorescence by using a fiber-optic probe placed at the left ventricular free wall. LVP was measured by using a saline-filled latex balloon and transducer. Drugs were infused for 2 min, 30 min before, and for 2 min, 30 min after 30-min global ischemia. IR injury worsened Ca2+-contraction coupling, as seen from decreased orientation and repositioning of the loop rightward and downward and reduced cooperativity of contraction and relaxation with or without drugs. Dobutamine (4 microM) worsened, whereas dopamine (8 microM) improved Ca2+-contraction coupling before and after IR injury. Dobutamine and dopamine improved cooperativity of contraction and relaxation after IR injury, whereas only dopamine increased cooperativity of relaxation before IR injury. Digoxin (1 microM) improved Ca2+-contraction coupling and cooperativity of contraction after but not before ischemia. Levosimendan (1 microM) did not alter Ca2+-contraction coupling or cooperativity, despite producing concomitant increases in contractility, relaxation, and Ca2+ flux before and after ischemia. Dynamic indexes based on LVP-[Ca2+] diagrams (area, shape, position) can be used to identify and measure alterations in Ca2+-contraction coupling during administration of positive inotropic drugs in isolated hearts before and after IR injury.
正性肌力药物可能会减轻或加剧缺血再灌注（IR）损伤对心脏兴奋-收缩偶联的有害影响。我们：1）使用环面积、方向和位置指数量化同时测量的肌浆Ca2+浓度（[Ca2+]）与等容左心室压力（LVP）之间的相空间关系；2）通过线性建模在全心IR损伤前后给予正性肌力药物期间完整心脏中[Ca2+]与LVP发展速率之间的相空间关系来量化协同性。未起搏的离体豚鼠心脏用Krebs-Ringer溶液（37℃，1.25 mM CaCl2）恒压灌注。通过置于左心室游离壁的光纤探针利用indo 1荧光以比率法测量[Ca2+]。使用充满盐水的乳胶气球和换能器测量LVP。在30分钟全心缺血前30分钟和缺血后30分钟分别输注药物2分钟。IR损伤使Ca2+-收缩偶联恶化，表现为环的方向降低、环向右下方重新定位以及无论有无药物时收缩和舒张的协同性降低。多巴酚丁胺（4 microM）使IR损伤前后的Ca2+-收缩偶联恶化，而多巴胺（8 microM）改善了IR损伤前后的Ca2+-收缩偶联。多巴酚丁胺和多巴胺改善了IR损伤后的收缩和舒张协同性，而只有多巴胺在IR损伤前增加了舒张协同性。地高辛（1 microM）在缺血后而非缺血前改善了Ca2+-收缩偶联和收缩协同性。左西孟旦（1 microM）尽管在缺血前后伴随收缩性、舒张和Ca2+通量增加，但并未改变Ca2+-收缩偶联或协同性。基于LVP-[Ca2+]图（面积、形状、位置）的动态指数可用于识别和测量在IR损伤前后离体心脏给予正性肌力药物期间Ca2+-收缩偶联的改变。
