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Diaphragm pacing (DP) is a useful and cost-effective alternative to mechanical ventilation in patients with ventilator-dependent spinal cord injury and central hypoventilation syndrome. Patients with SCI should be carefully screened to assess the integrity of their phrenic nerves. In eligible patients, DP improves mobility, speech, olfaction, and quality of life. The stigma of being attached to a mechanical device and risk of ventilator disconnection are eliminated. There is also some evidence that DP results in a reduction in the rate of respiratory tract infections. DP is associated with infrequent side effects and complications, such as wire breakage, radiofrequency failure, and infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

After cervical spinal cord injuries, many patients are unable to sustain independent ventilation because of a disruption of diaphragm innervation and respiratory functioning. If phrenic nerve function is preserved, the patient may be able to tolerate exogenous pacing of the diaphragm via electrical stimulation. Previously this was accomplished by stimulation directly to the phrenic nerves, but may be accomplished less invasively by percutaneously stimulating the diaphragm itself. The benefits, when compared with mechanical ventilation, include a lower rate of pulmonary complications, improved venous return, more normal breathing and speech, facilitation of eating, cost-effectiveness, and increased patient mobility., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Diaphragm pacing is a clinically useful modality providing artificial ventilatory support in patients with ventilator dependent spinal cord injury. Since this technique is successful in providing full-time ventilatory support in only ~50% of patients, better methods are needed. In this paper, we review a novel method of inspiratory muscle activation involving the application of electrical stimulation applied to the ventral surface of the upper thoracic spinal cord at high stimulus frequencies (300 Hz). In an animal model, high frequency spinal cord stimulation (HF-SCS) results in synchronous activation of both the diaphragm and inspiratory intercostal muscles. Since this method results in an asynchronous pattern of EMG activity and mean peak firing frequencies similar to those observed during spontaneous breathing, HF-SCS is a more physiologic form of inspiratory muscle activation. Further, ventilation can be maintained on a long-term basis with repetitive stimulation at low stimulus amplitudes (<1 mA). These preliminary results suggest that HF-SCS holds promise as a more successful method of inspiratory muscle pacing., (Copyright © 2013 Elsevier B.V. All rights reserved.)

As demonstrated in a canine model, high frequency spinal cord stimulation (HF-SCS) is a novel and more physiologic method of electrical activation of the inspiratory muscles compared to current techniques. The dog model, however, has significant limitations due to cost and societal concerns. Since the rodent respiratory system is also a relevant model for the study of neuronal circuitry function, the aims of the present study were to a) assess the effects of HF-SCS and b) determine the methodology of application of this technique in rats. In 9 Sprague Dawley rats, diaphragm multiunit and single motor unit EMG activity were assessed during spontaneous breathing and HF-SCS applied on the ventral epidural surface of the spinal cord at the T2 level following C1 spinal section. As in dogs, HF-SCS results in the activation of the diaphragm at physiological firing frequencies and the generation of large inspired volumes. Mean maximum firing frequencies of the diaphragm during spontaneous breathing and HF-SCS were 23.3 ± 1.4 Hz (range: 9.8-51.6 Hz) and 26.6 ± 1.3 Hz; range: 12.0-72.9 Hz, respectively, at comparable inspired volumes. Moreover, HF-SCS was successful in pacing these animals over a 60-min period without evidence of system fatigue. Our results suggest that, similar to the dog model, HF-SCS in the rat results in the activation of spinal cord tracts which synapse with the phrenic motoneuron pool, allowing the processing of the stimulus and consequent physiologic activation of the inspiratory muscles. The rat may be a useful model for further studies evaluating phrenic motoneuron physiology., (Copyright © 2013 Elsevier Inc. All rights reserved.)

