Alterations in respiratory muscle activation in the ischemic fatigued canine diaphragm

The purpose of the present study was to examine the respiratory motor response to diaphragm fatigue. Studies were performed using in situ diaphragm muscle strips dissected from the left costal diaphragm in anesthetized dogs. The left inferior phrenic artery was isolated, and diaphragmatic strip fatigue was elicited by occluding this vessel. Strip tension, strip electromyographic activity, parasternal electromyographic activity, and the electromyogram of the right hemidiaphragm were recorded during spontaneous breathing efforts before, during, and after periods of phrenic arterial occlusion. In separate trials, we examined the neuromuscular responses to phrenic arterial occlusion at arterial PCO2 (PaCO2) of 40, 55, and 75 Torr. No fatigue and no alteration in electromyographic activities were observed in trials at PaCO2 of 40 Torr. During trials at PaCO2 of 55 and 75 Torr, however, diaphragm tension fell, the peak height of the diaphragm strip electromyogram decreased, and the peak heights of the parasternal and right hemidiaphragm electromyograms increased. Relief of phrenic arterial occlusion resulted in a return of strip tension and all electromyograms toward base-line values. In additional experiments, the left phrenic nerve was sectioned in the chest after producing fatigue. Phrenic section was followed by an increase in the peak height of the left phrenic neurogram (recorded above the site of section). This latter finding suggests that diaphragm strip motor drive may be reflexly inhibited during the development of fatigue by neural traffic carried along phrenic afferents.     

Effects of diaphragmatic ischemia on the inspiratory motor drive.

To assess the effect of diaphragmatic ischemia on the inspiratory motor drive, we studied the in situ isolated and innervated left diaphragm in anesthetized, vagotomized, and mechanically ventilated dogs. The arterial and venous vessels of the left diaphragm were catheterized and isolated from the systemic circulation. Inspiratory muscle activation was assessed by recording the integrated electromyographic (EMG) activity of the left and right costal diaphragms and parasternal intercostal and alae nasi muscles. Tension generated by the left diaphragm during spontaneous breathing attempts was also measured. In eight animals, left diaphragmatic ischemia was induced by occluding the phrenic artery for 20 min, followed by 10 min of reperfusion. This elicited a progressive increase in EMG activity of the left and right diaphragms and parasternal and alae nasi muscles to 170, 157, 152, and 128% of baseline values, respectively, an increase in the frequency of breathing efforts, and no change in left diaphragmatic spontaneous tension. Thus the ratio of left diaphragmatic EMG to tension rose progressively during ischemia. During reperfusion, only the frequency of breathing efforts and alae nasi EMG recovered completely. In four additional animals, left diaphragmatic ischemia was induced after the left phrenic nerve was sectioned. Neither EMG activity of inspiratory muscles nor respiratory timing changed significantly during ischemia. In conclusion, diaphragmatic ischemia increases inspiratory motor drive through activation of phrenic afferents. The changes in alae nasi activity and respiratory timing indicate that this influence is achieved through supraspinal pathways.     

Failure of pulmonary acidosis to increase respiratory drive.

Experiments were performed to determine whether increases in acidity isolated to the pulmonary circulation would stimulate hypothesized pulmonary chemoreceptors and increase respiratory drive in the anesthetized paralyzed mechanically ventilated cat (n = 9). Respiratory drive was assessed by measuring the frequency and amplitude of the integrated phrenic neurogram. To create an isolated pulmonary acidosis, blood returning to the lung was acidified by infusion of 0.3 M lactic acid (1.91 ml/min) into the inferior vena cava, while systemic arterial pH was restored to near normal levels by simultaneous infusion of base (0.3 M NaOH) into the left atrium. Six minutes after the start of this dual infusion of acid and base, right ventricular (pulmonary) pH decreased from 7.286 to 7.179 and PCO2 increased 7 Torr. Systemic arterial pH and PCO2 were unchanged from measurements immediately before the infusion. This level of pulmonary acidosis failed to increase respiratory drive as assessed by phrenic activity. To test the sensitivity of the preparation to known systemic arterial chemical stimuli, a combined pulmonary and systemic acidosis was elicited by infusion of 0.3 M lactic acid into the inferior vena cava and 0.3 M NaCl into the left atrium. This infusion significantly lowered both systemic arterial and pulmonary arterial pH (7.343 to 7.155 for systemic arterial pH and 7.286 to 7.067 for pulmonary pH) and increased phrenic efferent activity 45%. We conclude that phrenic efferent activity is unaffected by moderate reductions in the pH of the pulmonary circulation in the absence of a significant systemic arterial acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of separate hemidiaphragm contraction on left phrenic artery flow and O2 consumption

