Author + information
- Received April 1, 1992
- Revision received June 22, 1992
- Accepted June 23, 1992
- Published online January 1, 1993.
- Hideo Kusuoka, MD, PhD,
- Maria C.Camilion de Hurtado, MD, PhD and
- Eduardo Marban, MD, PhD, FACC∗
- ↵∗Address for correspondence: Eduardo Marban, MD, PhD, Department of Medicine, The Johns Hopkins University School of Medicine, 844 Ross Building, 720 North Rutland Avenue, Baltimore, Maryland 21205.
Objectives. This study was conducted to elucidate the role of sodium/calcium (Na+/Ca2+) exchange in the mechanism of myocardial stunning.
Background. Cellular Ca2+overload mediated by Na+/Ca2+exchange during reperfusion has been proposed as a mechanism for myocardial stunning. Because no specific pharmacologic inhibitors of the exchanger are available, we increased extracellular sodium concentration ([Na]0) during the early phase of reperfusion to decrease the driving force for Ca2+influx through the pathway.
Methods. Isovolumetric left ventricular pressure and phosphorus-31 nuclear magnetic resonance spectra were measured in isolated perfused ferret hearts. Hearts were reperfused with different solutions after 15 min of total global ischemia at 37 °C.
Results. Hearts reperfused with standard solution ([Na]0= 140 mmol/liter; the stunned hearts, n = 8) showed only 69 ± 3% (mean ± SEM) recovery of developed pressure relative to preischemic control developed pressure, In contrast, hearts reperfused with a high [Na]0solution ([Na]0= 268 mmol/liter) during the initial 5 min, followed by a gradual decrease of [Na]0to the standard level over 25 min (the high [Na]0group, n = 8) showed significantly better recovery of developed pressure (85 ± 2%, p < 0.05 vs. the stunned hearts). in contrast, reperfusion with solutions in which the additional Na was substituted either by 256 mmol/liter sucrose or 128 mmol/liter chollne chloride did not improve functional recovery, indicating that the beneficial effects of high [Na]0reperfusion are not due to either high ionic strength or high osmolarity. Phosphorus-31 nuclear magnetic resonance spectra showed no correlation between functional recovery and intramyocardial contents of phosphorus compounds or pH.
Conclusions. High [Na]0reperfusion protects against stunning, supporting the concept that Na+/Ca2+exchange plays an important role in the mechanism of stunned myocardium.
☆ This study was supported by Specialized Center of Research Grant HL17655 from the National Institutes of Health, Bethesda, Maryland and an International Exchange Fellowship to Dr. de Hurtado from the Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) of Argentina, Buenos Aires, Argentina.
- Received April 1, 1992.
- Revision received June 22, 1992.
- Accepted June 23, 1992.