High frequency spinal cord stimulation (HF-SCS) is a method of inspiratory muscle activation resulting in phrenic motoneuron activation via stimulation of spinal cord pathways. The specific pathways mediating this response, however, are unknown. The aim of this study was to assess the potential role of upper cervical (C1-C4) pre-phrenic interneurons (UCI) and localize the pathways in the thoracic spinal cord mediating activation of phrenic motoneurons during HF-SCS. In 7 anesthetized, spinalized (C1 level) dogs, HF-SCS was applied at the T2 level. Diaphragm EMG, inspired volume and airway pressure generation were monitored before and following sequential spinal cord sections at the C4 and C8 levels. Section at the C4 level and dorsal columns at C8 resulted in no significant changes. However, lateral funiculi section (C8 level) resulted in significant reductions in each parameter. We conclude that during upper thoracic HF-SCS, the phrenic motoneuron pools are activated via spinal pathways located in the lateral funiculus but UCI are not involved., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In contrast to previous methods of electrical stimulation of the inspiratory muscles, high frequency spinal cord stimulation (HF-SCS) results in more physiological activation of these muscles. The spatial distribution of activation to the external intercostal muscles by this method is unknown. In anaesthetized dogs, multiunit and single motor unit (SMU) EMG activity was monitored in the dorsal portion of the 3rd, 5th and 7th interspaces and ventral portion of the 3rd interspace during spontaneous breathing and HF-SCS following C2 spinal section. Stimulus amplitude during HF-SCS was adjusted such that inspired volumes matched spontaneous breathing (Protocol 1). During HF-SCS, mean peak SMU firing frequency was highest in the 3rd interspace (dorsal) (18.8 ± 0.3 Hz) and significantly lower in the 3rd interspace (ventral) (12.2 ± 0.2 Hz) and 5th interspace (dorsal) (15.3 ± 0.3 Hz) (P <0.05 for each comparison). Similar rostrocaudal and dorsoventral gradients of activity were observed during spontaneous breathing prior to C2 section. No significant activity was observed in the 7th interspace during either spontaneous breathing or HF-SCS. Since peak discharge frequencies of the SMUs were higher and rib cage movement greater during HF-SCS compared to spontaneous breathing, stimulus amplitude during HF-SCS was adjusted such that rib cage movement matched (Protocol 2). Under these conditions, mean peak SMU frequencies and rostrocaudal and dorsoventral gradients of activity during HF-SCS were not significantly different compared to spontaneous breathing. These results indicate that (a) the topographic pattern of electrical activation of the external intercostal muscles during HF-SCS is similar to that occurring during spontaneous breathing and (b) differential descending synaptic input from supraspinal centres is not a required component of the differential spatial distribution of external intercostal muscle activation. HF-SCS may provide a more physiological method of inspiratory muscle pacing.

Despite clinically available methods of diaphragm pacing, most patients with ventilator-dependent tetraplegia are still dependent on mechanical ventilation. Given the significant disadvantages of these devices, additional pacing options are needed. The objective of this study was to evaluate a novel and potentially more physiological method of inspiratory muscle activation, which involves the application of high-frequency (>200 Hz) stimulation to the ventral surface of the spinal cord in the high thoracic region. Studies were performed in 13 anesthetized dogs. High-frequency spinal cord stimulation (HF-SCS) results in the activation of both the diaphragm and inspiratory intercostal muscles, in concert, at physiological firing frequencies and the generation of large inspired volumes. Mean maximum firing frequencies of motor units in the parasternal (2nd interspace), the external intercostal (3rd interspace), and the diaphragm muscles were 10.6 +/- 0.4, 11.7 +/- 0.4, and 10.4 +/- 0.3 Hz, respectively. These values were not significantly different from those occurring during spontaneous breathing at comparable inspired volumes. Maximum inspired volume was 0.93 +/- 0.01 liter, which approximates the inspiratory capacity of these animals. Moreover, ventilation can be maintained on a chronic basis by this method (6 h) without evidence of system fatigue. Our results suggest that HF-SCS results in activation of spinal cord tracts that synapse with the inspiratory motoneuron pools, allowing processing of the stimulus and consequent physiological activation of the inspiratory muscles. HF-SCS has the potential to provide an effective method of inspiratory muscle pacing.

