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Ventricular arrhythmias parallel cardiac histamine efflux after coronary artery occlusion in the dog
1Department of Pharmacology, Cornell University Medical College, New York, NY 10021.
Insights
Cardiac histamine release increases during acute myocardial ischemia, correlating with the severity of early ventricular arrhythmias and infarct size. This finding links histamine efflux to ischemic heart events.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Cardiac histamine release is a known trigger for ventricular arrhythmias.
- The role of histamine efflux from ischemic myocardium is debated.
Purpose of the Study:
- To investigate if coronary artery occlusion causes cardiac histamine efflux.
- To determine the association between histamine efflux and early ischemic ventricular arrhythmias.
Main Methods:
- Occlusion of the left anterior descending coronary artery in dogs.
- Continuous electrocardiogram monitoring and frequent coronary sinus blood sampling during ischemia.
- Measurement of histamine concentrations in coronary sinus blood.
Main Results:
- Coronary sinus histamine concentration significantly increased post-occlusion (0.06 to 0.61 ng/ml).
- Higher peak histamine levels were observed in dogs experiencing ventricular fibrillation (0.86 ng/ml vs. 0.37 ng/ml).
- Total cardiac histamine efflux correlated directly with ventricular premature contractions (r=0.81) and infarct size (r=0.91).
Conclusions:
- Acute myocardial ischemia leads to increased cardiac histamine efflux.
- Histamine efflux is associated with the development and severity of early ischemic ventricular arrhythmias.
- Histamine may play a significant role in the pathophysiology of acute myocardial ischemia and arrhythmias.
Abstract:
Release of cardiac histamine by immunologic and pharmacologic stimuli is known to provoke ventricular arrhythmias. Augmented histamine efflux from ischemic myocardium has been proposed but remains controversial. The purpose of this study was to determine whether cardiac histamine efflux is precipitated by coronary artery occlusion and if so, whether histamine efflux is associated with the development of early ischemic ventricular arrhythmias. The left anterior descending coronary artery was occluded while recording a continuous electrocardiogram and coronary sinus blood was sampled frequently during the first 30 min of coronary artery occlusion in pentobarbital-anesthetized, open-chest dogs. Coronary sinus histamine concentration rose from a mean baseline of 0.06 +/- 0.10 ng/ml (+/- SD) before coronary artery occlusion to a mean peak of 0.61 +/- 0.40 ng/ml after coronary artery occlusion (p less than 0.0001; n = 14). The median peak coronary sinus histamine concentration was significantly greater in dogs that suffered ventricular fibrillation after coronary artery occlusion (n = 4) than in those that did not (n = 10) (0.86 ng/ml vs. 0.37 ng/ml; p = 0.05). The area under the coronary sinus histamine concentration-vs.-time curve ("total cardiac histamine efflux") correlated directly with the total number of ventricular premature contractions during the first 30 min after coronary artery occlusion (r = 0.81; p less than 0.005; n = 10), and with infarct size (r = 0.91; p less than 0.01; n = 6). Thus, during acute myocardial ischemia, the coronary sinus histamine concentration increases simultaneously with the development of early ischemic ventricular arrhythmias and in proportion to their severity.