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Arrhythmogenic effects of catecholamines are decreased in heart failure induced by rapid pacing in dogs
Insights
The failing heart shows reduced sensitivity to the arrhythmogenic effects of catecholamines, suggesting they are markers, not direct causes, of ventricular arrhythmias in heart failure. This study used a canine model to investigate cardiac responses to norepinephrine.
Area of Science:
- Cardiology
- Electrophysiology
- Heart Failure Research
Background:
- Elevated circulating catecholamines are linked to arrhythmias in heart failure.
- The direct role of catecholamines in causing ventricular arrhythmias versus being severity markers remains unclear.
Purpose of the Study:
- To determine the failing heart's sensitivity to the arrhythmogenic effects of exogenous norepinephrine.
- To investigate if catecholamines directly contribute to ventricular arrhythmias in a heart failure model.
Main Methods:
- A rapid pacing model was used to induce heart failure in dogs (n=14).
- Control dogs (n=9) underwent similar procedures without pacing.
- The arrhythmogenic threshold dose (ATD) of norepinephrine was measured to assess cardiac sensitivity.
Main Results:
- The ATD for norepinephrine significantly increased in the heart failure group (1.62 to 16.65 µg/kg, P < 0.01).
- No significant change in ATD was observed in the control group (1.08 to 2.53 µg/kg, P > 0.10).
- Isoproterenol did not alter action potential duration in failing heart tissues, unlike in control tissues.
Conclusions:
- The failing heart exhibits decreased sensitivity to the arrhythmogenic effects of catecholamines.
- This suggests catecholamines may be markers of heart failure severity rather than direct arrhythmogenic agents.
Abstract:
Increased circulating catecholamines are considered to be arrhythmogenic in heart failure. It is unclear whether increased circulating catecholamines contribute directly to ventricular arrhythmias or are only markers of the severity of heart failure. The present study determined the sensitivity of the failing heart to the arrhythmogenic effect of exogenous norepinephrine in a rapid pacing-induced model of heart failure in dogs (240 beats for 4 wk, n = 14). A similarly operated, non-paced group served as controls (n = 9). Cardiac sensitivity to the arrhythmogenic effect of catecholamines was determined by measuring the minimal dose of exogenous norepinephrine that induced ventricular tachycardia (arrhythmogenic threshold dose, ATD). ATD significantly increased after development of heart failure in heart-failure group (1.62 +/- 0.32 microgram/kg at baseline vs. 16.65 +/- 3.48 micrograms/kg at restudy, P < 0.01), whereas no significant change was noted in the control group (1.08 +/- 0.36 microgram/kg at baseline vs. 2.53 +/- 0.36 micrograms/kg at restudy, P > 0.10). Action potential duration was unchanged by superfusion with 10(-7) M isoproterenol in both ventricular muscles (230.2 +/- 6.1 vs. 229.7 +/- 5.3 ms, P = NS) and Purkinje fibers (273.2 +/- 6.5 vs. 283.8 +/- 4.2 ms, P = NS) from the failing hearts, although isoproterenol induced a shortening in the control group (204.8 +/- 0.9 vs. 181.3 +/- 1.6 ms in ventricular muscles, P < 0.01; 313.8 +/- 6.5 vs. 279.5 +/- 5.7 ms in Purkinje fibers, P < 0.01). We conclude that the failing heart has a decreased sensitivity to the arrhythmogenic effect of catecholamines.