Lower thoracic spinal cord stimulation (SCS) results in the generation of large positive airway pressures. The potential effects of diaphragm co-activation during SCS were investigated in 10 anesthetized dogs. Diaphragm compound action potentials (CMAPs) were present during SCS at the T10 and T12 levels. In group 1, airway (Paw) and trans-diaphragmatic (Pdi) pressures were monitored during supramaximal SCS before and after phrenicotomy. In group 2, pressures were monitored before and after C2 section to evaluate the potential influence of supraspinal centers. Following phrenicotomy in group 1, the reduction in Pdi during SCS was associated with increases in Paw. In group 2, diaphragm CMAPs and active Pdi increased following C2 section, while Paw fell. Following phrenicotomy, Paw increased significantly. In intact animals therefore, changes in Paw during SCS are affected by the interaction between inhibitory and excitatory influences on diaphragm activation. We conclude that lower thoracic SCS results in substantial diaphragm co-activation and secondary reductions in airway pressure generation.

Objective: To evaluate the usefulness of combined intercostal and diaphragm pacing to maintain independence from mechanical ventilation., Design: A prospective trial., Setting: Clinical research center at a large tertiary hospital., Participants: Four ventilator-dependent subjects with spinal cord injury with only unilateral phrenic nerve function., Intervention: During an initial surgical procedure, a multipolar epidural disk electrode was positioned on the ventral surface of the upper-thoracic spinal cord via a hemilaminectomy to activate the inspiratory intercostal muscles. A phrenic nerve electrode was implanted unilaterally via the thoracic approach., Main Outcome Measures: Inspired volume production and duration that subjects could be comfortably maintained when off mechanical ventilatory support., Results: Initial maximum inspired volumes from combined intercostal and diaphragm stimulation ranged between .23 and .93L and significantly increased over the course of reconditioning period to between 0.55 and 1.31L; subjects could be maintained off mechanical ventilation between 16 and 24 hours a day., Conclusions: Combined intercostal and unilateral diaphragm pacing may be a useful therapeutic modality capable of maintaining long-term ventilatory support in patients with only unilateral phrenic nerve function.

Background: Electrical stimulation of the phrenic nerve motor point of the diaphragm through laparoscopic implantation of a pacing system is an option for high spinal cord-injured patients with chronic respiratory insufficiency. This study assesses the operative learning curve for the initial series of patients., Method: A series of six patients underwent laparoscopic placement of a diaphragm pacing system. The operative procedure was divided into the following four steps for analysis and rapid adjustment after each operation: exposure of the diaphragm, mapping of the phrenic nerve motor point, implantation of the pacing electrodes, and final routing of the wires to the external system., Results: The first case required two operations, and the second case was unsuccessful because of a nonfunctioning phrenic nerve that led to a change in the preoperative screening criteria. The operative time decreased from 469 min for the first operation to 165 min for the sixth operation. The significant time decrease can be attributed to changes in the mapping and routing aspects of the operation. Key changes during this series that helped to reduce the operative time include abandonment of a software-dependent mapping technique, development of a grid algorithm for mapping, software improvement to increase the speed of stimulation and mapping, refinement of the mapping probe to maintain adequate suction on the diaphragm, shortening of the electrode lengths, and experience with the implantation of connections to the external electrodes. Presently, all five of the successfully implanted patients can be maintained on prolonged ventilatory support with the device., Conclusion: Analysis of every step of this investigational procedure enabled us to make rapid changes in surgical protocol, leading to decreases in operative times and expectant improvements in patient safety and efficacy. In this series, analysis was the key to developing a low-risk cost-effective outpatient diaphragm pacing system.

