The Impact of Hemodynamic Reflex Compensation Following Myocardial Infarction on Subsequent Ventricular Remodeling

Patients who survive a myocardial infarction (MI) are at high risk for ventricular dilation and heart failure. While infarct size is an important determinant of post-MI remodeling, different patients with the same size infarct often display different levels of left ventricular (LV) dilation. The acute physiologic response to MI involves reflex compensation, whereby increases in heart rate (HR), arterial resistance, venoconstriction, and contractility of the surviving myocardium act to maintain mean arterial pressure (MAP). We hypothesized that variability in reflex compensation might underlie some of the reported variability in post-MI remodeling, a hypothesis that is difficult to test using experimental data alone because some reflex responses are difficult or impossible to measure directly. We, therefore, employed a computational model to estimate the balance of compensatory mechanisms from experimentally reported hemodynamic data. We found a strikingly wide range of compensatory reflex profiles in response to MI in dogs and verified that pharmacologic blockade of sympathetic and parasympathetic reflexes nearly abolished this variability. Then, using a previously published model of postinfarction remodeling, we showed that observed variability in compensation translated to variability in predicted LV dilation consistent with published data. Treatment with a vasodilator shifted the compensatory response away from arterial and venous vasoconstriction and toward increased HR and myocardial contractility. Importantly, this shift reduced predicted dilation, a prediction that matched prior experimental studies. Thus, postinfarction reflex compensation could represent both a source of individual variability in the extent of LV remodeling and a target for therapies aimed at reducing that remodeling.

Study of Cutaneous Reflex Compensation During Locomotion After Nerve Section in the Cat

In the cat, section of all cutaneous nerves of the hindfeet except the tibial (Tib) nerve supplying the plantar surface results in a long-lasting decrease in the intensity of Tib stimulation needed for a threshold response in flexor muscles and an increase in the amplitude of the phase-dependent responses recorded in various muscles during locomotion. Stimulating through chronically implanted nerve cuffs ensured a stable stimulation over time. The increase in reflex amplitude was well above the small increase in the amplitude of the locomotor bursts themselves that results from the denervation. Short latency responses (P1) were seen in flexor muscles, especially at the knee (semitendinosus) and ankle (tibialis anterior and extensor digitorum longus), with stimuli applied in the swing phase and also to a lesser degree in the later part of the cycle. Longer latency responses (P2) were increased in hip, knee, and ankle flexors, as well as in a contralateral extensor (vastus lateralis) when applied in late stance. Responses evoked from stimulating the proximal end of sectioned nerves were not larger than before neurectomy. This suggests that the increased responsiveness to Tib stimulation is not simply caused by an increase in motoneuron excitability, because this would have resulted in a nonspecific increase of responses to stimulation of any nerve. It is concluded that the adult locomotor system is capable of central reorganization to enhance specific remaining cutaneous reflex pathways after a partial cutaneous denervation of the paw.

Cross-bridge mechanisms underlying the history-dependent properties of muscle spindles and stretch reflexes

The effects of prior movement on the force responses of skeletal muscle are compared with the effects of movement history on the changes in firing rate of muscle spindle receptors. Prior release results in the linearization of the mechanical properties of skeletal muscles, which can be provisionally explained by cross-bridge models of muscular contraction. The history-dependence of responses of muscle spindle receptors in unanesthetized decerebrate preparations appears to result from the kinetics of cycling and noncycling cross-bridges. The results of this comparison indicate that the integration of mechanical properties of muscle and spindle receptor promotes stiffness regulation.Key words: predictive control, muscular stiffness, muscle receptors, reflex compensation, cross-bridge cycling, nonlinear mechanical properties, feline motor control.

Intrinsic Properties and Reflex Compensation in Reinnervated Triceps Surae Muscles of the Cat: Effect of Movement History

Effects of prior motion on ramp stretch responses of reflexive and areflexive muscles were measured in decerebrate cats. Soleus and gastrocnemius muscles were rendered areflexive by reinnervation a minimum of 9 mo before the terminal experiments. The introduction of a shortening phase prior to the ramp stretch increased the normalized initial stiffness of muscles and decreased the tendency to yield of the reinnervated muscles as compared with the case in which muscles contracted isometrically prior to stretch. Yielding was compensated by reflex action for all amplitudes of prior shortening in soleus and gastrocnemius muscles. The comparison of responses of untreated and reinnervated muscles indicated that the contribution of reflex action progressively declined with the amplitude of prior shortening as the extent of yielding diminished. In soleus muscle, during a variable delay period of isometric contraction interposed between shortening and lengthening force generation, initial stiffness and yielding returned to levels seen with isometric contractile history. However, these attributes recovered at different rates, suggesting that distinct processes are responsible for initial stiffness and yielding. Yielding was compensated for by reflex action regardless of the length of the interposed delay or of the amplitude of the prior shortening. These and previous findings indicate that the stretch reflex regulates muscular stiffness for a wide range of conditions. This regulation apparently arises from complementary mechanical properties of intrafusal and extrafusal muscle.