Blockade of frontocortical-brain stem pathway prevents ventricular fibrillation of ischemic heart

1981 ◽  
Vol 240 (2) ◽  
pp. H156-H163 ◽  
Author(s):  
J. E. Skinner ◽  
J. C. Reed

The hypothesis tested was that functional blockade of a pathway known to travel from the frontal cortex through the posterior hypothalamus to the brain stem might prevent the occurrence of ventricular fibrillation (VF) in the ischemic heart of conscious stressed pigs. The hypothesis was based on previous findings that 1) psychological stress is a necessary factor for the initiation of VF in the ischemic heart of conscious pigs, 2) the frontal cortex and its related thalamic gating mechanism, uniquely show neuroelectric responses to stressful stimuli, and 3) direct electric stimulation of either the frontal cortex, posterior hypothalamus, or fields of Forel will produce ventricular arrhythmias and myocardial necrosis. In the present study it was found that cryogenic blockade of the forebrain, posterior hypothalamus, or fields of Forel prevents or delays VF after left anterior descending coronary artery occlusion in conscious stressed pigs (P less than 0.01). Blockade of control structures adjacent to these loci in another group of pigs had no effect on VF latency. Neither heart rate nor electroencephalographic changes could explain the differences between the groups. The results show that blockade of the frontocortical-brain stem pathway prevents the lethal consequences of myocardial ischemia in stressed animals.

2010 ◽  
Vol 298 (1) ◽  
pp. H102-H111 ◽  
Author(s):  
William H. Barry ◽  
Xiu Q. Zhang ◽  
Michael E. Halkos ◽  
Jakob Vinten-Johansen ◽  
Noriko Saegusa ◽  
...  

Heparin desulfated at the 2- O and 3- O positions (ODSH) decreases canine myocardial reperfusion injury. We hypothesized that this occurs from effects on ion channels rather than solely from anti-inflammatory activities, as previously proposed. We studied closed-chest pigs with balloon left anterior descending coronary artery occlusion (75-min) and reperfusion (3-h). ODSH effects on [Na+]i (Na Green) and [Ca2+]i (Fluo-3) were measured by flow cytometry in rabbit ventricular myocytes after 45-min of simulated ischemia [metabolic inhibition with 2 mM cyanide, 0 glucose, 37°C, pacing at 0.5 Hz; i.e., pacing-metabolic inhibition (PMI)]. Na+/Ca2+ exchange (NCX) activity and Na+ channel function were assessed by voltage clamping. ODSH (15 mg/kg) 5 min before reperfusion significantly decreased myocardial necrosis, but neutrophil influx into reperfused myocardium was not consistently reduced. ODSH (100 μg/ml) reduced [Na+]i and [Ca2+]i during PMI. The NCX inhibitor KB-R7943 (10 μM) or the late Na+ current ( INa-L) inhibitor ranolazine (10 μM) reduced [Ca2+]i during PMI and prevented effects of ODSH on Ca2+ loading. ODSH also reduced the increase in Na+ loading in paced myocytes caused by 10 nM sea anemone toxin II, a selective activator of INa-L. ODSH directly stimulated NCX and reduced INa-L. These results suggest that in the intact heart ODSH reduces Na+ influx during early reperfusion, when INa-L is activated by a burst of reactive oxygen production. This reduces Na+ overload and thus Ca2+ influx via NCX. Stimulation of Ca2+ extrusion via NCX later after reperfusion may also reduce myocyte Ca2+ loading and decrease infarct size.


Life Sciences ◽  
1991 ◽  
Vol 49 (8) ◽  
pp. 587-594 ◽  
Author(s):  
Judith M.B. Pinto ◽  
Debra A. Kirby ◽  
David A. Johnson ◽  
Bernard Lown

1991 ◽  
Vol 261 (1) ◽  
pp. H63-H69 ◽  
Author(s):  
G. M. De Ferrari ◽  
E. Vanoli ◽  
M. Stramba-Badiale ◽  
S. S. Hull ◽  
R. D. Foreman ◽  
...  

The role of vagal tone and reflexes in the genesis of life-threatening arrhythmias was investigated in a clinically relevant animal model for sudden cardiac death. Forty-five dogs with a healed anterior myocardial infarction in which transient myocardial ischemia during exercise did not induce malignant arrhythmias were utilized for the study. They underwent a further exercise and ischemia test in which atropine (75 micrograms/kg) was injected before coronary artery occlusion. Novel occurrence of ventricular arrhythmia, or worsening of the type of arrhythmia present in the control test, occurred in 23 of 45 dogs (51%) and ventricular fibrillation occurred in 11 of 45 (24%, P = 0.001). Analysis of heart rate response to acute ischemia in the control test indicates that these 11 animals had powerful vagal reflexes during coronary artery occlusion, compared with the 34 survivors (-32 +/- 35 vs. +2 +/- 27 beats/min, P = 0.003). This study indicates that approximately 75% of animals resistant to ventricular fibrillation are characterized by weak sympathetic reflexes in response to acute myocardial ischemia. In the remaining 25% powerful vagal reflexes counteract concomitant reflex sympathetic hyperactivity, decrease heart rate, and are essential for survival.


1967 ◽  
Vol 53 (3) ◽  
pp. 335-340 ◽  
Author(s):  
Roque Pifarré ◽  
Taro Yokoyama ◽  
Apolinar C. Ilano ◽  
Charles A. Hufnagel

1973 ◽  
Vol 33 (3) ◽  
pp. 353-363 ◽  
Author(s):  
KEITH A. REIMER ◽  
MARGARET M. RASMUSSEN ◽  
ROBERT B. JENNINGS

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