Background: For patients with high spinal cord injury and chronic respiratory insufficiency, electrically induced diaphragm pacing is an alternative to long-term positive pressure ventilation. The goal of this study was to laparoscopically assess the phrenic nerve motor point of the diaphragm and then implant electrodes to produce chronic negative pressure ventilation., Methods: Patients undergoing elective laparoscopic procedures (volunteer patient group) underwent a series of electrical stimuli (2 to 24 mA at 100-microsecond pulse widths) with a mapping probe to identify the motor point through qualitative visualization of diaphragm motion and quantitative measurement of the abdominal pressure to assess the strength of the contraction. After Food and Drug Administration and Institutional Review Board approval, tetraplegic patients (spinal cord injured patient group) who were ventilator dependent underwent mapping and implantation of electrodes for pacing in both diaphragms., Results: In the volunteer group, 28 patients underwent 3 to 50 stimulations per diaphragm to identify the motor points. Throughout this series the surgical tools and software were improved to allow rapid motor point location with a grid-mapping algorithm. In the spinal cord injured group, 5 of 6 patients had electrodes successfully implanted at the motor point to produce adequate tidal volumes. The one failure caused a change in our inclusion criteria to include fluoroscopic confirmation of diaphragm movement during surface nerve stimulation. Three patients are completely free of the ventilator, and the other 2 are progressively increasing their time off the ventilator with conditioning., Conclusions: Mapping and implantation of the electrodes can be done laparoscopically, providing for a low-risk, cost-effective, outpatient, diaphragm pacing system that will support the respiratory needs of patients.

In patients with diaphragm paralysis, ventilation to the basal lung zones is reduced, whereas in patients with paralysis of the rib cage muscles, ventilation to the upper lung zones in reduced. Inspiration produced by either rib cage muscle or diaphragm contraction alone, therefore, may result in mismatching of ventilation and perfusion and in gas-exchange impairment. To test this hypothesis, we assessed gas exchange in 11 anesthetized dogs during ventilation produced by either diaphragm or intercostal muscle contraction alone. Diaphragm activation was achieved by phrenic nerve stimulation. Intercostal muscle activation was accomplished by electrical stimulation by using electrodes positioned epidurally at the T(2) spinal cord level. Stimulation parameters were adjusted to provide a constant tidal volume and inspiratory flow rate. During diaphragm (D) and intercostal muscle breathing (IC), mean arterial Po(2) was 97.1 +/- 2.1 and 88.1 +/- 2.7 Torr, respectively (P < 0.01). Arterial Pco(2) was lower during D than during IC (32.6 +/- 1.4 and 36.6 +/- 1.8 Torr, respectively; P < 0.05). During IC, oxygen consumption was also higher than that during D (0.13 +/- 0.01 and 0.09 +/- 0.01 l/min, respectively; P < 0.05). The alveolar-arterial oxygen difference was 11.3 +/- 1.9 and 7.7 +/- 1.0 Torr (P < 0.01) during IC and D, respectively. These results indicate that diaphragm breathing is significantly more efficient than intercostal muscle breathing. However, despite marked differences in the pattern of inspiratory muscle contraction, the distribution of ventilation remains well matched to pulmonary perfusion resulting in preservation of normal gas exchange.

In patients with ventilator-dependent tetraplegia, phrenic nerve pacing (PNP) provides significant clinical advantages compared with mechanical ventilation. This technique however generally requires a thoracotomy with its associated risks and in-patient hospital stay and carries some risk of phrenic nerve injury. We have developed a method by which the phrenic nerves can be activated via intramuscular diaphragm electrodes. In one patient with ventilator-dependent tetraplegia, two intramuscular diaphragm electrodes were implanted into each hemidiaphragm near the phrenic nerve motor points via laparoscopic surgery. The motor points were identified employing a previously devised mapping technique. Because inspired volumes were suboptimal on the right, a second laparoscopic procedure was necessary to position electrodes near the anterior and posterior branches of the right phrenic nerve. During bilateral stimulation, inspired volume was 580 ml. After a reconditioning program of progressively increasing diaphragm pacing, maximum inspired volumes on the left and right hemidiaphragms increased significantly. Maximum combined bilateral stimulation was 1120 ml. Importantly, the patient has been able to comfortably tolerate full-time pacing. If confirmed in additional patients, PNP with intramuscular diaphragm electrodes via laparoscopic surgery may provide a less invasive and less costly alternative to conventional PNP.

