Effects of acidosis on muscle contractile function have been studied extensively. However, the relative effects of different types of extracellular acidosis on left ventricular (LV) contractile function, especially the temporal features of contraction, have not been investigated in a single model. We constituted perfusion buffers of identical ionic composition, including Ca2+concentration ([Ca2+]), to mimic physiological control condition (pH 7.40) and three types of acidosis with pH of 7.03: inorganic (IA), respiratory (RA), and lactic (LA). Isolated rabbit hearts ( n = 9) were perfused with acidotic buffers chosen at random, each preceded by the control buffer. Under steady-state conditions, instantaneous LV pressure (Pv) and volume (Vv) were recorded for a range of Vv. The results were as follows. 1) LV passive (end-diastolic) elastance increased with IA and RA. However, this increase may not be a direct effect of acidosis; it can be explained on the basis of myocardial turgor. 2) Although LV inotropic state (peak active Pv and elastance) was depressed by all three acidotic buffers, the magnitude of inotropic depression was significantly less for LA. 3) Temporal features of Pv were altered differently. Whereas IA and RA reduced time to peak Pv( t max) and hastened isovolumic relaxation at a common level of LV wall stress, LA significantly increased t max and retarded relaxation. These results and a model-based interpretation suggest that cooperative feedback (i.e., force-activation interaction) plays an important role in acidosis-induced changes in LV contractile function. Furthermore, it is proposed that LA-induced responses comprise two components, one due to intracellular acidosis and the other due to pH-independent effects of lactate ions.

In isovolumically beating hearts, the speed of left ventricular (LV) relaxation is uniquely determined by peak active stress (ςmax). In contrast, such a succinct description of relaxation is lacking for the ejection beats, although ejection is generally thought to hasten relaxation. We set out to determine how ejection modifies the relaxation-ςmax relationship obtained in the isovolumically beating hearts. Experiments were performed on five isolated rabbit hearts subjected to various loading conditions. Instantaneous LV pressure and volume were recorded and converted to active stress, from which isovolumic relaxation time ( T r) was defined as the time for stress to fall from 75 to 25% of ςmax (isovolumic beats) or its end-ejection value (ejection beats). Steady-state and transient isovolumic beat and steady-state ejection beat data were used to develop a multiple regression model. This model identified stress, current beat ejection, and previous beat ejection history as independent predictor variables of T r and fit the data well in all hearts ( r 2 > 0.98). Furthermore, this model could predict relaxation in transient ejection beats ( r 2 = 0.80 for all hearts). Whereas the coefficient for the current beat ejection was negative (i.e., negative effect or hastening relaxation), the ejection history coefficient was positive (i.e., positive effect or slowing relaxation). The sum of these two coefficients was negative, corresponding to the commonly observed net negative effect of ejection on relaxation. The expected positive inotropic effect of ejection was also observed. The dissipations of both positive inotropic and relaxation effects were slow, suggesting a nonmechanical underlying mechanism(s). We postulate that these two effects are linked and caused by ejection-mediated changes in myofilament Ca2+ sensitivity.

Pain is one of the most common reasons for patients to visit the emergency department. The ever-growing research on emergency department analgesia has challenged the current practices with respect to the optimal analgesic regimen for acute musculoskeletal pain, safe and judicious opioid prescribing, appropriate utilization of non-opioid therapeutics, and non-pharmacological treatment modalities. This clinical review is set to provide evidence-based answers to these challenging questions.