Related Experiment Videos
Effects of leukotrienes B4 and C4 on coronary circulation and myocardial contractility
Insights
Leukotriene C4 (LTC4) constricts coronary arteries and weakens heart muscle contractility, potentially contributing to anaphylactic shock. Leukotriene B4 (LTB4) did not affect heart function but caused a drop in white blood cells.
Area of Science:
- Cardiovascular Physiology
- Immunology
- Pharmacology
Background:
- Arachidonic acid metabolism yields prostaglandins, thromboxanes, and leukotrienes.
- Leukotrienes are implicated in anaphylactic shock's cardiovascular effects.
- Investigating leukotriene actions on coronary vessels and myocardial contractility is crucial.
Purpose of the Study:
- To determine the effects of leukotriene B4 (LTB4) and leukotriene C4 (LTC4) on coronary artery blood flow and myocardial contractility.
- To explore the potential role of LTC4 in anaphylactic shock.
Main Methods:
- LTB4 and LTC4 were administered directly into the left circumflex (LCx) coronary artery of anesthetized sheep.
- Coronary artery blood flow and myocardial contractility were measured.
- The effects of the leukotriene receptor antagonist FPL 55712 were assessed.
Main Results:
- LTB4 had no impact on coronary flow or contractility but induced transient neutropenia.
- LTC4 caused dose-dependent reductions in LCx coronary artery flow and myocardial systolic shortening.
- The reduction in contractility exceeded that predicted by flow reduction, suggesting a direct negative inotropic effect of LTC4.
- FPL 55712 blocked LTC4-induced vasoconstriction but only partially inhibited its negative inotropic effects.
Conclusions:
- LTC4 is a potent vasoconstrictor and negative inotropic agent affecting the coronary vasculature and myocardium.
- LTC4 may play a significant role in the pathophysiology of anaphylactic shock.
- LTB4 exhibits potent chemotactic properties but does not directly affect cardiac function in this model.
Abstract:
Arachidonic acid is metabolized to prostaglandins and thromboxane via the cyclooxygenase pathway and to leukotrienes B4, C4, D4, and E4 via the lipooxygenase pathway. A possible role played by leukotrienes in cardiogenic shock resulting from anaphylaxis prompted us to investigate the action of these compounds on coronary vessels and myocardial contractility. In this study leukotriene B4 (LTB4) and C4 (LTC4) were injected directly into the left circumflex (LCx) coronary artery of nine anesthetized Suffolk sheep. LTB4 had no effect on coronary artery blood flow or myocardial contractility, but 3 X 10(-9) mole induced profound transient circulating neutropenia, reflecting the potent chemotactic and chemokinetic properties of this compound. Injecting as little as 1.6 X 10(-11) mole of LTC4 caused a 14.5 +/- 4.3% (mean +/- SE) reduction of LCx coronary artery flow while 1.6 X 10(-10) mole caused a 26.5 +/- 3.7% decrease of LCx coronary artery flow and an 18.1 +/- 3.2% decrease in systolic shortening of the myocardial region supplied by the LCx coronary artery. Since the decrease in systolic shortening was far greater than that expected on the basis of the reduction in coronary artery flow, we postulate that LTC4 has a direct negative inotropic effect. FPL 55712, a receptor antagonist of leukotrienes C4, D4, and E4, blocked the vasoconstriction induced by LTC4 but only partially blocked the negative inotropic effects of LTC4. LTC4 is a potent vasoconstrictor and negative inotropic agent and may play an important role in anaphylactic shock.