This study assessed the ability of functional magnetic stimulation (FMS) to activate the respiratory muscles in dogs. With the animal supine, FMS of the phrenic nerves using a high-speed magnetic stimulator was performed by placing a round magnetic coil (MC) at the carotid triangle. Following hyperventilation-induced apnea, changes in volume (deltaV) and airway pressure (deltaP) against an occluded airway were determined. FMS of the phrenic nerves produced substantial inspired function (deltaV = 373 +/- 20.5 mL and deltaP = -20 +/- 2.0 cm H2O). After bilateral phrenectomies, maximal inspired deltaV (219 +/- 12.2 mL) and deltaP (-10 +/- 1.0 cm H2O) were produced when the MC was placed near the C6-C7 spinous processes, while maximal expired deltaV (-199 +/- 22.5 mL) and deltaP (11 +/- 2.3 cm H2O) were produced following stimulation near the T9-T10 spinous processes. We conclude: (1) FMS of either the phrenic or upper intercostal nerves results in inspired volume production; (2) FMS of the lower intercostal nerves generates expired volume production; and (3) FMS of the respiratory muscles may be a useful noninvasive tool for artificial ventilation and assisted cough in patients with spinal cord injuries or other neurological disorders.

Recent studies suggest that chest wall reflexes may have a role in modulating diaphragm activation. The purpose of this study was to more closely examine this issue by assessing the diaphragmatic motor response to airway occlusion. Studies were performed in vagotomized mongrel dogs anesthetized with pentobarbital sodium. Diaphragmatic electromyogram (EMG) and phrenic neurogram (ENG) responses to airway occlusion were evaluated at different precontractile respiratory muscle lengths, achieved by passive inflation and deflation with a volume syringe during the preceding expiration. Lung volume was expressed as the corresponding change in airway pressure. At functional residual capacity, deflation (-5 cmH2O), and large inflation (+25 cmH2O), phrenic ENG during occlusion was 90 +/- 2 (SE), 84 +/- 5, and 86 +/- 3% of the preceding control breaths, respectively (n = 9). Qualitatively similar, but somewhat more pronounced, responses were observed on diaphragmatic EMG. With small lung inflations, the degree of reduction of phrenic ENG with airway occlusion was less. Consequently, the relationship between airway pressure and degree of inhibition was best described as a reverse parabola with the maximum at approximately +10-15 cmH2O. Responses were not significantly affected by bilateral cervical phrenicotomy. Complete section of the spinal cord at the high thoracic level (T1-T2) abolished the observed reduction in phrenic ENG in response to airway occlusion. Our results demonstrate 1) the existence of nonvagal nonphrenic reflex control of diaphragm activation most likely secondary to activation of intercostal afferents and 2) that the magnitude of this reflex is highly dependent on factors related to lung volume.

