A canine model of chronic heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Twenty closed-chest dogs underwent three to nine intracoronary embolizations performed 1-3 wk apart. Embolizations were discontinued when left ventricular (LV) ejection fraction was less than 35%. LV ejection fraction was 64 +/- 2% at baseline and decreased to 21 +/- 1% at 3 mo after the last embolization (P less than 0.001). During the same period, LV end-diastolic pressure increased from 6 +/- 1 to 22 +/- 3 mmHg (P less than 0.001); LV end-diastolic volume increased from 64 +/- 3 to 101 +/- 6 6 ml (P less than 0.001), and cardiac output decreased from 2.9 +/- 0.2 to 2.3 +/- 0.1 l/min (P less than 0.01). These changes were accompanied by significant increases of pulmonary artery wedge pressure and systemic vascular resistance. Plasma norepinephrine increased from 332 +/- 17 pg/ml at baseline to 791 +/- 131 pg/ml at 3 mo after the last embolization (P less than 0.01); plasma levels of atrial natriuretic factor increased from 12.7 +/- 10.0 to 28.8 +/- 8.6 pmol/l (P less than 0.01), whereas plasma renin activity remained unchanged. Gross and microscopic postmortem examination showed patchy myocardial fibrosis and LV hypertrophy. We conclude that multiple intracoronary embolizations with microspheres, separated in time, can lead to chronic heart failure in dogs. The preparation is stable and reproducible and manifests many of the sequelae of heart failure that result from loss of contractile myocardium.
A turtle with a complete transection of the spinal cord, termed a spinal turtle, exhibits three types or "forms" of the scratch reflex: the rostral scratch, pocket scratch, and caudal scratch (21). Each scratch form is elicited by tactile stimulation of a site on the body surface innervated by afferents entering the spinal cord caudal to the transection. We recorded electromyographic (EMG) potentials from the hindlimb during each of the three forms of the scratch in the spinal turtle (see Fig. 1). Common to all scratch forms is the rhythmic alternation of the activity of the hip protractor muscle (VP-HP) and hip retractor muscle (HR-KF). Each form of the scratch displays a characteristic timing of the activity of the knee extensor muscle (FT-KE) with respect to the cycle of activity of the hip muscles VP-HP and HR-KF. In a rostral scratch, activation of FT-KE occurs during the latter portion of VP-HP activation. In a pocket scratch, activation of FT-KE occurs during HR-KF activation. In a caudal scratch, activation of FT-KE occurs after the cessation of HR-KF activation. The timing characteristics of these muscle activity patterns correspond to the timing characteristics of changes in the angles of the knee joint and the hip joint obtained with movement analyses (21). We recorded electroneurographic (ENG) potentials from peripheral nerves of the hindlimb during each of the three forms of the "fictive" scratch in the spinal turtle immobilized with neuromuscular blockade (see Fig. 4). Common to all forms of the fictive scratch is the rhythmic alternation of the activity of hip protractor motor neurons (VP-HP) and hip retractor motor neurons (HR-KF). Each form displays a characteristic timing of the activity of knee extensor motor neurons (FT-KE) with respect to the cycle of VP-HP and HR-KF motor neuron activity. The timing characteristics of these motor neuron activity patterns are similar to the timing characteristics of the muscle activity patterns obtained in the preparation with movement (cf. Figs. 1 and 4). The motor pattern for each scratch form is generated centrally within the spinal cord. In the spinal immobilized preparation, neuromuscular blockade prevents both limb movement and phasic sensory input, and complete spinal transection isolates the cord from supraspinal input.(ABSTRACT TRUNCATED AT 400 WORDS)
1. The turtle spinal cord produces three forms of the fictive scratch reflex in response to tactile stimulation of sites on the body surface. Common to all three forms is the rhythmic alternation of activity between hip protractor and hip retractor motoneurones. Hip protractor motoneurone activity is monitored via nerves innervating the hip protractor muscle puboischiofemoralis internus pars anteroventralis (VP‐HP). Hip retractor activity is monitored via nerves innervating several monoarticular hip retractor muscles, one hip adductor muscle, and several biarticular hip retractor‐knee flexor muscles (HR‐KF). Each form is characterized by the timing of activity of motoneurones innervating femorotibialis (FT‐KE), a monoarticular knee extensor muscle, within this alternating cycle (Robertson, Mortin, Keifer & Stein, 1985). In the present study, intracellular recordings revealed a corresponding regulation of synaptic drive to knee extensor motoneurones with respect to the synaptic drive to the motoneurones innervating antagonist muscles of the hip. These patterns of synaptic activation give rise to the distinct motor pattern underlying each form of the scratch reflex. 