Dysthyroidism and heart failure: from clinical case to pathophysiology

Dysthyroidism affects cardiovascular function in many ways and can cause heart failure. The physiopathological mechanisms underlying the development of heart failure involve both direct intranuclear transcriptional effects of thyroid hormones and specific haemodynamic consequences of vascular modifications induced by dysthyroidism. Phospholamban regulatory action on diastolic ventricular function appears to play a pivotal role in mediating both direct T3 action and adrenal effects on myocardial contractility, possibly explaining the way dysthyroidism mimics sympathoadrenergic alterations on cardiovascular function. Therapeutical approach to cardiovascular disorders in dysthyroidism should focus on both thyroid hormones dysregulation and sympathoadrenergic activity, to attempt a reversal of the associated derangements.

Effects of coca chewing on metabolic and hormonal changes during graded incremental exercise to maximum

We examined the effects of 1 h of coca chewing on metabolic and hormonal responses during incremental exercise to exhaustion in traditional coca chewers (C; n = 8), and the results were compared with a group of nonchewers (n = 13). For 1 h, C chewed approximately 12 g of coca leaves that resulted in the apparition of cocaine in blood that reached 72 +/- 9 ng/ml. In resting conditions, even though sympathoadrenergic activity (as assessed by norepinephrine and epinephrine plasma levels) was similar in both groups, C displayed a higher level of plasma free fatty acids. Oxygen uptake measured at exhaustion and delta work efficiency during exercise were similar in both groups. During the incremental exercise, C displayed a significantly lower arterial oxygen saturation that cannot be explained by a reduced ventilatory response after coca chewing. In fact, even at maximal exercise, both ventilatory output and ventilatory equivalent were higher in C compared with nonchewers. It is concluded that the beneficial effects of coca chewing on exercise tolerance reported frequently by traditional coca users is not related to either an improved maximal exercise capacity or an increased work efficiency. However, during incremental exercise, coca chewing appeared to result in an increased free fatty acid availability that could be beneficial for prolonged submaximal exercise.

Plasma and platelet catecholamine and catecholamine sulfate response to various exercise tests

We tested the hypothesis that platelet and plasma catecholamine sulfates (CA-S) and platelet catecholamines (CA) reflect the overall sympathoadrenergic activation by exercise of 1 h duration. Ten well-trained subjects performed a low-intensity [62% maximum O2 consumption (VO2max); LI] and a high-intensity exercise test (77% VO2max; HI) and two tests at a similar average power output that consisted of 20 min at 77% VO2max and 40 min at 62% VO2max (HI/LI) and vice versa (LI/HI). Plasma norepinephrine sulfate (NE-S) increased to higher levels after HI than after LI exercise (15.5 +/- 2.1 vs. 8.9 +/- 0.7 nmol/l). Immediately after HI/LI and LI/HI plasma NE-S was similarly increased (9.59 +/- 1.1 vs. 9.96 +/- 1.3 nmol/l), whereas norepinephrine was higher after LI/HI than after HI/LI (23.0 +/- 3.2 vs. 15.7 +/- 2.3 nmol/l). Platelet CA and CA-S were increased only after HI. In conclusion, the plasma NE-S response to exercise parallels the overall sympathetic activation. These results support the hypothesis that plasma NE-S measured immediately after exercise reflects the overall sympathoadrenergic activity over prolonged periods of exercise. Platelet CA and CA-S poorly reflect sympathoadrenergic activation.

Regulation of hepatic glucose production during exercise in humans: role of sympathoadrenergic activity

To investigate the role of sympathoadrenergic activity on glucose production (Ra) during exercise, eight healthy males bicycled 20 min at 41 +/- 2 and 74 +/- 4% maximal O2 uptake (VO2max; mean +/- SE) either without (control; Co) or with blockade of sympathetic nerve activity to liver and adrenal medulla by local anesthesia of the celiac ganglion (Bl). Epinephrine (Epi) was in some experiments infused during blockade to match (normal Epi) or exceed (high Epi) Epi levels during Co. A constant infusion of somatostatin and glucagon was given before and during exercise. At rest, insulin was infused at a rate maintaining euglycemia. During intense exercise, insulin infusion was halved to mimic physiological conditions. During exercise, Ra increased in Co from 14.4 +/- 1.0 to 27.8 +/- 3.0 mumol.min-1.kg-1 (41% VO2max) and to 42.3 +/- 5.2 (74% VO2max; P < 0.05). At 41% VO2max, plasma glucose decreased, whereas it increased during 74% VO2max. Ra was not influenced by Bl. In high Epi, Ra rose more markedly compared with control (P < 0.05), and plasma glucose did not fall during mild exercise and increased more during intense exercise (P < 0.05). Free fatty acid and glycerol concentrations were always lower during exercise with than without celiac blockade. We conclude that high physiological concentrations of Epi can enhance Ra in exercising humans, but normally Epi is not a major stimulus. The study suggests that neither sympathetic liver nerve activity is a major stimulus for Ra during exercise. The Ra response is enhanced by a decrease in insulin and probably by unknown stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential sympathetic-parasympathetic interactions in sinus node and AV junction

This study examined the effects and interactions evoked by various combinations of parasympathetic (P) and sympathetic (S) stimulations on sinus node automaticity and atrioventricular (AV) conduction (both anterograde and retrograde) in 11 two-mo old anesthetized puppies. The respective effects of these autonomic maneuvers were assessed by covariant analysis using a linear regression model of the form Y = alpha 0 + alpha 1 X base line + alpha 2 X sequence + alpha 3 X S + alpha 4 X S2 + alpha 5 X P + alpha 6 X P2 + alpha 7 X (P X S).... The effects of parasympathetic and sympathetic stimulation, of the quadratic term S2, and of the interaction term (P X S) were highly significant (P less than 0.0001) on both sinus node automaticity and AV conduction (anterograde and retrograde). In contrast, the effect of the quadratic term P2 was significant on sinus node automaticity only. Sequence of stimulation whether (SP) or (PS) had no significant effect on either chronotropic or dromotropic properties. Furthermore, whereas augmented antagonism with parasympathetic predominance over sympathetic activity was readily demonstrable in the control of sinus rate, the reverse, i.e., augmented antagonism with sympathetic preponderance over parasympathetic activity, was found to apply to the control of AV conduction (both anterograde and retrograde). Hence, the nature and extent of parasympathetic-sympathetic interactions vary considerably, depending on which cardiac structure and/or function is under scrutiny. It appears that AV conduction is especially sensitive to modulation of sympathoadrenergic activity, whereas sinus node automaticity is particularly responsive to cholinomimetic influences.