Recent studies have suggested that coronary and limb muscle vessels do not maximally vasodilate under conditions in which cardiac and limb muscle contractile function is dependent on the level of blood flow but, rather, maintain a "vasodilator reserve." If a vasodilator reserve is also present in the fatiguing diaphragm, it may be possible to augment flow to this muscle with vasodilator administration, improving muscle function. The purpose of the present study was therefore to examine the effect of administration of a potent vasodilator, nitroprusside, on the blood flow and contractile function of the fatiguing diaphragm. Studies were performed using an in situ canine diaphragmatic strip preparation that permitted direct measurement of force and blood flow; cardiac output was monitored with a thermodilution catheter. The effects of nitroprusside were examined with the diaphragm rhythmically contracting in response to both subfatiguing and fatiguing stimulation paradigms. For both contraction paradigms, nitroprusside infusions elicited appreciable increases in cardiac output. Nitroprusside infusions also produced significant increases in diaphragmatic blood flow during subfatiguing diaphragmatic contractions but had no effect on flow during fatiguing contractions. Nitroprusside also had no effect on the rate of diaphragmatic fatigue. These data suggest that, under the conditions examined, the diaphragm exhausts its vasodilator reserve during the development of fatigue and vasodilator administration has no appreciable effect on diaphragm blood flow and function. Moreover, although vasodilator drugs with actions similar to nitroprusside are used clinically to augment flow to vital organs, our data would indicate that these drugs have no functionally significant effect on blood flow to the fatiguing diaphragm.

The purpose of the present study was to determine whether the diaphragm, like limb muscles, generates high levels of intramuscular pressure during contraction. Studies were performed on in situ diaphragm strips in 15 dogs. An isometric force transducer was used to measure strip tension, and intramuscular pressure was assessed using both wick and balloon catheter techniques. Tension and intramuscular pressures were recorded during a series of graded contractions elicited by electrically stimulating strips via intramuscular electrodes. Similar techniques were used to record the tension and intramuscular pressures developed during graded contractions of a limb muscle, the vastus medialis. Intramuscular pressure was linearly related to tension in both the diaphragm and vastus medialis. However, for a given level of tension development, vastus medialis pressures were two- to threefold greater than those developed within the diaphragm. For example, at a tension of 2 kg/cm2 vastus medialis and diaphragm intramuscular pressures were 105 +/- 11 and 25 +/- 4 mmHg, respectively, when assessed with wick catheters, and were 159 +/- 11 and 48 +/- 5 mmHg, respectively, when assessed by the balloon catheter technique. These differences may reflect the fact that thick rounded muscles, like the vastus, may be capable of generating higher intramuscular pressures than the thin sheetlike diaphragm. To determine whether intradiaphragmatic pressure swings were large enough to explain the vascular compression produced by contraction, we measured phrenic arterial impedance during contraction in nine animals. In these animals the inferior phrenic artery was cannulated and pump perfused at a constant flow rate. With contraction, phrenic arterial pressure rose; i.e., phrenic arterial impedance increased.(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanisms by which aminophylline increases inspiratory muscle contractility are unclear. The present study compared the effects of aminophylline on cardiac as well as on diaphragm contractility and examined the interaction of aminophylline with verapamil, a calcium channel-blocking agent, on both types of muscle. Experiments were performed in mongrel dogs anesthetized with pentobarbitone. Diaphragm contractility was assessed from transdiaphragmatic pressure (Pdi) developed during supramaximal electrical stimulation of the cervical phrenic rootlets, and cardiac contractility was assessed from peak left ventricular (LV) pressure and its rate of rise (dPv/dt). Measurements were made before and after each of 3 sequential IV infusions of aminophylline (6 mg/kg) and subsequent IV infusions of verapamil (0.1 mg/kg bolus and 0.02 mg/kg/min for 5 to 7 min.). Transient decreases in Pdi were frequently observed immediately after aminophylline infusion in association with decreases in mean arterial blood pressure. With recovery of mean blood pressure, Pdi increased above baseline values. Aminophylline increased Pdi in a dose-dependent fashion over the entire frequency range studied (1 to 40 Hz). Aminophylline increased the rate of rise of Pdi (dPd/dt) without affecting the period over which pressure was