Cardiac function and chronotropic sensitivity to beta-adrenergic stimulation in sepsis

Abstract

An organism's cardiovascular response to sepsis is at least partly dependent on hormonal and neural modulation of myocardial function. We have investigated both intrinsic myocardial performance and one aspect of myocardial sensitivity to beta-adrenergic stimulation in a model of sepsis in which animals, at the time studied, exhibited bacteremia, normal arterial blood pressure and cardiac output, elevated heart rate, and elevated plasma catecholamines. Intrinsic myocardial contractile function, studied with the isolated, perfused working heart preparation, was depressed over a range of preloads in septic animals, whereas heart rate was elevated. To determine whether hearts from septic animals could respond normally to beta-adrenergic stimulation, we studied chronotropic responses to isoproterenol in both Langendorff perfused hearts and in isolated right atria. In langendorff perfused hearts from septic animals, basal rates were significantly increased and lower concentrations of isoproterenol elicited greater increases in heart rate. In isolated right atria from septic animals, basal rates were also elevated and the EC50 for the chronotropic response to isoproterenol was significantly less than in atria from control animals. The maximal heart rate response to isoproterenol was not significantly different from control. These results indicate that in sepsis, despite apparently adequate in vivo cardiac performance, intrinsic myocardial function is depressed, but chronotropic sensitivity to beta-adrenergic stimulation is increased.

Heart rate dynamics in iNOS knockout mice

“…The observation that responsiveness of isolated atria to isoproterenol is identical in mice before and 4 h post-LPS, corroborates previous reports which were unable to show impaired chronotropic responsiveness to adrenergic stimulation in experimental sepsis (Smith et al, 1986;Barker et al, 1990). McDonough and colleagues have shown that in early sepsis, despite intrinsic myocardial contractile dysfunction, the ability of the heart to modulate its inotropic and chronotropic state in response to β-adrenergic stimulation is intact or even increased (Smith et al, 1986;Smith and McDonough, 1998;Barker et al, 1990).…”

“…These data demonstrate that decreased endorgan responsiveness to the adrenergic system does not play a role in the alteration of HRV parameters following sepsis. The involvement of the myocardium in the injury resulting from sepsis has been somewhat controversial (Smith et al, 1986;Smith and McDonough, 1998;Barker et al, 1990;Matsuda et al, 2000). The observation that responsiveness of isolated atria to isoproterenol is identical in mice before and 4 h post-LPS, corroborates previous reports which were unable to show impaired chronotropic responsiveness to adrenergic stimulation in experimental sepsis (Smith et al, 1986;Barker et al, 1990).…”

Oroxylin A, but Not Vasopressin, Ameliorates Cardiac Dysfunction of Endotoxemic Rats

“…The rate of contraction of isolated atrial preparations from endotoxemic hearts also was significantly increased in the early-stage endotoxemia and remained increased until late-stage endotoxemia. These results are similar to those reported by others [29, 46, 47]. The rate of contractions in both stages was not affected by Oro-A or AVP, suggesting that both agents at the concentrations used do not directly affect these tissues or exhibit nonspecific effects.…”

RECRUITMENT OF FUNCTIONALLY ACTIVE HEART Β2-Adrenoceptors IN THE INITIAL PHASE OF ENDOTOXIC SHOCK IN PITHED RATS

“…So far, this phenomenon has only been described in the heart or atria isolated from rats in the early phase of sepsis induced by cecal ligation and puncture (8,9). Our results agree with the data obtained by Barker et al (8), who showed that the positive chronotropic effect of ISO and FEN was more markedly potentiated than that of PRE; this difference was attributed to the activation of " 2 -adrenoceptors by ISO and FEN and to the preferential activation of " 1 -adrenoceptors by PRE (8).…”

“…Thus, compared to tissues from control animals, the tachycardia elicited by the "-adrenoceptor agonists ISO, prenalterol (PRE), and fenoterol (FEN) was enhanced in isolated right atria obtained from rats subjected to cecal ligation and puncture, suggesting that the active population of "-adrenoceptors changes during septic shock (8,9). The evidence is, however, not unequivocal.…”