Phrenic arterial blood flow has been shown to increase during bilateral phrenic nerve stimulation (BPNS). However, the role of unilateral phrenic nerve stimulation [left (LPNS) or right (RPNS)] on the blood flow and O2 consumption of the contralateral hemidiaphragm is not known and is explored here. In six anesthetized, mechanically hyperventilated dogs, left phrenic arterial blood flow (Qlpha) was measured (Doppler technique). Supramaximal (10 V, 30 Hz, 0.25-ms duration) LPNS, RPNS, and BPNS at a pacing frequency 15/min and duty cycle of 0.50 were delivered in separate runs. Left hemidiaphragmatic blood samples for gas analyses were obtained by left phrenic venous cannulation. During RPNS, Qlpha and left hemidiaphragmatic O2 consumption (VO2ldi) did not change significantly compared with control. During LPNS and BPNS, there was a significant increase in Qlpha and VO2ldi (P less than 0.01). There was no significant difference in Qlpha and VO2ldi between LPNS and BPNS (P greater than 0.05). We conclude 1) that there is a complete independence of left-right hemidiaphragmatic circulation both at rest and during diaphragm pacing and 2) that during unilateral stimulation transdiaphragmatic pressure is not related to diaphragmatic blood flow.     

Chemical activation of thin-fiber phrenic afferents. 2. Cardiovascular responses

To assess the effects of groups III and IV (thin-fiber) phrenic afferents on arterial pressure, heart rate, and distribution of cardiac output, we injected capsaicin into phrenic arteries of in situ isolated and innervated left diaphragms of dogs anesthetized with chloralose, vagotomized, and mechanically ventilated. Blood flow in the ascending aorta, common carotid, renal, superior mesenteric, and femoral arteries was measured by electromagnetic and Doppler flow probes. Injection of 1 mg capsaicin into the left phrenic artery produced congruent to 15% increase in mean arterial pressure and congruent to 7% increase in heart rate with no change in aortic flow. Phrenic arterial flow decreased by 64%, renal arterial flow by 16%, and superior mesenteric arterial flow by 10%, whereas carotid flow increased by 13% and flow to the right gastrocnemius muscle did not change. Mean arterial pressure, heart rate, and blood flow distribution (with the exception of the decline in phrenic blood flow) returned to baseline within 60 s of the injection. Injection of 1.5 mg capsaicin into the right isolated and innervated gastrocnemius produced congruent to 35% increase in mean arterial pressure, 17% rise in heart rate, and no change in aortic blood flow. Phrenic and carotid arterial flow rose by 240 and 41%, respectively, whereas renal and superior mesenteric flow declined by 50 and 20%, respectively. In conclusion, thin-fiber phrenic afferents have an excitatory effect on arterial pressure and heart rate. They redistribute blood flow away from the renal and intestinal vascular beds and toward the carotid vascular bed. On the other hand, the cardiovascular reflex from thin-fiber phrenic afferents seems less potent than that from limb muscle afferents.     