developed or dissipated during single twitches. Aminophylline increased both peak LV pressure and dPv/dt. The magnitude of the cardiac response was greater than the diaphragmatic response. Subsequent verapamil infusion completely reversed the effects of aminophylline on LV contractility but had only a small effect on diaphragm contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanical interaction of the inspiratory muscles in the generation of changes in airway pressure is unclear. Using upper thoracic spinal cord stimulation to activate the intercostal muscles (IC) and bilateral supramaximal phrenic nerve stimulation to activate the diaphragm (D), we measured the changes in airway pressure produced by separate and combined IC and D activation over a wide range of lung volumes. Changes in parasternal IC and D length were assessed by sonomicrometry. With increasing lung volume, activation of the IC and D resulted in progressive decrements in generated airway pressure. Combined IC and D contraction produced greater negative swings in airway pressure than the arithmetic sum of separate IC and D contraction alone, indicating a synergistic effect. Moreover, synergism increased progressively with increasing lung volume. During combined muscle contraction, both the IC and D shortened less than during contraction of either muscle group alone. The tendency for the parasternal muscle to lengthen for a given change in airway pressure during D contraction alone increased with increasing lung volume, suggesting that the tendency for the rib cage to recoil inward increased progressively with increasing lung volume. Likewise, the tendency of the D to lengthen for a given change in airway pressure during IC contraction alone also increased progressively with increasing lung volume, suggesting that the tendency for the abdomen-D compartment to recoil inward also increased with increasing lung volume. We conclude that the IC and D interact synergistically to produce changes in airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of the present study was to examine the effect of amrinone, a drug known to augment cardiac output and dilate peripheral vascular beds, on diaphragm blood flow. Studies were performed on 12 anesthetized mechanically ventilated dogs in which strips of left costal diaphragm were developed in situ. Strip blood flow was assessed with a drop counter attached to a catheter tied into the phrenic veins' draining strips. Strip tension was measured with an isometric force transducer. Amrinone was administered as an intravenous bolus of 2 mg/kg followed by a continuous infusion of 25 micrograms.kg-1.min-1. Amrinone increased cardiac output and resting diaphragm blood flow [from 1.8 +/- 0.1 to 3.2 +/- 3 (SE) l/min and from 13 +/- 2 to 29 +/- 6 (SE) ml.100 g-1.min-1, respectively, P less than 0.001 for both comparisons]. Amrinone also increased blood flow during periods of rhythmic contraction (tension time indexes of 0.1-0.4, P less than 0.05 for comparisons of flow with and without amrinone at each tension time index) and increased the magnitude of the postcontraction hyperemia (P less than 0.02 for comparisons of hyperemic flow with and without amrinone at tension time indexes of 0.3 and 0.4). Graded occlusion of the inferior vena cava produced reductions in arterial pressure, cardiac output, and diaphragm blood flow both before and after amrinone. Both cardiac output and diaphragm blood flow were greater after amrinone, however, at all levels of blood pressure examined. These findings indicate that amrinone can override diaphragm vasoregulatory systems and augment diaphragm blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

The distribution of motor drive to the costal and crural diaphragm and parasternal intercostal muscles was evaluated during progressive isocapnic hypoxia in anesthetized dogs. Bipolar stainless steel wire electrodes were placed unilaterally into the costal and crural portions of the diaphragm and into the parasternal intercostal muscle in the second or third intercostal space. Both peak and rate of rise of electromyographic activity of each chest wall muscle increased in curvilinear fashion in response to progressive hypoxia. Both crural and parasternal intercostal responses, however, were greater than those of the costal diaphragm. The onset of crural activation preceded that of the costal portion of the diaphragm and parasternal intercostal muscle activation. Despite differences in the degree of activation among the various chest wall muscles, the rate of increase in activation for any given muscle was linearly related to the rate of increases for the other two. This suggests that respiratory drive during progressive hypoxia increases in fixed proportion to the different chest wall inspiratory muscles. Our findings lend further support to the concept that the costal and crural diaphragm are governed by separate neural control mechanisms and, therefore, may be considered separate muscles.