Interaction between afterload and contractility in the newborn heart: Evidence of homeometric autoregulation in the intact circulation

Abstract

This study in newborn lambs demonstrates that stepwise increases in afterload increase contractility considerably and that this enables the heart to maintain stroke volume at different levels of afterload. This forms direct evidence for the existence of homeometric autoregulation in the intact newborn heart.

Enhancement of Contractility With Sustained Afterload in the Intact Murine Heart

“…These results were subsequently reproduced in this model during phenylephrine infusion by Little et al 32 and in our laboratory during nonpharmacological increases in afterload induced by inflation of a balloon in the proximal descending aorta. 33 Klautz and coworkers 27 showed in newborn lambs that increased afterload led to an increase in E es and a leftward shift of the pressure-volume relation. Our results in the intact murine LV are consistent with these studies, where again the dominant demonstration of lengthdependent activation was via a leftward shift of the line that defined end-systolic elastance.…”

Physiologic changes after brain death

“…The cellular mechanisms include reduced affinity of contractile proteins to Ca 2ϩ , decreased release of intracellular Ca 2ϩ , and reduced activation of mechanosensitive Ca 2ϩ -channels. [15][16][17][18] Although there is strong evidence for the direct effects of loading conditions on contractile function, the interrelation of coronary perfusion and contractility is more complex. Decreased coronary perfusion pressure may directly decrease contractility via the "gardenhose" effect.…”

“…14 The reduction of pre-and afterload leads to a reduction of the contractile state of the myocardium by the Frank-Starling mechanism and by the Anrep effect. 15,16 The latter postulates the existence of a control system that maintains optimal stroke work over a wide range of afterload conditions by mechanisms other than neural reflexes. The cellular mechanisms include reduced affinity of contractile proteins to Ca 2ϩ , decreased release of intracellular Ca 2ϩ , and reduced activation of mechanosensitive Ca 2ϩ -channels.…”

Role of Nitric Oxide in Cardiovascular Responses to Endotoxemia in Neonatal Lambs

“…However, evaluating the effects of NO on contractility is complicated by the fact that measures of contractility are dependent upon the state of systemic vascular function, preload and afterload [20]. To elucidate the action of NO on contractility, we used a measure which is independent of loading conditions, thus enabling us to isolate the effects of contractility intrinsic to the heart as opposed to apparent influences on the heart which may be induced from changes in afterload [14,18,19,21]. Although the measurement of Ees requires transducers which are invasive, all animals were studied in a controlled fashion relative to a stable hemodynamic baseline [10,14].…”

“…The hemodynamic variables analyzed included arterial blood pressure, systemic blood flow, LV systolic pressure, LV diastolic pressure, maximum positive LV dp/dt, maximum negative LV dp/dt, LV diastolic relaxation rate, Ù, and end-systolic elastance (Ees). A multiple-regression approach possesses several advantages over a conventional analysis of variance [14,18,19]: (1) it enabled comparison of the mean values of the hemodynamic variables between groups during the 30-min infusion phase (T1) and the subsequent 90-min response phase (T2); (2) it facilitated the evaluation of linear trends within groups between the infusion and response phases; and (3) took into account the evaluation of between-lamb effects. The equation and coding of variables is summarized in the legend of table 1.…”