Diaphragmatic intramuscular pressure in relation to tension, shortening, and blood flow

We used an in situ isolated diaphragmatic preparation in anesthetized dogs to relate intramuscular pressure (IMP) to the blood flow, tension, and shortening of the diaphragm. In this preparation, the diaphragm shortens in a fashion similar to the intact diaphragm. Tension was measured by transducers attached to the left costal margin, which was detached from the rib cage and abdomen; IMP was measured by a miniature transducer placed between muscle fibers; length was measured by sonomicrometry; and diaphragmatic blood flow was monitored by measuring left phrenic arterial flow. In protocol 1, the relationships between tension, shortening, and IMP were assessed by stimulating the diaphragm for 2 s at various frequencies. Tension and shortening increased with increasing stimulation frequency up to 50 Hz with no change thereafter. Tension was linearly related to IMP. Similarly, there was a linear relationship between the degree of shortening and IMP; however, the slopes varied considerably between dogs. In protocol 2, the diaphragm was paced intermittently (12 trains/min, duty cycle of 0.5) with a gradual increase in stimulation frequency. Blood flow during contraction phase rose slightly at low tension and then declined significantly when tension exceeded 30% of maximum, whereas relaxation-phase flow increased with the increase in tension. IMP rose linearly with the increase in tension, and the IMP, at the point where contraction-phase flow became severely limited, was 50 +/- 14 mmHg (mean +/- SE). We conclude the following. 1) IMP is linearly related to tension and shortening; however, because tension and shortening changed simultaneously during contractions, the independent relationship of either tension or shortening and IMP remained untested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chemical activation of thin-fiber phrenic afferents: respiratory responses

In supine chloralose-anesthetized and mechanically ventilated dogs, we assessed the effects of group III and IV thin-fiber phrenic afferents on cardiorespiratory control by injecting capsaicin into the phrenic artery of an in situ isolated and innervated left diaphragm. Inspiratory motor drive was assessed by measuring the electromyogram of left and right diaphragm, left parasternal, and mylohyoid muscles in five protocols. 1) Three boluses (2 ml) of capsaicin (1, 10, and 50 micrograms/ml) were injected 30 min apart. Only the 50-micrograms/ml injection elicited a significant increase in arterial pressure, heart rate, and inspiratory motor drive. 2) Repeated doses of capsaicin were tested. The pressor and hyperpneic responses were weakened. 3) High doses of capsaicin (100 and 500 micrograms/ml) were given. Hyperpneic and pressor responses were similar to those elicited by the 50-micrograms/ml dose. 4) When the left phrenic nerve was sectioned, the pressor and hyperpneic responses to the 50-micrograms/ml injection were abolished. 5) Capsaicin (50 micrograms/ml) was infused into the arterial supply of the in situ vascularly isolated and innervated gastrocnemius. Arterial pressure, breathing frequency, and inspiratory motor drive to all inspiratory muscles increased significantly and to a greater degree than in the diaphragm. In conclusion, diaphragmatic thin-fiber afferents have an excitatory effect on the inspiratory motor drive and arterial pressure that is similar to that seen in limb muscles.     

In vivo contractile properties of fatigued diaphragm

The effects of fatigue on diaphragmatic contractility in vivo are unknown. In this study we used sonomicrometry to examine the velocity of shortening and lengthening and the amount of shortening in the fresh and fatigued canine hemidiaphragm (8 dogs) including the force generated. Fatigue was produced by epiphrenic stimulation of the left phrenic nerve; the right hemidiaphragm acted as the control. We found that 1) hemidiaphragmatic fatigue caused an increase in frequency with reduced tidal volume; 2) fatigue resulted in a near complete cessation of tidal shortening during spontaneous breathing; 3) there was an initial decrease in central activation (electromyogram) to the fatigued hemidiaphragm, an indication of central fatigue; 4) force-frequency curves showed a considerable and prolonged loss of the amount of shortening, velocity, and force generated by the fatigued hemidiaphragm during supramaximal stimulation, an indication of peripheral fatigue; and 5) during spontaneous breathing in the fatigued hemidiaphragm, tidal shortening remained reduced for up to 3 h, whereas in the right right hemidiaphragm tidal shortening and electromyographic activity did not change. We conclude that fatigue of a hemidiaphragm alters the spontaneous breathing pattern and produces profound modifications in its contractile properties without altering contralateral hemidiaphragmatic performance.     

Activity of nitric oxide synthase in the ventilatory muscle vasculature

We evaluated in the in situ vascularly isolated canine diaphragm the role of nitric oxide (NO) in the regulation of basal vascular resistance and vascular responses to increased muscle activity (active hyperemia), brief occlusions of the phrenic artery (reactive hyperemia), and changes in arterial pressure. The vasculature of the left hemidiaphragm was either pump-perfused at a fixed flow rate or autoperfused with arterial blood from the femoral artery. Endothelial nitric oxide synthase (NOS) activity was inhibited by intraphrenic infusion of L-arginine analogues such as N(G)-nitro-L-arginine, N(G)-nitro-L-arginine methyl ester and argininosuccinic acid. Active hyperemia was produced by low (2 Hz) frequency stimulation of the left phrenic nerve. Reactive hyperemia was measured in response to 10, 20, 30, 60, and 120 sec duration occlusions of the left phrenic artery and was quantified in terms of postocclusive blood flow, vascular resistance, hyperemic duration, and hyperemic volume. Infusion of NOS inhibitors into the vasculature of the resting diaphragm increased phrenic vascular resistance significantly and to a similar extent. Reactive hyperemic volume and reactive hyperemic duration were also significantly attenuated after NOS inhibition, however, peak reactive hyperemic dilation was not influenced by NOS inhibition. It was also found that enhanced NO release contribute by about 41% to active dilation elicited by continuous 2 Hz stimulation. In addition, NOS inhibition had no effect on O2 consumption of the resting diaphragm, but significantly attenuated the rise in diaphragmatic O2 consumption during during 2 Hz stimulation. The decline in diaphragmatic O2 consumption was due to reduction in blood flow. These results indicate that NO release plays a significant role in the regulation of diaphragmatic vascular tone and O2 consumption.     

Role of endothelium-derived relaxing factor in active hyperemia of the canine diaphragm.

To assess the effect of endothelium-derived relaxing factor (EDRF) on diaphragmatic vascular resistance at rest and during contractions, we studied an in situ isolated diaphragm preparation in anesthetized and mechanically ventilated dogs. The arterial supply of the left diaphragm (phrenic artery) was catheterized and perfused with arterial blood at a fixed flow rate. Drugs were infused through a side port of the arterial catheter at 1/100th of the phrenic arterial flow. The inferior phrenic vein was catheterized to complete the isolation from the systemic circulation. Three sets of experiments were performed. In set 1 (n = 3), we infused endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) dilators at increasing concentrations. ACh and SNP infusion elicited a dose-dependent decline in phrenic vascular resistance (Rphr) at concentrations greater than 10(-8) M and 0.50 micrograms/ml, respectively. In set 2 (n = 15), we infused an inhibitor of EDRF synthesis and release, L-argininosuccinic acid (ArgSA), at increasing concentrations (10(-4), 3 x 10(-4), and 6 x 10(-4) M). ArgSA produced a dose-dependent increase in Rphr. Infusion of another EDRF inhibitor (NG-nitro-L-arginine, LNA, 6 x 10(-4) M) elicited increase in Rphr similar to that induced by ArgSA. In set 3 (n = 25), we infused ArgSA or LNA (6 x 10(-4) M) simultaneously with ACh and SNP and during sustained (2-Hz) contractions of the diaphragm. Both ArgSA and LNA completely reversed ACh vasodilation, whereas SNP vasodilation was reversed by 26 and 11%, respectively. ArgSA or LNA infusion during contractions reversed vasodilation by 48 and 52%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapid shallow breathing evoked by capsaicin from isolated pulmonary circulation

Recently Green et al. (J. Appl. Physiol. 57:562-567, 1984) reported that pulmonary C-fibers initiate the prompt apnea evoked by pulmonary arterial injections of capsaicin; however, their role in the subsequent rapid shallow breathing of the pulmonary chemoreflex is still in dispute. To determine whether this reflex tachypnea is triggered by pulmonary C-fibers rather than by afferents further downstream, we separately perfused the pulmonary and systemic circulations in dogs anesthetized with either halothane or alpha-chloralose as the lungs were ventilated with a servo-controlled ventilator driven by phrenic nerve activity. Injection of capsaicin (10 micrograms/kg) into the pulmonary artery of the isolated pulmonary circulation evoked an immediate apnea followed by rapid shallow breathing. Injection of the same dose of capsaicin into the left atrium of the isolated pulmonary circulation had no effect. By contrast, when capsaicin was administered at a slower rate into the pulmonary artery (10-20 micrograms X kg-1 X min-1) rapid shallow breathing occurred but without apnea. Our results are consistent with the hypothesis that in spontaneously breathing animals, stimulation of pulmonary C-fibers can evoke rapid shallow breathing.     

