Key result
Chronic norepinephrine infusion in conscious dogs did not elicit functional desensitization to acute norepinephrine challenge unless neural reflex mechanisms were blocked or denervated.
Why the study?
Does chronic norepinephrine infusion induce catecholamine desensitization in conscious dogs?
Does chronic norepinephrine infusion induce catecholamine desensitization in conscious dogs?
Neural reflex mechanisms play a major role in masking the physiological expression of cardiac desensitization to chronic catecholamine exposure in conscious dogs.
Intact reflexes may mask desensitization in conscious models; leaves open translation to clinical catecholamine responses.
To study chronic catecholamine desensitization, mini-osmotic pumps were implanted subcutaneously to deliver NE, (0.5 micrograms/kg/min) or saline over 3-4 wk in dogs instrumented with left ventricular (LV) pressure gauges and arterial and left atrial pressure catheters. An acute challenge to NE (0.4 micrograms/kg/min) in intact, conscious dogs increased LV dP/dt by 1,531 +/- 208 mmHg/s before NE pumps, and by a similar amount, 1,340 +/- 166 mmHg/s, 3-4 wk after NE pumps. In contrast, an acute challenge to isoproterenol (ISO, 0.4 micrograms/kg/min) increased LV dP/dt by 5,344 +/- 532 mmHg/s before NE pumps, and significantly less (P less than 0.05; 2,425 +/- 175 mmHg/s) after NE pumps. In the presence of ganglionic and alpha 1-adrenergic blockades, NE (0.4 micrograms/kg/min) increased LV dP/dt by 3,656 +/- 468 mmHg/s before NE pumps and significantly less (P less than 0.01; 1,459 +/- 200 mmHg/s) after NE pumps. Confirming this, an acute challenge to NE (0.4 micrograms/kg/min) in dogs with arterial baroreceptor denervation increased LV dP/dt by 3,732 +/- 896 mmHg/s before NE pumps, and significantly less (P less than 0.05, 1,725 +/- 408 mmHg/s) after NE pumps. In addition, in cardiac denervated dogs, NE (0.4 micrograms/kg/min) increased LV dP/dt by 9,901 +/- 1,404 mmHg/s before NE pumps and significantly less (P less than 0.01, 2,690 +/- 306 mmHg/s) after NE pumps. Desensitization of heart rate responses to NE challenge was also more apparent in the absence of reflex mechanisms. Thus, neural reflex mechanisms play a major role in physiological expression of cardiac desensitization to catecholamines in conscious dogs.
No takes yet. Share an insight, caveat, or question.
Nejima et al. (1990) studied Catecholamine desensitization (n=41). Norepinephrine (NE) infusion vs. Baseline (before NE pumps) was evaluated on Increase in LV dP/dt in response to acute NE challenge (0.4 µg/kg/min) in intact dogs. Chronic norepinephrine infusion in conscious dogs did not elicit functional desensitization to acute norepinephrine challenge unless neural reflex mechanisms were blocked or denervated.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: