Abstract 2279: Decreased Myofibril Calcium Sensitivity in Isolated Pig Myocytes Following Long Duration Ventricular Fibrillation and Resuscitation
Introduction: Postresuscitation myocardial dysfunction is a major issue following return of spontaneous circulation (ROSC) after sudden cardiac death and resuscitation. Poor cardiac contractility can have a number of causes including impaired intracellular calcium (Ca) handling or decreased myofibril Ca sensitivity. We measured contractility and Ca transients in isolated myocytes. We tested the hypothesis that poor cardiac contractility following prolonged ventricular fibrillation (VF) and resuscitation is due to decreased myofibril Ca sensitivity.
Methods: Eight anesthetized swine (50+/−12 kg) were divided into two groups:
7 minutes of VF followed by open chest heart compressions and
open-chest time controls.
Thirty minutes after ROSC, hearts were removed and left ventricular myocytes isolated by enzymatic digestion. Cells were incubated in 5 ÂμM fluo 3-AM ester and field stimulated at 3 cycle lengths: 500, 1000, and 1000 ms. Cells were bathed with two Ca concentrations: 1.5 and 4 mM. Cell shortening was recorded using a video edge detection system and Ca transients were recorded using a photomultiplier tube.
Results: Seventy-two control and 73 VF cells were studied. Peak Ca transients (peak F/F0) were 11.2% greater in VF cells compared to controls (3.9+/−1.4 vs. 3.5+/−1.7 ANOVA, P<0.05). Decreasing stimulation cycle length significantly decreased peak F/F0. Increased bath Ca concentration tended to increase peak F/F0. Cell shortening was not different between VF and Con (6.2+/−3.3 and 6.6+/−4.7 microns, respectively). Decreasing cycle length decreased cell shortening. Increased bath Ca concentration increased cell shortening.
Conclusions: Despite larger Ca transients in the VF cells compared to controls, there was no difference in cell shortening. More intracellular Ca was needed to maintain cell shortening. These data suggest that myofibril Ca sensitivity is decreased early following ROSC, but increased Ca transients, possibly due to the catecholamine surge following ROSC, can maintain contractility. Future studies are needed to determine if the Ca transients return to control levels and persistent decreased myofibril Ca sensitivity is a cause of poor contractility detected in the later post-ROSC period in vivo.