Determinants of diaphragm motion in unilateral diaphragmatic paralysis.

Cranial displacement of a hemidiaphragm during sniffs is a cardinal sign of unilateral diaphragmatic paralysis in clinical practice. However, we have recently observed that isolated stimulation of one phrenic nerve in dogs causes the contralateral (inactive) hemidiaphragm to move caudally. In the present study, therefore, we tested the idea that, in unilateral diaphragmatic paralysis, the pattern of inspiratory muscle contraction plays a major role in determining the motion of the inactive hemidiaphragm. We induced a hemidiaphragmatic paralysis in six anesthetized dogs and assessed the contour of the diaphragm during isolated unilateral phrenic nerve stimulation and during spontaneous inspiratory efforts. Whereas the inactive hemidiaphragm moved caudally in the first instance, it moved cranially in the second. The parasternal intercostal muscles were then severed to reduce the contribution of the rib cage muscles to inspiratory efforts and to enhance the force generated by the intact hemidiaphragm. Although the change in pleural pressure (DeltaPpl) was unaltered, the cranial displacement of the paralyzed hemidiaphragm was consistently reduced. A pneumothorax was finally induced to eliminate DeltaPpl during unilateral phrenic nerve stimulation, and this enhanced the caudal displacement of the inactive hemidiaphragm. These observations indicate that, in unilateral diaphragmatic paralysis, the motion of the inactive hemidiaphragm is largely determined by the balance between the force related to DeltaPpl and the force generated by the intact hemidiaphragm.     

Influence of substance P on carotid sinus nerve baro- and chemoreceptor activity in rabbits.

Substance P (SP) is abundant in the carotid sinus nerve (CSN) and has been implicated in baro- and chemoreceptor reflexes. We examined the effect of SP on blood pressure, heart rate, phrenic nerve activity, hindlimb perfusion pressure, and cardiac contractile strength in urethane-anesthetized rabbits with bilaterally cut cervical sympathetic, vagus, and aortic depressor nerves. Retrograde simultaneous injection of SP (0.5-2.7 micrograms/kg in 0.2-0.3 ml saline) into both carotid sinus areas via the internal carotid arteries decreased blood pressure (by 56%), heart rate (by 13%), cardiac contractility (by 25%) and phrenic nerve activity (by 77%). The effect on hindlimb perfusion pressure was variable. There was both a reflex effect and direct hindlimb vasodilation. In another group of rabbits, the carotid sinus areas were vascularly isolated and perfused with SP (0.19 micrograms/min dissolved in Locke's solution) or Locke's solution alone for 5 min. While carotid sinus perfusion pressure was maintained in the range of 80-120 mmHg, mean arterial blood pressure, heart rate, and unit activity from the CSN were recorded. SP increased the activity of 11 of 18 baroreceptor fibers and inhibited all of 20 chemoreceptor fibers. SP decreased mean arterial blood pressure and heart rate, but the changes were less than those obtained with injection of SP into nonisolated carotid sinus arteries because systemic effects of SP, which in some cases counteracted the reflex effects, were eliminated.     

Bradykinin causes hypotension by activating pulmonary sympathetic afferents in the rabbit.

Bradykinin (BK) activates sympathetic afferents in the heart, intestine, and kidney, and it alters hemodynamics. However, we know little about the influence of pulmonary sympathetic afferents on circulation. Activation of pulmonary afferents by directly injecting stimulants into the lung parenchyma permits examination of reflexes that originate in the lung without confounding effects from the systemic circulation. In the present study, we tested the hypothesis that pulmonary sympathetic afferents exert a significant influence on hemodynamics. We examined reflex effects of injecting BK (1 microg/kg in 0.1 ml) into the lung parenchyma on circulation in anesthetized, open-chest, artificially ventilated rabbits. BK significantly decreased mean arterial blood pressure (BP) (27 +/- 3 mmHg) and heart rate (19 +/- 4 beats/min). Both effects remained after bilateral vagotomy. To rule out possible direct systemic vasodilation by BK, we examined renal sympathetic nerve activity (RSNA) in response to BK injection and examined BP responses to injection of ACh (0.1 ml of 10-4 M). BK suppressed the RSNA before and after vagotomy. ACh did not change BP when injected into the lung parenchyma, but it decreased BP (31 +/- 3 mmHg) when injected into the right atrium. Our data indicate that activating pulmonary sympathetic afferents reflexly suppresses hemodynamics.     

