Intracellular calcium and ventricular function. Effects of nisoldipine on global ischemia in the isovolumic, coronary-perfused heart
| Autor: | I Amende, L A Bentivegna, A J Zeind, P Wenzlaff, W Grossman, J P Morgan |
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| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty Heart Ventricles Nisoldipine Diastole Ischemia Hemodynamics chemistry.chemical_element Coronary Disease In Vitro Techniques Calcium Contractility Internal medicine medicine Animals Calcium metabolism business.industry Ferrets General Medicine medicine.disease Perfusion chemistry Cardiology business Research Article medicine.drug |
| Zdroj: | Journal of Clinical Investigation. 89:2060-2065 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci115818 |
| Popis: | Ischemia-induced ventricular dysfunction has been shown to be associated with increased diastolic and systolic intracellular concentrations of free, ionized calcium ([Ca2+]i). The present study was designed to determine the effects of the Ca2+ antagonist nisoldipine on the relationship between [Ca2+]i and left ventricular contraction and relaxation during ischemia and reperfusion on a beat-to-beat basis. Nine isovolumic coronary-perfused ferret hearts were made globally ischemic for 3 min and reperfused for 10 min. Ischemia and reperfusion were repeated during perfusion with a buffer containing 10(-8) M nisoldipine. From left ventricular developed pressure, time to peak pressure and time to 50% pressure decline were obtained. [Ca2+]i was determined with the bioluminescent protein aequorin. Global ischemia caused a rapid decline in contractile function and a significant increase in diastolic [Ca2+]i, from 0.35 to 0.81 microM, and in systolic [Ca2+]i, from 0.61 to 0.96 microM. During reperfusion, [Ca2+]i returned to baseline while ventricular function was still impaired. Relaxation was more affected than systolic contractile function. Nisoldipine significantly reduced the ischemia-induced rise in diastolic [Ca2+]i to 0.62 microM, and in systolic [Ca2+]i to 0.77 microM, and lessened the decrease in contractile function. Nisoldipine significantly accelerated the decline in [Ca2+]i during reperfusion and improved recovery of contractility and relaxation. These effects were associated with a significant diminution in ischemic lactate production. Taken together, our results provide direct quantitative evidence on a beat-to-beat basis that the calcium antagonist nisoldipine can ameliorate ischemia-induced abnormalities in [Ca2+]i handling, an effect that was associated with improved myocardial function during early reperfusion. |
| Databáze: | OpenAIRE |
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