2. VP‐HP, HR‐KF and FT‐KE motoneurones all exhibited phasic depolarizing and hyperpolarizing changes in membrane voltage during the production of the rhythmic motor patterns underlying each stratch form. Membrane depolarization is caused by synaptic excitation (EPSPs) and gives rise to motoneurone discharge. Hyperpolarization is primarily the result of postsynaptic inhibition (IPSPs) mediated by an increased conductance of chloride ions (Cl‐) and ensures motor pool quiescence during antagonist activation. 3. VP‐HP motoneurones depolarized during activation of the VP‐HP motor pool and hyperpolarized during activation of the HR‐KF motor pool. HR‐KF motoneurones depolarized during activation of the HR‐KF motor pool and hyperpolarized during activation of the VP‐HP motor pool. In many cases, the amplitude of hyperpolarization was directly related to the intensity of the antagonist motor pool burst. During the rostral scratch, HR‐KF motor pool activity was sometimes deleted, along with the depolarizing wave in HR‐KF motoneurones and the hyperpolarizing wave in VP‐HP motoneurones. The interneurones providing the synaptic drive to these antagonist motoneurones appear, therefore, to have reciprocal activation patterns. 4. FT‐KE motoneurones depolarized during FT‐KE motor pool activation and hyperpolarized during FT‐KE motor pool quiescence. This alternation of opposing synaptic drive underlies the rhythmic activation of the FT‐KE motor pool during all scratch forms.(ABSTRACT TRUNCATED AT 400 WORDS)
In the preceding companion article (Berkowitz and Stein, 1994b), we showed that many descending propriospinal neurons in the turtle were rhythmically activated during two different motor patterns, fictive rostral scratching and fictive pocket scratching. In this article, we present phase analyses of the activity of each such neuron during fictive scratching. Each neuron's activity was concentrated in a particular phase of the ipsilateral hip flexor muscle nerve (VP-HP) activity cycle; each had a distinct "preferred phase." Each neuron's preferred phase during fictive rostral scratching was similar to its preferred phase during fictive pocket scratching. This result is consistent with the idea that some descending propriospinal neurons may contribute to the generation of both rostral scratching and pocket scratching. Many descending propriospinal neurons were rhythmically activated during fictive scratching evoked on either side of the body. This activity may contribute to production of bilateral hindlimb movements during scratching. It is also possible that synaptic interactions between the two sides of the spinal cord may be important in generating the motor patterns for movement of a single hindlimb. In addition, we present a model which illustrates that a population of propriospinal neurons, each of which is broadly tuned to a region of the body surface and is rhythmically activated in a constant phase of the hip control cycle, could mediate the selection and generation of rostral scratching and pocket scratching. Thus, the selection of an appropriate motor pattern and the production of the required knee-hip synergy may each be distributed over a diverse population of spinal cord neurons. This model requires that each such neuron project to both knee muscle and hip muscle motoneurons. According to this model, the process of selecting a motor pattern would not be completed until knee muscle motoneurons integrate overlapping excitatory and inhibitory inputs.
In a spinal turtle, unilateral stimulation in the rostral scratch receptive field elicited rhythmic fictive rostral scratching in ipsilateral hindlimb motor neurons; contralateral hip motor activity was also rhythmic and out-of-phase with ipsilateral hip motor activity. When left and right rostral scratch receptive fields were stimulated simultaneously, bilateral rhythmic fictive rostral scratching was produced; left hindlimb scratching was out-of-phase with right hindlimb scratching. Thus, spinal circuits coordinate interlimb phase during bilateral fictive scratching. We examined the contributions of contralateral spinal circuitry to the normal pattern of right hindlimb fictive rostral scratching by removing the left halves of the D7 segment and the hindlimb enlargement (D8-S2 segments). After left- hemicord removal, stimulation in the right rostral scratch receptive field usually elicited a variation of rostral scratching with rhythmic right hip flexor activity and no right hip extensor activity; thus, right hip flexor rhythm generation does not require left hindlimb enlargement circuitry. Normal right hindlimb rostral scratching with rhythmic alternation between hip flexor and extensor activities was rarely observed; thus, contralateral spinal circuitry contributes to the production of normal ipsilateral fictive rostral scratching. After left-hemicord removal, stimulation in the left rostral scratch receptive field elicited rhythmic right hip extensor activity; thus, contralateral spinal circuitry can generate a hip extensor rhythm during ipsilateral rostral scratch receptive field stimulation. Our observations and those of Berkowitz and Stein (1994a,b) support the concept that an ipsilateral hindlimb's normal rostral scratch motor pattern is generated by a modular central pattern generator that is bilaterally distributed in the spinal cord.
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