Abstract
The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na+-K+ pump inhibition (10 μM ouabain or K+-free perfusate) to induce VF. AC stimulation or Na+-K+ pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na+-K+ pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca2+ overload, and 2) abolition of spontaneous sacroplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 μM uniformly prevented the initiation of VF due to Na+-K+ pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 μM resulted in defibrillation during VF whether induced by AC or Na+-K+ pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1115-1123 |
| Number of pages | 9 |
| Journal | Circulation Research |
| Volume | 67 |
| Issue number | 5 |
| State | Published - 1990 |
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Keywords
- arrhythmia mechanism
- calcium channels
- calcium overload
- defibrillation
- glycoside toxicity
- ventricular fibrillation
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation. / Merillat, J. C.; Lakatta, Edward; Hano, O.; Guarnieri, T.
In: Circulation Research, Vol. 67, No. 5, 1990, p. 1115-1123.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation
AU - Merillat, J. C.
AU - Lakatta, Edward
AU - Hano, O.
AU - Guarnieri, T.
PY - 1990
Y1 - 1990
N2 - The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na+-K+ pump inhibition (10 μM ouabain or K+-free perfusate) to induce VF. AC stimulation or Na+-K+ pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na+-K+ pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca2+ overload, and 2) abolition of spontaneous sacroplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 μM uniformly prevented the initiation of VF due to Na+-K+ pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 μM resulted in defibrillation during VF whether induced by AC or Na+-K+ pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF.
AB - The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na+-K+ pump inhibition (10 μM ouabain or K+-free perfusate) to induce VF. AC stimulation or Na+-K+ pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na+-K+ pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca2+ overload, and 2) abolition of spontaneous sacroplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 μM uniformly prevented the initiation of VF due to Na+-K+ pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 μM resulted in defibrillation during VF whether induced by AC or Na+-K+ pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF.
KW - arrhythmia mechanism
KW - calcium channels
KW - calcium overload
KW - defibrillation
KW - glycoside toxicity
KW - ventricular fibrillation
UR - http://www.scopus.com/inward/record.url?scp=0025001686&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025001686&partnerID=8YFLogxK
M3 - Article
C2 - 2171799
AN - SCOPUS:0025001686
VL - 67
SP - 1115
EP - 1123
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 5
ER -