Are prostaglandins involved in atrial natriuretic peptide mechanisms of cardiovascular control?

Atrial natriuretic peptide (ANP) can excite cardiac nerve endings and invoke a decrease in arterial blood pressure and a reduction in renal sympathetic nerve activity. Our laboratory has previously demonstrated that this renal depressor reflex was invoked by systemic injection of ANP and not by the direct application of ANP to the epicardium, a major locus for vagal afferents. We now examine whether inhibition of prostaglandin synthesis impairs reflex responses that are normally associated with ANP injections. Renal sympathetic nerve activity, arterial blood pressure, and heart rate were recorded in anesthetized rats. Indomethacin was used to inhibit prostaglandin synthesis through the cyclooxygenase pathway. The ANP-mediated decrease in arterial blood pressure and renal sympathetic nerve activity, observed when prostaglandin synthesis was inhibited, did not differ significantly from the decreases observed in these parameters when prostaglandin synthesis was not inhibited. Heart rate remained unchanged. Our results suggest that the sympatho-inhibitory effects of ANP do not require prostaglandins as intermediary compounds.     

Effect of acute nutritional deprivation on diaphragm structure and function

The influence of 90 h of acute nutritional deprivation (ND) on the cross-sectional areas of muscle fibers and the contractile and fatigue properties of the adult rat diaphragm were determined. Isometric contractile properties and fatigue resistance of the diaphragm were measured by means of an in vitro nerve-muscle strip preparation. Contractions were evoked by using phrenic nerve stimulation (left hemidiaphragm) or direct muscle stimulation (right hemidiaphragm) in the presence of curare. Acute ND resulted in a 20% reduction in body weight. No significant decrements in diaphragm or soleus weights were noted in the ND animals compared with controls (CTL), whereas the weight of the medial gastrocnemius was reduced by 20% in the ND animals. Peak twitch and tetanic tensions (normalized for the weight of the diaphragm strip) were not reduced in ND compared with CTL animals after either nerve or muscle stimulation. The fatigue index of the diaphragm was significantly reduced in ND animals only after nerve stimulation. After the fatigue test, there was rapid recovery of the additional fatigue noted with nerve stimulation. The proportions of type I and II muscle fibers of the diaphragm were similar in the CTL and ND animals. No differences in diaphragm cross-sectional areas were noted for either type I or II muscle fibers in the CTL and ND animals. It is concluded that acute ND has no effect on diaphragm contractility or morphometry and only an inconsequential influence on diaphragm fatigue.     

Cardiorespiratory responses to chemical activation of right ventricular receptors

Previous reports have shown that activation of left ventricular receptors with sympathetic afferents elicits increases in respiratory output and arterial pressure. The purpose of the present study was to determine whether similar responses are produced by chemical activation of epicardial receptors in the right ventricle. Receptors were stimulated by applying either capsaicin (10 micrograms) or bradykinin (500 ng) to the epicardial surface of the right ventricle in anesthetized cats. Application of either chemical evoked an increase in respiratory output (phrenic nerve activity), a decrease in heart rate, and a nonsignificant increase in arterial pressure in intact cats. However, capsaicin and bradykinin produced significant increases in arterial pressure, heart rate, and respiratory output after bilateral cervical vagotomy. In contrast, a fall in both heart rate and arterial pressure with only small increases in respiratory output were evoked after bilateral removal of the stellate ganglia in cats with intact vagi. Only small responses to the chemical stimulation of right ventricular receptors persisted after combined vagotomy and stellate ganglionectomy. These findings suggest that 1) activation of epicardial receptors with sympathetic afferents originating in the right ventricle causes an increase in cardiorespiratory function, and 2) activation of right ventricular receptors with vagal afferents produces decreases in heart rate and arterial pressure.     

Stimulation of groups III and IV phrenic afferents reflexly decreases total lung resistance in dogs

Little is known about the reflex effect on airway caliber evoked by stimulation of phrenic afferents. Therefore, in chloralose-anesthetized, paralyzed dogs, we recorded airflow, airway pressure, arterial pressure, and heart rate while electrically stimulating a phrenic nerve. Total lung resistance was calculated breath by breath. The phrenic nerve was stimulated at 3, 5, 20, 70, 140, and 200 times motor threshold and the compound action potential was recorded. Stimulation of the phrenic nerve at three and five times threshold, which activated groups I, II, and a few group III fibers, had no effect on any of the variables measured. Stimulation at 20 times threshold, which activated many group III fibers and groups I and II fibers, reflexly decreased resistance. Stimulation at 70, 140, and 200 times threshold, which activated groups I-IV fibers, evoked progressively greater decreases in lung resistance. The reflex bronchodilation evoked by phrenic nerve stimulation was unaffected by propranolol or phentolamine but was abolished by atropine. We conclude that activation of groups III and IV phrenic nerve afferents reflexly decreased total lung resistance by withdrawing cholinergic tone to airway smooth muscle.     

Restriction of regional blood flow and diaphragmatic contractility

We have tested the hypothesis that the diaphragmatic head-to-head arterial anastomosis system should maintain adequate diaphragmatic function even during occlusion of some of its arteries. In six anesthetized open-chest dogs, left phrenic vein blood flow (Qphv) was measured by pulsed Doppler flowmetry. Contractility was measured by sonomicrometry in the left costal and crural diaphragm. The diaphragm was paced for 15 min by continuous bilateral supramaximal phrenic nerve stimulation. In five separate runs the following arteries were occluded at minute 5: 1) left phrenic artery, 2) internal mammary artery (IMA), 3) left phrenic artery and IMA, 4) descending aorta, and 5) descending aorta and IMA. Occlusion was then released at minute 10 of the run. In runs 1-3 there were no changes in contractility in costal or crural diaphragm and no changes in Qphv. However, in runs 4 and 5, Qphv decreased to 55.2 +/- 7.4 and 24.0 +/- 6.5% of control values, respectively. In run 4, percent maximum shortening from functional residual capacity (%LFRC) of the crural diaphragm decreased by 39.1%, while %LFRC of the costal diaphragm increased by 41.4% and abdominal pressure decreased by 47.0%. In run 5, abdominal pressure decreased by 53.5% and %LFRC of the crural and costal diaphragm decreased by 45.5 and 5.8%, respectively. Also relative postocclusion hyperemia was greater in run 5 (64.8%) than in run 4 (40.2%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reflex cardiorespiratory responses to pulmonary vascular congestion

The purpose of these studies was to determine the reflex responses of the cardiovascular system and central inspiratory activity caused by pulmonary vascular congestion. We used a canine preparation in which the left lung was isolated in situ and could be exposed to a variety of stimuli, including distension of the pulmonary capillaries with blood, without direct mechanical or chemical alterations on the circulation. We found that lung expansion to 30 cmH2O and stimulation of nerve endings of the left lung with capsaicin caused pronounced transient reflex bradycardia (-30 to -50 beats/min) and hypotension (-25 to -40 mmHg) and caused reflex cessation of inspiratory activity. Pressurizing the left pulmonary vessels by injecting blood in volumes sufficient to raise pulmonary transcapillary pressures to 30 mmHg caused no changes in heart rate, systemic arterial pressure, or inspiratory muscle activity. These results lead us to conclude that pulmonary vascular congestion does not stimulate pulmonary C-fibers or any other nerve endings to such a degree as to cause detectable changes in blood pressure, heart rate, or central inspiratory activity. Morphometric analysis revealed distended capillaries engorged with blood, but the alveolar wall surface area was not increased which raises the possibility that expansion of the alveolar membrane may be needed to mechanically initiate the C-fiber reflex.